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Patients with COVID-19 frequently experience a coagulopathy associated with a high incidence of thrombotic events leading to poor outcomes.,Here, biomarkers of coagulation (such as D-dimer, fibrinogen, platelet count), inflammation (such as interleukin-6) and immunity (such as lymphocyte count) as well as clinical scoring systems (such as SOFA, ISTH DIC and SIC score) can be helpful in predicting clinical course, need for hospital resources (such as ICU beds, intubation and ventilator therapy, and ECMO) and patient’s outcome in patients with COVID-19.,However, therapeutic options are actually limited to unspecific supportive therapy.,Whether viscoelastic testing can provide additional value in predicting clinical course, need for hospital resources and patient’s outcome or in guiding anticoagulation in COVID-19 associated coagulopathy is still incompletely understood and currently under investigation (eg, in the ROHOCO study).,This paper summarizes what we know already about COVID-19 associated coagulopathy and - perhaps even more importantly - characterizes important knowledge gaps.

Patients with coronavirus disease 2019 (COVID-19) have elevated D-dimer levels.,Early reports describe high venous thromboembolism (VTE) and disseminated intravascular coagulation (DIC) rates, but data are limited.,This multicenter retrospective study describes the rate and severity of hemostatic and thrombotic complications of 400 hospital-admitted COVID-19 patients (144 critically ill) primarily receiving standard-dose prophylactic anticoagulation.,Coagulation and inflammatory parameters were compared between patients with and without coagulation-associated complications.,Multivariable logistic models examined the utility of these markers in predicting coagulation-associated complications, critical illness, and death.,The radiographically confirmed VTE rate was 4.8% (95% confidence interval [CI], 2.9-7.3), and the overall thrombotic complication rate was 9.5% (95% CI, 6.8-12.8).,The overall and major bleeding rates were 4.8% (95% CI, 2.9-7.3) and 2.3% (95% CI, 1.0-4.2), respectively.,In the critically ill, radiographically confirmed VTE and major bleeding rates were 7.6% (95% CI, 3.9-13.3) and 5.6% (95% CI, 2.4-10.7), respectively.,Elevated D-dimer at initial presentation was predictive of coagulation-associated complications during hospitalization (D-dimer >2500 ng/mL, adjusted odds ratio [OR] for thrombosis, 6.79 [95% CI, 2.39-19.30]; adjusted OR for bleeding, 3.56 [95% CI, 1.01-12.66]), critical illness, and death.,Additional markers at initial presentation predictive of thrombosis during hospitalization included platelet count >450 × 109/L (adjusted OR, 3.56 [95% CI, 1.27-9.97]), C-reactive protein (CRP) >100 mg/L (adjusted OR, 2.71 [95% CI, 1.26-5.86]), and erythrocyte sedimentation rate (ESR) >40 mm/h (adjusted OR, 2.64 [95% CI, 1.07-6.51]).,ESR, CRP, fibrinogen, ferritin, and procalcitonin were higher in patients with thrombotic complications than in those without.,DIC, clinically relevant thrombocytopenia, and reduced fibrinogen were rare and were associated with significant bleeding manifestations.,Given the observed bleeding rates, randomized trials are needed to determine any potential benefit of intensified anticoagulant prophylaxis in COVID-19 patients.,•In addition to thrombotic complications, bleeding is a significant cause of morbidity in patients with COVID-19.,•D-dimer elevation at admission was predictive of bleeding, thrombosis, critical illness, and death in patients with COVID-19.,In addition to thrombotic complications, bleeding is a significant cause of morbidity in patients with COVID-19.,D-dimer elevation at admission was predictive of bleeding, thrombosis, critical illness, and death in patients with COVID-19.

To appraise the clinical and genetic evidence that low-density lipoproteins (LDLs) cause atherosclerotic cardiovascular disease (ASCVD).,We assessed whether the association between LDL and ASCVD fulfils the criteria for causality by evaluating the totality of evidence from genetic studies, prospective epidemiologic cohort studies, Mendelian randomization studies, and randomized trials of LDL-lowering therapies.,In clinical studies, plasma LDL burden is usually estimated by determination of plasma LDL cholesterol level (LDL-C).,Rare genetic mutations that cause reduced LDL receptor function lead to markedly higher LDL-C and a dose-dependent increase in the risk of ASCVD, whereas rare variants leading to lower LDL-C are associated with a correspondingly lower risk of ASCVD.,Separate meta-analyses of over 200 prospective cohort studies, Mendelian randomization studies, and randomized trials including more than 2 million participants with over 20 million person-years of follow-up and over 150 000 cardiovascular events demonstrate a remarkably consistent dose-dependent log-linear association between the absolute magnitude of exposure of the vasculature to LDL-C and the risk of ASCVD; and this effect appears to increase with increasing duration of exposure to LDL-C.,Both the naturally randomized genetic studies and the randomized intervention trials consistently demonstrate that any mechanism of lowering plasma LDL particle concentration should reduce the risk of ASCVD events proportional to the absolute reduction in LDL-C and the cumulative duration of exposure to lower LDL-C, provided that the achieved reduction in LDL-C is concordant with the reduction in LDL particle number and that there are no competing deleterious off-target effects.,Consistent evidence from numerous and multiple different types of clinical and genetic studies unequivocally establishes that LDL causes ASCVD.

The lipoprotein(a) pathway is a causal factor in coronary heart disease.,We used a genetic approach to distinguish the relevance of two distinct components of this pathway, apolipoprotein(a) isoform size and circulating lipoprotein(a) concentration, to coronary heart disease.,In this mendelian randomisation study, we measured lipoprotein(a) concentration and determined apolipoprotein(a) isoform size with a genetic method (kringle IV type 2 [KIV2] repeats in the LPA gene) and a serum-based electrophoretic assay in patients and controls (frequency matched for age and sex) from the Pakistan Risk of Myocardial Infarction Study (PROMIS).,We calculated odds ratios (ORs) for myocardial infarction per 1-SD difference in either LPA KIV2 repeats or lipoprotein(a) concentration.,In a genome-wide analysis of up to 17 503 participants in PROMIS, we identified genetic variants associated with either apolipoprotein(a) isoform size or lipoprotein(a) concentration.,Using a mendelian randomisation study design and genetic data on 60 801 patients with coronary heart disease and 123 504 controls from the CARDIoGRAMplusC4D consortium, we calculated ORs for myocardial infarction with variants that produced similar differences in either apolipoprotein(a) isoform size in serum or lipoprotein(a) concentration.,Finally, we compared phenotypic versus genotypic ORs to estimate whether apolipoprotein(a) isoform size, lipoprotein(a) concentration, or both were causally associated with coronary heart disease.,The PROMIS cohort included 9015 patients with acute myocardial infarction and 8629 matched controls.,In participants for whom KIV2 repeat and lipoprotein(a) data were available, the OR for myocardial infarction was 0·93 (95% CI 0·90-0·97; p<0·0001) per 1-SD increment in LPA KIV2 repeats after adjustment for lipoprotein(a) concentration and conventional lipid concentrations.,The OR for myocardial infarction was 1·10 (1·05-1·14; p<0·0001) per 1-SD increment in lipoprotein(a) concentration, after adjustment for LPA KIV2 repeats and conventional lipids.,Genome-wide analysis identified rs2457564 as a variant associated with smaller apolipoprotein(a) isoform size, but not lipoprotein(a) concentration, and rs3777392 as a variant associated with lipoprotein(a) concentration, but not apolipoprotein(a) isoform size.,In 60 801 patients with coronary heart disease and 123 504 controls, OR for myocardial infarction was 0·96 (0·94-0·98; p<0·0001) per 1-SD increment in apolipoprotein(a) protein isoform size in serum due to rs2457564, which was directionally concordant with the OR observed in PROMIS for a similar change.,The OR for myocardial infarction was 1·27 (1·07-1·50; p=0·007) per 1-SD increment in lipoprotein(a) concentration due to rs3777392, which was directionally concordant with the OR observed for a similar change in PROMIS.,Human genetic data suggest that both smaller apolipoprotein(a) isoform size and increased lipoprotein(a) concentration are independent and causal risk factors for coronary heart disease.,Lipoprotein(a)-lowering interventions could be preferentially effective in reducing the risk of coronary heart disease in individuals with smaller apolipoprotein(a) isoforms.,British Heart Foundation, US National Institutes of Health, Fogarty International Center, Wellcome Trust, UK Medical Research Council, UK National Institute for Health Research, and Pfizer.

microRNAs (miRNAs) post‐transcriptionally regulate cardiac repair following myocardial infarction (MI).,Omega‐3 polyunsaturated fatty acid (ω‐3 PUFAs) may support cardiac healing after MI, but the mechanism is unclear.,The fat‐1 transgenic mouse expresses a ω‐3 fatty acid desaturase which converts ω‐6 PUFAs to ω‐3 PUFAs in vivo.,MI was induced in fat‐1 transgenic (n = 30) and wild‐type (WT) mice (n = 30) using permanent ligation.,Other transgenic and WT mice underwent sham procedure (n = 30 and n = 30, respectively).,One week after occlusion, cardiac function was measured by echocardiography and the infarct size was assessed using histology and miRNA microarray profiling.,Expression of selected miRNA was confirmed using quantitative real‐time PCR.,One week following MI, the fat‐1 transgenic myocardium had better cardiac function, a smaller fibrotic area, and fewer apoptotic cardiomyocytes than WT myocardium.,Post‐MI profiling showed 33 miRNAs that were significantly up‐regulated, and 35 were down‐regulated, in fat‐1 group compared to the WT group (n = 3 and n = 2 mice, respectively).,Among selected apoptosis‐associated miRNAs, 9 miRNAs were up‐regulated (miR‐101a‐3p, miR‐128‐3p,miR‐133a‐5p,miR‐149‐5p,miR‐192‐5p,miR‐1a‐3p,miR‐208a‐3p,miR‐29c‐5p,miR‐30c‐2‐3p), and 3 were down‐regulated (miR‐210‐3p,miR‐21a‐3p,miR‐214‐3p) in fat‐1 transgenic mice compared with WT mice.,Kyoto encyclopaedia of genes and genomes (KEGG) pathway analysis indicated likely roles for these miRNAs in MI.,Furthermore, Bcl‐2 expression was increased, and caspase‐3 decreased, in infarcted fat‐1 transgenic mouse hearts compared to WT hearts.,ω‐3 PUFAs may have a protective effect on cardiomyocytes following MI through their modulation of apoptosis‐related miRNAs and target genes.

Chronic cardiac stress induces pathologic hypertrophy and fibrosis of the myocardium.,The microRNA-29 (miR-29) family has been found to prevent excess collagen expression in various organs, particularly through its function in fibroblasts.,Here, we show that miR-29 promotes pathologic hypertrophy of cardiac myocytes and overall cardiac dysfunction.,In a mouse model of cardiac pressure overload, global genetic deletion of miR-29 or antimiR-29 infusion prevents cardiac hypertrophy and fibrosis and improves cardiac function.,Targeted deletion of miR-29 in cardiac myocytes in vivo also prevents cardiac hypertrophy and fibrosis, indicating that the function of miR-29 in cardiac myocytes dominates over that in non-myocyte cell types.,Mechanistically, we found cardiac myocyte miR-29 to de-repress Wnt signaling by directly targeting four pathway factors.,Our data suggests that, cell- or tissue-specific antimiR-29 delivery may have therapeutic value for pathological cardiac remodeling and fibrosis.,MicroRNA-29 is known to reduce collagen production in fibroblasts thereby inhibiting fibrosis in various organs.,Here, Sassi et al. show that miR-29 can also enhance fibrotic signalling and pathological hypertrophy of the heart through its action in cardiomyocytes.

Hyperglycaemia associated with myocardial oxidative stress and fibrosis is the main cause of diabetic cardiomyopathy.,Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor has recently been reported to improve glycaemic control in patients with type 2 diabetes in an insulin-independent manner.,The aim of this study was to investigate the effect of empagliflozin on myocardium injury and the potential mechanism in type 2 diabetic KK-Ay mice.,Thirty diabetic KK-Ay mice were administered empagliflozin (10 mg/kg/day) by oral gavage daily for 8 weeks.,After 8 weeks, heart structure and function were evaluated by echocardiography.,Oxidants and antioxidants were measured and cardiac fibrosis was analysed using immunohistochemistry, Masson’s trichrome stain and Western blot.,Results showed that empagliflozin improved diabetic myocardial structure and function, decreased myocardial oxidative stress and ameliorated myocardial fibrosis.,Further study indicated that empagliflozin suppressed oxidative stress and fibrosis through inhibition of the transforming growth factor β/Smad pathway and activation of Nrf2/ARE signaling.,Glycaemic control with empagliflozin significantly ameliorated myocardial oxidative stress injury and cardiac fibrosis in diabetic mice.,Taken together, these results indicate that the empagliflozin is a promising agent for the prevention and treatment of diabetic cardiomyopathy.

Both incidence and mortality of acute coronary syndrome (ACS) among diabetic patients are much higher than those among nondiabetics.,Actually, there are many studies that addressed glycemic control and CV risk, whilst the literature on the role of tight glycemic control during ACS is currently poor.,Therefore, in this review, we critically discussed the studies that investigated this specific topic.,Hyperglycemia is implicated in vascular damage and cardiac myocyte death through different molecular mechanisms as advanced glycation end products, protein kinase C, polyol pathway flux, and the hexosamine pathway.,Moreover, high FFA concentrations may be toxic in acute ischemic myocardium due to several mechanisms, thus leading to endothelial dysfunction.,A reduction in free fatty acid plasma levels and an increased availability of glucose can be achieved by using a glucose-insulin-potassium infusion (GIKi) during AMI.,The GIKi is associated with an improvement of either long-term prognosis or left ventricular mechanical performance.,DIGAMI studies suggested blood glucose level as a significant and independent mortality predictor among diabetic patients with recent ACS, enhancing the important role of glucose control in their management.,Several mechanisms supporting the protective role of tight glycemic control during ACS, as well as position statements of Scientific Societies, were highlighted.

What are the cardiovascular effects in unselected patients with recent coronavirus disease 2019 (COVID-19)?,In this cohort study including 100 patients recently recovered from COVID-19 identified from a COVID-19 test center, cardiac magnetic resonance imaging revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), which was independent of preexisting conditions, severity and overall course of the acute illness, and the time from the original diagnosis.,These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.,This cohort study evaluates the presence of myocardial injury in unselected patients recently recovered from coronavirus disease 2019 (COVID-19).,Coronavirus disease 2019 (COVID-19) continues to cause considerable morbidity and mortality worldwide.,Case reports of hospitalized patients suggest that COVID-19 prominently affects the cardiovascular system, but the overall impact remains unknown.,To evaluate the presence of myocardial injury in unselected patients recently recovered from COVID-19 illness.,In this prospective observational cohort study, 100 patients recently recovered from COVID-19 illness were identified from the University Hospital Frankfurt COVID-19 Registry between April and June 2020.,Recent recovery from severe acute respiratory syndrome coronavirus 2 infection, as determined by reverse transcription-polymerase chain reaction on swab test of the upper respiratory tract.,Demographic characteristics, cardiac blood markers, and cardiovascular magnetic resonance (CMR) imaging were obtained.,Comparisons were made with age-matched and sex-matched control groups of healthy volunteers (n = 50) and risk factor-matched patients (n = 57).,Of the 100 included patients, 53 (53%) were male, and the mean (SD) age was 49 (14) years.,The median (IQR) time interval between COVID-19 diagnosis and CMR was 71 (64-92) days.,Of the 100 patients recently recovered from COVID-19, 67 (67%) recovered at home, while 33 (33%) required hospitalization.,At the time of CMR, high-sensitivity troponin T (hsTnT) was detectable (greater than 3 pg/mL) in 71 patients recently recovered from COVID-19 (71%) and significantly elevated (greater than 13.9 pg/mL) in 5 patients (5%).,Compared with healthy controls and risk factor-matched controls, patients recently recovered from COVID-19 had lower left ventricular ejection fraction, higher left ventricle volumes, and raised native T1 and T2.,A total of 78 patients recently recovered from COVID-19 (78%) had abnormal CMR findings, including raised myocardial native T1 (n = 73), raised myocardial native T2 (n = 60), myocardial late gadolinium enhancement (n = 32), or pericardial enhancement (n = 22).,There was a small but significant difference between patients who recovered at home vs in the hospital for native T1 mapping (median [IQR], 1119 [1092-1150] ms vs 1141 [1121-1175] ms; P = .008) and hsTnT (4.2 [3.0-5.9] pg/dL vs 6.3 [3.4-7.9] pg/dL; P = .002) but not for native T2 mapping.,None of these measures were correlated with time from COVID-19 diagnosis (native T1: r = 0.07; P = .47; native T2: r = 0.14; P = .15; hsTnT: r = −0.07; P = .50).,High-sensitivity troponin T was significantly correlated with native T1 mapping (r = 0.33; P < .001) and native T2 mapping (r = 0.18; P = .01).,Endomyocardial biopsy in patients with severe findings revealed active lymphocytic inflammation.,Native T1 and T2 were the measures with the best discriminatory ability to detect COVID-19-related myocardial pathology.,In this study of a cohort of German patients recently recovered from COVID-19 infection, CMR revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), independent of preexisting conditions, severity and overall course of the acute illness, and time from the original diagnosis.,These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.

To investigate the characteristics and clinical significance of myocardial injury in patients with severe coronavirus disease 2019 (COVID-19).,We enrolled 671 eligible hospitalized patients with severe COVID-19 from 1 January to 23 February 2020, with a median age of 63 years.,Clinical, laboratory, and treatment data were collected and compared between patients who died and survivors.,Risk factors of death and myocardial injury were analysed using multivariable regression models.,A total of 62 patients (9.2%) died, who more often had myocardial injury (75.8% vs.,9.7%; P < 0.001) than survivors.,The area under the receiver operating characteristic curve of initial cardiac troponin I (cTnI) for predicting in-hospital mortality was 0.92 [95% confidence interval (CI), 0.87-0.96; sensitivity, 0.86; specificity, 0.86; P < 0.001].,The single cut-off point and high level of cTnI predicted risk of in-hospital death, hazard ratio (HR) was 4.56 (95% CI, 1.28-16.28; P = 0.019) and 1.25 (95% CI, 1.07-1.46; P = 0.004), respectively.,In multivariable logistic regression, senior age, comorbidities (e.g. hypertension, coronary heart disease, chronic renal failure, and chronic obstructive pulmonary disease), and high level of C-reactive protein were predictors of myocardial injury.,The risk of in-hospital death among patients with severe COVID-19 can be predicted by markers of myocardial injury, and was significantly associated with senior age, inflammatory response, and cardiovascular comorbidities.

Since the appearance of the first case of coronavirus disease 2019 (COVID-19) a pandemic has emerged affecting millions of people worldwide.,Although the main clinical manifestations are respiratory, an increase in neurological conditions, specifically acute cerebrovascular disease, has been detected.,We present cerebrovascular disease case incidence in hospitalized patients with SARS-CoV-2 infection.,Patients were confirmed by microbiological/serological testing, or on chest CT semiology.,Available data on comorbidity, laboratory parameters, treatment administered, neuroimaging, neuropathological studies and clinical evolution during hospitalization, measured by the modified Rankin scale, were analysed.,A bivariate study was also designed to identify differences between ischaemic and haemorrhagic subtypes.,A statistical model of binary logistic regression and sensitivity analysis was designed to study the influence of independent variables over prognosis.,In our centre, there were 1683 admissions of patients with COVID-19 over 50 days, of which 23 (1.4%) developed cerebrovascular disease.,Within this group of patients, cerebral and chest CT scans were performed in all cases, and MRI in six (26.1%).,Histological samples were obtained in 6/23 cases (two brain biopsies, and four arterial thrombi).,Seventeen patients were classified as cerebral ischaemia (73.9%, with two arterial dissections), five as intracerebral haemorrhage (21.7%), and one leukoencephalopathy of posterior reversible encephalopathy type.,Haemorrhagic patients had higher ferritin levels at the time of stroke (1554.3 versus 519.2, P = 0.004).,Ischaemic strokes were unexpectedly frequent in the vertebrobasilar territory (6/17, 35.3%).,In the haemorrhagic group, a characteristic radiological pattern was identified showing subarachnoid haemorrhage, parieto-occipital leukoencephalopathy, microbleeds and single or multiple focal haematomas.,Brain biopsies performed showed signs of thrombotic microangiopathy and endothelial injury, with no evidence of vasculitis or necrotizing encephalitis.,The functional prognosis during the hospital period was unfavourable in 73.9% (17/23 modified Rankin scale 4-6), and age was the main predictive variable (odds ratio = 1.5; 95% confidence interval 1.012-2.225; P = 0.043).,Our series shows cerebrovascular disease incidence of 1.4% in patients with COVID-19 with high morbidity and mortality.,We describe pathological and radiological data consistent with thrombotic microangiopathy caused by endotheliopathy with a haemorrhagic predisposition.

Initial reports suggest a significant risk of thrombotic events, including stroke, in patients hospitalized with coronavirus disease 2019 (COVID-19).,However, there is little systematic data on stroke incidence and mechanisms, particularly in racially diverse populations in the United States.,We performed a retrospective, observational study of stroke incidence and mechanisms in all patients with COVID-19 hospitalized from March 15 to May 3, 2020, at 3 Philadelphia hospitals.,We identified 844 hospitalized patients with COVID-19 (mean age 59 years, 52% female, 68% Black); 20 (2.4%) had confirmed ischemic stroke; and 8 (0.9%) had intracranial hemorrhage.,Of the ischemic stroke patients, mean age was 64 years, with only one patient (5%) under age 50, and 80% were Black.,Conventional vascular risk factors were common, with 95% of patients having a history of hypertension and 60% a history of diabetes mellitus.,Median time from onset of COVID symptoms to stroke diagnosis was 21 days.,Stroke mechanism was cardioembolism in 40%, small vessel disease in 5%, other determined mechanism in 20%, and cryptogenic in 35%.,Of the 11 patients with complete vascular imaging, 3 (27%) had large vessel occlusion.,Newly positive antiphospholipid antibodies were present in >75% of tested patients.,Of the patients with intracranial hemorrhage, 5/8 (63%) were lobar intraparenchymal hemorrhages, and 3/8 (38%) were subarachnoid hemorrhage; 4/8 (50%) were on extracorporeal membrane oxygenation.,We found a low risk of acute cerebrovascular events in patients hospitalized with COVID-19.,Most patients with ischemic stroke had conventional vascular risk factors, and traditional stroke mechanisms were common.

While an expanding armamentarium of pharmacologic therapies has contributed to improved outcomes among adults with heart failure (HF) over the past two decades, this has also been accompanied by an increase in the number of medications taken by adults with HF.,The use of at least 10 medications, defined as hyperpolypharmacy, is particularly notable given its association with adverse outcomes.,We aimed to assess the prevalence and identify determinants of hyperpolypharmacy among adults with HF.,We studied adults aged ≥50 years with self-reported HF from the National Health And Nutrition Examination Survey (NHANES) in 2003-2014.,We calculated weighted means and percentages to describe patient characteristics.,We conducted a multivariable Poisson regression analysis to identify factors independently associated with hyperpolypharmacy; we adjusted for survey sampling, socio-demographics, comorbidity, geriatric conditions, and health care utilization.,We examined 947 participants, representing 4.6 million adults with HF.,The prevalence of hyperpolypharmacy was 26%.,In a multivariable regression analysis, comorbidity count, ≥10 ambulatory contacts, and ≥ 3 hospitalizations were independently associated with hyperpolypharmacy.,Interestingly, functional impairment and cognitive impairment were not independently associated with hyperpolypharmacy; while low annual household income and low educational status were each associated with an almost 2-fold increase in hyperpolypharmacy.,Hyperpolypharmacy is a common condition among adults with HF.,We additionally found that low household income and low educational status are independently associated with hyperpolypharmacy, suggesting that non-medical factors may be contributing to this potentially harmful condition.

Heart failure prevalence is increasing in older adults, and polypharmacy is a major problem in this population.,We compared medication regimen complexity using the validated patient-level Medication Regimen Complexity Index (pMRCI) tool in “young-old” (60-74 years) versus “old-old” (75-89 years) patients with heart failure.,We also compared pMRCI between patients with ischemic cardiomyopathy (ISCM) versus nonischemic cardiomyopathy (NISCM).,Medication lists were retrospectively abstracted from the electronic medical records of ambulatory patients aged 60-89 years with heart failure.,Medications were categorized into three types - heart failure prescription medications, other prescription medications, and over-the-counter (OTC) medications - and scored using the pMRCI tool.,The study evaluated 145 patients (n=80 young-old, n=65 old-old, n=85 ISCM, n=60 NISCM, mean age 73±7 years, 64% men, 81% Caucasian).,Mean total pMRCI scores (32.1±14.4, range 3-84) and total medication counts (13.3±4.8, range 2-30) were high for the entire cohort, of which 72% of patients were taking eleven or more total medications.,Total and subtype pMRCI scores and medication counts did not differ significantly between the young-old and old-old groups, with the exception of OTC medication pMRCI score (6.2±4 young-old versus 7.8±5.8 old-old, P=0.04).,With regard to heart failure etiology, total pMRCI scores and medication counts were significantly higher in patients with ISCM versus NISCM (pMRCI score 34.5±15.2 versus 28.8±12.7, P=0.009; medication count 14.1±4.9 versus 12.2±4.5, P=0.008), which was largely driven by other prescription medications.,Medication regimen complexity is high in older adults with heart failure, and differs based on heart failure etiology.,Additional work is needed to address polypharmacy and to determine if medication regimen complexity influences adherence and clinical outcomes in this population.

Increases in cardiac troponin indicative of myocardial injury are common in patients with coronavirus disease-2019 (COVID-19) and are associated with adverse outcomes such as arrhythmias and death.,These increases are more likely to occur in those with chronic cardiovascular conditions and in those with severe COVID-19 presentations.,The increased inflammatory, prothrombotic, and procoagulant responses following severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection increase the risk for acute nonischemic myocardial injury and acute myocardial infarction, particularly type 2 myocardial infarction, because of respiratory failure with hypoxia and hemodynamic instability in critically ill patients.,Myocarditis, stress cardiomyopathy, acute heart failure, and direct injury from SARS-CoV-2 are important etiologies, but primary noncardiac conditions, such as pulmonary embolism, critical illness, and sepsis, probably cause more of the myocardial injury.,The structured use of serial cardiac troponin has the potential to facilitate risk stratification, help make decisions about when to use imaging, and inform stage categorization and disease phenotyping among hospitalized COVID-19 patients.,•Increases in cardiac troponin indicative of myocardial injury are common and prognostic in COVID-19.,•Increases can be due to chronic injury, acute nonischemic injury, or acute MI.,•Troponin, along with inflammatory and thrombotic markers, may facilitate COVID-19 stage classification and risk stratification.,Increases in cardiac troponin indicative of myocardial injury are common and prognostic in COVID-19.,Increases can be due to chronic injury, acute nonischemic injury, or acute MI.,Troponin, along with inflammatory and thrombotic markers, may facilitate COVID-19 stage classification and risk stratification.

Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described.,In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020.,Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors.,We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death.,191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients).,Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03-1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61-12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64-128·55; p=0·0033) on admission.,Median duration of viral shedding was 20·0 days (IQR 17·0-24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors.,The longest observed duration of viral shedding in survivors was 37 days.,The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage.,Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.,Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Background: New treatments are needed to reduce myocardial infarct size (MI) and prevent heart failure (HF) following acute myocardial infarction (AMI), which are the leading causes of death and disability worldwide.,Studies in rodent AMI models showed that genetic and pharmacological inhibition of mitochondrial fission, induced by acute ischemia and reperfusion, reduced MI size.,Whether targeting mitochondrial fission at the onset of reperfusion is also cardioprotective in a clinically-relevant large animal AMI model remains to be determined.,Methods: Adult pigs (30-40 kg) were subjected to closed-chest 90-min left anterior descending artery ischemia followed by 72 h of reperfusion and were randomized to receive an intracoronary bolus of either mdivi-1 (1.2 mg/kg, a small molecule inhibitor of the mitochondrial fission protein, Drp1) or vehicle control, 10-min prior to reperfusion.,The left ventricular (LV) size and function were both assessed by transthoracic echocardiography prior to AMI and after 72 h of reperfusion.,MI size and the area-at-risk (AAR) were determined using dual staining with Tetrazolium and Evans blue.,Heart samples were collected for histological determination of fibrosis and for electron microscopic analysis of mitochondrial morphology.,Results: A total of 14 pigs underwent the treatment protocols (eight control and six mdivi-1).,Administration of mdivi-1 immediately prior to the onset of reperfusion did not reduce MI size (MI size as % of AAR: Control 49.2 ± 8.6 vs. mdivi-1 50.5 ± 11.4; p = 0.815) or preserve LV systolic function (LV ejection fraction %: Control 67.5 ± 0.4 vs. mdivi-1 59.6 ± 0.6; p = 0.420), when compared to vehicle control.,Similarly, there were no differences in mitochondrial morphology or myocardial fibrosis between mdivi-1 and vehicle control groups.,Conclusion: Our pilot study has shown that treatment with mdivi-1 (1.2 mg/kg) at the onset of reperfusion did not reduce MI size or preserve LV function in the clinically-relevant closed-chest pig AMI model.,A larger study, testing different doses of mdivi-1 or using a more specific Drp1 inhibitor are required to confirm these findings.

Mitochondria are key regulators of cell fate during disease.,They control cell survival via the production of ATP that fuels cellular processes and, conversely, cell death via the induction of apoptosis through release of pro-apoptotic factors such as cytochrome C.,Therefore, it is essential to have stringent quality control mechanisms to ensure a healthy mitochondrial network.,Quality control mechanisms are largely regulated by mitochondrial dynamics and mitophagy.,The processes of mitochondrial fission (division) and fusion allow for damaged mitochondria to be segregated and facilitate the equilibration of mitochondrial components such as DNA, proteins, and metabolites.,The process of mitophagy are responsible for the degradation and recycling of damaged mitochondria.,These mitochondrial quality control mechanisms have been well studied in chronic and acute pathologies such as Parkinson’s disease, Alzheimer’s disease, stroke, and acute myocardial infarction, but less is known about how these two processes interact and contribute to specific pathophysiologic states.,To date, evidence for the role of mitochondrial quality control in acute and chronic disease is divergent and suggests that mitochondrial quality control processes can serve both survival and death functions depending on the disease state.,This review aims to provide a synopsis of the molecular mechanisms involved in mitochondrial quality control, to summarize our current understanding of the complex role that mitochondrial quality control plays in the progression of acute vs chronic diseases and, finally, to speculate on the possibility that targeted manipulation of mitochondrial quality control mechanisms may be exploited for the rationale design of novel therapeutic interventions.

To evaluate the impact of the COVID-19 pandemic on patient admissions to Italian cardiac care units (CCUs).,We conducted a multicentre, observational, nationwide survey to collect data on admissions for acute myocardial infarction (AMI) at Italian CCUs throughout a 1 week period during the COVID-19 outbreak, compared with the equivalent week in 2019.,We observed a 48.4% reduction in admissions for AMI compared with the equivalent week in 2019 (P < 0.001).,The reduction was significant for both ST-segment elevation myocardial infarction [STEMI; 26.5%, 95% confidence interval (CI) 21.7-32.3; P = 0.009] and non-STEMI (NSTEMI; 65.1%, 95% CI 60.3-70.3; P < 0.001).,Among STEMIs, the reduction was higher for women (41.2%; P = 0.011) than men (17.8%; P = 0.191).,A similar reduction in AMI admissions was registered in North Italy (52.1%), Central Italy (59.3%), and South Italy (52.1%).,The STEMI case fatality rate during the pandemic was substantially increased compared with 2019 [risk ratio (RR) = 3.3, 95% CI 1.7-6.6; P < 0.001].,A parallel increase in complications was also registered (RR = 1.8, 95% CI 1.1-2.8; P = 0.009).,Admissions for AMI were significantly reduced during the COVID-19 pandemic across Italy, with a parallel increase in fatality and complication rates.,This constitutes a serious social issue, demanding attention by the scientific and healthcare communities and public regulatory agencies.

Acute respiratory failure and a systemic coagulopathy are critical aspects of the morbidity and mortality characterizing infection with severe acute respiratory distress syndrome-associated coronavirus-2, the etiologic agent of Coronavirus disease 2019 (COVID-19).,We examined skin and lung tissues from 5 patients with severe COVID-19 characterized by respiratory failure (n= 5) and purpuric skin rash (n = 3).,COVID-19 pneumonitis was predominantly a pauci-inflammatory septal capillary injury with significant septal capillary mural and luminal fibrin deposition and permeation of the interalveolar septa by neutrophils.,No viral cytopathic changes were observed and the diffuse alveolar damage (DAD) with hyaline membranes, inflammation, and type II pneumocyte hyperplasia, hallmarks of classic acute respiratory distress syndrome, were not prominent.,These pulmonary findings were accompanied by significant deposits of terminal complement components C5b-9 (membrane attack complex), C4d, and mannose binding lectin (MBL)-associated serine protease (MASP)2, in the microvasculature, consistent with sustained, systemic activation of the complement pathways.,The purpuric skin lesions similarly showed a pauci-inflammatory thrombogenic vasculopathy, with deposition of C5b-9 and C4d in both grossly involved and normally-appearing skin.,In addition, there was co-localization of COVID-19 spike glycoproteins with C4d and C5b-9 in the interalveolar septa and the cutaneous microvasculature of 2 cases examined.,In conclusion, at least a subset of sustained, severe COVID-19 may define a type of catastrophic microvascular injury syndrome mediated by activation of complement pathways and an associated procoagulant state.,It provides a foundation for further exploration of the pathophysiologic importance of complement in COVID-19, and could suggest targets for specific intervention.

Coronavirus disease 2019 (COVID-19) increases the risk of several non-pulmonary complications such as acute myocardial injury, renal failure or thromboembolic events.,A possible unifying explanation for these phenomena may be the presence of profound endothelial dysfunction and injury.,This review provides an overview on the association of endothelial dysfunction with COVID-19 and its therapeutic implications.,Endothelial dysfunction is a common feature of the key comorbidities that increase risk for severe COVID-19 such as hypertension, obesity, diabetes mellitus, coronary artery disease or heart failure.,Preliminary studies indicate that vascular endothelial cells can be infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and evidence of widespread endothelial injury and inflammation is found in advanced cases of COVID-19.,Prior evidence has established the crucial role of endothelial cells in maintaining and regulating vascular homeostasis and blood coagulation.,Aggravation of endothelial dysfunction in COVID-19 may therefore impair organ perfusion and cause a procoagulatory state resulting in both macro- and microvascular thrombotic events.,Angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and statins are known to improve endothelial dysfunction.,Data from smaller observational studies and other viral infections suggests a possible beneficial effect in COVID-19.,Other treatments that are currently under investigation for COVID-19 may also act by improving endothelial dysfunction in patients.,Focusing therapies on preventing and improving endothelial dysfunction could improve outcomes in COVID-19.,Several clinical trials are currently underway to explore this concept.,Image 1,•New evidence implicates endothelial dysfunction in the pathophysiology of COVID-19.,•It may explain complications such as multi-organ damage or thrombotic events.,•Targeted interventions such as RAS inhibitors or statins may improve outcomes.,•Studies on interventions that affect endothelial dysfunction are underway in COVID-19.,New evidence implicates endothelial dysfunction in the pathophysiology of COVID-19.,It may explain complications such as multi-organ damage or thrombotic events.,Targeted interventions such as RAS inhibitors or statins may improve outcomes.,Studies on interventions that affect endothelial dysfunction are underway in COVID-19.

Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described.,In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020.,Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors.,We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death.,191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients).,Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03-1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61-12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64-128·55; p=0·0033) on admission.,Median duration of viral shedding was 20·0 days (IQR 17·0-24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors.,The longest observed duration of viral shedding in survivors was 37 days.,The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage.,Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.,Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Coronavirus disease 2019 (COVID-19), currently a worldwide pandemic, is a viral illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,The suspected contribution of thrombotic events to morbidity and mortality in COVID-19 patients has prompted a search for novel potential options for preventing COVID-19-associated thrombotic disease.,In this article by the Global COVID-19 Thrombosis Collaborative Group, we describe novel dosing approaches for commonly used antithrombotic agents (especially heparin-based regimens) and the potential use of less widely used antithrombotic drugs in the absence of confirmed thrombosis.,Although these therapies may have direct antithrombotic effects, other mechanisms of action, including anti-inflammatory or antiviral effects, have been postulated.,Based on survey results from this group of authors, we suggest research priorities for specific agents and subgroups of patients with COVID-19.,Further, we review other agents, including immunomodulators, that may have antithrombotic properties.,It is our hope that the present document will encourage and stimulate future prospective studies and randomized trials to study the safety, efficacy, and optimal use of these agents for prevention or management of thrombosis in COVID-19.

Coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has rapidly evolved into a sweeping pandemic.,Its major manifestation is in the respiratory tract, and the general extent of organ involvement and the microscopic changes in the lungs remain insufficiently characterised.,Autopsies are essential to elucidate COVID‐19‐associated organ alterations.,This article reports the autopsy findings of 21 COVID‐19 patients hospitalised at the University Hospital Basel and at the Cantonal Hospital Baselland, Switzerland.,An in‐corpore technique was performed to ensure optimal staff safety.,The primary cause of death was respiratory failure with exudative diffuse alveolar damage and massive capillary congestion, often accompanied by microthrombi despite anticoagulation.,Ten cases showed superimposed bronchopneumonia.,Further findings included pulmonary embolism (n = 4), alveolar haemorrhage (n = 3), and vasculitis (n = 1).,Pathologies in other organ systems were predominantly attributable to shock; three patients showed signs of generalised and five of pulmonary thrombotic microangiopathy.,Six patients were diagnosed with senile cardiac amyloidosis upon autopsy.,Most patients suffered from one or more comorbidities (hypertension, obesity, cardiovascular diseases, and diabetes mellitus).,Additionally, there was an overall predominance of males and individuals with blood group A (81% and 65%, respectively).,All relevant histological slides are linked as open‐source scans in supplementary files.,This study provides an overview of postmortem findings in COVID‐19 cases, implying that hypertensive, elderly, obese, male individuals with severe cardiovascular comorbidities as well as those with blood group A may have a lower threshold of tolerance for COVID‐19.,This provides a pathophysiological explanation for higher mortality rates among these patients.

Atherosclerosis, a dominant and growing cause of death and disability worldwide, involves inflammation from its inception to the emergence of complications.,Targeting inflammatory pathways could therefore provide a promising new avenue to prevent and treat atherosclerosis.,Indeed, clinical studies have now demonstrated unequivocally that modulation of inflammation can forestall the clinical complications of atherosclerosis.,This progress pinpoints the need for preclinical investigations to refine strategies for combatting inflammation in the human disease.,In this Review, we consider a gamut of attractive possibilities for modifying inflammation in atherosclerosis, including targeting pivotal inflammatory pathways such as the inflammasomes, inhibiting cytokines, manipulating adaptive immunity and promoting pro-resolution mechanisms.,Along with lifestyle measures, pharmacological interventions to mute inflammation could complement traditional targets, such as lipids and hypertension, to make new inroads into the management of atherosclerotic risk.,The contribution of inflammation to atherosclerosis is substantial, and is just beginning to be understood.,In this Review, Soehnlein and Libby discuss how inflammation promotes atherosclerosis and its consequences, and how such processes could be targeted therapeutically.,The potential pitfalls of targeting immune processes - namely the increased potential for infections - are also discussed, along with ways to modulate cardiovascular therapies in time and space to make them more effective.

Disrupting the costimulatory CD40-CD40L dyad reduces atherosclerosis, but can result in immune suppression.,The authors recently identified small molecule inhibitors that block the interaction between CD40 and tumor necrosis factor receptor-associated factor (TRAF) 6 (TRAF-STOPs), while leaving CD40-TRAF2/3/5 interactions intact, thereby preserving CD40-mediated immunity.,This study evaluates the potential of TRAF-STOP treatment in atherosclerosis.,The effects of TRAF-STOPs on atherosclerosis were investigated in apolipoprotein E deficient (Apoe−/−) mice.,Recombinant high-density lipoprotein (rHDL) nanoparticles were used to target TRAF-STOPs to macrophages.,TRAF-STOP treatment of young Apoe−/− mice reduced atherosclerosis by reducing CD40 and integrin expression in classical monocytes, thereby hampering monocyte recruitment.,When Apoe−/− mice with established atherosclerosis were treated with TRAF-STOPs, plaque progression was halted, and plaques contained an increase in collagen, developed small necrotic cores, and contained only a few immune cells.,TRAF-STOP treatment did not impair “classical” immune pathways of CD40, including T-cell proliferation and costimulation, Ig isotype switching, or germinal center formation, but reduced CD40 and β2-integrin expression in inflammatory monocytes.,In vitro testing and transcriptional profiling showed that TRAF-STOPs are effective in reducing macrophage migration and activation, which could be attributed to reduced phosphorylation of signaling intermediates of the canonical NF-κB pathway.,To target TRAF-STOPs specifically to macrophages, TRAF-STOP 6877002 was incorporated into rHDL nanoparticles.,Six weeks of rHDL-6877002 treatment attenuated the initiation of atherosclerosis in Apoe−/− mice.,TRAF-STOPs can overcome the current limitations of long-term CD40 inhibition in atherosclerosis and have the potential to become a future therapeutic for atherosclerosis.

COVID-19 is an infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).,Apart from respiratory complications, acute cerebrovascular disease (CVD) has been observed in some patients with COVID-19.,Therefore, we described the clinical characteristics, laboratory features, treatment and outcomes of CVD complicating SARS-CoV-2 infection.,Demographic and clinical characteristics, laboratory findings, treatments and clinical outcomes were collected and analysed.,Clinical characteristics and laboratory findings of patients with COVID-19 with or without new-onset CVD were compared.,Of 219 patients with COVID-19, 10 (4.6%) developed acute ischaemic stroke and 1 (0.5%) had intracerebral haemorrhage.,COVID-19 with new onset of CVD were significantly older (75.7±10.8 years vs 52.1±15.3 years, p<0.001), more likely to present with severe COVID-19 (81.8% vs 39.9%, p<0.01) and were more likely to have cardiovascular risk factors, including hypertension, diabetes and medical history of CVD (all p<0.05).,In addition, they were more likely to have increased inflammatory response and hypercoagulable state as reflected in C reactive protein (51.1 (1.3-127.9) vs 12.1 (0.1-212.0) mg/L, p<0.05) and D-dimer (6.9 (0.3-20.0) vs 0.5 (0.1-20.0) mg/L, p<0.001).,Of 10 patients with ischemic stroke; 6 received antiplatelet treatment with aspirin or clopidogrel; and 3 of them died.,The other four patients received anticoagulant treatment with enoxaparin and 2 of them died.,As of 24 March 2020, six patients with CVD died (54.5%).,Acute CVD is not uncommon in COVID-19.,Our findings suggest that older patients with risk factors are more likely to develop CVD.,The development of CVD is an important negative prognostic factor which requires further study to identify optimal management strategy to combat the COVID-19 outbreak.

Little evidence of increased thrombotic risk is available in COVID-19 patients.,Our purpose was to assess thrombotic risk in severe forms of SARS-CoV-2 infection.,All patients referred to 4 intensive care units (ICUs) from two centers of a French tertiary hospital for acute respiratory distress syndrome (ARDS) due to COVID-19 between March 3rd and 31st 2020 were included.,Medical history, symptoms, biological data and imaging were prospectively collected.,Propensity score matching was performed to analyze the occurrence of thromboembolic events between non-COVID-19 ARDS and COVID-19 ARDS patients.,150 COVID-19 patients were included (122 men, median age 63 [53; 71] years, SAPSII 49 [37; 64] points).,Sixty-four clinically relevant thrombotic complications were diagnosed in 150 patients, mainly pulmonary embolisms (16.7%). 28/29 patients (96.6%) receiving continuous renal replacement therapy experienced circuit clotting.,Three thrombotic occlusions (in 2 patients) of centrifugal pump occurred in 12 patients (8%) supported by ECMO.,Most patients (> 95%) had elevated D-dimer and fibrinogen.,No patient developed disseminated intravascular coagulation.,Von Willebrand (vWF) activity, vWF antigen and FVIII were considerably increased, and 50/57 tested patients (87.7%) had positive lupus anticoagulant.,Comparison with non-COVID-19 ARDS patients (n = 145) confirmed that COVID-19 ARDS patients (n = 77) developed significantly more thrombotic complications, mainly pulmonary embolisms (11.7 vs.,2.1%, p < 0.008).,Coagulation parameters significantly differed between the two groups.,Despite anticoagulation, a high number of patients with ARDS secondary to COVID-19 developed life-threatening thrombotic complications.,Higher anticoagulation targets than in usual critically ill patients should therefore probably be suggested.,The online version of this article (10.1007/s00134-020-06062-x) contains supplementary material, which is available to authorized users.

Reports of widespread thromboses and disseminated intravascular coagulation (DIC) in patients with coronavirus disease 19 (COVID-19) have been rapidly increasing in number.,Key features of this disorder include a lack of bleeding risk, only mildly low platelet counts, elevated plasma fibrinogen levels, and detection of both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and complement components in regions of thrombotic microangiopathy (TMA).,This disorder is not typical DIC.,Rather, it might be more similar to complement-mediated TMA syndromes, which are well known to rheumatologists who care for patients with severe systemic lupus erythematosus or catastrophic antiphospholipid syndrome.,This perspective has critical implications for treatment.,Anticoagulation and antiviral agents are standard treatments for DIC but are gravely insufficient for any of the TMA disorders that involve disorders of complement.,Mediators of TMA syndromes overlap with those released in cytokine storm, suggesting close connections between ineffective immune responses to SARS-CoV-2, severe pneumonia and life-threatening microangiopathy.,A subset of patients with coronavirus disease 19 (COVID-19) develop a thrombotic disorder that resembles a virally induced, complement-mediated thrombotic microangiopathy.,Here, the authors present the theory and evidence for this disease model and discuss important considerations for treatment.

COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation.,Reports on the incidence of thrombotic complications are however not available.,We evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction or systemic arterial embolism in all COVID-19 patients admitted to the ICU of 2 Dutch university hospitals and 1 Dutch teaching hospital.,We studied 184 ICU patients with proven COVID-19 pneumonia of whom 23 died (13%), 22 were discharged alive (12%) and 139 (76%) were still on the ICU on April 5th 2020.,All patients received at least standard doses thromboprophylaxis.,The cumulative incidence of the composite outcome was 31% (95%CI 20-41), of which CTPA and/or ultrasonography confirmed VTE in 27% (95%CI 17-37%) and arterial thrombotic events in 3.7% (95%CI 0-8.2%).,PE was the most frequent thrombotic complication (n = 25, 81%).,Age (adjusted hazard ratio (aHR) 1.05/per year, 95%CI 1.004-1.01) and coagulopathy, defined as spontaneous prolongation of the prothrombin time > 3 s or activated partial thromboplastin time > 5 s (aHR 4.1, 95%CI 1.9-9.1), were independent predictors of thrombotic complications.,The 31% incidence of thrombotic complications in ICU patients with COVID-19 infections is remarkably high.,Our findings reinforce the recommendation to strictly apply pharmacological thrombosis prophylaxis in all COVID-19 patients admitted to the ICU, and are strongly suggestive of increasing the prophylaxis towards high-prophylactic doses, even in the absence of randomized evidence.

Although the pathophysiology underlying severe COVID19 remains poorly understood, accumulating data suggest that a lung‐centric coagulopathy may play an important role.,Elevated D‐dimer levels which correlated inversely with overall survival were recently reported in Chinese cohort studies.,Critically however, ethnicity has major effects on thrombotic risk, with a 3-4‐fold lower risk in Chinese compared to Caucasians and a significantly higher risk in African‐Americans.,In this study, we investigated COVID19 coagulopathy in Caucasian patients.,Our findings confirm that severe COVID19 infection is associated with a significant coagulopathy that correlates with disease severity.,Importantly however, Caucasian COVID19 patients on low molecular weight heparin thromboprophylaxis rarely develop overt disseminated intravascular coagulation (DIC).,In rare COVID19 cases where DIC does develop, it tends to be restricted to late‐stage disease.,Collectively, these data suggest that the diffuse bilateral pulmonary inflammation observed in COVID19 is associated with a novel pulmonary‐specific vasculopathy termed pulmonary intravascular coagulopathy (PIC) as distinct to DIC.,Given that thrombotic risk is significantly impacted by race, coupled with the accumulating evidence that coagulopathy is important in COVID19 pathogenesis, our findings raise the intriguing possibility that pulmonary vasculopathy may contribute to the unexplained differences that are beginning to emerge highlighting racial susceptibility to COVID19 mortality.

We recently reported a high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 admitted to the intensive care units (ICUs) of three Dutch hospitals.,In answering questions raised regarding our study, we updated our database and repeated all analyses.,We re-evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction and/or systemic arterial embolism in all COVID-19 patients admitted to the ICUs of 2 Dutch university hospitals and 1 Dutch teaching hospital from ICU admission to death, ICU discharge or April 22nd 2020, whichever came first.,We studied the same 184 ICU patients as reported on previously, of whom a total of 41 died (22%) and 78 were discharged alive (43%).,The median follow-up duration increased from 7 to 14 days.,All patients received pharmacological thromboprophylaxis.,The cumulative incidence of the composite outcome, adjusted for competing risk of death, was 49% (95% confidence interval [CI] 41-57%).,The majority of thrombotic events were PE (65/75; 87%).,In the competing risk model, chronic anticoagulation therapy at admission was associated with a lower risk of the composite outcome (Hazard Ratio [HR] 0.29, 95%CI 0.091-0.92).,Patients diagnosed with thrombotic complications were at higher risk of all-cause death (HR 5.4; 95%CI 2.4-12).,Use of therapeutic anticoagulation was not associated with all-cause death (HR 0.79, 95%CI 0.35-1.8).,In this updated analysis, we confirm the very high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 pneumonia.

Thirty percent of Covid‐19 patients admitted to intensive care units present with thrombotic complications despite thromboprophylaxis.,Bed rest, obesity, hypoxia, coagulopathy, and acute excessive inflammation are potential mechanisms reported by previous studies.,Better understanding of the underlying mechanisms leading to thrombosis is crucial for developing more appropriate prophylaxis and treatment strategies.,We aimed to assess fibrinolytic activity and thrombin generation in 78 Covid‐19 patients.,Forty‐eight patients admitted to the intensive care unit and 30 patients admitted to the internal medicine department were included in the study.,All patients received thromboprophylaxis.,We measured fibrinolytic parameters (tissue plasminogen activator, PAI‐1, thrombin activatable fibrinolysis inhibitor, alpha2 anti‐plasmin, and tissue plasminogen activator‐modified ROTEM device), thrombin generation, and other coagulation tests (D‐dimer, fibrinogen, factor VIII, antithrombin).,We observed two key findings: a high thrombin generation capacity that remained within normal values despite heparin therapy and a hypofibrinolysis mainly associated with increased PAI‐1 levels.,A modified ROTEM is able to detect both hypercoagulability and hypofibrinolysis simultaneously in Covid‐19 patients with thrombosis.

Chilblains (‘COVID toes’) are being seen with increasing frequency in children and young adults during the COVID‐19 pandemic.,Detailed histopathological descriptions of COVID‐19 chilblains have not been reported, and causality of SARS‐CoV‐2 has not yet been established.,To describe the histopathological features of COVID‐19 chilblains and to explore the presence of SARS‐CoV‐2 in the tissue.,We examined skin biopsies from seven paediatric patients presenting with chilblains during the COVID‐19 pandemic.,Immunohistochemistry for SARS‐CoV‐2 was performed in all cases and electron microscopy in one.,Histopathology showed variable degrees of lymphocytic vasculitis ranging from endothelial swelling and endotheliitis to fibrinoid necrosis and thrombosis.,Purpura, superficial and deep perivascular lymphocytic inflammation with perieccrine accentuation, oedema, and mild vacuolar interface damage were also seen.,SARS‐CoV‐2 immunohistochemistry was positive in endothelial cells and epithelial cells of eccrine glands.,Coronavirus particles were found in the cytoplasm of endothelial cells on electron microscopy.,Although the clinical and histopathological features were similar to other forms of chilblains, the presence of viral particles in the endothelium and the histological evidence of vascular damage support a causal relation of the lesions with SARS‐CoV‐2.,Endothelial damage induced by the virus could be the key mechanism in the pathogenesis of COVID‐19 chilblains and perhaps also in a group of patients severely affected by COVID‐19 presenting with features of microangiopathic damage.,What is already known about this topic?,Despite the high number of cases of chilblains seen during the COVID‐19 pandemic, a definite causative role for SARS‐CoV‐2 has not yet been proven.Different pathogenetic hypotheses have been proposed, including coagulation anomalies, interferon release and external factors.,Despite the high number of cases of chilblains seen during the COVID‐19 pandemic, a definite causative role for SARS‐CoV‐2 has not yet been proven.,Different pathogenetic hypotheses have been proposed, including coagulation anomalies, interferon release and external factors.,What does this study add?,The demonstration of SARS‐CoV‐2 in endothelial cells of skin biopsies by immunohistochemistry and electron microscopy confirms that these lesions are part of the spectrum of COVID‐19.,Virus‐induced vascular damage and secondary ischaemia could explain the pathophysiology of COVID‐19 chilblains.Our findings support the hypothesis that widespread endothelial infection by SARS‐CoV‐2 could have a pathogenetic role in the severe forms of COVID‐19.,The demonstration of SARS‐CoV‐2 in endothelial cells of skin biopsies by immunohistochemistry and electron microscopy confirms that these lesions are part of the spectrum of COVID‐19.,Virus‐induced vascular damage and secondary ischaemia could explain the pathophysiology of COVID‐19 chilblains.,Our findings support the hypothesis that widespread endothelial infection by SARS‐CoV‐2 could have a pathogenetic role in the severe forms of COVID‐19.,Linked Comment: Wetter.,Br J Dermatol 2020; 183:611.

To quantify rates of organ specific dysfunction in individuals with covid-19 after discharge from hospital compared with a matched control group from the general population.,Retrospective cohort study.,NHS hospitals in England.,47 780 individuals (mean age 65, 55% men) in hospital with covid-19 and discharged alive by 31 August 2020, exactly matched to controls from a pool of about 50 million people in England for personal and clinical characteristics from 10 years of electronic health records.,Rates of hospital readmission (or any admission for controls), all cause mortality, and diagnoses of respiratory, cardiovascular, metabolic, kidney, and liver diseases until 30 September 2020.,Variations in rate ratios by age, sex, and ethnicity.,Over a mean follow-up of 140 days, nearly a third of individuals who were discharged from hospital after acute covid-19 were readmitted (14 060 of 47 780) and more than 1 in 10 (5875) died after discharge, with these events occurring at rates four and eight times greater, respectively, than in the matched control group.,Rates of respiratory disease (P<0.001), diabetes (P<0.001), and cardiovascular disease (P<0.001) were also significantly raised in patients with covid-19, with 770 (95% confidence interval 758 to 783), 127 (122 to 132), and 126 (121 to 131) diagnoses per 1000 person years, respectively.,Rate ratios were greater for individuals aged less than 70 than for those aged 70 or older, and in ethnic minority groups compared with the white population, with the largest differences seen for respiratory disease (10.5 (95% confidence interval 9.7 to 11.4) for age less than 70 years v 4.6 (4.3 to 4.8) for age ≥70, and 11.4 (9.8 to 13.3) for non-white v 5.2 (5.0 to 5.5) for white individuals).,Individuals discharged from hospital after covid-19 had increased rates of multiorgan dysfunction compared with the expected risk in the general population.,The increase in risk was not confined to the elderly and was not uniform across ethnicities.,The diagnosis, treatment, and prevention of post-covid syndrome requires integrated rather than organ or disease specific approaches, and urgent research is needed to establish the risk factors.

Coronavirus disease 2019 (COVID-19) induces myocardial injury, either direct myocarditis or indirect injury due to systemic inflammatory response.,Myocardial involvement has been proved to be one of the primary manifestations of COVID-19 infection, according to laboratory test, autopsy, and cardiovascular magnetic resonance (CMR).,However, the middle-term outcome of cardiac involvement after the patients were discharged from the hospital is yet unknown.,The present study aimed to evaluate mid-term cardiac sequelae in recovered COVID-19 patients by CMR,A total of 47 recovered COVID-19 patients were prospectively recruited and underwent CMR examination.,The CMR protocol consisted of black blood fat-suppressed T2 weighted imaging, T2 star mapping, left ventricle (LV) cine imaging, pre- and post-contrast T1 mapping, and late gadolinium enhancement (LGE).,LGE were assessed in mixed both recovered COVID-19 patients and healthy controls.,The LV and right ventricle (RV) function and LV mass were assessed and compared with healthy controls.,A total of 44 recovered COVID-19 patients and 31 healthy controls were studied.,LGE was found in 13 (30%) of COVID-19 patients.,All LGE lesions were located in the mid myocardium and/or sub-epicardium with a scattered distribution.,Further analysis showed that LGE-positive patients had significantly decreased LV peak global circumferential strain (GCS), RV peak GCS, RV peak global longitudinal strain (GLS) as compared to non-LGE patients (p < 0.05), while no difference was found between the non-LGE patients and healthy controls.,Myocardium injury existed in 30% of COVID-19 patients.,These patients have depressed LV GCS and peak RV strains at the 3-month follow-up.,CMR can monitor the COVID-19-induced myocarditis progression, and CMR strain analysis is a sensitive tool to evaluate the recovery of LV and RV dysfunction.

Severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) has first emerged from China in December 2019 and causes coronavirus induced disease 19 (COVID-19).,Since then researchers worldwide have been struggling to detect the possible pathogenesis of this disease.,COVID-19 showed a wide range of clinical behavior from asymptomatic to severe acute respiratory disease syndrome.,However, the etiology of susceptibility to severe lung injury is not yet fully understood.,Angiotensin-converting enzyme1 (ACE1) convert angiotensin I into Angiotensin II that was further metabolized by ACE 2 (ACE2).,The binding ACE2 receptor to SARS-CoV-2 facilitate its enter into the host cell.,The interaction and imbalance between ACE1 and ACE2 play a crucial role in the pathogenesis of lung injury.,Thus, the aim of this study was to investigate the association of ACE1 I/D polymorphism with severity of Covid-19.,The study included RT-PCR confirmed 269 cases of Covid-19.,All cases were genotyped for ACE1 I/D polymorphism using polymerase chain reaction and followed by statistical analysis (SPSS, version 15.0).,We found that ACE1 DD genotype, frequency of D allele, older age (≥46 years), unmarried status, and presence of diabetes and hypertension were significantly higher in severe COVID-19 patient.,ACE1 ID genotype was significantly independently associated with high socio-economic COVID-19 patients (OR: 2.48, 95% CI: 1.331-4.609).,These data suggest that the ACE1 genotype may impact the incidence and clinical outcome of COVID-19 and serve as a predictive marker for COVID-19 risk and severity.

•The Angiotensin system has been implicated in the pathogenesis of COVID-19.,•Functional ACE/ACE2 polymorphisms might contribute to the outcome of COVID-19.,•Severe COVID-19 was associated with hypertension, male gender, and ACE-DD genotype.,•The ACE2 polymorphism was not associated with the disease outcome.,•ACE2 showed no coding variants that could explain an increased risk of COVID-19.,The Angiotensin system has been implicated in the pathogenesis of COVID-19.,Functional ACE/ACE2 polymorphisms might contribute to the outcome of COVID-19.,Severe COVID-19 was associated with hypertension, male gender, and ACE-DD genotype.,The ACE2 polymorphism was not associated with the disease outcome.,ACE2 showed no coding variants that could explain an increased risk of COVID-19.,The Angiotensin system is implicated in the pathogenesis of COVID-19.,First, ACE2 is the cellular receptor for SARS-CoV-2, and expression of the ACE2 gene could regulate the individuaĺs susceptibility to infection.,In addition, the balance between ACE1 and ACE2 activity has been implicated in the pathogenesis of respiratory diseases and could play a role in the severity of COVID-19.,Functional ACE1/ACE2 gene polymorphisms have been associated with the risk of cardiovascular and pulmonary diseases, and could thus also contribute to the outcome of COVID-19.,We studied 204 COVID-19 patients (137 non-severe and 67 severe-ICU cases) and 536 age-matched controls.,The ACE1 insertion/deletion and ACE2 rs2285666 polymorphism were determined.,Variables frequencies were compared between the groups by logistic regression.,We also sequenced the ACE2 coding nucleotides in a group of patients.,Severe COVID-19 was associated with hypertension male gender (p < 0.001), hypertension (p = 0.006), hypercholesterolaemia (p = 0.046), and the ACE1-DD genotype (p = 0.049).,In the multiple logistic regression hypertension (p = 0.02, OR = 2.26, 95%CI = 1.12-4.63) and male gender (p = 0.002; OR = 3.15, 95%CI = 1.56-6.66) remained as independent significant predictors of severity.,The ACE2 polymorphism was not associated with the disease outcome.,The ACE2 sequencing showed no coding sequence variants that could explain an increased risk of developing COVID-19.,In conclusion, an adverse outcome of COVID-19 was associated with male gender, hypertension, hypercholesterolemia and the ACE1 genotype.,Our work suggested that the ACE1-I/D might influence COVID-19 severity, but the effect was dependent on the hypertensive status.,This result requires further validation in other large cohorts.

Venous thromboembolic events have been one of the main causes of mortality among hospitalized patients with coronavirus disease 2019 (COVID-19) pneumonia.,The aim of our study was to describe the prevalence of deep vein thrombosis (DVT) in noncritically ill patients with COVID-19 pneumonia and correlate such observations with the thromboprophylaxis received.,We performed a prospective cohort study of 67 patients admitted to the hospital for COVID-19 pneumonia.,The diagnosis was confirmed using polymerase chain reaction testing of nasopharyngeal specimens.,The deep veins were examined using compression duplex ultrasonography with the transducer on B-mode.,The patients were separated into two groups for statistical analysis: those receiving low-molecular-weight heparin prophylaxis and those receiving intermediate or complete anticoagulation treatment.,Risk analysis and logistic regression were performed.,Of the 67 patients, 57 were included in the present study after applying the inclusion and exclusion criteria; 49.1% were women, and the patient mean age was 71.3 years.,All 57 patients had undergone compression duplex ultrasonography.,Of these 57 patients, 6 were diagnosed with DVT, for an in-hospital rate of DVT in patients with COVID-19 pneumonia of 10.5%.,All the patients who had presented with DVT had been receiving low-molecular-weight heparin prophylaxis.,The patients receiving prophylactic anticoagulation treatment had a greater risk of DVT (16.21%; 95% confidence interval, 0.04-0.28; P = .056) compared with those receiving intermediate or complete anticoagulation treatment.,We also found a protective factor for DVT in the intermediate or complete anticoagulation treatment group (odds ratio, 0.19; 95% confidence interval, 0.08-0.46; P < .05).,Noncritically ill, hospitalized patients with COVID-19 pneumonia have a high risk of DVT despite receipt of correct, standard thromboprophylaxis.

The aim of this study was to determine the frequency of venous thromboembolism in critically ill coronavirus disease 2019 patients and associate a degree of inflammatory marker elevation to venous thromboembolism development.,An observational study that identified patients with severe coronavirus disease 2019 between March 12, 2020, and March 31, 2020.,Data reported are those available through May 6, 2020.,A multicenter study including three Indianapolis area academic hospitals.,Two-hundred forty consecutive patients with confirmed severe acute respiratory syndrome coronavirus 2 infection were admitted to one of three hospitals.,One-hundred nine critically ill coronavirus disease 2019 patients admitted to the ICU were included in the analysis.,All patients received routine subcutaneous chemical venous thromboembolism prophylaxis.,The primary outcome of this study was to determine the frequency of venous thromboembolism and the degree of inflammatory and coagulation marker elevation associated with venous thromboembolism development.,Descriptive statistics outlined the frequency of venous thromboembolism at any time during severe coronavirus disease 2019.,Clinical course and laboratory metrics were compared between patients that developed venous thromboembolism and patients that did not develop venous thromboembolism.,Hypercoagulable thromboelastography was defined as two or more hypercoagulable parameters.,One-hundred nine patients developed severe coronavirus disease 2019 requiring ICU care.,The mean (± sd) age was 61 ± 16 years and 57% were male.,Seventy-five patients (69%) were discharged home, 7 patients (6%) remain in the hospital, and 27 patients (25%) died.,Venous thromboembolism was diagnosed in 31 patients (28%) 8 ± 7 days after hospital admission, including two patients diagnosed with venous thromboembolism at presentation to the hospital.,Elevated admission d-dimer and peak d-dimer were associated with venous thromboembolism development (p < 0.05). d-dimer greater than 2,600 ng/mL predicted venous thromboembolism with an area under the receiver operating characteristic curve of 0.760 (95% CI, 0.661-0.858; p < 0.0001), sensitivity of 89.7%, and specificity of 59.5%.,Twelve patients (11%) had thromboelastography performed and 58% of these patients had a hypercoagulable study.,The calculated coagulation index was hypercoagulable in 50% of patients with thromboelastography.,These data show that coronavirus disease 2019 results in a hypercoagulable state.,Routine chemical venous thromboembolism prophylaxis may be inadequate in preventing venous thromboembolism in severe coronavirus disease 2019.

Supplemental Digital Content is available in the text.,Several studies have suggested a role for the gut microbiota in inflammation and atherogenesis.,A causal relation relationship between gut microbiota, inflammation, and atherosclerosis has not been explored previously.,Here, we investigated whether a proinflammatory microbiota from Caspase1−/− (Casp1−/−) mice accelerates atherogenesis in Ldlr−/− mice.,We treated female Ldlr−/− mice with antibiotics and subsequently transplanted them with fecal microbiota from Casp1−/− mice based on a cohousing approach.,Autologous transplantation of fecal microbiota of Ldlr−/− mice served as control.,Mice were cohoused for 8 or 13 weeks and fed chow or high-fat cholesterol-rich diet.,Fecal samples were collected, and factors related to inflammation, metabolism, intestinal health, and atherosclerotic phenotypes were measured.,Unweighted Unifrac distances of 16S rDNA (ribosomal DNA) sequences confirmed the introduction of the Casp1−/− and Ldlr−/− microbiota into Ldlr−/− mice (referred to as Ldlr−/−(Casp1−/−) or Ldlr−/−(Ldlr−/−) mice).,Analysis of atherosclerotic lesion size in the aortic root demonstrated a significant 29% increase in plaque size in 13-week high-fat cholesterol-fed Ldlr−/−(Casp1−/−) mice compared with Ldlr−/−(Ldlr−/−) mice.,We found increased numbers of circulating monocytes and neutrophils and elevated proinflammatory cytokine levels in plasma in high-fat cholesterol-fed Ldlr−/−(Casp1−/−) compared with Ldlr−/−(Ldlr−/−) mice.,Neutrophil accumulation in the aortic root of Ldlr−/−(Casp1−/−) mice was enhanced compared with Ldlr−/−(Ldlr−/−) mice.,16S-rDNA-encoding sequence analysis in feces identified a significant reduction in the short-chain fatty acid-producing taxonomies Akkermansia, Christensenellaceae, Clostridium, and Odoribacter in Ldlr−/−(Casp1−/−) mice.,Consistent with these findings, cumulative concentrations of the anti-inflammatory short-chain fatty acids propionate, acetate and butyrate in the cecum were significantly reduced in 13-week high-fat cholesterol-fed Ldlr−/−(Casp1−/−) compared with Ldlr−/−(Ldlr−/−) mice.,Introduction of the proinflammatory Casp1−/− microbiota into Ldlr−/− mice enhances systemic inflammation and accelerates atherogenesis.

The gut microbiota has been linked to cardiovascular diseases.,However, the composition and functional capacity of the gut microbiome in relation to cardiovascular diseases have not been systematically examined.,Here, we perform a metagenome-wide association study on stools from 218 individuals with atherosclerotic cardiovascular disease (ACVD) and 187 healthy controls.,The ACVD gut microbiome deviates from the healthy status by increased abundance of Enterobacteriaceae and Streptococcus spp. and, functionally, in the potential for metabolism or transport of several molecules important for cardiovascular health.,Although drug treatment represents a confounding factor, ACVD status, and not current drug use, is the major distinguishing feature in this cohort.,We identify common themes by comparison with gut microbiome data associated with other cardiometabolic diseases (obesity and type 2 diabetes), with liver cirrhosis, and rheumatoid arthritis.,Our data represent a comprehensive resource for further investigations on the role of the gut microbiome in promoting or preventing ACVD as well as other related diseases.,The gut microbiota may play a role in cardiovascular diseases.,Here, the authors perform a metagenome-wide association study on stools from individuals with atherosclerotic cardiovascular disease and healthy controls, identifying microbial strains and functions associated with the disease.

Patients with coronavirus disease 2019 (COVID-19) have elevated D-dimer levels.,Early reports describe high venous thromboembolism (VTE) and disseminated intravascular coagulation (DIC) rates, but data are limited.,This multicenter retrospective study describes the rate and severity of hemostatic and thrombotic complications of 400 hospital-admitted COVID-19 patients (144 critically ill) primarily receiving standard-dose prophylactic anticoagulation.,Coagulation and inflammatory parameters were compared between patients with and without coagulation-associated complications.,Multivariable logistic models examined the utility of these markers in predicting coagulation-associated complications, critical illness, and death.,The radiographically confirmed VTE rate was 4.8% (95% confidence interval [CI], 2.9-7.3), and the overall thrombotic complication rate was 9.5% (95% CI, 6.8-12.8).,The overall and major bleeding rates were 4.8% (95% CI, 2.9-7.3) and 2.3% (95% CI, 1.0-4.2), respectively.,In the critically ill, radiographically confirmed VTE and major bleeding rates were 7.6% (95% CI, 3.9-13.3) and 5.6% (95% CI, 2.4-10.7), respectively.,Elevated D-dimer at initial presentation was predictive of coagulation-associated complications during hospitalization (D-dimer >2500 ng/mL, adjusted odds ratio [OR] for thrombosis, 6.79 [95% CI, 2.39-19.30]; adjusted OR for bleeding, 3.56 [95% CI, 1.01-12.66]), critical illness, and death.,Additional markers at initial presentation predictive of thrombosis during hospitalization included platelet count >450 × 109/L (adjusted OR, 3.56 [95% CI, 1.27-9.97]), C-reactive protein (CRP) >100 mg/L (adjusted OR, 2.71 [95% CI, 1.26-5.86]), and erythrocyte sedimentation rate (ESR) >40 mm/h (adjusted OR, 2.64 [95% CI, 1.07-6.51]).,ESR, CRP, fibrinogen, ferritin, and procalcitonin were higher in patients with thrombotic complications than in those without.,DIC, clinically relevant thrombocytopenia, and reduced fibrinogen were rare and were associated with significant bleeding manifestations.,Given the observed bleeding rates, randomized trials are needed to determine any potential benefit of intensified anticoagulant prophylaxis in COVID-19 patients.,•In addition to thrombotic complications, bleeding is a significant cause of morbidity in patients with COVID-19.,•D-dimer elevation at admission was predictive of bleeding, thrombosis, critical illness, and death in patients with COVID-19.,In addition to thrombotic complications, bleeding is a significant cause of morbidity in patients with COVID-19.,D-dimer elevation at admission was predictive of bleeding, thrombosis, critical illness, and death in patients with COVID-19.

Emerging evidence shows that severe coronavirus disease 2019 (COVID-19) can be complicated by a significant coagulopathy, that likely manifests in the form of both microthrombosis and VTE.,This recognition has led to the urgent need for practical guidance regarding prevention, diagnosis, and treatment of VTE.,A group of approved panelists developed key clinical questions by using the PICO (Population, Intervention, Comparator, Outcome) format that addressed urgent clinical questions regarding the prevention, diagnosis, and treatment of VTE in patients with COVID-19.,MEDLINE (via PubMed or Ovid), Embase, and Cochrane Controlled Register of Trials were systematically searched for relevant literature, and references were screened for inclusion.,Validated evaluation tools were used to grade the level of evidence to support each recommendation.,When evidence did not exist, guidance was developed based on consensus using the modified Delphi process.,The systematic review and critical analysis of the literature based on 13 Population, Intervention, Comparator, Outcome questions resulted in 22 statements.,Very little evidence exists in the COVID-19 population.,The panel thus used expert consensus and existing evidence-based guidelines to craft the guidance statements.,The evidence on the optimal strategies to prevent, diagnose, and treat VTE in patients with COVID-19 is sparse but rapidly evolving.

The prevalence of venous thromboembolic event (VTE) and arterial thromboembolic event (ATE) thromboembolic events in patients with COVID-19 remains largely unknown.,In this meta-analysis, we systematically searched for observational studies describing the prevalence of VTE and ATE in COVID-19 up to 30 September 2020.,We analysed findings from 102 studies (64 503 patients).,The frequency of COVID-19-related VTE was 14.7% (95% CI 12.1% to 17.6%, I2=94%; 56 studies; 16 507 patients).,The overall prevalence rates of pulmonary embolism (PE) and leg deep vein thrombosis were 7.8% (95% CI 6.2% to 9.4%, I2=94%; 66 studies; 23 117 patients) and 11.2% (95% CI 8.4% to 14.3%, I2=95%; 48 studies; 13 824 patients), respectively.,Few were isolated subsegmental PE.,The VTE prevalence was significantly higher in intensive care unit (ICU) (23.2%, 95% CI 17.5% to 29.6%, I2=92%, vs 9.0%, 95% CI 6.9% to 11.4%, I2=95%; pinteraction<0.0001) and in series systematically screening patients compared with series testing symptomatic patients (25.2% vs 12.7%, pinteraction=0.04).,The frequency rates of overall ATE, acute coronary syndrome, stroke and other ATE were 3.9% (95% CI 2.0% to to 3.0%, I2=96%; 16 studies; 7939 patients), 1.6% (95% CI 1.0% to 2.2%, I2=93%; 27 studies; 40 597 patients) and 0.9% (95% CI 0.5% to 1.5%, I2=84%; 17 studies; 20 139 patients), respectively.,Metaregression and subgroup analyses failed to explain heterogeneity of overall ATE.,High heterogeneity limited the value of estimates.,Patients admitted in the ICU for severe COVID-19 had a high risk of VTE.,Conversely, further studies are needed to determine the specific effects of COVID-19 on the risk of ATE or VTE in less severe forms of the disease.

COVID-19 has rapidly impacted on mortality worldwide.1 There is unprecedented urgency to understand who is most at risk of severe outcomes, requiring new approaches for timely analysis of large datasets.,Working on behalf of NHS England we created OpenSAFELY: a secure health analytics platform covering 40% of all patients in England, holding patient data within the existing data centre of a major primary care electronic health records vendor.,Primary care records of 17,278,392 adults were pseudonymously linked to 10,926 COVID-19 related deaths.,COVID-19 related death was associated with: being male (hazard ratio 1.59, 95%CI 1.53-1.65); older age and deprivation (both with a strong gradient); diabetes; severe asthma; and various other medical conditions.,Compared to people with white ethnicity, black and South Asian people were at higher risk even after adjustment for other factors (HR 1.48, 1.29-1.69 and 1.45, 1.32-1.58 respectively).,We have quantified a range of clinical risk factors for COVID-19 related death in the largest cohort study conducted by any country to date.,OpenSAFELY is rapidly adding further patients’ records; we will update and extend results regularly.

The prevalence of venous thromboembolic event (VTE) and arterial thromboembolic event (ATE) thromboembolic events in patients with COVID-19 remains largely unknown.,In this meta-analysis, we systematically searched for observational studies describing the prevalence of VTE and ATE in COVID-19 up to 30 September 2020.,We analysed findings from 102 studies (64 503 patients).,The frequency of COVID-19-related VTE was 14.7% (95% CI 12.1% to 17.6%, I2=94%; 56 studies; 16 507 patients).,The overall prevalence rates of pulmonary embolism (PE) and leg deep vein thrombosis were 7.8% (95% CI 6.2% to 9.4%, I2=94%; 66 studies; 23 117 patients) and 11.2% (95% CI 8.4% to 14.3%, I2=95%; 48 studies; 13 824 patients), respectively.,Few were isolated subsegmental PE.,The VTE prevalence was significantly higher in intensive care unit (ICU) (23.2%, 95% CI 17.5% to 29.6%, I2=92%, vs 9.0%, 95% CI 6.9% to 11.4%, I2=95%; pinteraction<0.0001) and in series systematically screening patients compared with series testing symptomatic patients (25.2% vs 12.7%, pinteraction=0.04).,The frequency rates of overall ATE, acute coronary syndrome, stroke and other ATE were 3.9% (95% CI 2.0% to to 3.0%, I2=96%; 16 studies; 7939 patients), 1.6% (95% CI 1.0% to 2.2%, I2=93%; 27 studies; 40 597 patients) and 0.9% (95% CI 0.5% to 1.5%, I2=84%; 17 studies; 20 139 patients), respectively.,Metaregression and subgroup analyses failed to explain heterogeneity of overall ATE.,High heterogeneity limited the value of estimates.,Patients admitted in the ICU for severe COVID-19 had a high risk of VTE.,Conversely, further studies are needed to determine the specific effects of COVID-19 on the risk of ATE or VTE in less severe forms of the disease.

The objectives were to investigate and compare the risks and incidences of venous thromboembolism (VTE) between the 2 groups of patients with coronavirus disease 2019 (COVID-19) pneumonia and community-acquired pneumonia (CAP).,Medical records of 616 pneumonia patients who were admitted to the Yichang Central People’s Hospital in Hubei, China, from January 1 to March 23, 2020, were retrospectively reviewed.,The patients with COVID-19 pneumonia were treated in the dedicated COVID-19 units, and the patients with CAP were admitted to regular hospital campus.,Risks of VTE were assessed using the Padua prediction score.,All the patients received pharmaceutical or mechanical VTE prophylaxis.,VTE was diagnosed using Duplex ultrasound or computed tomography pulmonary angiogram.,Differences between COVID-19 and CAP groups were compared statistically.,All statistical tests were 2 sided, and P<0.05 was considered as statistically significant.,All data managements and analyses were performed by IBM SPSS, version 24, software (SPSS, Inc, Chicago, IL).,Of the 616 patients, 256 had COVID-19 pneumonia and 360 patients had CAP.,The overall rate of VTE was 2% in COVID-19 pneumonia group and 3.6% in CAP group, respectively (P=0.229).,In these two groups, 15.6% of the COVID-19 pneumonia patients and 10% of the CAP patients were categorized as high risk for VTE (Padua score, >4), which were significantly different (P=0.036).,In those high-risk patients, the incidence of VTE was 12.5% in COVID-19 pneumonia group and 16.7% in CAP group (P=0.606).,Subgroup analysis of the critically ill patients showed that VTE rate was 6.7% in COVID-19 group versus 13% in CAP group (P=0.484).,In-hospital mortality of COVID-19 and CAP was 6.3% and 3.9%, respectively (P=0.180).,Our study suggested that COVID-19 pneumonia was associated with hypercoagulable state.,However, the rate of VTE in COVID-19 pneumonia patients was not significantly higher than that in CAP patients.

Coronavirus disease 2019 (COVID-19) is a viral infection that can, in severe cases, result in cytokine storm, systemic inflammatory response and coagulopathy that is prognostic of poor outcomes.,While some, but not all, laboratory findings appear similar to sepsis-associated disseminated intravascular coagulopathy (DIC), COVID-19- induced coagulopathy (CIC) appears to be more prothrombotic than hemorrhagic.,It has been postulated that CIC may be an uncontrolled immunothrombotic response to COVID-19, and there is growing evidence of venous and arterial thromboembolic events in these critically ill patients.,Clinicians around the globe are challenged with rapidly identifying reasonable diagnostic, monitoring and anticoagulant strategies to safely and effectively manage these patients.,Thoughtful use of proven, evidence-based approaches must be carefully balanced with integration of rapidly emerging evidence and growing experience.,The goal of this document is to provide guidance from the Anticoagulation Forum, a North American organization of anticoagulation providers, regarding use of anticoagulant therapies in patients with COVID-19.,We discuss in-hospital and post-discharge venous thromboembolism (VTE) prevention, treatment of suspected but unconfirmed VTE, laboratory monitoring of COVID-19, associated anticoagulant therapies, and essential elements for optimized transitions of care specific to patients with COVID-19.

Few data are available on the rate and characteristics of thromboembolic complications in hospitalized patients with COVID-19.,We studied consecutive symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02.2020-10.04.2020).,The primary outcome was any thromboembolic complication, including venous thromboembolism (VTE), ischemic stroke, and acute coronary syndrome (ACS)/myocardial infarction (MI).,Secondary outcome was overt disseminated intravascular coagulation (DIC).,We included 388 patients (median age 66 years, 68% men, 16% requiring intensive care [ICU]).,Thromboprophylaxis was used in 100% of ICU patients and 75% of those on the general ward.,Thromboembolic events occurred in 28 (7.7% of closed cases; 95%CI 5.4%-11.0%), corresponding to a cumulative rate of 21% (27.6% ICU, 6.6% general ward).,Half of the thromboembolic events were diagnosed within 24 h of hospital admission.,Forty-four patients underwent VTE imaging tests and VTE was confirmed in 16 (36%).,Computed tomography pulmonary angiography (CTPA) was performed in 30 patients, corresponding to 7.7% of total, and pulmonary embolism was confirmed in 10 (33% of CTPA).,The rate of ischemic stroke and ACS/MI was 2.5% and 1.1%, respectively.,Overt DIC was present in 8 (2.2%) patients.,The high number of arterial and, in particular, venous thromboembolic events diagnosed within 24 h of admission and the high rate of positive VTE imaging tests among the few COVID-19 patients tested suggest that there is an urgent need to improve specific VTE diagnostic strategies and investigate the efficacy and safety of thromboprophylaxis in ambulatory COVID-19 patients.,•COVID-19 is characterized by coagulation activation and endothelial dysfunction.,Few data are available on thromboembolic complications.,•We studied symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02-10.04.2020).,•Venous and arterial thromboembolic events occurred in 8% of hospitalized patients (cumulative rate 21.0%) and 50% of events were diagnosed within 24 h of hospital admission.,•Forty-four (11% of total) patients underwent VTE imaging tests; 16 were positive (36% of tests), suggesting underestimation of thromboembolic complications.,•There is an urgent need to investigate VTE diagnostic strategies and the impact of thromboprophylaxis in ambulatory COVID-19 patients.,COVID-19 is characterized by coagulation activation and endothelial dysfunction.,Few data are available on thromboembolic complications.,We studied symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02-10.04.2020).,Venous and arterial thromboembolic events occurred in 8% of hospitalized patients (cumulative rate 21.0%) and 50% of events were diagnosed within 24 h of hospital admission.,Forty-four (11% of total) patients underwent VTE imaging tests; 16 were positive (36% of tests), suggesting underestimation of thromboembolic complications.,There is an urgent need to investigate VTE diagnostic strategies and the impact of thromboprophylaxis in ambulatory COVID-19 patients.

In this hypothesis paper, we suggest that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may induce intravascular pulmonary thrombosis, which may result in the rapid worsening of clinical conditions and, eventually, exitus.,Previously published papers have demonstrated that increased levels of D-dimer at hospital admission correlate with a more severe disease (0.5 mg/L) or occurrence of death (1 mg/L).,The potential prothrombotic action of the SARS-CoV-2 is supported by the topographical involvement of the lung regions with a predilection for the lower lobe with peripheral involvement.,If this hypothesis is demonstrated, this could suggest the benefit of using antithrombotic/coagulation regimens for SARS-CoV-2 and, at the same time, the urgency to identify drugs that could alter the inflammatory storm, thus protecting the vessel wall.

The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades.,We provide a comprehensive review of the clinical course of COVID-19, its comorbidities, and mechanistic considerations for future therapies.,While COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects multiple organs, particularly the cardiovascular system.,Risk of severe infection and mortality increase with advancing age and male sex.,Mortality is increased by comorbidities: cardiovascular disease, hypertension, diabetes, chronic pulmonary disease, and cancer.,The most common complications include arrhythmia (atrial fibrillation, ventricular tachyarrhythmia, and ventricular fibrillation), cardiac injury [elevated highly sensitive troponin I (hs-cTnI) and creatine kinase (CK) levels], fulminant myocarditis, heart failure, pulmonary embolism, and disseminated intravascular coagulation (DIC).,Mechanistically, SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane angiotensin-converting enzyme 2 (ACE2) -a homologue of ACE-to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes.,This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction (MI).,While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis.,Hence, patients should not discontinue their use.,Moreover, renin-angiotensin-aldosterone system (RAAS) inhibitors might be beneficial in COVID-19.,Initial immune and inflammatory responses induce a severe cytokine storm [interleukin (IL)-6, IL-7, IL-22, IL-17, etc.] during the rapid progression phase of COVID-19.,Early evaluation and continued monitoring of cardiac damage (cTnI and NT-proBNP) and coagulation (D-dimer) after hospitalization may identify patients with cardiac injury and predict COVID-19 complications.,Preventive measures (social distancing and social isolation) also increase cardiovascular risk.,Cardiovascular considerations of therapies currently used, including remdesivir, chloroquine, hydroxychloroquine, tocilizumab, ribavirin, interferons, and lopinavir/ritonavir, as well as experimental therapies, such as human recombinant ACE2 (rhACE2), are discussed.

In this study, we report three cases of spontaneous intracranial hemorrhage in patients who were initially hospitalized at our tertiary care center in Washington, DC with symptoms of COVID-19.,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was diagnosed in all three patients, who were critically ill, requiring intubation and ventilatory support.,During their protracted hospitalizations, subsequent imaging disclosed intracranial hemorrhages, including intracerebral and subarachnoid hemorrhages, in the context of anticoagulation and coagulopathy.,We believe this is related to the tropism of SARS-CoV-2 to the endothelial lining of the cerebral vasculature via their angiotensin-converting enzyme (ACE) II receptors.,Given our findings, we advocate heightened vigilance for intracerebral hemorrhage events, and scanning when practicable, in COVID-19 patients which have prolonged ventilatory support and depressed neurologic examinations.

Italy is one of the most affected countries by the coronavirus disease 2019 (COVID-19).,The responsible pathogen is named severe acute respiratory syndrome coronavirus (SARS-CoV-2).,The clinical spectrum ranges from asymptomatic infection to severe pneumonia, leading to intensive care unit admission.,Evidence of cerebrovascular complications associated with SARS-CoV-2 is limited.,We herein report six patients who developed acute stroke during COVID-19 infection.,A retrospective case series of patients diagnosed with COVID-19 using reverse-transcriptase polymerase chain reaction (RT-PCR) on nasopharyngeal swabs, who developed clinical and neuroimaging evidence of acute stroke during SARS-CoV-2 infection.,Six patients were identified (5 men); median age was 69 years (range 57-82).,Stroke subtypes were ischemic (4, 67%) and hemorrhagic (2, 33%).,All patients but one had pre-existing vascular risk factors.,One patient developed encephalopathy prior to stroke, characterized by focal seizures and behavioral abnormalities.,COVID-19-related pneumonia was severe (i.e., requiring critical care support) in 5/6 cases (83%).,Liver enzyme alteration and lactate dehydrogenase (LDH) elevation were registered in all cases.,Four patients (67%) manifested acute kidney failure prior to stroke.,Four patients (67%) had abnormal coagulation tests.,The outcome was poor in the majority of the patients: five died (83%) and the remaining one (17%) remained severely neurologically affected (mRS: 4).,Both ischemic and hemorrhagic stroke can complicate the course of COVI-19 infection.,In our series, stroke developed mostly in patients with severe pneumonia and multiorgan failure, liver enzymes and LDH were markedly increased in all cases, and the outcome was poor.

The Bergamo province, which is extensively affected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic, is a natural observatory of virus manifestations in the general population.,In the past month we recorded an outbreak of Kawasaki disease; we aimed to evaluate incidence and features of patients with Kawasaki-like disease diagnosed during the SARS-CoV-2 epidemic.,All patients diagnosed with a Kawasaki-like disease at our centre in the past 5 years were divided according to symptomatic presentation before (group 1) or after (group 2) the beginning of the SARS-CoV-2 epidemic.,Kawasaki- like presentations were managed as Kawasaki disease according to the American Heart Association indications.,Kawasaki disease shock syndrome (KDSS) was defined by presence of circulatory dysfunction, and macrophage activation syndrome (MAS) by the Paediatric Rheumatology International Trials Organisation criteria.,Current or previous infection was sought by reverse-transcriptase quantitative PCR in nasopharyngeal and oropharyngeal swabs, and by serological qualitative test detecting SARS-CoV-2 IgM and IgG, respectively.,Group 1 comprised 19 patients (seven boys, 12 girls; aged 3·0 years [SD 2·5]) diagnosed between Jan 1, 2015, and Feb 17, 2020.,Group 2 included ten patients (seven boys, three girls; aged 7·5 years [SD 3·5]) diagnosed between Feb 18 and April 20, 2020; eight of ten were positive for IgG or IgM, or both.,The two groups differed in disease incidence (group 1 vs group 2, 0·3 vs ten per month), mean age (3·0 vs 7·5 years), cardiac involvement (two of 19 vs six of ten), KDSS (zero of 19 vs five of ten), MAS (zero of 19 vs five of ten), and need for adjunctive steroid treatment (three of 19 vs eight of ten; all p<0·01).,In the past month we found a 30-fold increased incidence of Kawasaki-like disease.,Children diagnosed after the SARS-CoV-2 epidemic began showed evidence of immune response to the virus, were older, had a higher rate of cardiac involvement, and features of MAS.,The SARS-CoV-2 epidemic was associated with high incidence of a severe form of Kawasaki disease.,A similar outbreak of Kawasaki-like disease is expected in countries involved in the SARS-CoV-2 epidemic.,None.

The purpose of this study was to identify the clinical features and laboratory factors that are predictive of intravenous immunoglobulin (IVIG)-resistant Kawasaki disease.,Multiple databases were searched for relevant studies on IVIG-resistant Kawasaki disease published from January 2002 to April 2017.,Eligible studies were retrieved by manual review of the references.,Stata 12 was used for the meta-analysis.,Weighted mean differences and odds ratios with 95% confidence intervals were calculated for several indices.,Twenty-eight studies involving 26,260 patients comprising 4442 IVIG-resistant Kawasaki disease patients and 21,818 IVIG-sensitive Kawasaki disease patients were included.,The meta-analysis showed that the erythrocyte sedimentation rate (ESR) in the IVIG-resistant group was significantly higher than that in the IVIG-sensitive group, and that platelet count and hemoglobin levels were significantly lower in the IVIG-resistant group.,The patients with oral mucosa alterations, cervical lymphadenopathy, swelling of the extremities, polymorphous rash, and initial administration of IVIG ≤ 4.0 days after the onset of symptoms were more likely to be IVIG resistant.,Conclusion: The initial administration of IVIG ≤ 4.0 days after the onset of symptoms increased ESR and decreased hemoglobin and platelet counts, oral mucosa alterations, cervical lymphadenopathy, swelling of the extremities, and polymorphous rash and are the risk factors for IVIG-resistant Kawasaki disease.What is Known:• Recent reports on this topic are about aspartate aminotransferase (AST), alanine aminotransferase (ALT), gammaglutamyl transferase, total bilirubin, white blood cells, platelets, erythrocyte sedimentation rate (ESR), polymorphonuclear leukocytes (PMN), C-reactive protein (CRP), pro-brain natriuretic peptide (BNP), albumin, and sodium as the risk factors in the IVIG-resistant Kawasaki disease; however, no studies have been published on clinical features as predictors of IVIG resistance.What is New:• This meta-analysis identified the clinical features, the initial administration of IVIG ≤ 4.0 days after the onset of symptoms, and much more comprehensive laboratory indicators, such as hemoglobin, as predictors of IVIG-resistant Kawasaki disease.,The online version of this article (10.1007/s00431-018-3182-2) contains supplementary material, which is available to authorized users.

•Serious cardiac arrhythmias may be the consequence of direct effects of COVID-19 infection, but also the outcome of the deleterious effects of systemic illness and the adverse proarrhythmic reactions to drugs employed in the treatment of this pandemic•Drug combinations, especially of QT-prolonging agents, can lead to higher arrhythmogenicity, compared with single drug therapies•Furthermore, critically ill COVID-19 patients often have comorbidities that can trigger life-threatening ventricular arrhythmias, while acute myocardial injury increases the prevalence of arrhythmias•ECG and QTc monitoring and taking appropriate measures are of critical importance to prevent, detect and manage cardiac arrhythmias in COVID-19 patients•Contactless monitoring and telemetry for inpatients, especially those admitted to the ICU, as well as for outpatients needing continued management, has recently been facilitated by implementing digital health monitoring tools,Serious cardiac arrhythmias may be the consequence of direct effects of COVID-19 infection, but also the outcome of the deleterious effects of systemic illness and the adverse proarrhythmic reactions to drugs employed in the treatment of this pandemic,Drug combinations, especially of QT-prolonging agents, can lead to higher arrhythmogenicity, compared with single drug therapies,Furthermore, critically ill COVID-19 patients often have comorbidities that can trigger life-threatening ventricular arrhythmias, while acute myocardial injury increases the prevalence of arrhythmias,ECG and QTc monitoring and taking appropriate measures are of critical importance to prevent, detect and manage cardiac arrhythmias in COVID-19 patients,Contactless monitoring and telemetry for inpatients, especially those admitted to the ICU, as well as for outpatients needing continued management, has recently been facilitated by implementing digital health monitoring tools,As the coronavirus 2019 (COVID-19) pandemic marches unrelentingly, more patients with cardiac arrhythmias are emerging due to the effects of the virus on the respiratory and cardiovascular (CV) systems and the systemic inflammation that it incurs, and also as a result of the proarrhythmic effects of COVID-19 pharmacotherapies and other drug interactions and the associated autonomic imbalance that enhance arrhythmogenicity.,The most worrisome of all arrhythmogenic mechanisms is the QT prolonging effect of various anti-COVID pharmacotherapies that can lead to polymorphic ventricular tachycardia in the form of torsade des pointes and sudden cardiac death.,It is therefore imperative to monitor the QT interval during treatment; however, conventional approaches to such monitoring increase the transmission risk for the staff and strain the health system.,Hence, there is dire need for contactless monitoring and telemetry for inpatients, especially those admitted to the intensive care unit, as well as for outpatients needing continued management.,In this context, recent technological advances have ushered in a new era in implementing digital health monitoring tools that circumvent these obstacles.,All these issues are herein discussed and a large body of recent relevant data are reviewed.

Amiodarone, one of the most widely prescribed antiarrhythmic drugs to treat both ventricular and supraventricular arrhythmias, has been identified as a candidate drug for use against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,We present the rationale of using amiodarone in the COVID-19 scenario, as well as whether or not amiodarone administration represents a potential strategy to prevent SARS-CoV-2 infection, rather than simply used to treat patients already symptomatic and/or with severe coronavirus disease 2019 (COVID-19), based on current evidence.

We describe the first case of acute cardiac injury directly linked to myocardial localization of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in a 69‐year‐old patient with flu‐like symptoms rapidly degenerating into respiratory distress, hypotension, and cardiogenic shock.,The patient was successfully treated with venous‐arterial extracorporeal membrane oxygenation (ECMO) and mechanical ventilation.,Cardiac function fully recovered in 5 days and ECMO was removed.,Endomyocardial biopsy demonstrated low‐grade myocardial inflammation and viral particles in the myocardium suggesting either a viraemic phase or, alternatively, infected macrophage migration from the lung.

This case series study evaluates the association of underlying cardiovascular disease and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19).,What is the impact of underlying cardiovascular disease (CVD) and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19)?,In this case series study of 187 patients with COVID-19, 27.8% of patients had myocardial injury, which resulted in cardiac dysfunction and arrhythmias.,Myocardial injury has a significant association with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury were relatively favorable.,It is reasonable to triage patients with COVID-19 according to the presence of underlying CVD and evidence of myocardial injury for prioritized treatment and even more aggressive strategies.,Increasing numbers of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) are occurring in several countries and continents.,Information regarding the impact of cardiovascular complication on fatal outcome is scarce.,To evaluate the association of underlying cardiovascular disease (CVD) and myocardial injury with fatal outcomes in patients with COVID-19.,This retrospective single-center case series analyzed patients with COVID-19 at the Seventh Hospital of Wuhan City, China, from January 23, 2020, to February 23, 2020.,Analysis began February 25, 2020.,Demographic data, laboratory findings, comorbidities, and treatments were collected and analyzed in patients with and without elevation of troponin T (TnT) levels.,Among 187 patients with confirmed COVID-19, 144 patients (77%) were discharged and 43 patients (23%) died.,The mean (SD) age was 58.50 (14.66) years.,Overall, 66 (35.3%) had underlying CVD including hypertension, coronary heart disease, and cardiomyopathy, and 52 (27.8%) exhibited myocardial injury as indicated by elevated TnT levels.,The mortality during hospitalization was 7.62% (8 of 105) for patients without underlying CVD and normal TnT levels, 13.33% (4 of 30) for those with underlying CVD and normal TnT levels, 37.50% (6 of 16) for those without underlying CVD but elevated TnT levels, and 69.44% (25 of 36) for those with underlying CVD and elevated TnTs.,Patients with underlying CVD were more likely to exhibit elevation of TnT levels compared with the patients without CVD (36 [54.5%] vs 16 [13.2%]).,Plasma TnT levels demonstrated a high and significantly positive linear correlation with plasma high-sensitivity C-reactive protein levels (β = 0.530, P < .001) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (β = 0.613, P < .001).,Plasma TnT and NT-proBNP levels during hospitalization (median [interquartile range (IQR)], 0.307 [0.094-0.600]; 1902.00 [728.35-8100.00]) and impending death (median [IQR], 0.141 [0.058-0.860]; 5375 [1179.50-25695.25]) increased significantly compared with admission values (median [IQR], 0.0355 [0.015-0.102]; 796.90 [401.93-1742.25]) in patients who died (P = .001; P < .001), while no significant dynamic changes of TnT (median [IQR], 0.010 [0.007-0.019]; 0.013 [0.007-0.022]; 0.011 [0.007-0.016]) and NT-proBNP (median [IQR], 352.20 [174.70-636.70]; 433.80 [155.80-1272.60]; 145.40 [63.4-526.50]) was observed in survivors (P = .96; P = .16).,During hospitalization, patients with elevated TnT levels had more frequent malignant arrhythmias, and the use of glucocorticoid therapy (37 [71.2%] vs 69 [51.1%]) and mechanical ventilation (31 [59.6%] vs 14 [10.4%]) were higher compared with patients with normal TnT levels.,The mortality rates of patients with and without use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was 36.8% (7 of 19) and 21.4% (36 of 168) (P = .13).,Myocardial injury is significantly associated with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury is relatively favorable.,Myocardial injury is associated with cardiac dysfunction and arrhythmias.,Inflammation may be a potential mechanism for myocardial injury.,Aggressive treatment may be considered for patients at high risk of myocardial injury.

Various neurological manifestations have been reported in the literature associated with COVID-19, which in the current study are classified into Central Nervous System (CNS) related manifestations including headache, dizziness, impaired consciousness, acute cerebrovascular disease, epilepsy, and Peripheral Nervous System (PNS) related manifestations such as hyposmia/anosmia, hypogeusia/ageusia, muscle pain, and Guillain-Barre syndrome.,During the current context of COVID-19 pandemic, physicians should be aware of wide spectrum of neurological COVID-19 sign and symptoms for early diagnosis and isolation of patients.,In this regard, COVID-19 has been associated with many neurological manifestations such as confusion, anosmia, and ageusia.,Also, various evidences support the possible CNS roles in the COVID-19 pathophysiology.,In this regard, further investigation of CNS involvement of SARS-COV-2 is suggested.

•Coronoviruses not only affect the respiratory system, but also have deleterious effects on the central nervous system.,•Most neurological diseases could be caused by coronoviruses invasion.,•Coronoviruses cause nerve damage via diverse pathways.,Coronoviruses not only affect the respiratory system, but also have deleterious effects on the central nervous system.,Most neurological diseases could be caused by coronoviruses invasion.,Coronoviruses cause nerve damage via diverse pathways.,Viral infections have detrimental impacts on neurological functions, and even to cause severe neurological damage.,Very recently, coronaviruses (CoV), especially severe acute respiratory syndrome CoV 2 (SARS-CoV-2), exhibit neurotropic properties and may also cause neurological diseases.,It is reported that CoV can be found in the brain or cerebrospinal fluid.,The pathobiology of these neuroinvasive viruses is still incompletely known, and it is therefore important to explore the impact of CoV infections on the nervous system.,Here, we review the research into neurological complications in CoV infections and the possible mechanisms of damage to the nervous system.

The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades.,We provide a comprehensive review of the clinical course of COVID-19, its comorbidities, and mechanistic considerations for future therapies.,While COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects multiple organs, particularly the cardiovascular system.,Risk of severe infection and mortality increase with advancing age and male sex.,Mortality is increased by comorbidities: cardiovascular disease, hypertension, diabetes, chronic pulmonary disease, and cancer.,The most common complications include arrhythmia (atrial fibrillation, ventricular tachyarrhythmia, and ventricular fibrillation), cardiac injury [elevated highly sensitive troponin I (hs-cTnI) and creatine kinase (CK) levels], fulminant myocarditis, heart failure, pulmonary embolism, and disseminated intravascular coagulation (DIC).,Mechanistically, SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane angiotensin-converting enzyme 2 (ACE2) -a homologue of ACE-to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes.,This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction (MI).,While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis.,Hence, patients should not discontinue their use.,Moreover, renin-angiotensin-aldosterone system (RAAS) inhibitors might be beneficial in COVID-19.,Initial immune and inflammatory responses induce a severe cytokine storm [interleukin (IL)-6, IL-7, IL-22, IL-17, etc.] during the rapid progression phase of COVID-19.,Early evaluation and continued monitoring of cardiac damage (cTnI and NT-proBNP) and coagulation (D-dimer) after hospitalization may identify patients with cardiac injury and predict COVID-19 complications.,Preventive measures (social distancing and social isolation) also increase cardiovascular risk.,Cardiovascular considerations of therapies currently used, including remdesivir, chloroquine, hydroxychloroquine, tocilizumab, ribavirin, interferons, and lopinavir/ritonavir, as well as experimental therapies, such as human recombinant ACE2 (rhACE2), are discussed.

Mortality from coronavirus disease 2019 (COVID-19) is strongly associated with cardiovascular disease, diabetes, and hypertension.,These disorders share underlying pathophysiology related to the renin-angiotensin system (RAS) that may be clinically insightful.,In particular, activity of the angiotensin-converting enzyme 2 (ACE2) is dysregulated in cardiovascular disease, and this enzyme is used by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to initiate the infection.,Cardiovascular disease and pharmacologic RAS inhibition both increase ACE2 levels, which may increase the virulence of SARS-CoV-2 within the lung and heart.,Conversely, mechanistic evidence from related coronaviruses suggests that SARS-CoV-2 infection may downregulate ACE2, leading to toxic overaccumulation of angiotensin II that induces acute respiratory distress syndrome and fulminant myocarditis.,RAS inhibition could mitigate this effect.,With conflicting mechanistic evidence, we propose key clinical research priorities necessary to clarify the role of RAS inhibition in COVID-19 mortality that could be rapidly addressed by the international research community.,The association between coronavirus disease 2019 (COVID-19) mortality and cardiovascular disease is likely mediated by dysregulation of the renin-angiotensin system (RAS).,Pharmacoepidemiologic studies are needed to clarify whether RAS inhibition mediates this association and is helpful or harmful.

Coronavirus disease-2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, because of excessive inflammation, platelet activation, endothelial dysfunction, and stasis.,In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy.,Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease.,Herein, the authors review the current understanding of the pathogenesis, epidemiology, management, and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, of those with pre-existing thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.,•COVID-19 may predispose patients to arterial and venous thrombosis.,•Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,•Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,•The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic.,COVID-19 may predispose patients to arterial and venous thrombosis.,Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic.

Acute respiratory failure and a systemic coagulopathy are critical aspects of the morbidity and mortality characterizing infection with severe acute respiratory distress syndrome-associated coronavirus-2, the etiologic agent of Coronavirus disease 2019 (COVID-19).,We examined skin and lung tissues from 5 patients with severe COVID-19 characterized by respiratory failure (n= 5) and purpuric skin rash (n = 3).,COVID-19 pneumonitis was predominantly a pauci-inflammatory septal capillary injury with significant septal capillary mural and luminal fibrin deposition and permeation of the interalveolar septa by neutrophils.,No viral cytopathic changes were observed and the diffuse alveolar damage (DAD) with hyaline membranes, inflammation, and type II pneumocyte hyperplasia, hallmarks of classic acute respiratory distress syndrome, were not prominent.,These pulmonary findings were accompanied by significant deposits of terminal complement components C5b-9 (membrane attack complex), C4d, and mannose binding lectin (MBL)-associated serine protease (MASP)2, in the microvasculature, consistent with sustained, systemic activation of the complement pathways.,The purpuric skin lesions similarly showed a pauci-inflammatory thrombogenic vasculopathy, with deposition of C5b-9 and C4d in both grossly involved and normally-appearing skin.,In addition, there was co-localization of COVID-19 spike glycoproteins with C4d and C5b-9 in the interalveolar septa and the cutaneous microvasculature of 2 cases examined.,In conclusion, at least a subset of sustained, severe COVID-19 may define a type of catastrophic microvascular injury syndrome mediated by activation of complement pathways and an associated procoagulant state.,It provides a foundation for further exploration of the pathophysiologic importance of complement in COVID-19, and could suggest targets for specific intervention.

Although cerebral white matter lesions (WMLs) are considered as a risk factor for vascular dementia, data on their impact on cerebral hemodynamics are scarce.,We test and compare transcranial Doppler (TCD) features in WML patients with or without associated cognitive impairment.,A sample of non-demented elderly patients with WMLs was consecutively recruited.,Mean blood flow velocity (MBFV), pulsatility index (PI), peak systolic blood flow velocity (PSV), end-diastolic blood flow velocity (EDV), and resistivity index (RI) were recorded from the middle cerebral artery bilaterally.,Global cognitive functioning, frontal lobe abilities, functional status, and WML severity were also assessed.,161 patients satisfying the clinical criteria for vascular cognitive impairment-no dementia (VCI-ND) were age-matched with 97 presenting WMLs without any cognitive deficit.,VCI-ND patients exhibited a decrease in MBFV and EDV, as well as an increase in PI, RI, and PSV.,Moreover, a significant correlation between all TCD parameters and the severity of executive dysfunction was observed, whereas PI, RI, and EDV were significantly correlated with the WML load.,VCI-ND showed a hemodynamic pattern indicative of cerebral hypoperfusion and enhanced vascular resistance.,These changes may be considered as the TCD correlate of VCI-ND due to microcirculation pathology.,TCD provides useful indices of the occurrence and severity of small vessel disease and executive dysfunction in elderly patients at risk of future dementia.

In the last years, there has been a significant growth in the literature exploiting transcranial magnetic stimulation (TMS) with the aim at gaining further insights into the electrophysiological and neurochemical basis underlying vascular cognitive impairment (VCI).,Overall, TMS points at enhanced brain cortical excitability and synaptic plasticity in VCI, especially in patients with overt dementia, and neurophysiological changes seem to correlate with disease process and progress.,These findings have been interpreted as part of a glutamate-mediated compensatory effect in response to vascular lesions.,Although a single TMS parameter owns low specificity, a panel of measures can support the VCI diagnosis, predict progression, and possibly identify early markers of “brain at risk” for future dementia, thus making VCI a potentially preventable cause of both vascular and degenerative dementia in late life.,Moreover, TMS can be also exploited to select and evaluate the responders to specific drugs, as well as to become an innovative rehabilitative tool in the attempt to restore impaired neural plasticity.,The present review provides a perspective of the different TMS techniques by further understanding the cortical electrophysiology and the role of distinctive neurotransmission pathways and networks involved in the pathogenesis and pathophysiology of VCI and its subtypes.

What are the cardiovascular effects in unselected patients with recent coronavirus disease 2019 (COVID-19)?,In this cohort study including 100 patients recently recovered from COVID-19 identified from a COVID-19 test center, cardiac magnetic resonance imaging revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), which was independent of preexisting conditions, severity and overall course of the acute illness, and the time from the original diagnosis.,These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.,This cohort study evaluates the presence of myocardial injury in unselected patients recently recovered from coronavirus disease 2019 (COVID-19).,Coronavirus disease 2019 (COVID-19) continues to cause considerable morbidity and mortality worldwide.,Case reports of hospitalized patients suggest that COVID-19 prominently affects the cardiovascular system, but the overall impact remains unknown.,To evaluate the presence of myocardial injury in unselected patients recently recovered from COVID-19 illness.,In this prospective observational cohort study, 100 patients recently recovered from COVID-19 illness were identified from the University Hospital Frankfurt COVID-19 Registry between April and June 2020.,Recent recovery from severe acute respiratory syndrome coronavirus 2 infection, as determined by reverse transcription-polymerase chain reaction on swab test of the upper respiratory tract.,Demographic characteristics, cardiac blood markers, and cardiovascular magnetic resonance (CMR) imaging were obtained.,Comparisons were made with age-matched and sex-matched control groups of healthy volunteers (n = 50) and risk factor-matched patients (n = 57).,Of the 100 included patients, 53 (53%) were male, and the mean (SD) age was 49 (14) years.,The median (IQR) time interval between COVID-19 diagnosis and CMR was 71 (64-92) days.,Of the 100 patients recently recovered from COVID-19, 67 (67%) recovered at home, while 33 (33%) required hospitalization.,At the time of CMR, high-sensitivity troponin T (hsTnT) was detectable (greater than 3 pg/mL) in 71 patients recently recovered from COVID-19 (71%) and significantly elevated (greater than 13.9 pg/mL) in 5 patients (5%).,Compared with healthy controls and risk factor-matched controls, patients recently recovered from COVID-19 had lower left ventricular ejection fraction, higher left ventricle volumes, and raised native T1 and T2.,A total of 78 patients recently recovered from COVID-19 (78%) had abnormal CMR findings, including raised myocardial native T1 (n = 73), raised myocardial native T2 (n = 60), myocardial late gadolinium enhancement (n = 32), or pericardial enhancement (n = 22).,There was a small but significant difference between patients who recovered at home vs in the hospital for native T1 mapping (median [IQR], 1119 [1092-1150] ms vs 1141 [1121-1175] ms; P = .008) and hsTnT (4.2 [3.0-5.9] pg/dL vs 6.3 [3.4-7.9] pg/dL; P = .002) but not for native T2 mapping.,None of these measures were correlated with time from COVID-19 diagnosis (native T1: r = 0.07; P = .47; native T2: r = 0.14; P = .15; hsTnT: r = −0.07; P = .50).,High-sensitivity troponin T was significantly correlated with native T1 mapping (r = 0.33; P < .001) and native T2 mapping (r = 0.18; P = .01).,Endomyocardial biopsy in patients with severe findings revealed active lymphocytic inflammation.,Native T1 and T2 were the measures with the best discriminatory ability to detect COVID-19-related myocardial pathology.,In this study of a cohort of German patients recently recovered from COVID-19 infection, CMR revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), independent of preexisting conditions, severity and overall course of the acute illness, and time from the original diagnosis.,These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through ACE2 receptors, leading to coronavirus disease (COVID-19)-related pneumonia, while also causing acute myocardial injury and chronic damage to the cardiovascular system.,Therefore, particular attention should be given to cardiovascular protection during treatment for COVID-19.

•Venous thrombosis is common in patients with severe COVID-19 pneumonia.,•Many of these thromboses may be immunothromboses due to local inflammation, rather than thromboembolic disease.,•Anticoagulated patients with COVID-19 pneumonia have a risk of major bleeding.,Venous thrombosis is common in patients with severe COVID-19 pneumonia.,Many of these thromboses may be immunothromboses due to local inflammation, rather than thromboembolic disease.,Anticoagulated patients with COVID-19 pneumonia have a risk of major bleeding.

Coagulopathy in COVID-19 is a burning issue and strategies to prevent thromboembolic events are debated and highly heterogeneous.,The objective was to determine incidence and risk factors of venous thromboembolism (VTE) in COVID-19 inpatients receiving thromboprophylaxis.,In this retrospective French cohort study, patients hospitalized in medical wards non-ICU with confirmed COVID-19 and adequate thromboprophylaxis were included.,A systematic low limb venous duplex ultrasonography was performed at hospital discharge or earlier if deep venous thrombosis (DVT) was clinically suspected.,Chest angio-CT scan was performed when pulmonary embolism (PE) was suspected.,Of 71 patients, 16 developed VTE (22.5%) and 7 PE (10%) despite adequate thromboprophylaxis.,D-dimers at baseline were significantly higher in patients with DVT (p < 0.001).,Demographics, comorbidities, disease manifestations, severity score, and other biological parameters, including inflammatory markers, were similar in patients with and without VTE.,The negative predictive value of a baseline D-dimer level < 1.0 µg/ml was 90% for VTE and 98% for PE.,The positive predictive value for VTE was 44% and 67% for D-dimer level ≥ 1.0 µg/ml and ≥ 3 µg/ml, respectively.,The association between D-dimer level and VTE risk increased by taking into account the latest available D-dimer level prior to venous duplex ultrasonography for the patients with monitoring of D-dimer.,Despite thromboprophylaxis, the risk of VTE is high in COVID-19 non-ICU inpatients.,Increased D-dimer concentrations of more than 1.0 μg/ml predict the risk of venous thromboembolism.,D-dimer level-guided aggressive thromboprophylaxis regimens using higher doses of heparin should be evaluated in prospective studies.

Hypertension can originate from early-life adverse environmental in utero exposure to dexamethasone (DEX) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).,Since DEX and TCDD are related to the aryl hydrocarbon receptor (AHR) signaling pathway, we examined whether resveratrol, an AHR modulator and antioxidant, could prevent programmed hypertension via regulating AHR signaling and oxidative stress.,Groups of four-month-old male rat offspring were studied (n = 7-8 per group): control, DEX (0.1 mg/kg i.p. from a gestational age of 16 to 22 days), TCDD (200 ng/kg in four once-weekly oral doses), DEX + TCDD, and DEX + TCDD + R (resveratrol 0.05% in drinking water throughout pregnancy and lactation).,Maternal TCDD exposure aggravated prenatal DEX-induced hypertension in adult male offspring, which maternal resveratrol therapy prevented.,Maternal TCDD exposure aggravated DEX-induced oxidative damage in offspring kidneys, which was prevented by resveratrol therapy.,Maternal resveratrol therapy decreased asymmetric and symmetric dimethylarginine (ADMA and SDMA) levels, thereby preventing combined DEX and TCDD exposure-induced programmed hypertension.,Increases in renal Ahrr and Cyp1a1 expression induced by DEX + TCDD exposure were restored by resveratrol therapy.,The beneficial effects of resveratrol on DEX + TCDD-induced hypertension relate to reduced renal mRNA expression of Ren, Ace, and Agtr1a expression.,Thus, the beneficial effects of resveratrol on DEX + TCDD-induced hypertension include reduction of oxidative stress, restoration of nitric oxide (NO) bioavailability, blockade of the renin-angiotensin system (RAS), and antagonizing AHR signaling pathway.

Cardiovascular disease (CVD) remains a major cause of high morbidity and mortality in patients with chronic kidney disease (CKD).,Numerous CVD risk factors in CKD patients have been described, but these do not fully explain the high pervasiveness of CVD or increased mortality rates in CKD patients.,In CKD the loss of urinary excretory function results in the retention of various substances referred to as “uremic retention solutes”.,Many of these molecules have been found to exert toxicity on virtually all organ systems of the human body, leading to the clinical syndrome of uremia.,In recent years, an increasing body of evidence has been accumulated that suggests that uremic toxins may contribute to an increased cardiovascular disease (CVD) burden associated with CKD.,This review examined the evidence from several clinical and experimental studies showing an association between uremic toxins and CVD.,Special emphasis is addressed on emerging data linking gut microbiota with the production of uremic toxins and the development of CKD and CVD.,The biological toxicity of some uremic toxins on the myocardium and the vasculature and their possible contribution to cardiovascular injury in uremia are also discussed.,Finally, various therapeutic interventions that have been applied to effectively reduce uremic toxins in patients with CKD, including dietary modifications, use of prebiotics and/or probiotics, an oral intestinal sorbent that adsorbs uremic toxins and precursors, and innovative dialysis therapies targeting the protein-bound uremic toxins are also highlighted.,Future studies are needed to determine whether these novel therapies to reduce or remove uremic toxins will reduce CVD and related cardiovascular events in the long-term in patients with chronic renal failure.

A multisystem inflammatory syndrome in children (MIS-C) is associated with coronavirus disease 2019.,The New York State Department of Health (NYSDOH) established active, statewide surveillance to describe hospitalized patients with the syndrome.,Hospitals in New York State reported cases of Kawasaki’s disease, toxic shock syndrome, myocarditis, and potential MIS-C in hospitalized patients younger than 21 years of age and sent medical records to the NYSDOH.,We carried out descriptive analyses that summarized the clinical presentation, complications, and outcomes of patients who met the NYSDOH case definition for MIS-C between March 1 and May 10, 2020.,As of May 10, 2020, a total of 191 potential cases were reported to the NYSDOH.,Of 95 patients with confirmed MIS-C (laboratory-confirmed acute or recent severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection) and 4 with suspected MIS-C (met clinical and epidemiologic criteria), 53 (54%) were male; 31 of 78 (40%) were black, and 31 of 85 (36%) were Hispanic.,A total of 31 patients (31%) were 0 to 5 years of age, 42 (42%) were 6 to 12 years of age, and 26 (26%) were 13 to 20 years of age.,All presented with subjective fever or chills; 97% had tachycardia, 80% had gastrointestinal symptoms, 60% had rash, 56% had conjunctival injection, and 27% had mucosal changes.,Elevated levels of C-reactive protein, d-dimer, and troponin were found in 100%, 91%, and 71% of the patients, respectively; 62% received vasopressor support, 53% had evidence of myocarditis, 80% were admitted to an intensive care unit, and 2 died.,The median length of hospital stay was 6 days.,The emergence of multisystem inflammatory syndrome in children in New York State coincided with widespread SARS-CoV-2 transmission; this hyperinflammatory syndrome with dermatologic, mucocutaneous, and gastrointestinal manifestations was associated with cardiac dysfunction.

A new multisystem inflammatory syndrome apparently related to infection with SARS-CoV-2 has recently been reported in older children (known as MIS-C), manifested by severe abdominal pain, cardiac dysfunction and shock.,Here, I discuss the similarities and differences between MIS-C and Kawasaki disease, focusing on their epidemiology, aetiology and pathophysiological mechanisms.,In this Comment, Anne Rowley discusses what we know so far about the recently described multisystem inflammatory syndrome in older children associated with SARS-CoV-2 infection and how it differs from Kawasaki disease.

COVID-19-associated coagulopathy (CAC) characterized by the elevated D-dimer without remarkable changes of other global coagulation markers is associated with various thrombotic complications and disease severity.,The purpose of this review is to elucidate the pathophysiology of this unique coagulopathy.,The authors performed online search of published medical literature through PubMed using the MeSH (Medical Subject Headings) term "COVID-19," "SARS-CoV-2," "coronavirus," "coagulopathy," and "thrombus.",Then, selected 51 articles that closely relevant to coagulopathy in COVID-19.,The primary targets of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are the pneumocytes, immune cells, and vascular endothelial cells.,The alveolar damage and the pulmonary microvascular thrombosis are the major causes of acute lung injury in COVID-19.,The endotheliopathy that occurs is due to direct SARS-CoV-2 infection and activation of other pathways that include the immune system and thromboinflammatory responses leading to what is termed CAC.,As a result, both microvascular and macrovascular thrombotic events occur in arterial, capillary, venule, and large vein vascular beds to produce multiorgan dysfunction and thrombotic complications.,In addition to the endothelial damage, SARS-CoV-2 also can cause vasculitis and presents as a systemic inflammatory vascular disease.,Clinical management of COVID-19 includes anticoagulation but novel therapies for endotheliopathy, hypercoagulability, and vasculitis are needed.,The endotheliopathy due to direct endothelial infection with SARS-COV-2 and the indirect damage caused by inflammation play the predominant role in the development of CAC.,The intensive control of thromboinflammation is necessary to improve the outcome of this highly detrimental contagious disease.

The dysfunction of the renin-angiotensin system (RAS) has been observed in coronavirus infection disease (COVID-19) patients, but whether RAS inhibitors, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs), are associated with clinical outcomes remains unknown.,COVID-19 patients with hypertension were enrolled to evaluate the effect of RAS inhibitors.,We observed that patients receiving ACEI or ARB therapy had a lower rate of severe diseases and a trend toward a lower level of IL-6 in peripheral blood.,In addition, ACEI or ARB therapy increased CD3 and CD8 T cell counts in peripheral blood and decreased the peak viral load compared to other antihypertensive drugs.,This evidence supports the benefit of using ACEIs or ARBs to potentially contribute to the improvement of clinical outcomes of COVID-19 patients with hypertension.

Clinical studies reveal changes in blood eosinophil counts and eosinophil cationic proteins that may serve as risk factors for human coronary heart diseases.,Here we report an increase of blood or heart eosinophil counts in humans and mice after myocardial infarction (MI), mostly in the infarct region.,Genetic or inducible depletion of eosinophils exacerbates cardiac dysfunction, cell death, and fibrosis post-MI, with concurrent acute increase of heart and chronic increase of splenic neutrophils and monocytes.,Mechanistic studies reveal roles of eosinophil IL4 and cationic protein mEar1 in blocking H2O2- and hypoxia-induced mouse and human cardiomyocyte death, TGF-β-induced cardiac fibroblast Smad2/3 activation, and TNF-α-induced neutrophil adhesion on the heart endothelial cell monolayer.,In vitro-cultured eosinophils from WT mice or recombinant mEar1 protein, but not eosinophils from IL4-deficient mice, effectively correct exacerbated cardiac dysfunctions in eosinophil-deficient ∆dblGATA mice.,This study establishes a cardioprotective role of eosinophils in post-MI hearts.,Blood eosinophil (EOS) counts may serve as risk factors for human coronary heart diseases.,Here the authors show that increased circulating and myocardial EOS after myocardial infarction play a cardioprotective role by reducing cardiomyocyte death, cardiac fibroblast activation and fibrosis, and endothelium activation-mediated inflammatory cell accumulation.

We characterized the dynamics of eosinophils in blood and in the infarcted myocardium in patients and in a swine model of reperfused myocardial infarction (MI).,The association of eosinophil dynamics with various outcomes was assessed.,Serial eosinophil count and pre-discharge cardiac magnetic resonance were carried out in a prospective series of 620 patients with a first ST-elevation MI.,In a swine model of reperfused MI, the dynamics of circulating eosinophils and their presence in the infarcted myocardium were determined.,In autopsies from chronic MI patients, eosinophils were quantified.,Patient eosinophil count sharply decreased 12h post-reperfusion compared to arrival.,A lower minimum eosinophil count was associated with more extensive edema, microvascular obstruction, and infarct size as measured by cardiac magnetic resonance, and also with a higher rate of cardiac events (death, re-infarction, or heart failure) during follow-up.,In the experimental model, eosinophil count boosted during ischemia and dropped back immediately post-reperfusion.,Myocardial samples revealed progressive eosinophil migration into the infarcted myocardium, especially areas with microvascular obstruction.,Markers of eosinophil maturation and survival (interleukin-5), degranulation (eosinophil cationic protein) and migration (eotoxin-1) were detected in the blood of patients, and in porcine myocardium.,Eosinophil infiltration was detected in autopsies from chronic MI patients.,Eosinopenia post-MI was associated with an impaired cardiac structure and adverse events.,The decay in circulating eosinophils soon after reperfusion mirrors their migration into the infarcted myocardium, as reflected by their presence in heart samples from swine and patients.,Further studies are needed to understanding this unexplored pathway and its therapeutic implications.

Coronavirus disease 2019 (COVID‐19) can lead to systemic coagulation activation and thrombotic complications.,To investigate the incidence of objectively confirmed venous thromboembolism (VTE) in hospitalized patients with COVID‐19.,Single‐center cohort study of 198 hospitalized patients with COVID‐19.,Seventy‐five patients (38%) were admitted to the intensive care unit (ICU).,At time of data collection, 16 (8%) were still hospitalized and 19% had died.,During a median follow‐up of 7 days (IQR, 3‐13), 39 patients (20%) were diagnosed with VTE of whom 25 (13%) had symptomatic VTE, despite routine thrombosis prophylaxis.,The cumulative incidences of VTE at 7, 14 and 21 days were 16% (95% CI, 10‐22), 33% (95% CI, 23‐43) and 42% (95% CI 30‐54) respectively.,For symptomatic VTE, these were 10% (95% CI, 5.8‐16), 21% (95% CI, 14‐30) and 25% (95% CI 16‐36).,VTE appeared to be associated with death (adjusted HR, 2.4; 95% CI, 1.02‐5.5).,The cumulative incidence of VTE was higher in the ICU (26% (95% CI, 17‐37), 47% (95% CI, 34‐58), and 59% (95% CI, 42‐72) at 7, 14 and 21 days) than on the wards (any VTE and symptomatic VTE 5.8% (95% CI, 1.4‐15), 9.2% (95% CI, 2.6‐21), and 9.2% (2.6‐21) at 7, 14, and 21 days).,The observed risk for VTE in COVID‐19 is high, particularly in ICU patients, which should lead to a high level of clinical suspicion and low threshold for diagnostic imaging for DVT or PE.,Future research should focus on optimal diagnostic and prophylactic strategies to prevent VTE and potentially improve survival.

Little evidence of increased thrombotic risk is available in COVID-19 patients.,Our purpose was to assess thrombotic risk in severe forms of SARS-CoV-2 infection.,All patients referred to 4 intensive care units (ICUs) from two centers of a French tertiary hospital for acute respiratory distress syndrome (ARDS) due to COVID-19 between March 3rd and 31st 2020 were included.,Medical history, symptoms, biological data and imaging were prospectively collected.,Propensity score matching was performed to analyze the occurrence of thromboembolic events between non-COVID-19 ARDS and COVID-19 ARDS patients.,150 COVID-19 patients were included (122 men, median age 63 [53; 71] years, SAPSII 49 [37; 64] points).,Sixty-four clinically relevant thrombotic complications were diagnosed in 150 patients, mainly pulmonary embolisms (16.7%). 28/29 patients (96.6%) receiving continuous renal replacement therapy experienced circuit clotting.,Three thrombotic occlusions (in 2 patients) of centrifugal pump occurred in 12 patients (8%) supported by ECMO.,Most patients (> 95%) had elevated D-dimer and fibrinogen.,No patient developed disseminated intravascular coagulation.,Von Willebrand (vWF) activity, vWF antigen and FVIII were considerably increased, and 50/57 tested patients (87.7%) had positive lupus anticoagulant.,Comparison with non-COVID-19 ARDS patients (n = 145) confirmed that COVID-19 ARDS patients (n = 77) developed significantly more thrombotic complications, mainly pulmonary embolisms (11.7 vs.,2.1%, p < 0.008).,Coagulation parameters significantly differed between the two groups.,Despite anticoagulation, a high number of patients with ARDS secondary to COVID-19 developed life-threatening thrombotic complications.,Higher anticoagulation targets than in usual critically ill patients should therefore probably be suggested.,The online version of this article (10.1007/s00134-020-06062-x) contains supplementary material, which is available to authorized users.

There has been significant controversy regarding the effects of pre‐hospitalization use of renin‐angiotensin system (RAS) inhibitors on the prognosis of hypertensive COVID‐19 patients.,We retrospectively assessed 2,297 hospitalized COVID‐19 patients at Tongji Hospital in Wuhan, China, from January 10th to March 30th, 2020; and identified 1,182 patients with known hypertension on pre‐hospitalization therapy.,We compared the baseline characteristics and in‐hospital mortality between hypertensive patients taking RAS inhibitors (N=355) versus non‐RAS inhibitors (N=827).,Of the 1,182 hypertensive patients (median age 68 years, 49.1% male), 12/355 (3.4%) patients died in the RAS inhibitors group vs.,95/827 (11.5%) patients in the non‐RAS inhibitors group (p<0.0001).,Adjusted hazard ratio for mortality was 0.28 (95% CI 0.15‐0.52, p<0.0001) at 45 days in the RAS inhibitors group compared with non‐RAS inhibitors group.,Similar findings were observed when patients taking angiotensin receptor blockers (N=289) or angiotensin converting enzyme inhibitors (N=66) were separately compared with non‐RAS inhibitors group.,The RAS inhibitors group compared with non‐RAS inhibitors group had lower levels of C‐reactive protein (median 13.5 vs.,24.4 pg/mL; p=0.007) and interleukin‐6 (median 6.0 vs.,8.5 pg/mL; p=0.026) on admission.,The protective effect of RAS inhibitors on mortality was confirmed in a meta‐analysis of published data when our data were added to previous studies (odd ratio 0.44, 95% CI 0.29-0.65, p<0.0001).,In a large single center retrospective analysis we observed a protective effect of pre‐hospitalization use of RAS inhibitors on mortality in hypertensive COVID‐19 patients; which might be associated with reduced inflammatory response.

The effect of chronic use of renin-angiotensin-aldosterone system (RAAS) inhibitors on the severity of COVID-19 infection is still unclear in patients with hypertension.,We aimed to investigate the association between chronic use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) and COVID-19 related outcomes in hypertensive patients.,A single center study was conducted on 133 consecutive hypertensive subjects presenting to the Emergency Department with acute respiratory symptoms and/or fever who were diagnosed with COVID-19 infection between 9th and 31st March 2020.,All patients were grouped according to their chronic antihypertensive medications (ACEIs, N=40; ARBs, N=42; not on RAAS inhibitors, N=51).,There was no statistical difference between ACEIs and ARBs groups in terms of hospital admission rate, oxygen therapy and need for non-invasive ventilation.,Patients chronically treated with RAAS inhibitors showed a significantly lower rate of admission to semi-intensive/intensive care units, when compared to the non-RAAS population (odds ratio [OR] 0.25, CI95% 0.09-0.66 p=0.006).,Similarly, the risk of mortality was lower in the former group, although not reaching statistical significance (OR 0.56, CI95% 0.17-1.83, p=0.341).,Our data suggest that chronic use of RAAS inhibitors does not negatively affect clinical course of COVID-19 in hypertensive patients.,Further studies are needed to confirm this finding and determine whether RAAS inhibitors may have a protective effect on COVID 19-related morbidity and mortality.

This study investigated demographics, comorbidities, and death rate in hospitalized patients with confirmed COVID-19.,In addition, we hypothesized that functional status, according to the Clinical Frailty Scale (CFS), in patients aged 65 years or older is a better predictor of poor outcome than age and comorbidities.,A total of 255 randomly selected COVID-19 patients admitted to a university hospital were included and followed up for 60 days.,Patient data were extracted manually from the electronic health records with use of a standardized protocol.,The age of the study population ranged between 20 and 103 years (mean age 66 years ± 17 years).,Hypertension, diabetes mellitus, and obesity were the three most prevalent comorbidities.,At the 60-day follow-up, 70 patients (27%) had died.,In multivariate analyses, age, chronic kidney disease, and previous stroke were associated with death.,Most fatal cases (90%) occurred in patients aged 65 years or older.,Among such patients, CFS level was the only predictor of death in multivariate analyses.,This study shows that increasing age, chronic kidney disease, and previous stroke significantly contribute to a fatal outcome in hospitalized patients with COVID-19.,In patients aged 65 years or older, CFS level was the strongest prognostic factor for death.

Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described.,In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020.,Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors.,We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death.,191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients).,Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03-1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61-12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64-128·55; p=0·0033) on admission.,Median duration of viral shedding was 20·0 days (IQR 17·0-24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors.,The longest observed duration of viral shedding in survivors was 37 days.,The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage.,Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.,Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

An important feature of severe acute respiratory syndrome coronavirus 2 pathogenesis is COVID-19-associated coagulopathy, characterised by increased thrombotic and microvascular complications.,Previous studies have suggested a role for endothelial cell injury in COVID-19-associated coagulopathy.,To determine whether endotheliopathy is involved in COVID-19-associated coagulopathy pathogenesis, we assessed markers of endothelial cell and platelet activation in critically and non-critically ill patients admitted to the hospital with COVID-19.,In this single-centre cross-sectional study, hospitalised adult (≥18 years) patients with laboratory-confirmed COVID-19 were identified in the medical intensive care unit (ICU) or a specialised non-ICU COVID-19 floor in our hospital.,Asymptomatic, non-hospitalised controls were recruited as a comparator group for biomarkers that did not have a reference range.,We assessed markers of endothelial cell and platelet activation, including von Willebrand Factor (VWF) antigen, soluble thrombomodulin, soluble P-selectin, and soluble CD40 ligand, as well as coagulation factors, endogenous anticoagulants, and fibrinolytic enzymes.,We compared the level of each marker in ICU patients, non-ICU patients, and controls, where applicable.,We assessed correlations between these laboratory results with clinical outcomes, including hospital discharge and mortality.,Kaplan-Meier analysis was used to further explore the association between biochemical markers and survival.,68 patients with COVID-19 were included in the study from April 13 to April 24, 2020, including 48 ICU and 20 non-ICU patients, as well as 13 non-hospitalised, asymptomatic controls.,Markers of endothelial cell and platelet activation were significantly elevated in ICU patients compared with non-ICU patients, including VWF antigen (mean 565% [SD 199] in ICU patients vs 278% [133] in non-ICU patients; p<0·0001) and soluble P-selectin (15·9 ng/mL [4·8] vs 11·2 ng/mL [3·1]; p=0·0014).,VWF antigen concentrations were also elevated above the normal range in 16 (80%) of 20 non-ICU patients.,We found mortality to be significantly correlated with VWF antigen (r = 0·38; p=0·0022) and soluble thrombomodulin (r = 0·38; p=0·0078) among all patients.,In all patients, soluble thrombomodulin concentrations greater than 3·26 ng/mL were associated with lower rates of hospital discharge (22 [88%] of 25 patients with low concentrations vs 13 [52%] of 25 patients with high concentrations; p=0·0050) and lower likelihood of survival on Kaplan-Meier analysis (hazard ratio 5·9, 95% CI 1·9-18·4; p=0·0087).,Our findings show that endotheliopathy is present in COVID-19 and is likely to be associated with critical illness and death.,Early identification of endotheliopathy and strategies to mitigate its progression might improve outcomes in COVID-19.,This work was supported by a gift donation from Jack Levin to the Benign Hematology programme at Yale, and the National Institutes of Health.

Acute respiratory failure and a systemic coagulopathy are critical aspects of the morbidity and mortality characterizing infection with severe acute respiratory distress syndrome-associated coronavirus-2, the etiologic agent of Coronavirus disease 2019 (COVID-19).,We examined skin and lung tissues from 5 patients with severe COVID-19 characterized by respiratory failure (n= 5) and purpuric skin rash (n = 3).,COVID-19 pneumonitis was predominantly a pauci-inflammatory septal capillary injury with significant septal capillary mural and luminal fibrin deposition and permeation of the interalveolar septa by neutrophils.,No viral cytopathic changes were observed and the diffuse alveolar damage (DAD) with hyaline membranes, inflammation, and type II pneumocyte hyperplasia, hallmarks of classic acute respiratory distress syndrome, were not prominent.,These pulmonary findings were accompanied by significant deposits of terminal complement components C5b-9 (membrane attack complex), C4d, and mannose binding lectin (MBL)-associated serine protease (MASP)2, in the microvasculature, consistent with sustained, systemic activation of the complement pathways.,The purpuric skin lesions similarly showed a pauci-inflammatory thrombogenic vasculopathy, with deposition of C5b-9 and C4d in both grossly involved and normally-appearing skin.,In addition, there was co-localization of COVID-19 spike glycoproteins with C4d and C5b-9 in the interalveolar septa and the cutaneous microvasculature of 2 cases examined.,In conclusion, at least a subset of sustained, severe COVID-19 may define a type of catastrophic microvascular injury syndrome mediated by activation of complement pathways and an associated procoagulant state.,It provides a foundation for further exploration of the pathophysiologic importance of complement in COVID-19, and could suggest targets for specific intervention.

The coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 that has significant implications for the cardiovascular care of patients.,First, those with COVID-19 and pre-existing cardiovascular disease have an increased risk of severe disease and death.,Second, infection has been associated with multiple direct and indirect cardiovascular complications including acute myocardial injury, myocarditis, arrhythmias, and venous thromboembolism.,Third, therapies under investigation for COVID-19 may have cardiovascular side effects.,Fourth, the response to COVID-19 can compromise the rapid triage of non-COVID-19 patients with cardiovascular conditions.,Finally, the provision of cardiovascular care may place health care workers in a position of vulnerability as they become hosts or vectors of virus transmission.,We hereby review the peer-reviewed and pre-print reports pertaining to cardiovascular considerations related to COVID-19 and highlight gaps in knowledge that require further study pertinent to patients, health care workers, and health systems.,•Patients with pre-existing CVD appear to have worse outcomes with COVID-19.,•CV complications include biomarker elevations, myocarditis, heart failure, and venous thromboembolism, which may be exacerbated by delays in care.,•Therapies under investigation for COVID-19 may have significant drug-drug interactions with CV medications.,•Health care workers and health systems should take measures to ensure safety while providing high-quality care for COVID-19 patients.,Patients with pre-existing CVD appear to have worse outcomes with COVID-19.,CV complications include biomarker elevations, myocarditis, heart failure, and venous thromboembolism, which may be exacerbated by delays in care.,Therapies under investigation for COVID-19 may have significant drug-drug interactions with CV medications.,Health care workers and health systems should take measures to ensure safety while providing high-quality care for COVID-19 patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through ACE2 receptors, leading to coronavirus disease (COVID-19)-related pneumonia, while also causing acute myocardial injury and chronic damage to the cardiovascular system.,Therefore, particular attention should be given to cardiovascular protection during treatment for COVID-19.

This study aims to explore the effect of hypertension on disease progression and prognosis in patients with coronavirus disease 2019 (COVID-19).,A total of 310 patients diagnosed with COVID-19 were studied.,A comparison was made between two groups of patients, those with hypertension and those without hypertension.,Their demographic data, clinical manifestations, laboratory indicators, and treatment methods were collected and analyzed.,A total of 310 patients, including 113 patients with hypertension and 197 patients without hypertension, were included in the analysis.,Compared with patients without hypertension, patients with hypertension were older, were more likely to have diabetes and cerebrovascular disease, and were more likely to be transferred to the intensive care unit.,The neutrophil count and lactate dehydrogenase, fibrinogen, and D-dimer levels in hypertensive patients were significantly higher than those in nonhypertensive patients (P < 0.05).,However, multivariate analysis (adjusted for age and sex) failed to show that hypertension was an independent risk factor for COVID-19 mortality or severity.,COVID-19 patients with hypertension were more likely than patients without hypertension to have severe pneumonia, excessive inflammatory reactions, organ and tissue damage, and deterioration of the disease.,Patients with hypertension should be given additional attention to prevent worsening of their condition.

There is concern about the potential of an increased risk related to medications that act on the renin-angiotensin-aldosterone system in patients exposed to coronavirus disease 2019 (Covid-19), because the viral receptor is angiotensin-converting enzyme 2 (ACE2).,We assessed the relation between previous treatment with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative result on Covid-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive.,Using Bayesian methods, we compared outcomes in patients who had been treated with these medications and in untreated patients, overall and in those with hypertension, after propensity-score matching for receipt of each medication class.,A difference of at least 10 percentage points was prespecified as a substantial difference.,Among 12,594 patients who were tested for Covid-19, a total of 5894 (46.8%) were positive; 1002 of these patients (17.0%) had severe illness.,A history of hypertension was present in 4357 patients (34.6%), among whom 2573 (59.1%) had a positive test; 634 of these patients (24.6%) had severe illness.,There was no association between any single medication class and an increased likelihood of a positive test.,None of the medications examined was associated with a substantial increase in the risk of severe illness among patients who tested positive.,We found no substantial increase in the likelihood of a positive test for Covid-19 or in the risk of severe Covid-19 among patients who tested positive in association with five common classes of antihypertensive medications.

Coronavirus disease 2019 (COVID-19) is a rapidly expanding global pandemic caused by severe acute respiratory syndrome coronavirus 2, resulting in significant morbidity and mortality.,A substantial minority of patients hospitalized develop an acute COVID-19 cardiovascular syndrome, which can manifest with a variety of clinical presentations but often presents as an acute cardiac injury with cardiomyopathy, ventricular arrhythmias, and hemodynamic instability in the absence of obstructive coronary artery disease.,The cause of this injury is uncertain but is suspected to be related to myocarditis, microvascular injury, systemic cytokine-mediated injury, or stress-related cardiomyopathy.,Although histologically unproven, severe acute respiratory syndrome coronavirus 2 has the potential to directly replicate within cardiomyocytes and pericytes, leading to viral myocarditis.,Systemically elevated cytokines are also known to be cardiotoxic and have the potential to result in profound myocardial injury.,Prior experience with severe acute respiratory syndrome coronavirus 1 has helped expedite the evaluation of several promising therapies, including antiviral agents, interleukin-6 inhibitors, and convalescent serum.,Management of acute COVID-19 cardiovascular syndrome should involve a multidisciplinary team including intensive care specialists, infectious disease specialists, and cardiologists.,Priorities for managing acute COVID-19 cardiovascular syndrome include balancing the goals of minimizing healthcare staff exposure for testing that will not change clinical management with early recognition of the syndrome at a time point at which intervention may be most effective.,This article aims to review the best available data on acute COVID-19 cardiovascular syndrome epidemiology, pathogenesis, diagnosis, and treatment.,From these data, we propose a surveillance, diagnostic, and management strategy that balances potential patient risks and healthcare staff exposure with improvement in meaningful clinical outcomes.

Studies have reminded that cardiovascular metabolic comorbidities made patients more susceptible to suffer 2019 novel corona virus (2019-nCoV) disease (COVID-19), and exacerbated the infection.,The aim of this analysis is to determine the association of cardiovascular metabolic diseases with the development of COVID-19.,A meta-analysis of eligible studies that summarized the prevalence of cardiovascular metabolic diseases in COVID-19 and compared the incidences of the comorbidities in ICU/severe and non-ICU/severe patients was performed.,Embase and PubMed were searched for relevant studies.,A total of six studies with 1527 patients were included in this analysis.,The proportions of hypertension, cardia-cerebrovascular disease and diabetes in patients with COVID-19 were 17.1%, 16.4% and 9.7%, respectively.,The incidences of hypertension, cardia-cerebrovascular diseases and diabetes were about twofolds, threefolds and twofolds, respectively, higher in ICU/severe cases than in their non-ICU/severe counterparts.,At least 8.0% patients with COVID-19 suffered the acute cardiac injury.,The incidence of acute cardiac injury was about 13 folds higher in ICU/severe patients compared with the non-ICU/severe patients.,Patients with previous cardiovascular metabolic diseases may face a greater risk of developing into the severe condition and the comorbidities can also greatly affect the prognosis of the COVID-19.,On the other hand, COVID-19 can, in turn, aggravate the damage to the heart.

Increases in cardiac troponin indicative of myocardial injury are common in patients with coronavirus disease-2019 (COVID-19) and are associated with adverse outcomes such as arrhythmias and death.,These increases are more likely to occur in those with chronic cardiovascular conditions and in those with severe COVID-19 presentations.,The increased inflammatory, prothrombotic, and procoagulant responses following severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection increase the risk for acute nonischemic myocardial injury and acute myocardial infarction, particularly type 2 myocardial infarction, because of respiratory failure with hypoxia and hemodynamic instability in critically ill patients.,Myocarditis, stress cardiomyopathy, acute heart failure, and direct injury from SARS-CoV-2 are important etiologies, but primary noncardiac conditions, such as pulmonary embolism, critical illness, and sepsis, probably cause more of the myocardial injury.,The structured use of serial cardiac troponin has the potential to facilitate risk stratification, help make decisions about when to use imaging, and inform stage categorization and disease phenotyping among hospitalized COVID-19 patients.,•Increases in cardiac troponin indicative of myocardial injury are common and prognostic in COVID-19.,•Increases can be due to chronic injury, acute nonischemic injury, or acute MI.,•Troponin, along with inflammatory and thrombotic markers, may facilitate COVID-19 stage classification and risk stratification.,Increases in cardiac troponin indicative of myocardial injury are common and prognostic in COVID-19.,Increases can be due to chronic injury, acute nonischemic injury, or acute MI.,Troponin, along with inflammatory and thrombotic markers, may facilitate COVID-19 stage classification and risk stratification.

The coronavirus disease 2019 (COVID-19) outbreak, along with implementation of lockdown and strict public movement restrictions, in Greece has affected hospital visits and admissions.,We aimed to investigate trends of cardiac disease admissions during the outbreak of the pandemic and possible associations with the applied restrictive measures.,This is a retrospective observational study.,Data for 4970 patients admitted via the cardiology emergency department (ED) across 3 large-volume urban hospitals in Athens and 2 regional/rural hospitals from February 3, 2020, up to April 12 were recorded.,Data from the equivalent (for the COVID-19 outbreak) time period of 2019 and from the postlockdown time period were also collected.,A falling trend of cardiology ED visits and hospital admissions was observed starting from the week when the restrictive measures due to COVID-19 were implemented.,Compared with the pre-COVID-19 outbreak time period, acute coronary syndrome (ACS) [145 (29/week) vs. 60 (12/week), −59%, P < 0.001], ST elevation myocardial infarction [46 (9.2/week) vs.,21 (4.2/week), −54%, P = 0.002], and non-ST elevation ACS [99 cases (19.8/week) vs.,39 (7.8/week), −60% P < 0.001] were reduced at the COVID-19 outbreak time period.,Reductions were also noted for heart failure worsening and arrhythmias.,The ED visits in the postlockdown period were significantly higher than in the COVID-19 outbreak time period (1511 vs 660; P < 0.05).,Our data show significant drops in cardiology visits and admissions during the COVID-19 outbreak time period.,Whether this results from restrictive measures or depicts a true reduction of cardiac disease cases warrants further investigation.,•The coronavirus disease 2019 (COVID-19) outbreak has led to an unprecedented health system overload.,•The restrictive measures in Greece resulted in a low number of COVID-19 cases.,•Hospital visits and cardiovascular events have diminished after implementation of restrictive measures.,•Acute coronary syndromes reduced by approximately 55%, despite limited incidence of COVID-19.,•The multifactorial etiology of this finding should be thoroughly investigated.,The coronavirus disease 2019 (COVID-19) outbreak has led to an unprecedented health system overload.,The restrictive measures in Greece resulted in a low number of COVID-19 cases.,Hospital visits and cardiovascular events have diminished after implementation of restrictive measures.,Acute coronary syndromes reduced by approximately 55%, despite limited incidence of COVID-19.,The multifactorial etiology of this finding should be thoroughly investigated.

COVID-19 affects millions of patients worldwide, with clinical presentation ranging from isolated thrombosis to acute respiratory distress syndrome (ARDS) requiring ventilator support.,Neutrophil extracellular traps (NETs) originate from decondensed chromatin released to immobilize pathogens, and they can trigger immunothrombosis.,We studied the connection between NETs and COVID-19 severity and progression.,We conducted a prospective cohort study of COVID-19 patients (n = 33) and age- and sex-matched controls (n = 17).,We measured plasma myeloperoxidase (MPO)-DNA complexes (NETs), platelet factor 4, RANTES, and selected cytokines.,Three COVID-19 lung autopsies were examined for NETs and platelet involvement.,We assessed NET formation ex vivo in COVID-19 neutrophils and in healthy neutrophils incubated with COVID-19 plasma.,We also tested the ability of neonatal NET-inhibitory factor (nNIF) to block NET formation induced by COVID-19 plasma.,Plasma MPO-DNA complexes increased in COVID-19, with intubation (P < .0001) and death (P < .0005) as outcome.,Illness severity correlated directly with plasma MPO-DNA complexes (P = .0360), whereas Pao2/fraction of inspired oxygen correlated inversely (P = .0340).,Soluble and cellular factors triggering NETs were significantly increased in COVID-19, and pulmonary autopsies confirmed NET-containing microthrombi with neutrophil-platelet infiltration.,Finally, COVID-19 neutrophils ex vivo displayed excessive NETs at baseline, and COVID-19 plasma triggered NET formation, which was blocked by nNIF.,Thus, NETs triggering immunothrombosis may, in part, explain the prothrombotic clinical presentations in COVID-19, and NETs may represent targets for therapeutic intervention.,•NETs contribute to microthrombi through platelet-neutrophil interactions in COVID-19 ARDS.•nNIF blocks NETs induced by COVID-19 plasma and represents a potential therapeutic intervention in COVID-19.,NETs contribute to microthrombi through platelet-neutrophil interactions in COVID-19 ARDS.,nNIF blocks NETs induced by COVID-19 plasma and represents a potential therapeutic intervention in COVID-19.

Emerging evidence shows that severe coronavirus disease 2019 (COVID‐19) can be complicated with coagulopathy, namely disseminated intravascular coagulation, which has a rather prothrombotic character with high risk of venous thromboembolism.,The incidence of venous thromboembolism among COVID‐19 patients in intensive care units appears to be somewhat higher compared to that reported in other studies including such patients with other disease conditions.,D‐dimer might help in early recognition of these high‐risk patients and also predict outcome.,Preliminary data show that in patients with severe COVID‐19, anticoagulant therapy appears to be associated with lower mortality in the subpopulation meeting sepsis‐induced coagulopathy criteria or with markedly elevated d‐dimer.,Recent recommendations suggest that all hospitalized COVID‐19 patients should receive thromboprophylaxis, or full therapeutic‐intensity anticoagulation if such an indication is present.

The aim of this study was to investigate the clinical characteristics of Corona Virus Disease 2019 in Taizhou, China.,A single center retrospective observational study was performed between Jan 1, 2020 and Mar 11, 2020 at Taizhou Public Health Medical Center, Zhejiang, China.,All patients with confirmed Corona Virus Disease 2019 were enrolled, and their clinical data were gathered by reviewing electronic medical records.,Outcomes of severely ill patients and non-severely ill patients were compared.,Of 145 hospitalized patients with COVID-19, the average age was 47.5 years old (standard deviation, 14.6) and 54.5% were men.,Hypertension was the most common comorbidity (15.2%), followed by diabetes mellitus (9.7%).,Common symptoms included dry cough (81.4%), fever (75.2%), anorexia (42.8%), fatigue (40.7%), chest tightness (32.4%), diarrhea (26.9%) and dizziness (20%).,According to imaging examination, 79.3% patients showed bilateral pneumonia, 18.6% showed unilateral pneumonia, 61.4% showed ground-glass opacity, and 2.1% showed no abnormal result.,Compared with non-severely ill patients, severely ill patients were older (mean, years, 52.8 vs.,45.3, p < 0.01), had a higher proportion of diabetes mellitus (16.3% vs.,6.9%, p = 0.08), had a higher body mass index (mean, 24.78 vs.,23.20, p = 0.02) and were more likely to have fever (90.7% vs.,68.6%, p = 0.01), anorexia (60.5% vs.,35.3%, p = 0.01), chest tightness (60.5% vs.20.6%, p < 0.01) and dyspnea (7.0% vs. 0%, p = 0.03).,Of the 43 severely ill patients, 6 (14%) received high-flow nasal cannula oxygen therapy, and 1 (2.3%) received invasive mechanical ventilation.,Older patients or patients with comorbidities such as obesity or diabetes mellitus were more likely to have severe condition.,Treatments of COVID-19 is still experimental and more clinical trials are needed.

Coronavirus disease 2019 (COVID-19) has been demonstrated to be the cause of pneumonia.,Nevertheless, it has not been reported as the cause of acute myocarditis or fulminant myocarditis.,A 63-year-old male was admitted with pneumonia and cardiac symptoms.,He was genetically confirmed as having COVID-19 according to sputum testing on the day of admission.,He also had elevated troponin I (Trop I) level (up to 11.37 g/L) and diffuse myocardial dyskinesia along with a decreased left ventricular ejection fraction (LVEF) on echocardiography.,The highest level of interleukin-6 was 272.40 pg/ml.,Bedside chest radiographs showed typical ground-glass changes indicative of viral pneumonia.,Laboratory test results for viruses that cause myocarditis were all negative.,The patient conformed to the diagnostic criteria of the Chinese expert consensus statement for fulminant myocarditis.,After receiving antiviral therapy and mechanical life support, Trop I was reduced to 0.10 g/L, and interleukin-6 was reduced to 7.63 pg/mL.,Moreover, the LVEF of the patient gradually recovered to 68%.,The patient died of aggravation of secondary infection on the 33rd day of hospitalization.,COVID-19 patients may develop severe cardiac complications such as myocarditis and heart failure.,This is the first report of COVID-19 complicated with fulminant myocarditis.,The mechanism of cardiac pathology caused by COVID-19 needs further study.

Spain has been one of the countries more heavily stricken by SARS‐CoV‐2, which has had huge implications for stroke care.,The aim was to analyse the impact of the COVID‐19 epidemic outbreak on reperfusion therapies for acute ischaemic stroke in the northwest of Spain.,This was a Spanish multicentre retrospective observational study based on data from tertiary hospitals of the NORDICTUS network.,All patients receiving reperfusion therapy for ischaemic stroke between 30 December 2019 and 3 May 2020 were recorded, and their baseline, clinical and radiological characteristics, extra‐ and intra‐hospital times of action, Code Stroke activation pathway, COVID‐19 status, reperfusion rate, and short‐term outcome before and after the setting of the emergency state were analysed.,A total of 796 patients received reperfusion therapies for ischaemic stroke.,There was a decrease in the number of patients treated per week (46.5 patients per week vs.,39.0 patients per week, P = 0.043) and a delay in out‐of‐hospital (95.0 vs.,110.0 min, P = 0.001) and door‐to‐needle times (51.0 vs.,55.0, P = 0.038).,Patients receiving endovascular therapy obtained less successful reperfusion rates (92.9% vs.,86.6%, P = 0.016).,COVID‐19 patients had more in‐hospital mortality.,A decrease in the number of patients benefiting from reperfusion therapies was found, with a delay in out‐of‐hospital and door‐to‐needle times and worse reperfusion rates in northwest Spain.,COVID‐19 patients had more in‐hospital mortality.

The 2019 novel coronavirus outbreak and its associated disease (coronavirus disease 2019 [COVID-19]) have created a worldwide pandemic.,Early data suggest higher rate of ischemic stroke in severe COVID-19 infection.,We evaluated whether a relationship exists between emergent large vessel occlusion (ELVO) and the ongoing COVID-19 outbreak.,This is a retrospective, observational case series.,Data were collected from all patients who presented with ELVO to the Mount Sinai Health System Hospitals across New York City during the peak 3 weeks of hospitalization and death from COVID-19.,Patients’ demographic, comorbid conditions, cardiovascular risk factors, COVID-19 disease status, and clinical presentation were extracted from the electronic medical record.,Comparison was made between COVID-19 positive and negative cohorts.,The incidence of ELVO stroke was compared with the pre-COVID period.,Forty-five consecutive ELVO patients presented during the observation period.,Fifty-three percent of patients tested positive for COVID-19.,Total patients’ mean (±SD) age was 66 (±17).,Patients with COVID-19 were significantly younger than patients without COVID-19, 59±13 versus 74±17 (odds ratio [95% CI], 0.94 [0.81-0.98]; P=0.004).,Seventy-five percent of patients with COVID-19 were male compared with 43% of patients without COVID-19 (odds ratio [95% CI], 3.99 [1.12-14.17]; P=0.032).,Patients with COVID-19 were less likely to be White (8% versus 38% [odds ratio (95% CI), 0.15 (0.04-0.81); P=0.027]).,In comparison to a similar time duration before the COVID-19 outbreak, a 2-fold increase in the total number of ELVO was observed (estimate: 0.78 [95% CI, 0.47-1.08], P≤0.0001).,More than half of the ELVO stroke patients during the peak time of the New York City’s COVID-19 outbreak were COVID-19 positive, and those patients with COVID-19 were younger, more likely to be male, and less likely to be White.,Our findings also suggest an increase in the incidence of ELVO stroke during the peak of the COVID-19 outbreak.

Supplemental Digital Content is available in the text.,Patients with coronavirus disease 2019 (COVID-19) who develop cardiac injury are reported to experience higher rates of malignant cardiac arrhythmias.,However, little is known about these arrhythmias-their frequency, the underlying mechanisms, and their impact on mortality.,We extracted data from a registry (NCT04358029) regarding consecutive inpatients with confirmed COVID-19 who were receiving continuous telemetric ECG monitoring and had a definitive disposition of hospital discharge or death.,Between patients who died versus discharged, we compared a primary composite end point of cardiac arrest from ventricular tachycardia/fibrillation or bradyarrhythmias such as atrioventricular block.,Among 800 patients with COVID-19 at Mount Sinai Hospital with definitive dispositions, 140 patients had telemetric monitoring, and either died (52) or were discharged (88).,The median (interquartile range) age was 61 years (48-74); 73% men; and ethnicity was White in 34%.,Comorbidities included hypertension in 61%, coronary artery disease in 25%, ventricular arrhythmia history in 1.4%, and no significant comorbidities in 16%.,Compared with discharged patients, those who died had elevated peak troponin I levels (0.27 versus 0.02 ng/mL) and more primary end point events (17% versus 4%, P=0.01)-a difference driven by tachyarrhythmias.,Fatal tachyarrhythmias invariably occurred in the presence of severe metabolic imbalance, while atrioventricular block was largely an independent primary event.,Hospitalized patients with COVID-19 who die experience malignant cardiac arrhythmias more often than those surviving to discharge.,However, these events represent a minority of cardiovascular deaths, and ventricular tachyarrhythmias are mainly associated with severe metabolic derangement.,URL: https://www.clinicaltrials.gov; Unique identifier: NCT04358029.

No studies investigated the prevalence of arrhythmias among clinically‐stable patients affected by COVID‐19 infection.,We assessed prevalence, type, and burden of arrhythmias, by a single‐day snapshot in seven non‐intensive COVID Units at a third‐level center.,We enrolled 132 inhospital patients (mean age 65±14y; 66% males) newly diagnosed with COVID‐19 infection.,Arrhythmic episodes were detected in 12 patients (9%).,In detail, 8 had atrial fibrillation, and 4 self‐limiting supraventricular tachyarrhythmias.,There were no cases of ventricular arrhythmias or new‐onset atrioventricular blocks.,In addition, we report no patients with QTc interval >450 ms.,Our single‐day snapshot survey suggests that the prevalence of arrhythmias among clinically stable COVID‐19 patients is low.,In particular, no life‐threatening arrhythmic events occurred.

Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described.,In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020.,Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors.,We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death.,191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients).,Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03-1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61-12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64-128·55; p=0·0033) on admission.,Median duration of viral shedding was 20·0 days (IQR 17·0-24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors.,The longest observed duration of viral shedding in survivors was 37 days.,The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage.,Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.,Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

To delineate the clinical characteristics of patients with coronavirus disease 2019 (covid-19) who died.,Retrospective case series.,Tongji Hospital in Wuhan, China.,Among a cohort of 799 patients, 113 who died and 161 who recovered with a diagnosis of covid-19 were analysed.,Data were collected until 28 February 2020.,Clinical characteristics and laboratory findings were obtained from electronic medical records with data collection forms.,The median age of deceased patients (68 years) was significantly older than recovered patients (51 years).,Male sex was more predominant in deceased patients (83; 73%) than in recovered patients (88; 55%).,Chronic hypertension and other cardiovascular comorbidities were more frequent among deceased patients (54 (48%) and 16 (14%)) than recovered patients (39 (24%) and 7 (4%)).,Dyspnoea, chest tightness, and disorder of consciousness were more common in deceased patients (70 (62%), 55 (49%), and 25 (22%)) than in recovered patients (50 (31%), 48 (30%), and 1 (1%)).,The median time from disease onset to death in deceased patients was 16 (interquartile range 12.0-20.0) days.,Leukocytosis was present in 56 (50%) patients who died and 6 (4%) who recovered, and lymphopenia was present in 103 (91%) and 76 (47%) respectively.,Concentrations of alanine aminotransferase, aspartate aminotransferase, creatinine, creatine kinase, lactate dehydrogenase, cardiac troponin I, N-terminal pro-brain natriuretic peptide, and D-dimer were markedly higher in deceased patients than in recovered patients.,Common complications observed more frequently in deceased patients included acute respiratory distress syndrome (113; 100%), type I respiratory failure (18/35; 51%), sepsis (113; 100%), acute cardiac injury (72/94; 77%), heart failure (41/83; 49%), alkalosis (14/35; 40%), hyperkalaemia (42; 37%), acute kidney injury (28; 25%), and hypoxic encephalopathy (23; 20%).,Patients with cardiovascular comorbidity were more likely to develop cardiac complications.,Regardless of history of cardiovascular disease, acute cardiac injury and heart failure were more common in deceased patients.,Severe acute respiratory syndrome coronavirus 2 infection can cause both pulmonary and systemic inflammation, leading to multi-organ dysfunction in patients at high risk.,Acute respiratory distress syndrome and respiratory failure, sepsis, acute cardiac injury, and heart failure were the most common critical complications during exacerbation of covid-19.

Atrial fibrillation (AF) increases the risk of developing a stroke by 20%.,AF related strokes are associated with greater morbidity.,Historically, warfarin was the anticoagulant of choice for stroke prevention in patients with AF but lately patients are being switched or started on direct oral anticoagulants (DOACs).,DOACs are promoted as safer alternatives to warfarin and it is expected that they will be associated with fewer challenges both for patients and healthcare professionals.,This systematic narrative review aimed to explore perspectives of patients and professionals on medicines optimisation of oral anticoagulation with vitamin K antagonists and DOACs in atrial fibrillation.,Prospero registration CRD42018091591.,Systematic searches undertaken of research studies (qualitative and quantitative), published February 2018 to November 2020 from several databases (Web of Science, Scopus, Medline Via Ovid, CINHAL via Ebsco, and PubMED via NCBI) following PRISMA methodology.,Data were organised using Covidence software.,Two reviewers independently assessed the quality of the included studies and synthesized the findings (thematic analysis approach).,Thirty-four studies were included.,Studies were critically appraised using established critical appraisal tools (Qualsyst) and a risk of bias was assigned.,Clinicians considered old age and the associated complexities such as co-morbidities and the increased potential for bleeding as potential barriers to optimising anticoagulation.,Whereas patients’ health and medication beliefs influenced adherence.,Notably, structured patient support was important in enhancing safety and effective anticoagulation.,For both patients and clinicians, confidence and experience of safe anticoagulation was influenced by the presence of co-morbidities, poor knowledge and understanding of AF and the purpose of anticoagulation.,Age, complex multimorbidity and polypharmacy influence prescribing, with DOACs being perceived to be safer than warfarin.,This systematic narrative review suggests that interventions are needed to support patient self-management.,There are residual anxieties associated with long term anticoagulation in the context of complexities.,Not applicable.,The online version contains supplementary material available at 10.1186/s12875-021-01590-x.

Anticoagulation for stroke prevention in atrial fibrillation (AF) has, historically, been under-used in older people.,The aim of this study was to investigate prescribing of oral anticoagulants (OACs) for people aged ≥ 75 years in the UK before and after direct oral anticoagulants (DOACs) became available.,A cohort of patients aged ≥ 75 years with a diagnosis of AF was derived from the Clinical Practice Research Datalink (CPRD) between January 1, 2003, and December 27, 2017.,Patients were grouped as no OAC, incident OAC (OAC newly prescribed) or prevalent OAC (entered study on OAC).,Incidence and point prevalence of OAC prescribing were calculated yearly.,The risk of being prescribed an OAC if a co-morbidity was present was calculated; the risk difference (RD) was reported.,Kaplan-Meier curves were used to explore persistence with anticoagulation.,A Cox regression was used to model persistence with warfarin and DOACs over time.,The cohort comprised 165,596 patients (66,859 no OAC; 47,916 incident OAC; 50,821 prevalent OAC).,Incidence of OAC prescribing increased from 111 per 1000 person-years in 2003 to 587 per 1000 person-years in 2017.,Older patients (≥ 90 years) were 40% less likely to receive an OAC (RD −0.40, 95% CI −0.41 to −0.39) than younger individuals (75-84 years).,The likelihood of being prescribed an OAC was lower with a history of dementia (RD −0.34, 95% CI −0.35 to −0.33), falls (RD −0.17, 95% CI −0.18 to −0.16), major bleeds (RD −0.17, 95% CI −0.19 to −0.15) and fractures (RD −0.13, 95% CI −0.14 to −0.12).,Persistence with warfarin was higher than DOACs in the first year (0-1 year: HR 1.25, 95% CI 1.17-1.33), but this trend reversed by the third year of therapy (HR 0.75, 95% CI 0.63-0.89).,OAC prescribing for older people with AF has increased; however, substantial disparities persist with age and co-morbidities.,Whilst OACs should not be withheld solely due to the risk of falls, these results do not reflect this national guidance.,Furthermore, the under-prescribing of OACs for patients with dementia or advancing age may be due to decisions around risk-benefit management.,EUPAS29923.,First registered on: 27/06/2019.,The online version contains supplementary material available at 10.1186/s12916-021-02067-5.

Increases in cardiac troponin indicative of myocardial injury are common in patients with coronavirus disease-2019 (COVID-19) and are associated with adverse outcomes such as arrhythmias and death.,These increases are more likely to occur in those with chronic cardiovascular conditions and in those with severe COVID-19 presentations.,The increased inflammatory, prothrombotic, and procoagulant responses following severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection increase the risk for acute nonischemic myocardial injury and acute myocardial infarction, particularly type 2 myocardial infarction, because of respiratory failure with hypoxia and hemodynamic instability in critically ill patients.,Myocarditis, stress cardiomyopathy, acute heart failure, and direct injury from SARS-CoV-2 are important etiologies, but primary noncardiac conditions, such as pulmonary embolism, critical illness, and sepsis, probably cause more of the myocardial injury.,The structured use of serial cardiac troponin has the potential to facilitate risk stratification, help make decisions about when to use imaging, and inform stage categorization and disease phenotyping among hospitalized COVID-19 patients.,•Increases in cardiac troponin indicative of myocardial injury are common and prognostic in COVID-19.,•Increases can be due to chronic injury, acute nonischemic injury, or acute MI.,•Troponin, along with inflammatory and thrombotic markers, may facilitate COVID-19 stage classification and risk stratification.,Increases in cardiac troponin indicative of myocardial injury are common and prognostic in COVID-19.,Increases can be due to chronic injury, acute nonischemic injury, or acute MI.,Troponin, along with inflammatory and thrombotic markers, may facilitate COVID-19 stage classification and risk stratification.

We sought to study the impact of COVID‐19 pandemic on the presentation delay, severity, patterns of care, and reasons for delay among patients with ST‐elevation myocardial infarction (STEMI) in a non‐hot‐spot region.,COVID‐19 pandemic has significantly reduced the activations for STEMI in epicenters like Spain.,From January 1, 2020, to April 15, 2020, 143 STEMIs were identified across our integrated 18‐hospital system.,Pre‐ and post‐COVID‐19 cohorts were based on March 23rd, 2020, whenstay‐at‐home orders were initiated in Ohio.,We used presenting heart rate, blood pressure, troponin, new Q‐wave, and left ventricle ejection fraction (LVEF) to assess severity.,Duration of intensive care unit stay, total length of stay, door‐to‐balloon (D2B) time, and radial versus femoral access were used to assess patterns of care.,Post‐COVID‐19 presentation was associated with a lower admission LVEF (45 vs. 50%, p = .015), new Q‐wave, and higher initial troponin; however, these did not reach statistical significance.,Among post‐COVID‐19 patients, those with >12‐hr delay in presentation 31(%) had a longer average D2B time (88 vs. 53 min, p = .033) and higher peak troponin (58 vs.,8.5 ng/ml, p = .03).,Of these, 27% avoided the hospital due to fear of COVID‐19, 18% believed symptoms were COVID‐19 related, and 9% did not want to burden the hospital during the pandemic.,COVID‐19 has remarkably affected STEMI presentation and care.,Patients' fear and confusion about symptoms are integral parts of this emerging public health crisis.

The purpose of this study was to assess clinical characteristics and risk factors for mortality of patients with coronavirus disease 2019 (COVID-19) from Mexico, given that it currently is in active community transmission.,Multivariate logistic regression model and Kaplan-Meier survival curves were fitted to study odds of death of characteristics and comorbidities in patients with COVID-19 in Mexico.,Age, sex, and the most frequent comorbidities diabetes, obesity, and hypertension were significantly associated to the risk of death by COVID-19 (P < .0001).,Smoking habit was not identified as a risk factor for death.,Less-frequent comorbidities such as chronic obstructive pulmonary disease, chronic kidney disease, and patients with immunosuppressed conditions also showed a significant risk for death (P < .0001).,Hospitalized patients and those with pneumonia had serious risks for mortality (P < .0001), and more attention to specific conditions might be considered during clinical admission.,A more vulnerable positive patient is depicted by a male patient, older than 41 years, which increases their risk with more prevalent comorbidities such as diabetes, hypertension, and obesity.,Some implications on outcomes are discussed.

The aim of this study was to identify factors associated with the death of patients with COVID-19 pneumonia caused by the novel coronavirus SARS-CoV-2.,All clinical and laboratory parameters were collected prospectively from a cohort of patients with COVID-19 pneumonia who were hospitalised to Wuhan Pulmonary Hospital (Wuhan City, Hubei Province, China) between 25 December 2019 and 7 February 2020.,Univariate and multivariate logistic regression was performed to investigate the relationship between each variable and the risk of death of COVID-19 pneumonia patients.,In total, 179 patients with COVID-19 pneumonia (97 male and 82 female) were included in the present prospective study, of whom 21 died.,Univariate and multivariate logistic regression analysis revealed that age ≥65 years (OR 3.765, 95% CI 1.146-17.394; p=0.023), pre-existing concurrent cardiovascular or cerebrovascular diseases (OR 2.464, 95% CI 0.755-8.044; p=0.007), CD3+CD8+ T-cells ≤75 cells·μL−1 (OR 3.982, 95% CI 1.132-14.006; p<0.001) and cardiac troponin I ≥0.05 ng·mL−1 (OR 4.077, 95% CI 1.166-14.253; p<0.001) were associated with an increase in risk of mortality from COVID-19 pneumonia.,In a sex-, age- and comorbid illness-matched case-control study, CD3+CD8+ T-cells ≤75 cells·μL−1 and cardiac troponin I ≥0.05 ng·mL−1 remained as predictors for high mortality from COVID-19 pneumonia.,We identified four risk factors: age ≥65 years, pre-existing concurrent cardiovascular or cerebrovascular diseases, CD3+CD8+ T-cells ≤75 cells·μL−1 and cardiac troponin I ≥0.05 ng·mL−1.,The latter two factors, especially, were predictors for mortality of COVID-19 pneumonia patients.,These data showed that age ≥65 years, pre-existing concurrent cardiovascular or cerebrovascular diseases, CD3+CD8+ T-cells ≤75 cells·μL−1 and cardiac troponin I ≥0.05 ng·mL−1 were four risk factors predicting high mortality of COVID-19 pneumonia patientshttps://bit.ly/2Rh6Nqv

Nonsyndromic thoracic aortic diseases (NS‐TADs) are often silent entities until they present as life‐threatening emergencies.,Despite familial inheritance being common, screening is not the current standard of care in NS‐TADs.,We sought to determine the incidence of aortic diseases, the predictive accuracy of available screening tests, and the effectiveness of screening programs in relatives of patients affected by NS‐TADs.,A systematic literature search on PubMed/MEDLINE, Embase, and the Cochrane Library was conducted from inception to the end of December 2017.,The search was supplemented with the Online Mendelian Inheritance in Man database.,A total of 53 studies were included, and a total of 2696 NS‐TAD relatives were screened.,Screening was genetic in 49% of studies, followed by imaging techniques in 11% and a combination of the 2 in 40%.,Newly affected individuals were identified in 33%, 24%, and 15% of first‐, second‐, and third‐degree relatives, respectively.,Familial NS‐TADs were primarily attributed to single‐gene mutations, expressed in an autosomal dominant pattern with incomplete penetrance.,Specific gene mutations were observed in 25% of the screened families.,Disease subtype and genetic mutations stratified patients with respect to age of presentation, aneurysmal location, and aortic diameter before dissection.,Relatives of patients with sporadic NS‐TADs were also found to be affected.,No studies evaluated the predictive accuracy of imaging or genetic screening tests, or the clinical or cost‐effectiveness of an NS‐TAD screening program.,First‐ and second‐degree relatives of patients affected by both familial and sporadic NS‐TADs may benefit from personalized screening programs.

Thoracic aortic aneurysm/aortic dissection (TAAD) is a disorder with highly variable age of onset and phenotype.,We sought to determine the prevalence of pathogenic variants in TAAD-associated genes in a mixed cohort of sporadic and familial TAAD patients and identify relevant genotype-phenotype relationships.,We used a targeted PCR and next generation sequencing-based panel for genetic analysis of 15 TAAD associated genes in 1025 unrelated TAAD cases.,We identified 49 pathogenic or likely pathogenic (P/LP) variants in 47 cases (4.9% of those successfully sequenced).,Almost half of the variants were in non-syndromic cases with no known family history of aortic disease.,Twenty-five variants were within FBN1 and two patients were found to harbour two P/LP variants.,Presence of a related syndrome, younger age at presentation, family history of aortic disease and involvement of the ascending aorta increased the risk of carrying a P/LP variant.,Given the poor prognosis of TAAD that is undiagnosed prior to acute rupture or dissection, genetic analysis of both familial and sporadic cases of TAAD will lead to new diagnoses, more informed management and possibly reduced mortality through earlier, preclinical diagnosis in genetically determined cases and their family members.

Cardiac injury is associated with poor prognosis of 2019 novel coronavirus disease 2019 (COVID-19), but the risk factors for cardiac injury have not been fully studied.,In this study, we carried out a systematic analysis of clinical characteristics in COVID-19 patients to determine potential risk factors for cardiac injury complicated COVID-19 virus infection.,We systematically searched relevant literature published in Pubmed, Embase, Europe PMC, CNKI and other databases.,All statistical analyses were performed using STATA 16.0.,We analysed 5726 confirmed cases from 17 studies.,The results indicated that compared with non-cardiac-injured patients, patients with cardiac injury are older, with a greater proportion of male patients, with higher possibilities of existing comorbidities, with higher risks of clinical complications, need for mechanical ventilation, ICU transfer and mortality.,Moreover, C-reactive protein, procalcitonin, D-dimer, NT-proBNP and blood creatinine in patients with cardiac injury are also higher while lymphocyte counts and platelet counts decreased.,However, we fortuitously found that patients with cardiac injury did not present higher clinical specificity for chest distress (P = 0.304), chest pain (P = 0.334), palpitations (P = 0.793) and smoking (P = 0.234).,Similarly, the risk of concomitant arrhythmia (P = 0.103) did not increase observably either.,Age, male gender and comorbidities are risk factors for cardiac injury complicated COVID-19 infection.,Such patients are susceptible to complications and usually have abnormal results of laboratory tests, leading to poor outcomes.,Contrary to common cardiac diseases, cardiac injury complicated COVID-19 infection did not significantly induce chest distress, chest pain, palpitations or arrhythmias.,Our study indicates that early prevention should be applied to COVID-19 patients with cardiac injury to reduce adverse outcomes.

The coronavirus disease‐2019 (COVID‐19) pandemic has resulted in the worst global pandemic of our generation, affecting 215 countries with nearly 5.5 million cases.,The association between COVID‐19 and the cardiovascular system has been well described.,We sought to systematically review the current published literature on the different cardiac manifestations and the use of cardiac‐specific biomarkers in terms of their prognostic value in determining clinical outcomes and correlation to disease severity.,A systematic literature review across PubMed, Cochrane database, Embase, Google Scholar, and Ovid was performed according to PRISMA guidelines to identify relevant articles that discussed risk factors for cardiovascular manifestations, cardiac manifestations in COVID‐19 patients, and cardiac‐specific biomarkers with their clinical implications on COVID‐19.,Sixty‐one relevant articles were identified which described risk factors for cardiovascular manifestations, cardiac manifestations (including heart failure, cardiogenic shock, arrhythmia, and myocarditis among others) and cardiac‐specific biomarkers (including CK‐MB, CK, myoglobin, troponin, and NT‐proBNP).,Cardiovascular risk factors can play a crucial role in identifying patients vulnerable to developing cardiovascular manifestations of COVID‐19 and thus help to save lives.,A wide array of cardiac manifestations is associated with the interaction between COVID‐19 and the cardiovascular system.,Cardiac‐specific biomarkers provide a useful prognostic tool in helping identify patients with the severe disease early and allowing for escalation of treatment in a timely fashion.,COVID‐19 is an evolving pandemic with predominate respiratory manifestations, however, due to the interaction with the cardiovascular system; cardiac manifestations/complications feature heavily in this disease, with cardiac biomarkers providing important prognostic information.

Coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become pandemic, with substantial mortality.,To evaluate the pathologic changes of organ systems and the clinicopathologic basis for severe and fatal outcomes.,Prospective autopsy study.,Single pathology department.,11 deceased patients with COVID-19 (10 of whom were selected at random for autopsy).,Systematic macroscopic, histopathologic, and viral analysis (SARS-CoV-2 on real-time polymerase chain reaction assay), with correlation of pathologic and clinical features, including comorbidities, comedication, and laboratory values.,Patients' age ranged from 66 to 91 years (mean, 80.5 years; 8 men, 3 women).,Ten of the 11 patients received prophylactic anticoagulant therapy; venous thromboembolism was not clinically suspected antemortem in any of the patients.,Both lungs showed various stages of diffuse alveolar damage (DAD), including edema, hyaline membranes, and proliferation of pneumocytes and fibroblasts.,Thrombosis of small and mid-sized pulmonary arteries was found in various degrees in all 11 patients and was associated with infarction in 8 patients and bronchopneumonia in 6 patients.,Kupffer cell proliferation was seen in all patients, and chronic hepatic congestion in 8 patients.,Other changes in the liver included hepatic steatosis, portal fibrosis, lymphocytic infiltrates and ductular proliferation, lobular cholestasis, and acute liver cell necrosis, together with central vein thrombosis.,Additional frequent findings included renal proximal tubular injury, focal pancreatitis, adrenocortical hyperplasia, and lymphocyte depletion of spleen and lymph nodes.,Viral RNA was detectable in pharyngeal, bronchial, and colonic mucosa but not bile.,The sample was small.,COVID-19 predominantly involves the lungs, causing DAD and leading to acute respiratory insufficiency.,Death may be caused by the thrombosis observed in segmental and subsegmental pulmonary arterial vessels despite the use of prophylactic anticoagulation.,Studies are needed to further understand the thrombotic complications of COVID-19, together with the roles for strict thrombosis prophylaxis, laboratory, and imaging studies and early anticoagulant therapy for suspected pulmonary arterial thrombosis or thromboembolism.,None.,The clinicopathological basis for morbidity and mortality with SARS-CoV-2 infection is not well understood.,This study reports the clinical and autopsy findings of patients who died of COVID-19.

An increased risk of venous thromboembolism (VTE) in patients with COVID-19 pneumonia admitted to intensive care unit (ICU) has been reported.,Whether COVID-19 increases the risk of VTE in non-ICU wards remains unknown.,We aimed to evaluate the burden of asymptomatic deep vein thrombosis (DVT) in COVID-19 patients with elevated D-dimer levels.,In this prospective study consecutive patients hospitalized in non-intensive care units with diagnosis of COVID-19 pneumonia and D-dimer > 1000 ng/ml were screened for asymptomatic DVT with complete compression doppler ultrasound (CCUS).,The study was approved by the Institutional Ethics Committee.,The study comprised 156 patients (65.4% male).,All but three patients received standard doses of thromboprophylaxis.,Median days of hospitalization until CCUS was 9 (IQR 5-17).,CCUS was positive for DVT in 23 patients (14.7%), of whom only one was proximal DVT.,Seven patients (4.5%) had bilateral distal DVT.,Patients with DVT had higher median D-dimer levels: 4527 (IQR 1925-9144) ng/ml vs 2050 (IQR 1428-3235) ng/ml; p < 0.001.,D-dimer levels > 1570 ng/ml were associated with asymptomatic DVT (OR 9.1; CI 95% 1.1-70.1).,D-dimer showed an acceptable discriminative capacity (area under the ROC curve 0.72, 95% CI 0.61-0.84).,In patients admitted with COVID-19 pneumonia and elevated D-dimer levels, the incidence of asymptomatic DVT is similar to that described in other series.,Higher cut-off levels for D-dimer might be necessary for the diagnosis of DVT in COVID-19 patients.,•An increased risk of VTE in patients with COVID-19 pneumonia admitted to intensive care unit has been reported.,•The most consistent hemostatic abnormalities with COVID-19 include mild thrombocytopenia and increased D-dimer levels.,•In COVID-19 patients with high D-dimer levels, the incidence of asymptomatic DVT is similar to that described in other series.,•Higher cut-off levels for D-dimer might be necessary for the diagnosis of DVT in COVID-19 patients.,An increased risk of VTE in patients with COVID-19 pneumonia admitted to intensive care unit has been reported.,The most consistent hemostatic abnormalities with COVID-19 include mild thrombocytopenia and increased D-dimer levels.,In COVID-19 patients with high D-dimer levels, the incidence of asymptomatic DVT is similar to that described in other series.,Higher cut-off levels for D-dimer might be necessary for the diagnosis of DVT in COVID-19 patients.

Since its recognition in December 2019, covid-19 has rapidly spread globally causing a pandemic.,Pre-existing comorbidities such as hypertension, diabetes, and cardiovascular disease are associated with a greater severity and higher fatality rate of covid-19.,Furthermore, COVID-19 contributes to cardiovascular complications, including acute myocardial injury as a result of acute coronary syndrome, myocarditis, stress-cardiomyopathy, arrhythmias, cardiogenic shock, and cardiac arrest.,The cardiovascular interactions of COVID-19 have similarities to that of severe acute respiratory syndrome, Middle East respiratory syndrome and influenza.,Specific cardiovascular considerations are also necessary in supportive treatment with anticoagulation, the continued use of renin-angiotensin-aldosterone system inhibitors, arrhythmia monitoring, immunosuppression or modulation, and mechanical circulatory support.

This case series study evaluates the association of underlying cardiovascular disease and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19).,What is the impact of underlying cardiovascular disease (CVD) and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19)?,In this case series study of 187 patients with COVID-19, 27.8% of patients had myocardial injury, which resulted in cardiac dysfunction and arrhythmias.,Myocardial injury has a significant association with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury were relatively favorable.,It is reasonable to triage patients with COVID-19 according to the presence of underlying CVD and evidence of myocardial injury for prioritized treatment and even more aggressive strategies.,Increasing numbers of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) are occurring in several countries and continents.,Information regarding the impact of cardiovascular complication on fatal outcome is scarce.,To evaluate the association of underlying cardiovascular disease (CVD) and myocardial injury with fatal outcomes in patients with COVID-19.,This retrospective single-center case series analyzed patients with COVID-19 at the Seventh Hospital of Wuhan City, China, from January 23, 2020, to February 23, 2020.,Analysis began February 25, 2020.,Demographic data, laboratory findings, comorbidities, and treatments were collected and analyzed in patients with and without elevation of troponin T (TnT) levels.,Among 187 patients with confirmed COVID-19, 144 patients (77%) were discharged and 43 patients (23%) died.,The mean (SD) age was 58.50 (14.66) years.,Overall, 66 (35.3%) had underlying CVD including hypertension, coronary heart disease, and cardiomyopathy, and 52 (27.8%) exhibited myocardial injury as indicated by elevated TnT levels.,The mortality during hospitalization was 7.62% (8 of 105) for patients without underlying CVD and normal TnT levels, 13.33% (4 of 30) for those with underlying CVD and normal TnT levels, 37.50% (6 of 16) for those without underlying CVD but elevated TnT levels, and 69.44% (25 of 36) for those with underlying CVD and elevated TnTs.,Patients with underlying CVD were more likely to exhibit elevation of TnT levels compared with the patients without CVD (36 [54.5%] vs 16 [13.2%]).,Plasma TnT levels demonstrated a high and significantly positive linear correlation with plasma high-sensitivity C-reactive protein levels (β = 0.530, P < .001) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (β = 0.613, P < .001).,Plasma TnT and NT-proBNP levels during hospitalization (median [interquartile range (IQR)], 0.307 [0.094-0.600]; 1902.00 [728.35-8100.00]) and impending death (median [IQR], 0.141 [0.058-0.860]; 5375 [1179.50-25695.25]) increased significantly compared with admission values (median [IQR], 0.0355 [0.015-0.102]; 796.90 [401.93-1742.25]) in patients who died (P = .001; P < .001), while no significant dynamic changes of TnT (median [IQR], 0.010 [0.007-0.019]; 0.013 [0.007-0.022]; 0.011 [0.007-0.016]) and NT-proBNP (median [IQR], 352.20 [174.70-636.70]; 433.80 [155.80-1272.60]; 145.40 [63.4-526.50]) was observed in survivors (P = .96; P = .16).,During hospitalization, patients with elevated TnT levels had more frequent malignant arrhythmias, and the use of glucocorticoid therapy (37 [71.2%] vs 69 [51.1%]) and mechanical ventilation (31 [59.6%] vs 14 [10.4%]) were higher compared with patients with normal TnT levels.,The mortality rates of patients with and without use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was 36.8% (7 of 19) and 21.4% (36 of 168) (P = .13).,Myocardial injury is significantly associated with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury is relatively favorable.,Myocardial injury is associated with cardiac dysfunction and arrhythmias.,Inflammation may be a potential mechanism for myocardial injury.,Aggressive treatment may be considered for patients at high risk of myocardial injury.

Exposure to agents acting on the renin-angiotensin system was not associated with a risk increase of COVID-19 infection in 2 Italian matched case-control studies, 1 nested in hypertensive patients and the other in patients with cardiovascular diseases or diabetes.

Hypertension is a common comorbidity in hospitalized patients with COVID-19 infection.,This study aimed to estimate the risks of adverse events associated with in-hospital blood pressure (BP) control and the effects of angiotensin II receptor blocker (ARB) prescription in COVID-19 patients with concomitant hypertension.,In this retrospective cohort study, the anonymized medical records of COVID-19 patients were retrieved from an acute field hospital in Wuhan, China.,Clinical data, drug prescriptions, and laboratory investigations were collected for individual patients with diagnosed hypertension on admission.,Cox proportional hazards models were used to estimate the risks of adverse outcomes associated with BP control during the hospital stay.,Of 803 hypertensive patients, 67 (8.3%) were admitted to the ICU, 30 (3.7%) had respiratory failure, 26 (3.2%) had heart failure, and 35 (4.8%) died.,After adjustment for confounders, the significant predictors of heart failure were average systolic blood pressure (SBP) (hazard ratio (HR) per 10 mmHg 1.89, 95% confidence interval (CI): 1.15, 3.13) and pulse pressure (HR per 10 mmHg 2.71, 95% CI: 1.39, 5.29).,The standard deviations of SBP and diastolic BP were independently associated with mortality and ICU admission.,The risk estimates of poor BP control were comparable between patients receiving ARBs and those not receiving ARBs, with the only exception of a high risk of heart failure in the non-ARB group.,Poor BP control was independently associated with higher risks of adverse outcomes of COVID-19.,ARB drugs did not increase the risks of adverse events in hypertensive patients.

Standard evaluation and management of the patient with suspected or proven cardiovascular complications of coronavirus disease-2019 (COVID-19), the disease caused by severe acute respiratory syndrome related-coronavirus-2 (SARS-CoV-2), is challenging.,Routine history, physical examination, laboratory testing, electrocardiography, and plain x-ray imaging may often suffice for such patients, but given overlap between COVID-19 and typical cardiovascular diagnoses such as heart failure and acute myocardial infarction, need frequently arises for advanced imaging techniques to assist in differential diagnosis and management.,This document provides guidance in several common scenarios among patients with confirmed or suspected COVID-19 infection and possible cardiovascular involvement, including chest discomfort with electrocardiographic changes, acute hemodynamic instability, newly recognized left ventricular dysfunction, as well as imaging during the subacute/chronic phase of COVID-19.,For each, the authors consider the role of biomarker testing to guide imaging decision-making, provide differential diagnostic considerations, and offer general suggestions regarding application of various advanced imaging techniques.

The worldwide pandemic caused by the novel acute respiratory syndrome coronavirus 2 has resulted in a new and lethal disease termed coronavirus disease-2019 (COVID-19).,Although there is an association between cardiovascular disease and COVID-19, the majority of patients who need cardiovascular care for the management of ischemic heart disease may not be infected with this novel coronavirus.,The objective of this document is to provide recommendations for a systematic approach for the care of patients with an acute myocardial infarction (AMI) during the COVID-19 pandemic.,There is a recognition of two major challenges in providing recommendations for AMI care in the COVID-19 era.,Cardiovascular manifestations of COVID-19 are complex with patients presenting with AMI, myocarditis simulating an ST-elevation myocardial infarction (STEMI) presentation, stress cardiomyopathy, non-ischemic cardiomyopathy, coronary spasm, or nonspecific myocardial injury, and the prevalence of COVID-19 disease in the U.S. population remains unknown with risk of asymptomatic spread.,This document addresses the care of these patients focusing on 1) the varied clinical presentations; 2) appropriate personal protection equipment (PPE) for health care workers; 3) role of the Emergency Department, Emergency Medical System and the Cardiac Catheterization Laboratory; and 4) Regional STEMI systems of care.,During the COVID-19 pandemic, primary PCI remains the standard of care for STEMI patients at PCI capable hospitals when it can be provided in a timely fashion, with an expert team outfitted with PPE in a dedicated CCL room.,A fibrinolysis-based strategy may be entertained at non-PCI capable referral hospitals or in specific situations where primary PCI cannot be executed or is not deemed the best option.

In 2008 the Food and Drug Administration introduced a guidance for industry that requires the investigation of cardiovascular outcomes of glucose-lowering medications.,Since then, an increasing number of cardiovascular outcome trials have been completed in diabetes patients with high cardiovascular risk for members of the SGLT-2 and DPP4 inhibitors and GLP-1 receptor agonist classes.,The trials confirmed cardiovascular safety for all tested anti-hyperglycaemic drugs and, in addition empagliflozin, semaglutide and liraglutide could even reduce cardiovascular risk.,The present review summarizes the results of the DEVOTE, CANVAS, EXSCEL and ACE trials that tested cardiovascular safety of Insulin degludec, canagliflozin, once-weekly exenatide and acarbose and were published in 2017.,We provide context on these results by comparing them with earlier trials of glucose-lowering drugs and give an outlook on what to expect in coming years.

Previous studies regarding the cardioprotective effects of dipeptidyl peptidase 4 (DPP-4) inhibitors have not provided sufficient evidence of a relationship between DPP-4 inhibition and actual cardiovascular outcomes.,This study aimed to evaluate the impact of DPP-4 inhibitors on the survival of diabetic patients after first acute myocardial infarction (AMI).,This was a nationwide, propensity score-matched, case-control study of 186,112 first AMI patients, 72,924 of whom had diabetes.,A propensity score, one-to-one matching technique was used to match 2672 controls to 2672 patients in the DPP-4 inhibitor group for analysis.,Controls were matched based on gender, age, and a history of hypertension, dyslipidemia, diabetes, peripheral vascular disease, heart failure, cerebrovascular accident, end-stage renal disease, chronic obstructive pulmonary disease, and percutaneous coronary intervention.,DPP-4 inhibitors improve the overall 3-year survival rate (log rank P < 0.0001), whether male or female.,Cox proportional hazard regression showed DPP-4 inhibitor is beneficial in diabetes patients after AMI (HR = 0.86; 95% CI 0.78-0.95), especially in those patients with hypertension (HR = 0.87; 95% CI 0.78-0.97; P = 0.0103) and cerebrovascular disease (HR = 0.83; 95% CI 0.72-0.97; P = 0.018), but without dyslipidemia (HR = 0.78; 95% CI 0.67-0.92; P = 0.0029), without peripheral vascular disease (HR = 0.86; 95% CI 0.78-0.96; P = 0.0047), without heart failure (HR = 0.84; 95% CI 0.73-0.96; P = 0.0106), without end stage renal disease (HR = 0.86; 95% CI 0.77-0.95; P = 0.0035), and without chronic obstructive pulmonary disease (HR = 0.87; 95% CI 0.78-0.97; P = 0.0096).,DPP-4 inhibitor therapy improved long-term survival in diabetic patients after first AMI, regardless of gender.

Rationale: The global death toll from coronavirus disease (COVID-19) virus as of May 12, 2020, exceeds 286,000.,The risk factors for death were attributed to advanced age and comorbidities but have not been accurately defined.,Objectives: To report the clinical features of 85 fatal cases of COVID-19 in two hospitals in Wuhan.,Methods: Medical records were collected of 85 fatal cases of COVID-19 between January 9, 2020, and February 15, 2020.,Information recorded included medical history, exposure history, comorbidities, symptoms, signs, laboratory findings, computed tomographic scans, and clinical management.,Measurements and Main Results: The median age of the patients was 65.8 years, and 72.9% were male.,Common symptoms were fever (78 [91.8%]), shortness of breath (50 [58.8%]), fatigue (50 [58.8%]), and dyspnea (60 [70.6%]).,Hypertension, diabetes, and coronary heart disease were the most common comorbidities.,Notably, 81.2% of patients had very low eosinophil counts on admission.,Complications included respiratory failure (80 [94.1%]), shock (69 [81.2%]), acute respiratory distress syndrome (63 [74.1%]), and arrhythmia (51 [60%]), among others.,Most patients received antibiotic (77 [90.6%]), antiviral (78 [91.8%]), and glucocorticoid (65 [76.5%]) treatments.,A total of 38 (44.7%) and 33 (38.8%) patients received intravenous immunoglobulin and IFN-α2b, respectively.,Conclusions: In this depictive study of 85 fatal cases of COVID-19, most cases were males aged over 50 years with noncommunicable chronic diseases.,The majority of the patients died of multiple organ failure.,Early onset of shortness of breath may be used as an observational symptom for COVID-19 exacerbations.,Eosinophilopenia may indicate a poor prognosis.,A combination of antimicrobial drugs did not offer considerable benefit to the outcome of this group of patients.

This case series study evaluates the association of underlying cardiovascular disease and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19).,What is the impact of underlying cardiovascular disease (CVD) and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19)?,In this case series study of 187 patients with COVID-19, 27.8% of patients had myocardial injury, which resulted in cardiac dysfunction and arrhythmias.,Myocardial injury has a significant association with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury were relatively favorable.,It is reasonable to triage patients with COVID-19 according to the presence of underlying CVD and evidence of myocardial injury for prioritized treatment and even more aggressive strategies.,Increasing numbers of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) are occurring in several countries and continents.,Information regarding the impact of cardiovascular complication on fatal outcome is scarce.,To evaluate the association of underlying cardiovascular disease (CVD) and myocardial injury with fatal outcomes in patients with COVID-19.,This retrospective single-center case series analyzed patients with COVID-19 at the Seventh Hospital of Wuhan City, China, from January 23, 2020, to February 23, 2020.,Analysis began February 25, 2020.,Demographic data, laboratory findings, comorbidities, and treatments were collected and analyzed in patients with and without elevation of troponin T (TnT) levels.,Among 187 patients with confirmed COVID-19, 144 patients (77%) were discharged and 43 patients (23%) died.,The mean (SD) age was 58.50 (14.66) years.,Overall, 66 (35.3%) had underlying CVD including hypertension, coronary heart disease, and cardiomyopathy, and 52 (27.8%) exhibited myocardial injury as indicated by elevated TnT levels.,The mortality during hospitalization was 7.62% (8 of 105) for patients without underlying CVD and normal TnT levels, 13.33% (4 of 30) for those with underlying CVD and normal TnT levels, 37.50% (6 of 16) for those without underlying CVD but elevated TnT levels, and 69.44% (25 of 36) for those with underlying CVD and elevated TnTs.,Patients with underlying CVD were more likely to exhibit elevation of TnT levels compared with the patients without CVD (36 [54.5%] vs 16 [13.2%]).,Plasma TnT levels demonstrated a high and significantly positive linear correlation with plasma high-sensitivity C-reactive protein levels (β = 0.530, P < .001) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (β = 0.613, P < .001).,Plasma TnT and NT-proBNP levels during hospitalization (median [interquartile range (IQR)], 0.307 [0.094-0.600]; 1902.00 [728.35-8100.00]) and impending death (median [IQR], 0.141 [0.058-0.860]; 5375 [1179.50-25695.25]) increased significantly compared with admission values (median [IQR], 0.0355 [0.015-0.102]; 796.90 [401.93-1742.25]) in patients who died (P = .001; P < .001), while no significant dynamic changes of TnT (median [IQR], 0.010 [0.007-0.019]; 0.013 [0.007-0.022]; 0.011 [0.007-0.016]) and NT-proBNP (median [IQR], 352.20 [174.70-636.70]; 433.80 [155.80-1272.60]; 145.40 [63.4-526.50]) was observed in survivors (P = .96; P = .16).,During hospitalization, patients with elevated TnT levels had more frequent malignant arrhythmias, and the use of glucocorticoid therapy (37 [71.2%] vs 69 [51.1%]) and mechanical ventilation (31 [59.6%] vs 14 [10.4%]) were higher compared with patients with normal TnT levels.,The mortality rates of patients with and without use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was 36.8% (7 of 19) and 21.4% (36 of 168) (P = .13).,Myocardial injury is significantly associated with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury is relatively favorable.,Myocardial injury is associated with cardiac dysfunction and arrhythmias.,Inflammation may be a potential mechanism for myocardial injury.,Aggressive treatment may be considered for patients at high risk of myocardial injury.

Despite considerable advances in the treatment of multiple myeloma (MM) in the last decade, a substantial proportion of patients do not respond to current therapies or have a short duration of response.,Furthermore, these treatments can have notable morbidity and are not uniformly tolerated in all patients.,As there is no cure for MM, patients eventually become resistant to therapies, leading to development of relapsed/refractory MM.,Therefore, an unmet need exists for MM treatments with novel mechanisms of action that can provide durable responses, evade resistance to prior therapies, and/or are better tolerated.,B-cell maturation antigen (BCMA) is preferentially expressed by mature B lymphocytes, and its overexpression and activation are associated with MM in preclinical models and humans, supporting its potential utility as a therapeutic target for MM.,Moreover, the use of BCMA as a biomarker for MM is supported by its prognostic value, correlation with clinical status, and its ability to be used in traditionally difficult-to-monitor patient populations.,Here, we review three common treatment modalities used to target BCMA in the treatment of MM: bispecific antibody constructs, antibody-drug conjugates, and chimeric antigen receptor (CAR)-modified T-cell therapy.,We provide an overview of preliminary clinical data from trials using these therapies, including the BiTE® (bispecific T-cell engager) immuno-oncology therapy AMG 420, the antibody-drug conjugate GSK2857916, and several CAR T-cell therapeutic agents including bb2121, NIH CAR-BCMA, and LCAR-B38M.,Notable antimyeloma activity and high minimal residual disease negativity rates have been observed with several of these treatments.,These clinical data outline the potential for BCMA-targeted therapies to improve the treatment landscape for MM.,Importantly, clinical results to date suggest that these therapies may hold promise for deep and durable responses and support further investigation in earlier lines of treatment, including newly diagnosed MM.

Interim analyses of a phase I study with GSK2857916, an antibody-drug conjugate against B cell maturation antigen, have previously reported a 60% overall response and 7.9 months progression-free survival in relapsed/refractory multiple myeloma (MM).,We provide updated safety and efficacy results of the BMA117159 trial following an additional 14 months' follow-up.,This open-label, first-in-human, phase I study was conducted at nine centres in the USA, Canada and the UK, and included adults with MM and progressive disease after stem cell transplantation, alkylators, proteasome inhibitors, and immunomodulators.,In part 1, the recommended dose of 3.4 mg/kg was identified; in part 2, patients received GSK2857916 3.4 mg/kg once every 3 weeks.,Selected part 2 safety/tolerability and efficacy endpoints are reported.,Twenty-one (60.0%; 95% confidence interval (CI) 42.1-76.1) of 35 patients achieved partial response or better, including two stringent complete responses and three complete responses.,The median progression-free survival was 12 months and median duration of response was 14.3 months.,Thrombocytopenia and corneal events were commonly reported; no new safety signals were identified.,GSK2857916 was well tolerated and demonstrated a rapid, deep and durable response in heavily pre-treated patients with relapsed/refractory MM, consolidating the interim analyses conclusions that GSK2857916 is a promising treatment for these patients.

Doxorubicin is a chemotherapeutic drug used for the treatment of various malignancies; however, patients can experience cardiotoxic effects and this has limited the use of this potent drug.,The mechanisms by which doxorubicin kills cardiomyocytes has been elusive and despite extensive research the exact mechanisms remain unknown.,This review focuses on recent advances in our understanding of doxorubicin induced regulated cardiomyocyte death pathways including autophagy, ferroptosis, necroptosis, pyroptosis and apoptosis.,Understanding the mechanisms by which doxorubicin leads to cardiomyocyte death may help identify novel therapeutic agents and lead to more targeted approaches to cardiotoxicity testing.

The chemotherapy drug doxorubicin (Dox) is widely used for treating a variety of cancers.,However, its high cardiotoxicity hampered its clinical use.,Exosomes derived from stem cells showed a therapeutic effect against Dox-induced cardiomyopathy (DIC).,Previous studies reported that exosomes derived from mesenchymal stem cells (MSCs) pretreated with macrophage migration inhibitory factor (MIF) (exosomeMIF) showed a cardioprotective effect through modulating long noncoding RNAs/microRNAs (lncRNAs/miRs).,This study aimed to investigate the role of exosomeMIF in the treatment of DIC.,Exosomes were isolated from control MSCs (exosome) and MIF-pretreated MSCs (exosomeMIF).,Regulatory lncRNAs activated by MIF pretreatment were explored using genomics approaches.,Fluorescence-labeled exosomes were tracked in vitro by fluorescence imaging.,In vivo and in vitro, miR-221-3p mimic transfection enforced miR-221-3p overexpression, and senescence-associated β-galactosidase assay was applied to test cellular senescence.,Exosomal delivering LncRNA-NEAT1 induced therapeutic effect in vivo was confirmed by echocardiography.,It demonstrated that exosomesMIF recovered the cardiac function and exerted the anti-senescent effect through LncRNA-NEAT1 transfer against Dox.,TargetScan and luciferase assay showed that miR-221-3p targeted the Sirt2 3′-untranslated region.,Silencing LncRNA-NEAT1 in MSCs, miR-221-3p overexpression or Sirt2 silencing in cardiomyocytes decreased the exosomeMIF-induced anti-senescent effect against Dox.,The results indicated exosomeMIF serving as a promising anti-senescent effector against Dox-induced cardiotoxicity through LncRNA-NEAT1 transfer, thus inhibiting miR-221-3p and leading to Sirt2 activation.,The study proposed that exosomeMIF might have the potential to serve as a cardioprotective therapeutic agent during cancer chemotherapy.

What are the cardiovascular effects in unselected patients with recent coronavirus disease 2019 (COVID-19)?,In this cohort study including 100 patients recently recovered from COVID-19 identified from a COVID-19 test center, cardiac magnetic resonance imaging revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), which was independent of preexisting conditions, severity and overall course of the acute illness, and the time from the original diagnosis.,These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.,This cohort study evaluates the presence of myocardial injury in unselected patients recently recovered from coronavirus disease 2019 (COVID-19).,Coronavirus disease 2019 (COVID-19) continues to cause considerable morbidity and mortality worldwide.,Case reports of hospitalized patients suggest that COVID-19 prominently affects the cardiovascular system, but the overall impact remains unknown.,To evaluate the presence of myocardial injury in unselected patients recently recovered from COVID-19 illness.,In this prospective observational cohort study, 100 patients recently recovered from COVID-19 illness were identified from the University Hospital Frankfurt COVID-19 Registry between April and June 2020.,Recent recovery from severe acute respiratory syndrome coronavirus 2 infection, as determined by reverse transcription-polymerase chain reaction on swab test of the upper respiratory tract.,Demographic characteristics, cardiac blood markers, and cardiovascular magnetic resonance (CMR) imaging were obtained.,Comparisons were made with age-matched and sex-matched control groups of healthy volunteers (n = 50) and risk factor-matched patients (n = 57).,Of the 100 included patients, 53 (53%) were male, and the mean (SD) age was 49 (14) years.,The median (IQR) time interval between COVID-19 diagnosis and CMR was 71 (64-92) days.,Of the 100 patients recently recovered from COVID-19, 67 (67%) recovered at home, while 33 (33%) required hospitalization.,At the time of CMR, high-sensitivity troponin T (hsTnT) was detectable (greater than 3 pg/mL) in 71 patients recently recovered from COVID-19 (71%) and significantly elevated (greater than 13.9 pg/mL) in 5 patients (5%).,Compared with healthy controls and risk factor-matched controls, patients recently recovered from COVID-19 had lower left ventricular ejection fraction, higher left ventricle volumes, and raised native T1 and T2.,A total of 78 patients recently recovered from COVID-19 (78%) had abnormal CMR findings, including raised myocardial native T1 (n = 73), raised myocardial native T2 (n = 60), myocardial late gadolinium enhancement (n = 32), or pericardial enhancement (n = 22).,There was a small but significant difference between patients who recovered at home vs in the hospital for native T1 mapping (median [IQR], 1119 [1092-1150] ms vs 1141 [1121-1175] ms; P = .008) and hsTnT (4.2 [3.0-5.9] pg/dL vs 6.3 [3.4-7.9] pg/dL; P = .002) but not for native T2 mapping.,None of these measures were correlated with time from COVID-19 diagnosis (native T1: r = 0.07; P = .47; native T2: r = 0.14; P = .15; hsTnT: r = −0.07; P = .50).,High-sensitivity troponin T was significantly correlated with native T1 mapping (r = 0.33; P < .001) and native T2 mapping (r = 0.18; P = .01).,Endomyocardial biopsy in patients with severe findings revealed active lymphocytic inflammation.,Native T1 and T2 were the measures with the best discriminatory ability to detect COVID-19-related myocardial pathology.,In this study of a cohort of German patients recently recovered from COVID-19 infection, CMR revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), independent of preexisting conditions, severity and overall course of the acute illness, and time from the original diagnosis.,These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.

To compare demographic characteristics, clinical presentation, and outcomes of patients with and without concomitant cardiac disease, hospitalized for COVID-19 in Brescia, Lombardy, Italy.,The study population includes 99 consecutive patients with COVID-19 pneumonia admitted to our hospital between 4 March and 25 March 2020.,Fifty-three patients with a history of cardiac disease were compared with 46 without cardiac disease.,Among cardiac patients, 40% had a history of heart failure, 36% had atrial fibrillation, and 30% had coronary artery disease.,Mean age was 67 ± 12 years, and 80 (81%) patients were males.,No differences were found between cardiac and non-cardiac patients except for higher values of serum creatinine, N-terminal probrain natriuretic peptide, and high sensitivity troponin T in cardiac patients.,During hospitalization, 26% patients died, 15% developed thrombo-embolic events, 19% had acute respiratory distress syndrome, and 6% had septic shock.,Mortality was higher in patients with cardiac disease compared with the others (36% vs. 15%, log-rank P = 0.019; relative risk 2.35; 95% confidence interval 1.08-5.09).,The rate of thrombo-embolic events and septic shock during the hospitalization was also higher in cardiac patients (23% vs. 6% and 11% vs. 0%, respectively).,Hospitalized patients with concomitant cardiac disease and COVID-19 have an extremely poor prognosis compared with subjects without a history of cardiac disease, with higher mortality, thrombo-embolic events, and septic shock rates.

Macrophages promote both injury and repair following myocardial infarction, but discriminating functions within mixed populations remains challenging.,Here we used fate mapping and single-cell transcriptomics to demonstrate that at steady state, TIMD4+LYVE1+MHC-IIloCCR2− resident cardiac macrophages self-renew with negligible blood monocyte input.,Monocytes partially replaced resident TIMD4−LYVE1−MHC-IIhiCCR2− macrophages and fully replaced TIMD4−LYVE1−MHC-IIhiCCR2+ macrophages, revealing a hierarchy of monocyte contribution to functionally distinct macrophage subsets.,Ischemic injury reduced TIMD4+ and TIMD4− resident macrophage abundance within infarcted tissue while recruited, CCR2+ monocyte-derived macrophages adopted multiple cell fates, including those nearly indistinguishable from resident macrophages.,Despite this similarity, inducible depletion of resident macrophages using a Cx3cr1-based system led to impaired cardiac function and promoted adverse remodeling primarily within the peri-infarct zone, highlighting a non-redundant, cardioprotective role of resident cardiac macrophages.,Lastly, we demonstrate the ability of TIMD4 to be used as a durable lineage marker of a subset of resident cardiac macrophages.

Right ventricular (RV) remodeling represents a complex set of functional and structural adaptations in response to chronic pressure or volume overload due to various inborn defects or acquired diseases and is an important determinant of patient outcome.,However, the underlying molecular mechanisms remain elusive.,We investigated the time course of structural and functional changes in the RV in the murine model of pressure overload‐induced RV hypertrophy in C57Bl/6J mice.,Using magnetic resonance imaging, we assessed the changes of RV structure and function at different time points for a period of 21 days.,Pressure overload led to significant dilatation, cellular and chamber hypertrophy, myocardial fibrosis, and functional impairment of the RV.,Progressive remodeling of the RV after pulmonary artery banding (PAB) in mice was associated with upregulation of myocardial gene markers of hypertrophy and fibrosis.,Furthermore, remodeling of the RV was associated with accumulation and activation of mast cells in the RV tissue of PAB mice.,Our data suggest possible involvement of mast cells in the RV remodeling process in response to pressure overload.,Mast cells may thus represent an interesting target for the development of new therapeutic approaches directed specifically at the RV.

Although myocarditis and pericarditis were not observed as adverse events in coronavirus disease 2019 (COVID-19) vaccine trials, there have been numerous reports of suspected cases following vaccination in the general population.,We undertook a self-controlled case series study of people aged 16 or older vaccinated for COVID-19 in England between 1 December 2020 and 24 August 2021 to investigate hospital admission or death from myocarditis, pericarditis and cardiac arrhythmias in the 1-28 days following adenovirus (ChAdOx1, n = 20,615,911) or messenger RNA-based (BNT162b2, n = 16,993,389; mRNA-1273, n = 1,006,191) vaccines or a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive test (n = 3,028,867).,We found increased risks of myocarditis associated with the first dose of ChAdOx1 and BNT162b2 vaccines and the first and second doses of the mRNA-1273 vaccine over the 1-28 days postvaccination period, and after a SARS-CoV-2 positive test.,We estimated an extra two (95% confidence interval (CI) 0, 3), one (95% CI 0, 2) and six (95% CI 2, 8) myocarditis events per 1 million people vaccinated with ChAdOx1, BNT162b2 and mRNA-1273, respectively, in the 28 days following a first dose and an extra ten (95% CI 7, 11) myocarditis events per 1 million vaccinated in the 28 days after a second dose of mRNA-1273.,This compares with an extra 40 (95% CI 38, 41) myocarditis events per 1 million patients in the 28 days following a SARS-CoV-2 positive test.,We also observed increased risks of pericarditis and cardiac arrhythmias following a positive SARS-CoV-2 test.,Similar associations were not observed with any of the COVID-19 vaccines, apart from an increased risk of arrhythmia following a second dose of mRNA-1273.,Subgroup analyses by age showed the increased risk of myocarditis associated with the two mRNA vaccines was present only in those younger than 40.,A self-controlled case series using individual-patient-level data from over 38 million people aged 16 years and over, reveals an increased risk of myocarditis within a week of receiving a first dose of ChAdOx1, BNT162b2 and mRNA-1273 vaccines, which was further increased after a second dose of either mRNA vaccine.,SARS-CoV-2 infection was associated with even greater risk of myocarditis, as well as pericarditis and cardiac arrhythmia.

Reports have suggested an association between the development of myocarditis and the receipt of messenger RNA (mRNA) vaccines against coronavirus disease 2019 (Covid-19), but the frequency and severity of myocarditis after vaccination have not been extensively explored.,We searched the database of Clalit Health Services, the largest health care organization (HCO) in Israel, for diagnoses of myocarditis in patients who had received at least one dose of the BNT162b2 mRNA vaccine (Pfizer-BioNTech).,The diagnosis of myocarditis was adjudicated by cardiologists using the case definition used by the Centers for Disease Control and Prevention.,We abstracted the presentation, clinical course, and outcome from the patient’s electronic health record.,We performed a Kaplan-Meier analysis of the incidence of myocarditis up to 42 days after the first vaccine dose.,Among more than 2.5 million vaccinated HCO members who were 16 years of age or older, 54 cases met the criteria for myocarditis.,The estimated incidence per 100,000 persons who had received at least one dose of vaccine was 2.13 cases (95% confidence interval [CI], 1.56 to 2.70).,The highest incidence of myocarditis (10.69 cases per 100,000 persons; 95% CI, 6.93 to 14.46) was reported in male patients between the ages of 16 and 29 years.,A total of 76% of cases of myocarditis were described as mild and 22% as intermediate; 1 case was associated with cardiogenic shock.,After a median follow-up of 83 days after the onset of myocarditis, 1 patient had been readmitted to the hospital, and 1 had died of an unknown cause after discharge.,Of 14 patients who had left ventricular dysfunction on echocardiography during admission, 10 still had such dysfunction at the time of hospital discharge.,Of these patients, 5 underwent subsequent testing that revealed normal heart function.,Among patients in a large Israeli health care system who had received at least one dose of the BNT162b2 mRNA vaccine, the estimated incidence of myocarditis was 2.13 cases per 100,000 persons; the highest incidence was among male patients between the ages of 16 and 29 years.,Most cases of myocarditis were mild or moderate in severity.,(Funded by the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.)

The role of inflammation in diabetic retinopathy (DR) is well-established and dysregulation of a large number of inflammatory mediators is known.,These include cytokines, chemokines, growth factors, mediators of proteogenesis, and pro-apoptotic molecules.,This para-inflammation as a response is not directed to a particular pathogen or antigen but is rather directed toward the by-products of the diabetic milieu.,The inflammatory mediators take part in cascades that result in cellular level responses like neurodegeneration, pericyte loss, leakage, capillary drop out, neovascularization, etc.,There are multiple overlaps between the inflammatory pathways occurring within the diabetic retina due to a large number of mediators, their varied sources, and cross-interactions.,This makes understanding the role of inflammation in clinical manifestations of DR difficult.,Currently, mediator-based therapy for DR is being evaluated for interventions that target a specific step of the inflammatory cascade.,We reviewed the role of inflammation in DR and derived a simplified clinicopathological correlation between the sources and stimuli of inflammation, the inflammatory mediators and pathways, and the clinical manifestations of DR.,By doing so, we deliberate mediator-specific therapy for DR.,The cross-interactions between inflammatory mediators and the molecular cycles influencing the inflammatory cascades are crucial challenges to such an approach.,Future research should be directed to assess the feasibility of the pathology-based therapy for DR.

To assess vitreous levels of inflammatory cytokines and neurotrophins (NTs) in diabetic retinopathy (DR) and elucidate their potential roles.,A prospective study was performed on 50 vitreous samples obtained from patients with DR (n = 22) and the nondiabetic controls (n = 28).,All patients were candidates for vitrectomy.,Inflammatory cytokine and NT levels were determined with ELISA.,Potential source and role of NTs was determined by using human retinal Müller glia and mouse photoreceptor cells and challenging them with TNF-α or IL-1β, followed by detection of NTs and cell death.,Vitreous NT levels of all DR patients were significantly higher than those of nondiabetic controls (nerve growth factor [NGF, P = 0.0001], brain-derived neurotrophic factor [BDNF, P = 0.009], neurotrophin-3 [NT-3, P < 0.0001], neurotrophin-4 [NT-4, P = 0.0001], ciliary neurotrophic factor [CNTF, P = 0.0001], and glial cell-derived neurotrophic factor [GDNF, P = 0.008]).,Similarly, the levels of inflammatory mediators IL-1β (P < 0.0001), IL-6 (P = 0.0005), IL-8 (P < 0.0001), and TNF-α (P < 0.0001) were also higher in eyes with DR.,Interestingly, inflammatory cytokine and NT levels, particularly TNF-α (P < 0.05), IL-8 (P < 0.004), NT-3 (P = 0.012), NGF (P = 0.04), GDNF (P = 0.005), and CNTF (P = 0.002), were higher in eyes with nonproliferative diabetic retinopathy (NPDR) than in eyes with active proliferative diabetic retinopathy (PDR).,Cytokine stimulation of Müller glia resulted in production of NTs, and GDNF treatment reduced photoreceptor cell death in response to inflammation and oxidative stress.,Together, our study demonstrated that patients with DR have higher levels of both inflammatory cytokines and NTs in their vitreous.,Müller glia could be the potential source of NTs under inflammatory conditions to exert neuroprotection.

Recent studies using stress‐rest perfusion cardiovascular magnetic resonance (CMR) demonstrated a close correlation between myocardial ischemia and reduced fractional flow reserve (FFR).,However, its diagnostic concordance may be reduced in patients with multivessel disease.,We sought to evaluate the concordance of adenosine stress‐rest perfusion CMR for predicting reduced FFR, and to determine the additive value of measuring global coronary flow reserve (CFR) in the coronary sinus in multivessel disease.,Ninety‐six patients with angiographic luminal narrowing >50% underwent comprehensive CMR study and FFR measurements in 139 coronary vessels.,FFR <0.80 was considered hemodynamically significant.,Global CFR was quantified as the ratio of stress‐rest coronary sinus flow measured by phase‐contrast cine CMR.,In 25 patients with single‐vessel disease, visual assessment of perfusion CMR yielded high diagnostic concordance for predicting flow‐limiting stenosis, with the area under receiver operating characteristic curve of 0.93 on a per‐patient basis.,However, in 71 patients with multivessel disease, perfusion CMR underestimated flow‐limiting stenosis, resulting in the reduced area under receiver operating characteristic curve of 0.74.,When CFR of <2.0 measured in the coronary sinus was considered as global myocardial ischemia, combined assessment provided correct reclassifications in 7 patients with false‐negative myocardial ischemia, and improved the diagnostic concordance to 92% sensitivity and 73% specificity with the area under receiver operating characteristic curve of 0.88 (95% confidence interval, 0.80%-0.97%, P=0.002).,Visual analysis of stress‐rest perfusion CMR has limited concordance with FFR in patients with multivessel disease.,Multiparametric CMR integrating stress‐rest perfusion CMR and flow measurement in the coronary sinus is useful for detecting reduced FFR in multivessel disease.

Noninvasive assessment of coronary artery disease remains a challenging task, with a large armamentarium of diagnostic modalities.,Myocardial perfusion imaging (MPI) is widely used for this purpose whereby cardiac positron emission tomography (PET) is considered the gold standard.,Next to relative radiotracer distribution, PET allows for measurement of absolute myocardial blood flow.,This quantification of perfusion improves diagnostic accuracy and prognostic value.,Cardiac hybrid imaging relies on the fusion of anatomical and functional imaging using coronary computed tomography angiography and MPI, respectively, and provides incremental value as compared with either stand-alone modality.

Coronavirus disease 2019 (COVID-19) may predispose to venous thromboembolism.,We determined factors independently associated with computed tomography pulmonary angiography (CTPA)-confirmed pulmonary embolism (PE) in hospitalised severe COVID-19 patients.,Among all (n=349) patients hospitalised for COVID-19 in a university hospital in a French region with a high rate of COVID-19, we analysed patients who underwent CTPA for clinical signs of severe disease (oxygen saturation measured by pulse oximetry ≤93% or breathing rate ≥30 breaths·min−1) or rapid clinical worsening.,Multivariable analysis was performed using Firth penalised maximum likelihood estimates.,162 (46.4%) patients underwent CTPA (mean±sd age 65.6±13.0 years; 67.3% male (95% CI 59.5-75.5%).,PE was diagnosed in 44 (27.2%) patients.,Most PEs were segmental and the rate of PE-related right ventricular dysfunction was 15.9%.,By multivariable analysis, the only two significant predictors of CTPA-confirmed PE were D-dimer level and the lack of any anticoagulant therapy (OR 4.0 (95% CI 2.4-6.7) per additional quartile and OR 4.5 (95% CI 1.1-7.4), respectively).,Receiver operating characteristic curve analysis identified a D-dimer cut-off value of 2590 ng·mL−1 to best predict occurrence of PE (area under the curve 0.88, p<0.001, sensitivity 83.3%, specificity 83.8%).,D-dimer level >2590 ng·mL−1 was associated with a 17-fold increase in the adjusted risk of PE.,Elevated D-dimers (>2590 ng·mL−1) and absence of anticoagulant therapy predict PE in hospitalised COVID-19 patients with clinical signs of severity.,These data strengthen the evidence base in favour of systematic anticoagulation, and suggest wider use of D-dimer guided CTPA to screen for PE in acutely ill hospitalised patients with COVID-19.,We studied predictors of pulmonary embolism in severe COVID-19 and found that D-dimer level and lack of any anticoagulant therapy were associated with a 17-fold and four-fold increase in PE, respectively, in COVID-19 patients with clinical signs of severityhttps://bit.ly/2ETfAfo

Coronavirus disease 2019 (COVID‐19) is a pandemic disease currently affecting millions of people worldwide.,Its neurological implications are poorly understood, and further study is urgently required.,A hypercoagulable state has been reported in patients with severe COVID‐19, but nothing is known about coagulopathy in patients with milder disease.,We describe cases of patients in New York City presenting with stroke secondary to large vessel thrombosis without occlusion, incidentally found to have COVID‐19 with only mild respiratory symptoms.,This is in contrast to the venous thrombosis and microangiopathy that has been reported in patients with severe COVID‐19.,Our cases suggest that even in the absence of severe disease, patients with COVID‐19 may be at increased risk of thrombus formation leading to stroke, perhaps resulting from viral involvement of the endothelium.,Further systematic study is needed because this may have implications for primary and secondary stroke prevention in patients with COVID‐19.

Uremic toxin (UT) retention in chronic kidney disease (CKD) affects biological systems.,We aimed to identify the associations between UT, inflammatory biomarkers and biomarkers of the uremic cardiovascular response (BUCVR) and their impact on cardiovascular status as well as their roles as predictors of outcome in CKD patients.,CKD patients stages 3, 4 and 5 (n = 67) were recruited and UT (indoxyl sulfate/IS, p-cresil sulfate/pCS and indole-3-acetic acid/IAA); inflammatory biomarkers [Interleukin-6 (IL-6), high sensitivity C reactive protein (hsCRP), monocyte chemoattractant protein-1 (MCP-1), soluble vascular adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble Fas (sFas)] and BUCVRs [soluble CD36 (sCD36), soluble receptor for advanced glycation end products (sRAGE), fractalkine] was measured.,Patients were followed for 5.2 years and all causes of death was used as the primary outcome.,Artery segments collected at the moment of transplantation were used for the immunohistochemistry analysis in a separate cohort.,Estimated glomerular filtration rate (eGFR), circulating UT, plasma biomarkers of systemic and vascular inflammation and BUCVR were strongly interrelated.,Patients with plaque presented higher signs of UT-induced inflammation and arteries from CKD patients presented higher fractalkine receptor (CX3CR1) tissue expression.,Circulating IS (p = 0.03), pCS (p = 0.007), IL-6 (p = 0.026), sFas (p = 0.001), sCD36 (p = 0.01) and fractalkine (p = 0.02) were independent predictors of total mortality risk in CKD patients.,Our results reinforce the important role of uremic toxicity in the pathogenesis of cardiovascular disease (CVD) in CKD patients through an inflammatory pathway.

During chronic kidney disease progression, kidney-specific risk factors for cardiovascular disease come into play.,The present study investigated the impact of indoxyl sulfate, dietary tryptophan-derived uremic toxin, accumulated in the blood of patients with chronic kidney disease on hemostatic parameters, markers of inflammation, oxidative stress and monocyte to macrophage transition.,Fifty-one CKD patients not undergoing hemodialysis were enrolled in the study.,Coagulation factors, fibrinolytic parameters, adhesion molecules, endothelial dysfunction markers, oxidative stress as well as inflammation markers were examined using immune-enzymatic method.,Indoxyl sulfate levels were assessed using high-performance liquid chromatography.,Biochemical parameters were determined by routine laboratory techniques using an automated analyzers.,All assessed parameters were compared with controls and subjected to cross-sectional statistical analysis.,Elevated concentrations of indoxyl sulfate, the vast majority of parameters affecting hemostasis, and markers of renal insufficiency conditions were observed.,Part of hemostatic factors, namely tissue factor, von Willebrand factor, thrombomodulin, soluble urokinase-type plasminogen activator receptor, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion protein were correlated with the fraction of indoxyl sulfate.,A significant quantity of assessed parameters showed strong correlations with superoxide-dismutase, renal insufficiency rate, C-reactive protein, and neopterin.,Levels of indoxyl sulfate were independently associated with markers of impaired endothelial function (thrombomodulin, adhesion molecules), oxidative stress (superoxide-dismutase) and monocytes activation determinant (neopterin), which indicate unconventional links between these systems and the role of indoxyl sulfate.,Furthermore, parameters that correlated with the levels of indoxyl sulfate (von Willebrand factor, soluble urokinase-type plasminogen activator receptor, soluble intercellular adhesion molecule-1) were positively associated with the prevalence of cardiovascular disease in a CKD patients.,The study demonstrated that in conditions of chronic exposure to uremic toxins, indoxyl sulfate seems to be one of the “missing links” between impaired renal function and prevalence of cardiovascular events, especially hemostatic disorders.,The main functions of the action appear to be altered monocytes activation, intensified inflammatory process, and augmented oxidative stress by this uremic toxin.

Recent studies suggest that thrombotic complications are a common phenomenon in the novel SARS-CoV-2 infection.,The main objective of our study is to assess cumulative incidence of pulmonary embolism (PE) in non critically ill COVID-19 patients and to identify its predicting factors associated to the diagnosis of pulmonary embolism.,We retrospectevely reviewed 452 electronic medical records of patients admitted to Internal Medicine Department of a secondary hospital in Madrid during Covid 19 pandemic outbreak.,We included 91 patients who underwent a multidetector Computed Tomography pulmonary angiography(CTPA) during conventional hospitalization.,The cumulative incidence of PE was assessed ant the clinical, analytical and radiological characteristics were compared between patients with and without PE.,PE incidence was 6.4% (29/452 patients).,Most patients with a confirmed diagnosed with PE recieved low molecular weight heparin (LMWH): 79.3% (23/29).,D-dimer peak was significatly elevated in PE vs non PE patients (14,480 vs 7230 mcg/dL, p = 0.03).,In multivariate analysis of patients who underwent a CTPA we found that plasma D-dimer peak was an independen predictor of PE with a best cut off point of > 5000 µg/dl (OR 3.77; IC95% (1.18-12.16), p = 0.03).,We found ninefold increased risk of PE patients not suffering from dyslipidemia (OR 9.06; IC95% (1.88-43.60).,Predictive value of AUC for ROC is 75.5%.,We found a high incidence of PE in non critically ill hospitalized COVID 19 patients despite standard thromboprophylaxis.,An increase in D-dimer levels is an independent predictor for PE, with a best cut-off point of > 5000 µg/ dl.

Coagulopathy in COVID-19 is a burning issue and strategies to prevent thromboembolic events are debated and highly heterogeneous.,The objective was to determine incidence and risk factors of venous thromboembolism (VTE) in COVID-19 inpatients receiving thromboprophylaxis.,In this retrospective French cohort study, patients hospitalized in medical wards non-ICU with confirmed COVID-19 and adequate thromboprophylaxis were included.,A systematic low limb venous duplex ultrasonography was performed at hospital discharge or earlier if deep venous thrombosis (DVT) was clinically suspected.,Chest angio-CT scan was performed when pulmonary embolism (PE) was suspected.,Of 71 patients, 16 developed VTE (22.5%) and 7 PE (10%) despite adequate thromboprophylaxis.,D-dimers at baseline were significantly higher in patients with DVT (p < 0.001).,Demographics, comorbidities, disease manifestations, severity score, and other biological parameters, including inflammatory markers, were similar in patients with and without VTE.,The negative predictive value of a baseline D-dimer level < 1.0 µg/ml was 90% for VTE and 98% for PE.,The positive predictive value for VTE was 44% and 67% for D-dimer level ≥ 1.0 µg/ml and ≥ 3 µg/ml, respectively.,The association between D-dimer level and VTE risk increased by taking into account the latest available D-dimer level prior to venous duplex ultrasonography for the patients with monitoring of D-dimer.,Despite thromboprophylaxis, the risk of VTE is high in COVID-19 non-ICU inpatients.,Increased D-dimer concentrations of more than 1.0 μg/ml predict the risk of venous thromboembolism.,D-dimer level-guided aggressive thromboprophylaxis regimens using higher doses of heparin should be evaluated in prospective studies.

COVID-19 has rapidly impacted on mortality worldwide.1 There is unprecedented urgency to understand who is most at risk of severe outcomes, requiring new approaches for timely analysis of large datasets.,Working on behalf of NHS England we created OpenSAFELY: a secure health analytics platform covering 40% of all patients in England, holding patient data within the existing data centre of a major primary care electronic health records vendor.,Primary care records of 17,278,392 adults were pseudonymously linked to 10,926 COVID-19 related deaths.,COVID-19 related death was associated with: being male (hazard ratio 1.59, 95%CI 1.53-1.65); older age and deprivation (both with a strong gradient); diabetes; severe asthma; and various other medical conditions.,Compared to people with white ethnicity, black and South Asian people were at higher risk even after adjustment for other factors (HR 1.48, 1.29-1.69 and 1.45, 1.32-1.58 respectively).,We have quantified a range of clinical risk factors for COVID-19 related death in the largest cohort study conducted by any country to date.,OpenSAFELY is rapidly adding further patients’ records; we will update and extend results regularly.

The current pandemic coronavirus SARS-CoV-2 infects a wide age group but predominantly elderly individuals, especially men and those with cardiovascular disease.,Recent reports suggest an association with use of renin-angiotensin-aldosterone system (RAAS) inhibitors.,Angiotensin-converting enzyme 2 (ACE2) is a functional receptor for coronaviruses.,Higher ACE2 concentrations might lead to increased vulnerability to SARS-CoV-2 in patients on RAAS inhibitors.,We measured ACE2 concentrations in 1485 men and 537 women with heart failure (index cohort).,Results were validated in 1123 men and 575 women (validation cohort).,The median age was 69 years for men and 75 years for women.,The strongest predictor of elevated concentrations of ACE2 in both cohorts was male sex (estimate = 0.26, P < 0.001; and 0.19, P < 0.001, respectively).,In the index cohort, use of ACE inhibitors, angiotensin receptor blockers (ARBs), or mineralocorticoid receptor antagonists (MRAs) was not an independent predictor of plasma ACE2.,In the validation cohort, ACE inhibitor (estimate = -0.17, P = 0.002) and ARB use (estimate = -0.15, P = 0.03) were independent predictors of lower plasma ACE2, while use of an MRA (estimate = 0.11, P = 0.04) was an independent predictor of higher plasma ACE2 concentrations.,In two independent cohorts of patients with heart failure, plasma concentrations of ACE2 were higher in men than in women, but use of neither an ACE inhibitor nor an ARB was associated with higher plasma ACE2 concentrations.,These data might explain the higher incidence and fatality rate of COVID-19 in men, but do not support previous reports suggesting that ACE inhibitors or ARBs increase the vulnerability for COVID-19 through increased plasma ACE2 concentrations.

What are the cardiovascular effects in unselected patients with recent coronavirus disease 2019 (COVID-19)?,In this cohort study including 100 patients recently recovered from COVID-19 identified from a COVID-19 test center, cardiac magnetic resonance imaging revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), which was independent of preexisting conditions, severity and overall course of the acute illness, and the time from the original diagnosis.,These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.,This cohort study evaluates the presence of myocardial injury in unselected patients recently recovered from coronavirus disease 2019 (COVID-19).,Coronavirus disease 2019 (COVID-19) continues to cause considerable morbidity and mortality worldwide.,Case reports of hospitalized patients suggest that COVID-19 prominently affects the cardiovascular system, but the overall impact remains unknown.,To evaluate the presence of myocardial injury in unselected patients recently recovered from COVID-19 illness.,In this prospective observational cohort study, 100 patients recently recovered from COVID-19 illness were identified from the University Hospital Frankfurt COVID-19 Registry between April and June 2020.,Recent recovery from severe acute respiratory syndrome coronavirus 2 infection, as determined by reverse transcription-polymerase chain reaction on swab test of the upper respiratory tract.,Demographic characteristics, cardiac blood markers, and cardiovascular magnetic resonance (CMR) imaging were obtained.,Comparisons were made with age-matched and sex-matched control groups of healthy volunteers (n = 50) and risk factor-matched patients (n = 57).,Of the 100 included patients, 53 (53%) were male, and the mean (SD) age was 49 (14) years.,The median (IQR) time interval between COVID-19 diagnosis and CMR was 71 (64-92) days.,Of the 100 patients recently recovered from COVID-19, 67 (67%) recovered at home, while 33 (33%) required hospitalization.,At the time of CMR, high-sensitivity troponin T (hsTnT) was detectable (greater than 3 pg/mL) in 71 patients recently recovered from COVID-19 (71%) and significantly elevated (greater than 13.9 pg/mL) in 5 patients (5%).,Compared with healthy controls and risk factor-matched controls, patients recently recovered from COVID-19 had lower left ventricular ejection fraction, higher left ventricle volumes, and raised native T1 and T2.,A total of 78 patients recently recovered from COVID-19 (78%) had abnormal CMR findings, including raised myocardial native T1 (n = 73), raised myocardial native T2 (n = 60), myocardial late gadolinium enhancement (n = 32), or pericardial enhancement (n = 22).,There was a small but significant difference between patients who recovered at home vs in the hospital for native T1 mapping (median [IQR], 1119 [1092-1150] ms vs 1141 [1121-1175] ms; P = .008) and hsTnT (4.2 [3.0-5.9] pg/dL vs 6.3 [3.4-7.9] pg/dL; P = .002) but not for native T2 mapping.,None of these measures were correlated with time from COVID-19 diagnosis (native T1: r = 0.07; P = .47; native T2: r = 0.14; P = .15; hsTnT: r = −0.07; P = .50).,High-sensitivity troponin T was significantly correlated with native T1 mapping (r = 0.33; P < .001) and native T2 mapping (r = 0.18; P = .01).,Endomyocardial biopsy in patients with severe findings revealed active lymphocytic inflammation.,Native T1 and T2 were the measures with the best discriminatory ability to detect COVID-19-related myocardial pathology.,In this study of a cohort of German patients recently recovered from COVID-19 infection, CMR revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), independent of preexisting conditions, severity and overall course of the acute illness, and time from the original diagnosis.,These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.

COVID-19 is a disease with high mortality, and risk factors for worse clinical outcome have not been well-defined yet.,The aim of this study is to delineate the prognostic importance of presence of concomitant cardiac injury on admission in patients with COVID-19.,For this multi-center retrospective study, data of consecutive patients who were treated for COVID-19 between 20 March and 20 April 2020 were collected.,Clinical characteristics, laboratory findings and outcomes data were obtained from electronic medical records.,In-hospital clinical outcome was compared between patients with and without cardiac injury.,A total of 607 hospitalized patients with COVID-19 were included in the study; the median age was 62.5 ± 14.3 years, and 334 (55%) were male.,Cardiac injury was detected in 150 (24.7%) of patients included in the study.,Mortality rate was higher in patients with cardiac injury (42% vs.,8%; P < 0.01).,The frequency of patients who required ICU (72% vs. 19%), who developed acute kidney injury (14% vs. 1%) and acute respiratory distress syndrome (71%vs. 18%) were also higher in patients with cardiac injury.,In multivariate analysis, age, coronary artery disease (CAD), elevated CRP levels, and presence of cardiac injury [odds ratio (OR) 10.58, 95% confidence interval (CI) 2.42-46.27; P < 0.001) were found to be independent predictors of mortality.,In subgroup analysis, including patients free of history of CAD, presence of cardiac injury on admission also predicted mortality (OR 2.52, 95% CI 1.17-5.45; P = 0.018).,Cardiac injury on admission is associated with worse clinical outcome and higher mortality risk in COVID-19 patients including patients free of previous CAD diagnosis.

The COVID-19 pandemic has led to extensive morbidity and mortality throughout the world.,Clinical features that drive SARS-CoV-2 pathogenesis in humans include inflammation and thrombosis, but the mechanistic details underlying these processes remain to be determined.,In this study, we demonstrate endothelial disruption and vascular thrombosis in histopathologic sections of lungs from both humans and rhesus macaques infected with SARS-CoV-2.,To define key molecular pathways associated with SARS-CoV-2 pathogenesis in macaques, we performed transcriptomic analyses of bronchoalveolar lavage and peripheral blood and proteomic analyses of serum.,We observed macrophage infiltrates in lung and upregulation of macrophage, complement, platelet activation, thrombosis, and proinflammatory markers, including C-reactive protein, MX1, IL-6, IL-1, IL-8, TNFα, and NF-κB.,These results suggest a model in which critical interactions between inflammatory and thrombosis pathways lead to SARS-CoV-2-induced vascular disease.,Our findings suggest potential therapeutic targets for COVID-19.,Aid et al. show that SARS-CoV-2 causes endothelial disruption and vascular thrombosis in both human and rhesus macaques lungs by inducing an upregulation of proinflammatory cytokines.,Using an approach that combines histopathology and multiomics in macaques, they show the progression to vascular disease over time, which involves complement, macrophage, cytokine, and thrombosis cascades.

Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described.,In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020.,Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors.,We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death.,191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients).,Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03-1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61-12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64-128·55; p=0·0033) on admission.,Median duration of viral shedding was 20·0 days (IQR 17·0-24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors.,The longest observed duration of viral shedding in survivors was 37 days.,The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage.,Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.,Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Although COVID-19 has been reported to be associated with high rates of venous thromboembolism (VTE), the risk of VTE and bleeding after hospitalization for COVID-19 remains unclear, and the optimal hospital VTE prevention strategy is not known.,We collected retrospective observational data on thrombosis and bleeding in 303 consecutive adult patients admitted to the hospital for at least 24 hours for COVID-19.,Patients presenting with VTE on admission were excluded.,Data were collected until 90 days after admission or known death by using medical records and an established national VTE network.,Maximal level of care was ward based in 78% of patients, with 22% requiring higher dependency care (12% noninvasive ventilation, 10% invasive ventilation).,Almost all patients (97.0%) received standard thromboprophylaxis or were already receiving therapeutic anticoagulation (17.5%).,Symptomatic image-confirmed VTE occurred in 5.9% of patients during index hospitalization, and in 7.2% at 90 days after admission (23.9% in patients requiring higher dependency care); half the events were isolated segmental or subsegmental defects on lung imaging.,Bleeding occurred in 13 patients (4.3%) during index hospitalization (1.3% had major bleeding).,The majority of bleeds occurred in patients on the general ward, and 6 patients were receiving treatment-dose anticoagulation, highlighting the need for caution in intensifying standard thromboprophylaxis strategies.,Of 152 patients discharged from the hospital without an indication for anticoagulation, 97% did not receive thromboprophylaxis after discharge, and 3% received 7 days of treatment with low molecular weight heparin after discharge.,The rate of symptomatic VTE in this group at 42 days after discharge was 2.6%, highlighting the need for large prospective randomized controlled trials of extended thromboprophylaxis after discharge in COVID-19.,•The rate of symptomatic VTE in patients after hospitalization for COVID-19 was 2.6% at 42 days after discharge.,•Bleeding is a significant cause of morbidity in addition to thrombosis in patients admitted with COVID-19.,The rate of symptomatic VTE in patients after hospitalization for COVID-19 was 2.6% at 42 days after discharge.,Bleeding is a significant cause of morbidity in addition to thrombosis in patients admitted with COVID-19.

The association of severe coronavirus disease 2019 (COVID-19) with an increased risk of venous thromboembolism (VTE) has resulted in specific guidelines for its prevention and management.,The VTE risk appears highest in those with critical care admission.,The need for postdischarge thromboprophylaxis remains controversial, which is reflected in conflicting expert guideline recommendations.,Our local protocol provides thromboprophylaxis to COVID-19 patients during admission only.,We report postdischarge VTE data from an ongoing quality improvement program incorporating root-cause analysis of hospital-associated VTE (HA-VTE).,Following 1877 hospital discharges associated with COVID-19, 9 episodes of HA-VTE were diagnosed within 42 days, giving a postdischarge rate of 4.8 per 1000 discharges.,Over 2019, following 18 159 discharges associated with a medical admission; there were 56 episodes of HA-VTE within 42 days (3.1 per 1000 discharges).,The odds ratio for postdischarge HA-VTE associated with COVID-19 compared with 2019 was 1.6 (95% confidence interval, 0.77-3.1).,COVID-19 hospitalization does not appear to increase the risk of postdischarge HA-VTE compared with hospitalization with other acute medical illness.,Given that the risk-benefit ratio of postdischarge thromboprophylaxis remains uncertain, randomized controlled trials to evaluate the role of continuing thromboprophylaxis in COVID-19 patients following hospital discharge are required.,•The rate of symptomatic postdischarge VTE following hospitalization with COVID-19 is low.,The rate of symptomatic postdischarge VTE following hospitalization with COVID-19 is low.

Coronavirus disease 2019 (COVID-19), caused by a strain of coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic that has affected the lives of billions of individuals.,Extensive studies have revealed that SARS-CoV-2 shares many biological features with SARS-CoV, the zoonotic virus that caused the 2002 outbreak of severe acute respiratory syndrome, including the system of cell entry, which is triggered by binding of the viral spike protein to angiotensin-converting enzyme 2.,Clinical studies have also reported an association between COVID-19 and cardiovascular disease.,Pre-existing cardiovascular disease seems to be linked with worse outcomes and increased risk of death in patients with COVID-19, whereas COVID-19 itself can also induce myocardial injury, arrhythmia, acute coronary syndrome and venous thromboembolism.,Potential drug-disease interactions affecting patients with COVID-19 and comorbid cardiovascular diseases are also becoming a serious concern.,In this Review, we summarize the current understanding of COVID-19 from basic mechanisms to clinical perspectives, focusing on the interaction between COVID-19 and the cardiovascular system.,By combining our knowledge of the biological features of the virus with clinical findings, we can improve our understanding of the potential mechanisms underlying COVID-19, paving the way towards the development of preventative and therapeutic solutions.,The presence of cardiovascular comorbidities is linked with worse outcomes in patients with coronavirus disease 2019 (COVID-19), and COVID-19 can induce cardiovascular damage.,In this Review, Wu and colleagues summarize the latest mechanistic and clinical studies that contribute to our current understanding of COVID-19-related cardiovascular disease.,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), shares many biological features with SARS-CoV, the virus that causes severe acute respiratory syndrome, owing to 80% genomic sequence identity.The interaction between the viral spike (S) protein and angiotensin-converting enzyme 2, which triggers entry of the virus into host cells, is likely to be involved in the cardiovascular manifestations of COVID-19.,The presence of underlying cardiovascular comorbidities in patients with COVID-19 is associated with high mortality.COVID-19 can cause cardiovascular disorders, including myocardial injury, arrhythmias, acute coronary syndrome and venous thromboembolism.Several medications used for the treatment of COVID-19 have uncertain safety and efficacy profiles.,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), shares many biological features with SARS-CoV, the virus that causes severe acute respiratory syndrome, owing to 80% genomic sequence identity.,The interaction between the viral spike (S) protein and angiotensin-converting enzyme 2, which triggers entry of the virus into host cells, is likely to be involved in the cardiovascular manifestations of COVID-19.,The presence of underlying cardiovascular comorbidities in patients with COVID-19 is associated with high mortality.,COVID-19 can cause cardiovascular disorders, including myocardial injury, arrhythmias, acute coronary syndrome and venous thromboembolism.,Several medications used for the treatment of COVID-19 have uncertain safety and efficacy profiles.

The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades.,We provide a comprehensive review of the clinical course of COVID-19, its comorbidities, and mechanistic considerations for future therapies.,While COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects multiple organs, particularly the cardiovascular system.,Risk of severe infection and mortality increase with advancing age and male sex.,Mortality is increased by comorbidities: cardiovascular disease, hypertension, diabetes, chronic pulmonary disease, and cancer.,The most common complications include arrhythmia (atrial fibrillation, ventricular tachyarrhythmia, and ventricular fibrillation), cardiac injury [elevated highly sensitive troponin I (hs-cTnI) and creatine kinase (CK) levels], fulminant myocarditis, heart failure, pulmonary embolism, and disseminated intravascular coagulation (DIC).,Mechanistically, SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane angiotensin-converting enzyme 2 (ACE2) -a homologue of ACE-to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes.,This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction (MI).,While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis.,Hence, patients should not discontinue their use.,Moreover, renin-angiotensin-aldosterone system (RAAS) inhibitors might be beneficial in COVID-19.,Initial immune and inflammatory responses induce a severe cytokine storm [interleukin (IL)-6, IL-7, IL-22, IL-17, etc.] during the rapid progression phase of COVID-19.,Early evaluation and continued monitoring of cardiac damage (cTnI and NT-proBNP) and coagulation (D-dimer) after hospitalization may identify patients with cardiac injury and predict COVID-19 complications.,Preventive measures (social distancing and social isolation) also increase cardiovascular risk.,Cardiovascular considerations of therapies currently used, including remdesivir, chloroquine, hydroxychloroquine, tocilizumab, ribavirin, interferons, and lopinavir/ritonavir, as well as experimental therapies, such as human recombinant ACE2 (rhACE2), are discussed.

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2)-induced infection, the cause of coronavirus disease 2019 (COVID-19), is characterized by unprecedented clinical pathologies.,One of the most important pathologies, is hypercoagulation and microclots in the lungs of patients.,Here we study the effect of isolated SARS-CoV-2 spike protein S1 subunit as potential inflammagen sui generis.,Using scanning electron and fluorescence microscopy as well as mass spectrometry, we investigate the potential of this inflammagen to interact with platelets and fibrin(ogen) directly to cause blood hypercoagulation.,Using platelet-poor plasma (PPP), we show that spike protein may interfere with blood flow.,Mass spectrometry also showed that when spike protein S1 is added to healthy PPP, it results in structural changes to β and γ fibrin(ogen), complement 3, and prothrombin.,These proteins were substantially resistant to trypsinization, in the presence of spike protein S1.,Here we suggest that, in part, the presence of spike protein in circulation may contribute to the hypercoagulation in COVID-19 positive patients and may cause substantial impairment of fibrinolysis.,Such lytic impairment may result in the persistent large microclots we have noted here and previously in plasma samples of COVID-19 patients.,This observation may have important clinical relevance in the treatment of hypercoagulability in COVID-19 patients.

A significant amount of clinical and research interest in thrombosis is focused on large vessels (eg, stroke, myocardial infarction, deep venous thrombosis, etc.); however, thrombosis is often present in the microcirculation in a variety of significant human diseases, such as disseminated intravascular coagulation, thrombotic microangiopathy, sickle cell disease, and others.,Further, microvascular thrombosis has recently been demonstrated in patients with COVID-19, and has been proposed to mediate the pathogenesis of organ injury in this disease.,In many of these conditions, microvascular thrombosis is accompanied by inflammation, an association referred to as thromboinflammation.,In this review, we discuss endogenous regulatory mechanisms that prevent thrombosis in the microcirculation, experimental approaches to induce microvascular thrombi, and clinical conditions associated with microvascular thrombosis.,A greater understanding of the links between inflammation and thrombosis in the microcirculation is anticipated to provide optimal therapeutic targets for patients with diseases accompanied by microvascular thrombosis.

Despite a lack of clinical evidence, hydroxychloroquine and azithromycin are being administered widely to patients with verified or suspected coronavirus disease 2019 (COVID‐19).,Both drugs may increase risk of lethal arrhythmias associated with QT interval prolongation.,We analyzed a case series of COVID‐19-positive/suspected patients admitted between February 1, 2020, and April 4, 2020, who were treated with azithromycin, hydroxychloroquine, or a combination of both drugs.,We evaluated baseline and postmedication QT interval (corrected QT interval [QTc]; Bazett) using 12‐lead ECGs.,Critical QTc prolongation was defined as follows: (1) maximum QTc ≥500 ms (if QRS <120 ms) or QTc ≥550 ms (if QRS ≥120 ms) and (2) QTc increase of ≥60 ms.,Tisdale score and Elixhauser comorbidity index were calculated.,Of 490 COVID‐19-positive/suspected patients, 314 (64%) received either/both drugs and 98 (73 COVID‐19 positive and 25 suspected) met study criteria (age, 62±17 years; 61% men).,Azithromycin was prescribed in 28%, hydroxychloroquine in 10%, and both in 62%.,Baseline mean QTc was 448±29 ms and increased to 459±36 ms (P=0.005) with medications.,Significant prolongation was observed only in men (18±43 ms versus −0.2±28 ms in women; P=0.02).,A total of 12% of patients reached critical QTc prolongation.,Changes in QTc were highest with the combination compared with either drug, with much greater prolongation with combination versus azithromycin (17±39 ms versus 0.5±40 ms; P=0.07).,No patients manifested torsades de pointes.,Overall, 12% of patients manifested critical QTc prolongation, and the combination caused greater prolongation than either drug alone.,The balance between uncertain benefit and potential risk when treating COVID‐19 patients should be carefully assessed.

Coagulopathy is a common abnormality in patients with COVID‐19.,However, the exact incidence of venous thromboembolic event is unknown in anticoagulated, severe COVID‐19 patients.,Systematic assessment of venous thromboembolism (VTE) using complete duplex ultrasound (CDU) in anticoagulated COVID‐19 patients.,We performed a retrospective study in 2 French intensive care units (ICU) where CDU is performed as a standard of care.,A CDU from thigh to ankle at selected sites with Doppler waveforms and images was performed early during ICU stay in patients admitted with COVID‐19.,Anticoagulation dose was left to the discretion of the treating physician based on the individual risk of thrombosis.,Patients were classified as treated with prophylactic anticoagulation or therapeutic anticoagulation.,Pulmonary embolism was systematically searched in patients with persistent hypoxemia or secondary deterioration.,From March 19 to April 11, 2020, 26 consecutive patients with severe COVID‐19 were screened for VTE.,Eight patients (31%) were treated with prophylactic anticoagulation, whereas 18 patients (69%) were treated with therapeutic anticoagulation.,The overall rate of VTE in patients was 69%.,The proportion of VTE was significantly higher in patients treated with prophylactic anticoagulation when compared with the other group (100% vs 56%, respectively, P = .03).,Surprisingly, we found a high rate of thromboembolic events in COVID‐19 patients treated with therapeutic anticoagulation, with 56% of VTE and 6 pulmonary embolisms.,Our results suggest considering both systematic screening of VTE and early therapeutic anticoagulation in severe ICU COVID‐19 patients.

Selenoprotein P (SELENOP) is an established biomarker of selenium (Se) status.,Serum SELENOP becomes saturated with increasing Se intake, reaching maximal concentrations of 5-7 mg SELENOP/L at intakes of ca. 100-150 µg Se/d.,A biomarker for higher Se intake is missing.,We hypothesized that SELENOP may also reflect Se status in clinical applications of therapeutic dosages of selenite.,To this end, blood samples from two supplementation studies employing intravenous application of selenite at dosages >1 mg/d were analyzed.,Total Se was quantified by spectroscopy, and SELENOP by a validated ELISA.,The high dosage selenite infusions increased SELENOP in parallel to elevated Se concentrations relatively fast to final values partly exceeding 10 mg SELENOP/L.,Age or sex were not related to the SELENOP increase.,Western blot analyses of SELENOP verified the results obtained by ELISA, and indicated an unchanged pattern of immunoreactive protein isoforms.,We conclude that the saturation of SELENOP concentrations observed in prior studies with moderate Se dosages (<400 µg/d) may reflect an intermediate plateau of expression, rather than an absolute upper limit.,Circulating SELENOP seems to be a suitable biomarker for therapeutic applications of selenite exceeding the recommended upper intake levels.,Whether SELENOP is also capable of reflecting other supplemental selenocompounds in high dosage therapeutic applications remains to be investigated.

Selenium and coenzyme Q10 are both necessary for optimal cell function in the body.,The intake of selenium is low in Europe, and the endogenous production of coenzyme Q10 decreases as age increases.,Therefore, an intervention trial using selenium and coenzyme Q10 for four years as a dietary supplement was performed.,The main publication reported reduced cardiovascular mortality as a result of the intervention.,In the present sub-study the objective was to determine whether reduced cardiovascular (CV) mortality persisted after 12 years, in the supplemented population or in subgroups with diabetes, hypertension, ischemic heart disease or reduced functional capacity due to impaired cardiac function.,From a rural municipality in Sweden, four hundred forty-three healthy elderly individuals were included.,All cardiovascular mortality was registered, and no participant was lost to the follow-up.,Based on death certificates and autopsy results, mortality was registered.,After 12 years a significantly reduced CV mortality could be seen in those supplemented with selenium and coenzyme Q10, with a CV mortality of 28.1% in the active treatment group, and 38.7% in the placebo group.,A multivariate Cox regression analysis demonstrated a reduced CV mortality risk in the active treatment group (HR: 0.59; 95%CI 0.42-0.81; P = 0.001).,In those with ischemic heart disease, diabetes, hypertension and impaired functional capacity we demonstrated a significantly reduced CV mortality risk.,This is a 12-year follow-up of a group of healthy elderly participants that were supplemented with selenium and coenzyme Q10 for four years.,Even after twelve years we observed a significantly reduced risk for CV mortality in this group, as well as in subgroups of patients with diabetes, hypertension, ischemic heart disease or impaired functional capacity.,The results thus validate the results obtained in the 10-year evaluation.,The protective action was not confined to the intervention period, but persisted during the follow-up period.,The mechanisms behind this effect remain to be fully elucidated, although various effects on cardiac function, oxidative stress, fibrosis and inflammation have previously been identified.,Since this was a small study, the observations should be regarded as hypothesis-generating.,Clinicaltrials.gov NCT01443780.

Few data are available on the rate and characteristics of thromboembolic complications in hospitalized patients with COVID-19.,We studied consecutive symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02.2020-10.04.2020).,The primary outcome was any thromboembolic complication, including venous thromboembolism (VTE), ischemic stroke, and acute coronary syndrome (ACS)/myocardial infarction (MI).,Secondary outcome was overt disseminated intravascular coagulation (DIC).,We included 388 patients (median age 66 years, 68% men, 16% requiring intensive care [ICU]).,Thromboprophylaxis was used in 100% of ICU patients and 75% of those on the general ward.,Thromboembolic events occurred in 28 (7.7% of closed cases; 95%CI 5.4%-11.0%), corresponding to a cumulative rate of 21% (27.6% ICU, 6.6% general ward).,Half of the thromboembolic events were diagnosed within 24 h of hospital admission.,Forty-four patients underwent VTE imaging tests and VTE was confirmed in 16 (36%).,Computed tomography pulmonary angiography (CTPA) was performed in 30 patients, corresponding to 7.7% of total, and pulmonary embolism was confirmed in 10 (33% of CTPA).,The rate of ischemic stroke and ACS/MI was 2.5% and 1.1%, respectively.,Overt DIC was present in 8 (2.2%) patients.,The high number of arterial and, in particular, venous thromboembolic events diagnosed within 24 h of admission and the high rate of positive VTE imaging tests among the few COVID-19 patients tested suggest that there is an urgent need to improve specific VTE diagnostic strategies and investigate the efficacy and safety of thromboprophylaxis in ambulatory COVID-19 patients.,•COVID-19 is characterized by coagulation activation and endothelial dysfunction.,Few data are available on thromboembolic complications.,•We studied symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02-10.04.2020).,•Venous and arterial thromboembolic events occurred in 8% of hospitalized patients (cumulative rate 21.0%) and 50% of events were diagnosed within 24 h of hospital admission.,•Forty-four (11% of total) patients underwent VTE imaging tests; 16 were positive (36% of tests), suggesting underestimation of thromboembolic complications.,•There is an urgent need to investigate VTE diagnostic strategies and the impact of thromboprophylaxis in ambulatory COVID-19 patients.,COVID-19 is characterized by coagulation activation and endothelial dysfunction.,Few data are available on thromboembolic complications.,We studied symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02-10.04.2020).,Venous and arterial thromboembolic events occurred in 8% of hospitalized patients (cumulative rate 21.0%) and 50% of events were diagnosed within 24 h of hospital admission.,Forty-four (11% of total) patients underwent VTE imaging tests; 16 were positive (36% of tests), suggesting underestimation of thromboembolic complications.,There is an urgent need to investigate VTE diagnostic strategies and the impact of thromboprophylaxis in ambulatory COVID-19 patients.

This case series study evaluates the association of underlying cardiovascular disease and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19).,What is the impact of underlying cardiovascular disease (CVD) and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19)?,In this case series study of 187 patients with COVID-19, 27.8% of patients had myocardial injury, which resulted in cardiac dysfunction and arrhythmias.,Myocardial injury has a significant association with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury were relatively favorable.,It is reasonable to triage patients with COVID-19 according to the presence of underlying CVD and evidence of myocardial injury for prioritized treatment and even more aggressive strategies.,Increasing numbers of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) are occurring in several countries and continents.,Information regarding the impact of cardiovascular complication on fatal outcome is scarce.,To evaluate the association of underlying cardiovascular disease (CVD) and myocardial injury with fatal outcomes in patients with COVID-19.,This retrospective single-center case series analyzed patients with COVID-19 at the Seventh Hospital of Wuhan City, China, from January 23, 2020, to February 23, 2020.,Analysis began February 25, 2020.,Demographic data, laboratory findings, comorbidities, and treatments were collected and analyzed in patients with and without elevation of troponin T (TnT) levels.,Among 187 patients with confirmed COVID-19, 144 patients (77%) were discharged and 43 patients (23%) died.,The mean (SD) age was 58.50 (14.66) years.,Overall, 66 (35.3%) had underlying CVD including hypertension, coronary heart disease, and cardiomyopathy, and 52 (27.8%) exhibited myocardial injury as indicated by elevated TnT levels.,The mortality during hospitalization was 7.62% (8 of 105) for patients without underlying CVD and normal TnT levels, 13.33% (4 of 30) for those with underlying CVD and normal TnT levels, 37.50% (6 of 16) for those without underlying CVD but elevated TnT levels, and 69.44% (25 of 36) for those with underlying CVD and elevated TnTs.,Patients with underlying CVD were more likely to exhibit elevation of TnT levels compared with the patients without CVD (36 [54.5%] vs 16 [13.2%]).,Plasma TnT levels demonstrated a high and significantly positive linear correlation with plasma high-sensitivity C-reactive protein levels (β = 0.530, P < .001) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (β = 0.613, P < .001).,Plasma TnT and NT-proBNP levels during hospitalization (median [interquartile range (IQR)], 0.307 [0.094-0.600]; 1902.00 [728.35-8100.00]) and impending death (median [IQR], 0.141 [0.058-0.860]; 5375 [1179.50-25695.25]) increased significantly compared with admission values (median [IQR], 0.0355 [0.015-0.102]; 796.90 [401.93-1742.25]) in patients who died (P = .001; P < .001), while no significant dynamic changes of TnT (median [IQR], 0.010 [0.007-0.019]; 0.013 [0.007-0.022]; 0.011 [0.007-0.016]) and NT-proBNP (median [IQR], 352.20 [174.70-636.70]; 433.80 [155.80-1272.60]; 145.40 [63.4-526.50]) was observed in survivors (P = .96; P = .16).,During hospitalization, patients with elevated TnT levels had more frequent malignant arrhythmias, and the use of glucocorticoid therapy (37 [71.2%] vs 69 [51.1%]) and mechanical ventilation (31 [59.6%] vs 14 [10.4%]) were higher compared with patients with normal TnT levels.,The mortality rates of patients with and without use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was 36.8% (7 of 19) and 21.4% (36 of 168) (P = .13).,Myocardial injury is significantly associated with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury is relatively favorable.,Myocardial injury is associated with cardiac dysfunction and arrhythmias.,Inflammation may be a potential mechanism for myocardial injury.,Aggressive treatment may be considered for patients at high risk of myocardial injury.

To investigate whether severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-induced myocarditis constitutes an important mechanism of cardiac injury, a review was conducted of the published data and the authors’ experience was added from autopsy examination of 16 patients dying of SARS-CoV-2 infection.,Myocarditis is an uncommon pathologic diagnosis occurring in 4.5% of highly selected cases undergoing autopsy or endomyocardial biopsy.,Although polymerase chain reaction-detectable virus could be found in the lungs of most coronavirus disease-2019 (COVID-19)-infected subjects in our own autopsy registry, in only 2 cases was the virus detected in the heart.,It should be appreciated that myocardial inflammation alone by macrophages and T cells can be seen in noninfectious deaths and COVID-19 cases, but the extent of each is different, and in neither case do such findings represent clinically relevant myocarditis.,Given its extremely low frequency and unclear therapeutic implications, the authors do not advocate use of endomyocardial biopsy to diagnose myocarditis in the setting of COVID-19.

The degree of myocardial injury, as reflected by troponin elevation, and associated outcomes among U.S. hospitalized patients with coronavirus disease-2019 (COVID-19) are unknown.,The purpose of this study was to describe the degree of myocardial injury and associated outcomes in a large hospitalized cohort with laboratory-confirmed COVID-19.,Patients with COVID-19 admitted to 1 of 5 Mount Sinai Health System hospitals in New York City between February 27, 2020, and April 12, 2020, with troponin-I (normal value <0.03 ng/ml) measured within 24 h of admission were included (n = 2,736).,Demographics, medical histories, admission laboratory results, and outcomes were captured from the hospitals’ electronic health records.,The median age was 66.4 years, with 59.6% men.,Cardiovascular disease (CVD), including coronary artery disease, atrial fibrillation, and heart failure, was more prevalent in patients with higher troponin concentrations, as were hypertension and diabetes.,A total of 506 (18.5%) patients died during hospitalization.,In all, 985 (36%) patients had elevated troponin concentrations.,After adjusting for disease severity and relevant clinical factors, even small amounts of myocardial injury (e.g., troponin I >0.03 to 0.09 ng/ml; n = 455; 16.6%) were significantly associated with death (adjusted hazard ratio: 1.75; 95% CI: 1.37 to 2.24; p < 0.001) while greater amounts (e.g., troponin I >0.09 ng/dl; n = 530; 19.4%) were significantly associated with higher risk (adjusted HR: 3.03; 95% CI: 2.42 to 3.80; p < 0.001).,Myocardial injury is prevalent among patients hospitalized with COVID-19; however, troponin concentrations were generally present at low levels.,Patients with CVD are more likely to have myocardial injury than patients without CVD.,Troponin elevation among patients hospitalized with COVID-19 is associated with higher risk of mortality.

To evaluate the impact of the lockdown measures, consequent to the outbreak of COVID-19 pandemic, on the quality of pre-hospital and in-hospital care of patients with acute ischemic stroke.,This is an observational cohort study.,Data sources were the clinical reports of patients admitted during the first month of lockdown and discharged with a confirmed diagnosis of stroke or TIA.,Data were collected in the interval ranging from March 11th to April 11th 2020.,As controls, we evaluated the clinical reports of patients with stroke or TIA admitted in the same period of 2019.,The clinical reports of patients eligible for the study were 52 in 2020 (71.6 ± 12.2 years) and 41 in 2019 (73.7 ± 13.1 years).,During the lockdown, we observed a significant increase in onset-to-door time (median = 387 vs 161 min, p = 0.001), a significant reduction of the total number of thrombolysis (7 vs 13, p = 0.033), a non-significant increase of thrombectomy (15 vs 9, p = 0.451), and a significant increase in door-to-groin time (median = 120 vs 93 min, p = 0.048).,No relevant difference was observed between 2019 and 2020 in the total number of patients admitted.,Due to the COVID-19 pandemic and lockdown measures, the stroke care pathway changed, involving both pre-hospital and in-hospital performances.

Higher rates of strokes have been observed in patients with coronavirus disease 2019 (COVID-19), but data regarding the outcomes of COVID-19 patients suffering from acute ischemic stroke due to large vessel occlusion (LVO) are lacking.,We report our initial experience in the treatment of acute ischemic stroke with LVO in patients with COVID-19.,All consecutive patients with COVID-19 with acute ischemic stroke due to LVO treated in our institution during the 6 first weeks of the COVID-19 outbreak were included.,Baseline clinical and radiological findings, treatment, and short-term outcomes are reported.,We identified 10 patients with confirmed COVID-19 treated for an acute ischemic stroke due to LVO.,Eight were men, with a median age of 59.5 years.,Seven had none or mild symptoms of COVID-19 at stroke onset.,Median time from COVID-19 symptoms to stroke onset was 6 days.,All patients had brain imaging within 3 hours from symptoms onset.,Five patients had multi-territory LVO.,Five received intravenous alteplase.,All patients had mechanical thrombectomy.,Nine patients achieved successful recanalization (mTICI2B-3), none experienced early neurological improvement, 4 had early cerebral reocclusion, and a total of 6 patients (60%) died in the hospital.,Best medical care including early intravenous thrombolysis, and successful and prompt recanalization achieved with mechanical thrombectomy, resulted in poor outcomes in patients with COVID-19.,Although our results require further confirmation, a different pharmacological approach (antiplatelet or other) should be investigated to take in account inflammatory and coagulation disorders associated with COVID-19.

Hypercoagulability and endotheliopathy reported in patients with coronavirus disease 2019 (COVID-19) combined with strict and prolonged immobilization inherent to deep sedation and administration of neuromuscular blockers for Acute Respiratory Distress Syndrome (ARDS) may expose critically ill COVID-19 patients to an increased risk of venous thrombosis and pulmonary embolism (PE).,We aimed to assess the rate and to describe the clinical features and the outcomes of ARDS COVID-19 patients diagnosed with PE during ICU stay.,From March 13th to April 24th 2020, a total of 92 patients (median age: 61 years, 1st-3rd quartiles [55-70]; males: n = 73/92, 79%; baseline SOFA: 4 [3-7] and SAPS II: 31 [21-40]; invasive mechanical ventilation: n = 83/92, 90%; ICU mortality: n = 45/92, 49%) were admitted to our 41-bed COVID-19 ICU for ARDS due to COVID-19.,Among them, 26 patients (n = 26/92, 28%) underwent a Computed Tomography Pulmonary Angiography which revealed PE in 16 (n = 16/26, 62%) of them, accounting for 17% (n = 16/92) of the whole cohort.,PE was bilateral in 3 (19%) patients and unilateral in 13 (81%) patients.,The most proximal thrombus was localized in main (n = 4, 25%), lobar (n = 2, 12%) or segmental (n = 10, 63%) pulmonary artery.,Most of the thrombi (n = 13/16, 81%) were located in a parenchymatous condensation.,Only three of the 16 patients (19%) had lower limb venous thrombosis on Doppler ultrasound.,Three patients were treated with alteplase and anticoagulation (n = 3/16, 19%) while the 13 others (n = 13/16, 81%) were treated with anticoagulation alone.,ICU mortality was higher in patients with PE compared to that of patients without PE (n = 11/16, 69% vs. n = 2/10, 20%; p = 0.04).,The low rate of lower limb venous thrombosis together with the high rate of distal pulmonary thrombus argue for a local immuno-thrombotic process associated with the classic embolic process.,Further larger studies are needed to assess the real prevalence and the risk factors of pulmonary embolism/thrombosis together with its prognostic impact on critically ill patients with COVID-19.

This case series reports a systematic assessment of deep vein thrombosis among patients in an intensive care unit in France with severe coronavirus disease 2019 (COVID-19).

COVID-19 has rapidly impacted on mortality worldwide.1 There is unprecedented urgency to understand who is most at risk of severe outcomes, requiring new approaches for timely analysis of large datasets.,Working on behalf of NHS England we created OpenSAFELY: a secure health analytics platform covering 40% of all patients in England, holding patient data within the existing data centre of a major primary care electronic health records vendor.,Primary care records of 17,278,392 adults were pseudonymously linked to 10,926 COVID-19 related deaths.,COVID-19 related death was associated with: being male (hazard ratio 1.59, 95%CI 1.53-1.65); older age and deprivation (both with a strong gradient); diabetes; severe asthma; and various other medical conditions.,Compared to people with white ethnicity, black and South Asian people were at higher risk even after adjustment for other factors (HR 1.48, 1.29-1.69 and 1.45, 1.32-1.58 respectively).,We have quantified a range of clinical risk factors for COVID-19 related death in the largest cohort study conducted by any country to date.,OpenSAFELY is rapidly adding further patients’ records; we will update and extend results regularly.

The outbreak of the novel coronavirus in China (SARS‐CoV‐2) that began in December 2019 presents a significant and urgent threat to global health.,This study was conducted to provide the international community with a deeper understanding of this new infectious disease.,Epidemiological, clinical features, laboratory findings, radiological characteristics, treatment, and clinical outcomes of 135 patients in northeast Chongqing were collected and analyzed in this study.,A total of 135 hospitalized patients with COVID‐19 were enrolled.,The median age was 47 years (interquartile range, 36‐55), and there was no significant gender difference (53.3% men).,The majority of patients had contact with people from the Wuhan area.,Forty‐three (31.9%) patients had underlying disease, primarily hypertension (13 [9.6%]), diabetes (12 [8.9%]), cardiovascular disease (7 [5.2%]), and malignancy (4 [3.0%]).,Common symptoms included fever (120 [88.9%]), cough (102 [76.5%]), and fatigue (44 [32.5%]).,Chest computed tomography scans showed bilateral patchy shadows or ground glass opacity in the lungs of all the patients.,All patients received antiviral therapy (135 [100%]) (Kaletra and interferon were both used), antibacterial therapy (59 [43.7%]), and corticosteroids (36 [26.7%]).,In addition, many patients received traditional Chinese medicine (TCM) (124 [91.8%]).,It is suggested that patients should receive Kaletra early and should be treated by a combination of Western and Chinese medicines.,Compared to the mild cases, the severe ones had lower lymphocyte counts and higher plasma levels of Pt, APTT, d‐dimer, lactate dehydrogenase, PCT, ALB, C‐reactive protein, and aspartate aminotransferase.,This study demonstrates the clinic features and therapies of 135 COVID‐19 patients.,Kaletra and TCM played an important role in the treatment of the viral pneumonia.,Further studies are required to explore the role of Kaletra and TCM in the treatment of COVID‐19.,83.7% of the patients had contact history in Wuhan or had been to Wuhan or had contact with people from Wuhan.Common symptoms included fever, cough, and fatigue.,Other symptoms include myalgia, fatigue, dyspnea, anorexia, etc.Common complications of the patients include acute respiratory distress syndrome, acute cardiac injury, acute kidney injury, secondary infection and shock.,ICU patients were more likely to have these complications than non‐ICU patients.Compared with non‐ICU patients, ICU patients had lower lymphocyte count, and higher plasma levels of the Pt, APTT, D‐dimer, LDH, PCT, ALB, CRP, AST.All patients received antiviral therapy (kaletra or interferon), antibacterial therapy and corticosteroid and many received traditional chinese medicine.,It was suggested that patients should use kaletra early.,83.7% of the patients had contact history in Wuhan or had been to Wuhan or had contact with people from Wuhan.,Common symptoms included fever, cough, and fatigue.,Other symptoms include myalgia, fatigue, dyspnea, anorexia, etc.,Common complications of the patients include acute respiratory distress syndrome, acute cardiac injury, acute kidney injury, secondary infection and shock.,ICU patients were more likely to have these complications than non‐ICU patients.,Compared with non‐ICU patients, ICU patients had lower lymphocyte count, and higher plasma levels of the Pt, APTT, D‐dimer, LDH, PCT, ALB, CRP, AST.,All patients received antiviral therapy (kaletra or interferon), antibacterial therapy and corticosteroid and many received traditional chinese medicine.,It was suggested that patients should use kaletra early.

A higher incidence of thrombotic events, mainly pulmonary embolism (PE), has been reported in hospitalized patients with COVID-19.,The main objective was to assess clinical and laboratory differences in hospitalized COVID-19 patients according to occurrence of PE.,This retrospective study included all consecutive patients hospitalized with COVID-19 who underwent a computed tomography (CT) angiography for PE clinical suspicion.,Clinical data and median blood test results distributed into weekly periods from COVID-19 symptoms onset, were compared between PE and non-PE patients.,Ninety-two patients were included, 29 (32%) had PE.,PE patients were younger (63.9 (SD 13.7) vs 69.9 (SD 12.5) years).,Clinical symptoms and COVID-19 CT features were similar in both groups.,PE was diagnosed after a mean of 20.0 (SD 8.6) days from the onset of COVID-19 symptoms.,Corticosteroid boluses were more frequently used in PE patients (62% vs.,43%).,No patients met ISTH DIC criteria.,Any parameter was statistically significant or clinically relevant except for D-Dimer when comparing both groups.,Median values [IQR] of D-dimer in PE vs non-PE patients were: week 2 (2010.7 [770.1-11208.9] vs 626.0 [374.0-2382.2]; p = 0.004); week 3 (3893.1 [1388.2-6694.0] vs 1184.4 [461.8-2447.8]; p = 0.003); and week 4 (2736.3 [1202.1-8514.1] vs 1129.1 [542.5-2834.6]; p = 0.01).,Median fold-increase of D-dimer between week 1 and 2 differed between groups (6.64 [3.02-23.05] vs 1.57 [0.64-2.71], p = 0.003); ROC curve AUC was 0.879 (p = 0.003) with a sensitivity and specificity for PE of 86% and 80%, respectively.,Among hospitalized COVID-19 patients, D-dimer levels are higher at weeks 2, 3 and 4 after COVID-19 symptom onset in patients who develop PE.,This difference is more pronounced when the fold increase between weeks 1 and 2 is compared.

COVID-19 raises D-dimer (DD) levels even in the absence of pulmonary embolism (PE), resulting in an increase in computed tomography pulmonary angiogram (CTPA) requests.,Our purpose is to determine whether there are differences between DD values in PE-positive and PE-negative COVID-19 patients and, if so, to establish a new cutoff value which accurately determines when a CTPA is needed.,This study retrospectively analyzed all COVID-19 patients who underwent a CTPA due to suspected PE between March 1 and April 30, 2020, at Ramón y Cajal University Hospital, Madrid (Spain).,DD level comparisons between PE-positive and PE-negative groups were made using Student’s t test.,The optimal DD cutoff value to predict PE risk in COVID-19 patients was calculated in the ROC curve.,Two hundred forty-two patients were included in the study.,One hundred fifty-one (62%) were men and the median age was 68 years (IQR 55-78).,An increase of DD (median 3260; IQR 1203-9625 ng/mL) was detected in 205/242 (96%) patients. 73/242 (30%) of the patients were diagnosed with PE on CTPA.,The DD median value was significantly higher (p < .001) in the PE-positive group (7872, IQR 3150-22,494 ng/mL) compared with the PE-negative group (2009, IQR 5675-15,705 ng/mL).,The optimal cutoff value for DD to predict PE was 2903 ng/mL (AUC was 0.76 [CI 95% 0.69-0.83], sensitivity 81%).,The overall mortality rate was 16% (39/242).,A higher threshold (2903 ng/mL) for D-dimer could predict the risk of PE in COVID-19 patients with a sensitivity of 81%.

Since the outbreak of SARS‐CoV‐2, also known as COVID‐19, conflicting theories have circulated on the influence of angiotensin‐converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) on incidence and clinical course of COVID‐19, but data are scarce.,The COvid MEdicaTion (COMET) study is an observational, multinational study that focused on the clinical course of COVID‐19 (i.e. hospital mortality and intensive care unit [ICU] admission), and included COVID‐19 patients who were registered at the emergency department or admitted to clinical wards of 63 participating hospitals.,Pharmacists, clinical pharmacologists or treating physicians collected data on medication prescribed prior to admission.,The association between the medication and composite clinical endpoint, including mortality and ICU admission, was analysed by multivariable logistic regression models to adjust for potential confounders.,A total of 4870 patients were enrolled.,ACEi were used by 847 (17.4%) patients and ARB by 761 (15.6%) patients.,No significant association was seen with ACEi and the composite endpoint (adjusted odds ratio [OR] 0.94; 95% confidence interval [CI] 0.79 to 1.12), mortality (OR 1.03; 95%CI 0.84 to 1.27) or ICU admission (OR 0.96; 95%CI 0.78 to 1.19) after adjustment for covariates.,Similarly, no association was observed between ARB and the composite endpoint (OR 1.09; 95%CI 0.90 to 1.30), mortality (OR 1.12; OR 0.90 to 1.39) or ICU admission (OR 1.21; 95%CI 0.98 to 1.49).,In conclusion, we found no evidence of a harmful or beneficial effect of ACEi or ARB use prior to hospital admission on ICU admission or hospital mortality.

The hypothesis that been set forward that use of Renin Angiotensin Aldosterone System (RAAS) inhibitors is associated with COVID−19 severity.,We set-up a multicenter Italian collaboration (CORIST Project, ClinicalTrials.gov ID: NCT04318418) to retrospectively investigate the relationship between RAAS inhibitors and COVID−19 in-hospital mortality.,We also carried out an updated meta-analysis on the relevant studies.,We analyzed 4069 unselected patients with laboratory-confirmed SARS-CoV-2 infection and hospitalized in 34 clinical centers in Italy from February 19, 2020 to May 23, 2020.,The primary end-point in a time-to event analysis was in-hospital death, comparing patients who received angiotensin-converting-enzyme inhibitors (ACE-I) or angiotensin-receptor blockers (ARB) with patients who did not.,Articles for the meta-analysis were retrieved until July 13th, 2020 by searching in web-based libraries, and data were combined using the general variance-based method.,Out of 4069 COVID−19 patients, 13.5% and 13.3% received ACE-I or ARB, respectively.,Use of neither ACE-I nor ARB was associated with mortality (multivariable hazard ratio (HR) adjusted also for COVID−19 treatments: 0.96, 95% confidence interval 0.77-1.20 and HR = 0.89, 0.67-1.19 for ACE-I and ARB, respectively).,Findings were similar restricting the analysis to hypertensive (N = 2057) patients (HR = 1.00, 0.78-1.26 and HR = 0.88, 0.65-1.20) or when ACE-I or ARB were considered as a single group.,Results from the meta-analysis (19 studies, 29,057 COVID−19 adult patients, 9700 with hypertension) confirmed the absence of association.,In this observational study and meta-analysis of the literature, ACE-I or ARB use was not associated with severity or in-hospital mortality in COVID−19 patients.

Since the appearance of the first case of coronavirus disease 2019 (COVID-19) a pandemic has emerged affecting millions of people worldwide.,Although the main clinical manifestations are respiratory, an increase in neurological conditions, specifically acute cerebrovascular disease, has been detected.,We present cerebrovascular disease case incidence in hospitalized patients with SARS-CoV-2 infection.,Patients were confirmed by microbiological/serological testing, or on chest CT semiology.,Available data on comorbidity, laboratory parameters, treatment administered, neuroimaging, neuropathological studies and clinical evolution during hospitalization, measured by the modified Rankin scale, were analysed.,A bivariate study was also designed to identify differences between ischaemic and haemorrhagic subtypes.,A statistical model of binary logistic regression and sensitivity analysis was designed to study the influence of independent variables over prognosis.,In our centre, there were 1683 admissions of patients with COVID-19 over 50 days, of which 23 (1.4%) developed cerebrovascular disease.,Within this group of patients, cerebral and chest CT scans were performed in all cases, and MRI in six (26.1%).,Histological samples were obtained in 6/23 cases (two brain biopsies, and four arterial thrombi).,Seventeen patients were classified as cerebral ischaemia (73.9%, with two arterial dissections), five as intracerebral haemorrhage (21.7%), and one leukoencephalopathy of posterior reversible encephalopathy type.,Haemorrhagic patients had higher ferritin levels at the time of stroke (1554.3 versus 519.2, P = 0.004).,Ischaemic strokes were unexpectedly frequent in the vertebrobasilar territory (6/17, 35.3%).,In the haemorrhagic group, a characteristic radiological pattern was identified showing subarachnoid haemorrhage, parieto-occipital leukoencephalopathy, microbleeds and single or multiple focal haematomas.,Brain biopsies performed showed signs of thrombotic microangiopathy and endothelial injury, with no evidence of vasculitis or necrotizing encephalitis.,The functional prognosis during the hospital period was unfavourable in 73.9% (17/23 modified Rankin scale 4-6), and age was the main predictive variable (odds ratio = 1.5; 95% confidence interval 1.012-2.225; P = 0.043).,Our series shows cerebrovascular disease incidence of 1.4% in patients with COVID-19 with high morbidity and mortality.,We describe pathological and radiological data consistent with thrombotic microangiopathy caused by endotheliopathy with a haemorrhagic predisposition.

With the spread of coronavirus disease 2019 (COVID-19) during the current worldwide pandemic, there is mounting evidence that patients affected by the illness may develop clinically significant coagulopathy with thromboembolic complications including ischemic stroke.,However, there is limited data on the clinical characteristics, stroke mechanism, and outcomes of patients who have a stroke and COVID-19.,We conducted a retrospective cohort study of consecutive patients with ischemic stroke who were hospitalized between March 15, 2020, and April 19, 2020, within a major health system in New York, the current global epicenter of the pandemic.,We compared the clinical characteristics of stroke patients with a concurrent diagnosis of COVID-19 to stroke patients without COVID-19 (contemporary controls).,In addition, we compared patients to a historical cohort of patients with ischemic stroke discharged from our hospital system between March 15, 2019, and April 15, 2019 (historical controls).,During the study period in 2020, out of 3556 hospitalized patients with diagnosis of COVID-19 infection, 32 patients (0.9%) had imaging proven ischemic stroke.,Cryptogenic stroke was more common in patients with COVID-19 (65.6%) as compared to contemporary controls (30.4%, P=0.003) and historical controls (25.0%, P<0.001).,When compared with contemporary controls, COVID-19 positive patients had higher admission National Institutes of Health Stroke Scale score and higher peak D-dimer levels.,When compared with historical controls, COVID-19 positive patients were more likely to be younger men with elevated troponin, higher admission National Institutes of Health Stroke Scale score, and higher erythrocyte sedimentation rate.,Patients with COVID-19 and stroke had significantly higher mortality than historical and contemporary controls.,We observed a low rate of imaging-confirmed ischemic stroke in hospitalized patients with COVID-19.,Most strokes were cryptogenic, possibly related to an acquired hypercoagulability, and mortality was increased.,Studies are needed to determine the utility of therapeutic anticoagulation for stroke and other thrombotic event prevention in patients with COVID-19.

There is limited data concerning the prevalence of arrhythmias, particularly atrial fibrillation (AF), which may develop as a consequence of direct myocardial injury and the inflammatory state existing in COVID-19.,This single-center study included data concerning 658 COVID-19 patients, who were hospitalized in our institute, between April 20th, 2020 and July 30th, 2020.,Demographic data, findings of the imaging studies, and laboratory test results were retrieved from the institutional digital database.,New onset AF (NOAF) was identified in 33 patients (5%).,Patients who developed AF were older (72.42 ± 6.10 vs 53.78 ± 13.80, p < 0.001) and had higher frequencies of hypertension and heart failure compared to patients without NOAF (p < 0.001, for both).,The CHA2DS2-VASc score was higher in patients, who developed NOAF, compared to those who did not during hospitalization for COVID-19 (p < 0.001).,Subjects, who developed NOAF during hospitalization, had a higher leukocyte count, neutrophil / lymphocyte ratio (NLR), C-reactive protein, erythrocyte sedimentation rate, and procalcitonin levels compared to those without NOAF (p < 0.001 for all comparisons).,Diffuse lung infiltration was also more frequent in COVID-19 patients, who developed NOAF, during hospitalization (p = 0.015).,Multivariate logistic regression analysis demonstrated that age, CHA2DS2-VASc score, CRP, erythrocyte sedimentation rate, and presence of diffuse lung infiltration on thorax CT were predictive for NOAF.,The prevalence of NOAF in hospitalized COVID-19 patients is higher than the general population.,Age, CHA2DS2-VASc score, C-reactive protein, erythrocyte sedimentation rate, and presence of diffuse lung infiltration on thorax CT may be used to identify patients at high risk for development of NOAF.,Especially among these parameters, the presence of diffuse lung infiltration on thorax CT it was the most powerful independent predictor of NOAF development.

The impact of atrial arrhythmias on coronavirus disease 2019 (COVID‐19)‐associated outcomes are unclear.,We sought to identify prevalence, risk factors and outcomes associated with atrial arrhythmias among patients hospitalized with COVID‐19.,An observational cohort study of 1053 patients with severe acute respiratory syndrome coronavirus 2 infection admitted to a quaternary care hospital and a community hospital was conducted.,Data from electrocardiographic and telemetry were collected to identify atrial fibrillation (AF) or atrial flutter/tachycardia (AFL).,The association between atrial arrhythmias and 30‐day mortality was assessed with multivariable analysis.,Mean age of patients was 62 ± 17 years and 62% were men.,Atrial arrhythmias were identified in 166 (15.8%) patients, with AF in 154 (14.6%) patients and AFL in 40 (3.8%) patients.,Newly detected atrial arrhythmias occurred in 101 (9.6%) patients.,Age, male sex, prior AF, renal disease, and hypoxia on presentation were independently associated with AF/AFL occurrence.,Compared with patients without AF/AFL, patients with AF/AFL had significantly higher levels of troponin, B‐type natriuretic peptide, C‐reactive protein, ferritin and d‐dimer.,Mortality was significantly higher among patients with AF/AFL (39.2%) compared to patients without (13.4%; p < .001).,After adjustment for age and co‐morbidities, AF/AFL (adjusted odds ratio [OR]: 1.93; p = .007) and newly detected AF/AFL (adjusted OR: 2.87; p < .001) were independently associated with 30‐day mortality.,Atrial arrhythmias are common among patients hospitalized with COVID‐19.,The presence of AF/AFL tracked with markers of inflammation and cardiac injury.,Atrial arrhythmias were independently associated with increased mortality.

COVID-19 affects millions of patients worldwide, with clinical presentation ranging from isolated thrombosis to acute respiratory distress syndrome (ARDS) requiring ventilator support.,Neutrophil extracellular traps (NETs) originate from decondensed chromatin released to immobilize pathogens, and they can trigger immunothrombosis.,We studied the connection between NETs and COVID-19 severity and progression.,We conducted a prospective cohort study of COVID-19 patients (n = 33) and age- and sex-matched controls (n = 17).,We measured plasma myeloperoxidase (MPO)-DNA complexes (NETs), platelet factor 4, RANTES, and selected cytokines.,Three COVID-19 lung autopsies were examined for NETs and platelet involvement.,We assessed NET formation ex vivo in COVID-19 neutrophils and in healthy neutrophils incubated with COVID-19 plasma.,We also tested the ability of neonatal NET-inhibitory factor (nNIF) to block NET formation induced by COVID-19 plasma.,Plasma MPO-DNA complexes increased in COVID-19, with intubation (P < .0001) and death (P < .0005) as outcome.,Illness severity correlated directly with plasma MPO-DNA complexes (P = .0360), whereas Pao2/fraction of inspired oxygen correlated inversely (P = .0340).,Soluble and cellular factors triggering NETs were significantly increased in COVID-19, and pulmonary autopsies confirmed NET-containing microthrombi with neutrophil-platelet infiltration.,Finally, COVID-19 neutrophils ex vivo displayed excessive NETs at baseline, and COVID-19 plasma triggered NET formation, which was blocked by nNIF.,Thus, NETs triggering immunothrombosis may, in part, explain the prothrombotic clinical presentations in COVID-19, and NETs may represent targets for therapeutic intervention.,•NETs contribute to microthrombi through platelet-neutrophil interactions in COVID-19 ARDS.•nNIF blocks NETs induced by COVID-19 plasma and represents a potential therapeutic intervention in COVID-19.,NETs contribute to microthrombi through platelet-neutrophil interactions in COVID-19 ARDS.,nNIF blocks NETs induced by COVID-19 plasma and represents a potential therapeutic intervention in COVID-19.

Three months ago, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) broke out in Wuhan, China, and spread rapidly around the world.,Severe novel coronavirus pneumonia (NCP) patients have abnormal blood coagulation function, but their venous thromboembolism (VTE) prevalence is still rarely mentioned.,To determine the incidence of VTE in patients with severe NCP.,In this study, 81 severe NCP patients in the intensive care unit (ICU) of Union Hospital (Wuhan, China) were enrolled.,The results of conventional coagulation parameters and lower limb vein ultrasonography of these patients were retrospectively collected and analyzed.,The incidence of VTE in these patients was 25% (20/81), of which 8 patients with VTE events died.,The VTE group was different from the non‐VTE group in age, lymphocyte counts, activated partial thromboplastin time (APTT), D‐dimer, etc.,If 1.5 µg/mL was used as the D‐dimer cut‐off value to predicting VTE, the sensitivity was 85.0%, the specificity was 88.5%, and the negative predictive value (NPV) was 94.7%.,The incidence of VTE in patients with severe NCP is 25% (20/81), which may be related to poor prognosis.,The significant increase of D‐dimer in severe NCP patients is a good index for identifying high‐risk groups of VTE.

Machine learning (ML) is widely believed to be able to learn complex hidden interactions from the data and has the potential in predicting events such as heart failure (HF) readmission and death.,Recent studies have revealed conflicting results likely due to failure to take into account the class imbalance problem commonly seen with medical data.,We developed a new ML approach to predict 30 day HF readmission or death and compared the performance of this model with other commonly used prediction models.,We identified all Western Australian patients aged above 65 years admitted for HF between 2003 and 2008 in the linked Hospital Morbidity Data Collection.,Taking into consideration the class imbalance problem, we developed a multi‐layer perceptron (MLP)‐based approach to predict 30 day HF readmission or death and compared the predictive performances using the performance metrics, that is, area under the receiver operating characteristic curve (AUC), area under the precision-recall curve (AUPRC), sensitivity and specificity with other ML and regression models.,Out of the 10 757 patients with HF, 23.6% were readmitted or died within 30 days of hospital discharge.,We observed an AUC of 0.55, 0.53, 0.58, and 0.54 while an AUPRC of 0.39, 0.38, 0.46, and 0.38 for weighted random forest, weighted decision trees, logistic regression, and weighted support vector machines models, respectively.,The MLP‐based approach produced the highest AUC (0.62) and AUPRC (0.46) with 48% sensitivity and 70% specificity.,We show that for the medical data with class imbalance, the proposed MLP‐based approach is superior to other ML and regression techniques for the prediction of 30 day HF readmission or death.

Implantable-cardioverter defibrillators (ICD) detect and terminate life-threatening ventricular tachyarrhythmia with electric shocks after they occur.,This puts patients at risk if they are driving or in a situation where they can fall.,ICD’s shocks are also very painful and affect a patient’s quality of life.,It would be ideal if ICDs can accurately predict the occurrence of ventricular tachyarrhythmia and then issue a warning or provide preventive therapy.,Our study explores the use of ICD data to automatically predict ventricular arrhythmia using heart rate variability (HRV).,A 5 minute and a 10 second warning system are both developed and compared.,The participants for this study consist of 788 patients who were enrolled in the ICD arm of the Sudden Cardiac Death-Heart Failure Trial (SCD-HeFT).,Two groups of patient rhythms, regular heart rhythms and pre-ventricular-tachyarrhythmic rhythms, are analyzed and different HRV features are extracted.,Machine learning algorithms, including random forests (RF) and support vector machines (SVM), are trained on these features to classify the two groups of rhythms in a subset of the data comprising the training set.,These algorithms are then used to classify rhythms in a separate test set.,This performance is quantified by the area under the curve (AUC) of the ROC curve.,Both RF and SVM methods achieve a mean AUC of 0.81 for 5-minute prediction and mean AUC of 0.87-0.88 for 10-second prediction; an AUC over 0.8 typically warrants further clinical investigation.,Our work shows that moderate classification accuracy can be achieved to predict ventricular tachyarrhythmia with machine learning algorithms using HRV features from ICD data.,These results provide a realistic view of the practical challenges facing implementation of machine learning algorithms to predict ventricular tachyarrhythmia using HRV data, motivating continued research on improved algorithms and additional features with higher predictive power.

Recent studies suggest that thrombotic complications are a common phenomenon in the novel SARS-CoV-2 infection.,The main objective of our study is to assess cumulative incidence of pulmonary embolism (PE) in non critically ill COVID-19 patients and to identify its predicting factors associated to the diagnosis of pulmonary embolism.,We retrospectevely reviewed 452 electronic medical records of patients admitted to Internal Medicine Department of a secondary hospital in Madrid during Covid 19 pandemic outbreak.,We included 91 patients who underwent a multidetector Computed Tomography pulmonary angiography(CTPA) during conventional hospitalization.,The cumulative incidence of PE was assessed ant the clinical, analytical and radiological characteristics were compared between patients with and without PE.,PE incidence was 6.4% (29/452 patients).,Most patients with a confirmed diagnosed with PE recieved low molecular weight heparin (LMWH): 79.3% (23/29).,D-dimer peak was significatly elevated in PE vs non PE patients (14,480 vs 7230 mcg/dL, p = 0.03).,In multivariate analysis of patients who underwent a CTPA we found that plasma D-dimer peak was an independen predictor of PE with a best cut off point of > 5000 µg/dl (OR 3.77; IC95% (1.18-12.16), p = 0.03).,We found ninefold increased risk of PE patients not suffering from dyslipidemia (OR 9.06; IC95% (1.88-43.60).,Predictive value of AUC for ROC is 75.5%.,We found a high incidence of PE in non critically ill hospitalized COVID 19 patients despite standard thromboprophylaxis.,An increase in D-dimer levels is an independent predictor for PE, with a best cut-off point of > 5000 µg/ dl.

Coronavirus disease-2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, because of excessive inflammation, platelet activation, endothelial dysfunction, and stasis.,In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy.,Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease.,Herein, the authors review the current understanding of the pathogenesis, epidemiology, management, and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, of those with pre-existing thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.,•COVID-19 may predispose patients to arterial and venous thrombosis.,•Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,•Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,•The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic.,COVID-19 may predispose patients to arterial and venous thrombosis.,Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic.

Three months ago, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) broke out in Wuhan, China, and spread rapidly around the world.,Severe novel coronavirus pneumonia (NCP) patients have abnormal blood coagulation function, but their venous thromboembolism (VTE) prevalence is still rarely mentioned.,To determine the incidence of VTE in patients with severe NCP.,In this study, 81 severe NCP patients in the intensive care unit (ICU) of Union Hospital (Wuhan, China) were enrolled.,The results of conventional coagulation parameters and lower limb vein ultrasonography of these patients were retrospectively collected and analyzed.,The incidence of VTE in these patients was 25% (20/81), of which 8 patients with VTE events died.,The VTE group was different from the non‐VTE group in age, lymphocyte counts, activated partial thromboplastin time (APTT), D‐dimer, etc.,If 1.5 µg/mL was used as the D‐dimer cut‐off value to predicting VTE, the sensitivity was 85.0%, the specificity was 88.5%, and the negative predictive value (NPV) was 94.7%.,The incidence of VTE in patients with severe NCP is 25% (20/81), which may be related to poor prognosis.,The significant increase of D‐dimer in severe NCP patients is a good index for identifying high‐risk groups of VTE.

Acute respiratory failure and a systemic coagulopathy are critical aspects of the morbidity and mortality characterizing infection with severe acute respiratory distress syndrome-associated coronavirus-2, the etiologic agent of Coronavirus disease 2019 (COVID-19).,We examined skin and lung tissues from 5 patients with severe COVID-19 characterized by respiratory failure (n= 5) and purpuric skin rash (n = 3).,COVID-19 pneumonitis was predominantly a pauci-inflammatory septal capillary injury with significant septal capillary mural and luminal fibrin deposition and permeation of the interalveolar septa by neutrophils.,No viral cytopathic changes were observed and the diffuse alveolar damage (DAD) with hyaline membranes, inflammation, and type II pneumocyte hyperplasia, hallmarks of classic acute respiratory distress syndrome, were not prominent.,These pulmonary findings were accompanied by significant deposits of terminal complement components C5b-9 (membrane attack complex), C4d, and mannose binding lectin (MBL)-associated serine protease (MASP)2, in the microvasculature, consistent with sustained, systemic activation of the complement pathways.,The purpuric skin lesions similarly showed a pauci-inflammatory thrombogenic vasculopathy, with deposition of C5b-9 and C4d in both grossly involved and normally-appearing skin.,In addition, there was co-localization of COVID-19 spike glycoproteins with C4d and C5b-9 in the interalveolar septa and the cutaneous microvasculature of 2 cases examined.,In conclusion, at least a subset of sustained, severe COVID-19 may define a type of catastrophic microvascular injury syndrome mediated by activation of complement pathways and an associated procoagulant state.,It provides a foundation for further exploration of the pathophysiologic importance of complement in COVID-19, and could suggest targets for specific intervention.

The new coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has caused more than 210 000 deaths worldwide.,However, little is known about the causes of death and the virus's pathologic features.,To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests.,Prospective cohort study.,Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction-confirmed diagnosis of COVID-19.,The first 12 consecutive COVID-19-positive deaths.,Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed.,Clinical data and medical course were evaluated.,Results: Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital (n = 10) or outpatient sector (n = 2).,Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively).,Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients.,Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients.,In all patients, SARS-CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart.,Limited sample size.,The high incidence of thromboembolic events suggests an important role of COVID-19-induced coagulopathy.,Further studies are needed to investigate the molecular mechanism and overall clinical incidence of COVID-19-related death, as well as possible therapeutic interventions to reduce it.,University Medical Center Hamburg-Eppendorf.,Little is known of the pathologic changes that lead to death in patients with COVID-19.,This study reports the autopsy findings of consecutive patients who died with a diagnosis of COVID-19.

Little evidence of increased thrombotic risk is available in COVID-19 patients.,Our purpose was to assess thrombotic risk in severe forms of SARS-CoV-2 infection.,All patients referred to 4 intensive care units (ICUs) from two centers of a French tertiary hospital for acute respiratory distress syndrome (ARDS) due to COVID-19 between March 3rd and 31st 2020 were included.,Medical history, symptoms, biological data and imaging were prospectively collected.,Propensity score matching was performed to analyze the occurrence of thromboembolic events between non-COVID-19 ARDS and COVID-19 ARDS patients.,150 COVID-19 patients were included (122 men, median age 63 [53; 71] years, SAPSII 49 [37; 64] points).,Sixty-four clinically relevant thrombotic complications were diagnosed in 150 patients, mainly pulmonary embolisms (16.7%). 28/29 patients (96.6%) receiving continuous renal replacement therapy experienced circuit clotting.,Three thrombotic occlusions (in 2 patients) of centrifugal pump occurred in 12 patients (8%) supported by ECMO.,Most patients (> 95%) had elevated D-dimer and fibrinogen.,No patient developed disseminated intravascular coagulation.,Von Willebrand (vWF) activity, vWF antigen and FVIII were considerably increased, and 50/57 tested patients (87.7%) had positive lupus anticoagulant.,Comparison with non-COVID-19 ARDS patients (n = 145) confirmed that COVID-19 ARDS patients (n = 77) developed significantly more thrombotic complications, mainly pulmonary embolisms (11.7 vs.,2.1%, p < 0.008).,Coagulation parameters significantly differed between the two groups.,Despite anticoagulation, a high number of patients with ARDS secondary to COVID-19 developed life-threatening thrombotic complications.,Higher anticoagulation targets than in usual critically ill patients should therefore probably be suggested.,The online version of this article (10.1007/s00134-020-06062-x) contains supplementary material, which is available to authorized users.

Children were relatively spared during COVID-19 pandemic.,However, the recently reported hyperinflammatory syndrome with overlapping features of Kawasaki disease and toxic shock syndrome-“Paediatric Inflammatory Multisystem Syndrome-temporally associated with SARS-CoV-2” (PIMS-TS) has caused concern.,We describe cardiac findings and short-term outcomes in children with PIMS-TS at a tertiary children’s hospital.,Single-center observational study of children with PIMS-TS from 10th April to 9th May 2020.,Data on ECG and echocardiogram were retrospectively analyzed along with demographics, clinical features and blood parameters.,Fifteen children with median age of 8.8 (IQR 6.4-11.2) years were included, all were from African/Afro-Caribbean, South Asian, Mixed or other minority ethnic groups.,All showed raised inflammatory/cardiac markers (CRP, ferritin, Troponin I, CK and pro-BNP).,Transient valve regurgitation was present in 10 patients (67%).,Left Ventricular ejection fraction was reduced in 12 (80%), fractional shortening in 8 (53%) with resolution in all but 2.,Fourteen (93%) had coronary artery abnormalities, with normalization in 6.,ECG abnormalities were present in 9 (60%) which normalized in 6 by discharge.,Ten (67%) needed inotropes and/or vasopressors.,None needed extracorporeal life support.,Improvement in cardiac biochemical markers was closely followed by improvement in ECG/echocardiogram.,All patients were discharged alive and twelve (80%) have been reviewed since.,Our entire cohort with PIMS-TS had cardiac involvement and this degree of involvement is significantly more than other published series and emphasizes the need for specialist cardiac review.,We believe that our multi-disciplinary team approach was crucial for the good short-term outcomes.

The Bergamo province, which is extensively affected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic, is a natural observatory of virus manifestations in the general population.,In the past month we recorded an outbreak of Kawasaki disease; we aimed to evaluate incidence and features of patients with Kawasaki-like disease diagnosed during the SARS-CoV-2 epidemic.,All patients diagnosed with a Kawasaki-like disease at our centre in the past 5 years were divided according to symptomatic presentation before (group 1) or after (group 2) the beginning of the SARS-CoV-2 epidemic.,Kawasaki- like presentations were managed as Kawasaki disease according to the American Heart Association indications.,Kawasaki disease shock syndrome (KDSS) was defined by presence of circulatory dysfunction, and macrophage activation syndrome (MAS) by the Paediatric Rheumatology International Trials Organisation criteria.,Current or previous infection was sought by reverse-transcriptase quantitative PCR in nasopharyngeal and oropharyngeal swabs, and by serological qualitative test detecting SARS-CoV-2 IgM and IgG, respectively.,Group 1 comprised 19 patients (seven boys, 12 girls; aged 3·0 years [SD 2·5]) diagnosed between Jan 1, 2015, and Feb 17, 2020.,Group 2 included ten patients (seven boys, three girls; aged 7·5 years [SD 3·5]) diagnosed between Feb 18 and April 20, 2020; eight of ten were positive for IgG or IgM, or both.,The two groups differed in disease incidence (group 1 vs group 2, 0·3 vs ten per month), mean age (3·0 vs 7·5 years), cardiac involvement (two of 19 vs six of ten), KDSS (zero of 19 vs five of ten), MAS (zero of 19 vs five of ten), and need for adjunctive steroid treatment (three of 19 vs eight of ten; all p<0·01).,In the past month we found a 30-fold increased incidence of Kawasaki-like disease.,Children diagnosed after the SARS-CoV-2 epidemic began showed evidence of immune response to the virus, were older, had a higher rate of cardiac involvement, and features of MAS.,The SARS-CoV-2 epidemic was associated with high incidence of a severe form of Kawasaki disease.,A similar outbreak of Kawasaki-like disease is expected in countries involved in the SARS-CoV-2 epidemic.,None.

Supplemental Digital Content is available in the text.,Use of ACEIs (angiotensin-converting enzyme inhibitors) and ARBs (angiotensin II receptor blockers) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in patients with hypertension.,To determine the association between in-hospital use of ACEI/ARB and all-cause mortality in patients with hypertension and hospitalized due to COVID-19.,This retrospective, multi-center study included 1128 adult patients with hypertension diagnosed with COVID-19, including 188 taking ACEI/ARB (ACEI/ARB group; median age 64 [interquartile range, 55-68] years; 53.2% men) and 940 without using ACEI/ARB (non-ACEI/ARB group; median age 64 [interquartile range 57-69]; 53.5% men), who were admitted to 9 hospitals in Hubei Province, China from December 31, 2019 to February 20, 2020.,In mixed-effect Cox model treating site as a random effect, after adjusting for age, gender, comorbidities, and in-hospital medications, the detected risk for all-cause mortality was lower in the ACEI/ARB group versus the non-ACEI/ARB group (adjusted hazard ratio, 0.42 [95% CI, 0.19-0.92]; P=0.03).,In a propensity score-matched analysis followed by adjusting imbalanced variables in mixed-effect Cox model, the results consistently demonstrated lower risk of COVID-19 mortality in patients who received ACEI/ARB versus those who did not receive ACEI/ARB (adjusted hazard ratio, 0.37 [95% CI, 0.15-0.89]; P=0.03).,Further subgroup propensity score-matched analysis indicated that, compared with use of other antihypertensive drugs, ACEI/ARB was also associated with decreased mortality (adjusted hazard ratio, 0.30 [95% CI, 0.12-0.70]; P=0.01) in patients with COVID-19 and coexisting hypertension.,Among hospitalized patients with COVID-19 and coexisting hypertension, inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB nonusers.,While study interpretation needs to consider the potential for residual confounders, it is unlikely that in-hospital use of ACEI/ARB was associated with an increased mortality risk.

A potential association between the use of angiotensin-receptor blockers (ARBs) and angiotensin-converting-enzyme (ACE) inhibitors and the risk of coronavirus disease 2019 (Covid-19) has not been well studied.,We carried out a population-based case-control study in the Lombardy region of Italy.,A total of 6272 case patients in whom infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was confirmed between February 21 and March 11, 2020, were matched to 30,759 beneficiaries of the Regional Health Service (controls) according to sex, age, and municipality of residence.,Information about the use of selected drugs and patients’ clinical profiles was obtained from regional databases of health care use.,Odds ratios and 95% confidence intervals for associations between drugs and infection, with adjustment for confounders, were estimated by means of logistic regression.,Among both case patients and controls, the mean (±SD) age was 68±13 years, and 37% were women.,The use of ACE inhibitors and ARBs was more common among case patients than among controls, as was the use of other antihypertensive and non-antihypertensive drugs, and case patients had a worse clinical profile.,Use of ARBs or ACE inhibitors did not show any association with Covid-19 among case patients overall (adjusted odds ratio, 0.95 [95% confidence interval {CI}, 0.86 to 1.05] for ARBs and 0.96 [95% CI, 0.87 to 1.07] for ACE inhibitors) or among patients who had a severe or fatal course of the disease (adjusted odds ratio, 0.83 [95% CI, 0.63 to 1.10] for ARBs and 0.91 [95% CI, 0.69 to 1.21] for ACE inhibitors), and no association between these variables was found according to sex.,In this large, population-based study, the use of ACE inhibitors and ARBs was more frequent among patients with Covid-19 than among controls because of their higher prevalence of cardiovascular disease.,However, there was no evidence that ACE inhibitors or ARBs affected the risk of COVID-19.

Atrial fibrillation (AF) patients are routinely prescribed medications to prevent and treat complications, including those from common co-occurring comorbidities.,However, adherence to such medications may be suboptimal.,Therefore, we sought to identify risk factors for general medication non-adherence in a population of patients with atrial fibrillation.,Data were collected from a large, ethnically-diverse cohort of Kaiser Permanente Northern and Southern California adult members with incident diagnosed AF between January 1, 2006 and June 30, 2009.,Self-reported questionnaires were completed between May 1, 2010 and September 30, 2010, assessing patient socio-demographics, health behaviors, health status, medical history and medication adherence.,Medication adherence was assessed using a previously validated 3-item questionnaire.,Medication non-adherence was defined as either taking medication(s) as the doctor prescribed 75% of the time or less, or forgetting or choosing to skip one or more medication(s) once per week or more.,Electronic health records were used to obtain additional data on medical history.,Multivariable logistic regression analyses examined the associations between patient characteristics and self-reported general medication adherence among patients with complete questionnaire data.,Among 12,159 patients with complete questionnaire data, 6.3% (n = 771) reported medication non-adherence.,Minority race/ethnicity versus non-Hispanic white, not married/with partner versus married/with partner, physical inactivity versus physically active, alcohol use versus no alcohol use, any days of self-reported poor physical health, mental health and/or sleep quality in the past 30 days versus 0 days, memory decline versus no memory decline, inadequate versus adequate health literacy, low-dose aspirin use versus no low-dose aspirin use, and diabetes mellitus were associated with higher adjusted odds of non-adherence, whereas, ages 65-84 years versus < 65 years of age, a Charlson Comorbidity Index score ≥ 3 versus 0, and hypertension were associated with lower adjusted odds of non-adherence.,Several potentially preventable and/or modifiable risk factors related to medication non-adherence and a few non-modifiable risk factors were identified.,These risk factors should be considered when assessing medication adherence among patients diagnosed with AF.

Oral anticoagulants (OAC) are widely used in patients with cardiovascular diseases.,However, for optimal OAC self-care patients must have skills, among which health literacy (HL) is highlighted.,We aimed to describe the relation between HL and self-care in cardiovascular patients on OAC treatment.,Electronic searches were carried out in the PubMed, Scopus, Embase, CINAHL, Web of Science, Cochrane Library, SciELO, IME-Biomedicina, CUIDEN Plus and LILACS databases, limited to Spanish and English language and between January 2000-December 2016.,Papers reported on adults older than 18 years, taking OAC by themselves for at least three months.,PRISMA guidelines were used for paper selection.,We identified 142 articles and finally included 10; almost all of them about warfarin.,Our results suggest that in patients taking OAC treatments there is a positive relationship between HL and the level of knowledge.,In addition, a small percentage of participants on the selected papers recognized the side effects and complications associated with OAC treatment.,Lower HL level was associated with greater knowledge deficits and less adherence to treatment.,There is a paucity of research evaluating the effect of HL on diverse aspects of OAC treatments.,There is a need to expand the evidence base regarding appropriate HL screening tools, determinants of adequate knowledge and optimal behaviours related to OAC self-management.,The online version of this article (10.1186/s12889-018-6070-9) contains supplementary material, which is available to authorized users.

Patients with coronavirus disease 2019 (COVID-19) have elevated D-dimer levels.,Early reports describe high venous thromboembolism (VTE) and disseminated intravascular coagulation (DIC) rates, but data are limited.,This multicenter retrospective study describes the rate and severity of hemostatic and thrombotic complications of 400 hospital-admitted COVID-19 patients (144 critically ill) primarily receiving standard-dose prophylactic anticoagulation.,Coagulation and inflammatory parameters were compared between patients with and without coagulation-associated complications.,Multivariable logistic models examined the utility of these markers in predicting coagulation-associated complications, critical illness, and death.,The radiographically confirmed VTE rate was 4.8% (95% confidence interval [CI], 2.9-7.3), and the overall thrombotic complication rate was 9.5% (95% CI, 6.8-12.8).,The overall and major bleeding rates were 4.8% (95% CI, 2.9-7.3) and 2.3% (95% CI, 1.0-4.2), respectively.,In the critically ill, radiographically confirmed VTE and major bleeding rates were 7.6% (95% CI, 3.9-13.3) and 5.6% (95% CI, 2.4-10.7), respectively.,Elevated D-dimer at initial presentation was predictive of coagulation-associated complications during hospitalization (D-dimer >2500 ng/mL, adjusted odds ratio [OR] for thrombosis, 6.79 [95% CI, 2.39-19.30]; adjusted OR for bleeding, 3.56 [95% CI, 1.01-12.66]), critical illness, and death.,Additional markers at initial presentation predictive of thrombosis during hospitalization included platelet count >450 × 109/L (adjusted OR, 3.56 [95% CI, 1.27-9.97]), C-reactive protein (CRP) >100 mg/L (adjusted OR, 2.71 [95% CI, 1.26-5.86]), and erythrocyte sedimentation rate (ESR) >40 mm/h (adjusted OR, 2.64 [95% CI, 1.07-6.51]).,ESR, CRP, fibrinogen, ferritin, and procalcitonin were higher in patients with thrombotic complications than in those without.,DIC, clinically relevant thrombocytopenia, and reduced fibrinogen were rare and were associated with significant bleeding manifestations.,Given the observed bleeding rates, randomized trials are needed to determine any potential benefit of intensified anticoagulant prophylaxis in COVID-19 patients.,•In addition to thrombotic complications, bleeding is a significant cause of morbidity in patients with COVID-19.,•D-dimer elevation at admission was predictive of bleeding, thrombosis, critical illness, and death in patients with COVID-19.,In addition to thrombotic complications, bleeding is a significant cause of morbidity in patients with COVID-19.,D-dimer elevation at admission was predictive of bleeding, thrombosis, critical illness, and death in patients with COVID-19.

COVID-19 coagulopathy linked to increased D-dimer levels has been associated with high mortality (Fei Z et al. in Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.,Lancet (London, England) 395(10229):1054-62, 2020).,While D-dimer is accepted as a disseminated intravascular coagulation marker, rotational thromboelastometry (ROTEM) also detects fibrinolysis (Wright FL et al. in Fibrinolysis shutdown correlates to thromboembolic events in severe COVID-19 infection.,J Am Coll Surg (2020).,Available from https://pubmed.ncbi.nlm.nih.gov/32422349/ [cited 14 Jun 2020]; Schmitt FCF et al. in Acute fibrinolysis shutdown occurs early in septic shock and is associated with increased morbidity and mortality: results of an observational pilot study.,Ann Intensive Care 9(1):19, 2019).,We describe the ROTEM profile in severely ill COVID-19 patients and compare it with the standard laboratory coagulation test.,Adult patients diagnosed with COVID-19 admitted to the ICU were prospectively enrolled after Ethics Committee approval (HCB/2020/0371).,All patients received venous thromboembolism prophylaxis; those on therapeutic anticoagulation were excluded.,The standard laboratory coagulation test and ROTEM were performed simultaneously at 24-48 h after ICU admission.,Sequential organ failure assessment (SOFA), disseminated intravascular coagulation (DIC) and sepsis-induced coagulopathy (SIC) scores were calculated at sample collection.,Nineteen patients were included with median SOFA-score of 4 (2-6), DIC-score of 1 (0-3) and SIC-score of 1.8 (0.9).,Median fibrinogen, D-dimer levels and platelet count were 6.2 (4.8-7.6 g/L), 1000 (600-4200 ng/ml) and 236 (136-364 109/L), respectively.,Clot firmness was above the normal range in the EXTEM and FIBTEM tests while clot lysis was decreased.,There was no significant correlation between ROTEM or D-dimer parameters and the SOFA score.,In COVID-19 patients, the ROTEM pattern was characterized by a hypercoagulable state with decreased fibrinolytic capacity despite a paradoxical increase in D-dimer levels.,We suggest that, in COVID-19 patients, the lungs could be the main source of D-dimer, while a systemic hypofibrinolytic state coexists.,This hypothesis should be confirmed by future studies.