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Harnessing the immune system to overcome cytokine storm and reduce viral load in COVID 19 a review of the phases of illness and therapeutic agents Coronavirus disease 2019 COVID 19 is caused by Severe Acute Respiratory Syndrome Coronavirus 2 SARS CoV 2 previously named 2019 nCov a novel coronavirus that emerged in China in December 2019 and was declared a global pandemic by World Health Organization by March 11th 2020 Severe manifestations of COVID 19 are caused by a combination of direct tissue injury by viral replication and associated cytokine storm resulting in progressive organ damage We reviewed published literature between January 1st 2000 and June 30th 2020 excluding articles focusing on pediatric or obstetric population with a focus on virus host interactions and immunological mechanisms responsible for virus associated cytokine release syndrome CRS COVID 19 illness encompasses three main phases In phase 1 SARS CoV 2 binds with angiotensin converting enzyme ACE 2 receptor on alveolar macrophages and epithelial cells triggering toll like receptor TLR mediated nuclear factor kappa light chain enhancer of activated B cells NF ƙB signaling It effectively blunts an early IFN response allowing unchecked viral replication Phase 2 is characterized by hypoxia and innate immunity mediated pneumocyte damage as well as capillary leak Some patients further progress to phase 3 characterized by cytokine storm with worsening respiratory symptoms persistent fever and hemodynamic instability Important cytokines involved in this phase are interleukin IL 6 IL 1β and tumor necrosis factor TNF α This is typically followed by a recovery phase with production of antibodies against the virus We summarize published data regarding virus host interactions key immunological mechanisms responsible for virus associated CRS and potential opportunities for therapeutic interventions Evidence regarding SARS CoV 2 epidemiology and pathogenesis is rapidly evolving A better understanding of the pathophysiology and immune system dysregulation associated with CRS and acute respiratory distress syndrome in severe COVID 19 is imperative to identify novel drug targets and other therapeutic interventions

New Strategies to Improve Patient Adherence to Medications for Noncommunicable Diseases During and After the COVID 19 Era Identified via a Literature Review Noncommunicable diseases NCDs place a huge burden on healthcare systems and society as a whole Relatively early in the coronavirus disease 2019 COVID 19 pandemic clinicians became aware that in individuals infected with COVID 19 those with preexisting NCDs such as diabetes mellitus and cardiovascular disease CVD were at a greater risk of poor outcomes and mortality than those without The importance of adherence to medications and lifestyle changes to control and prevent NCDs has been a major focus for many years but with limited success the proportion of patients adherent and persistent to their medications remains very low There are many facets to adherence and persistence Recent evidence suggests that a patient centric approach is important and ensuring that a patient is both motivated and empowered is critical to improving adherence persistence The COVID 19 pandemic has brought many changes to the way in which patients with NCDs are managed with telemedicine and ehealth becoming more common Changes have also occurred in the way in which patients can gain access to medications during the pandemic The potential for these changes forms the basis of improving the management of patients with NCDs both during and after the pandemic Over the coming months a huge amount of work will be put into initiatives to promote adherence to COVID 19 vaccination programs Those at highest risk of severe COVID 19 such as people aged 80 years and older are likely to receive the vaccine first in some parts of world Finally social determinants of health are critical elements that can impact not just the likelihood of having an NCD or becoming infected with COVID 19 but also access to healthcare and a patients adherence and persistence with their treatments

Acute and Post Acute Neurological Complications of COVID 19 Coronavirus disease 2019 COVID 19 is an emerging global health emergency caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 SARS CoV 2 The global outbreak of SARS CoV 2 infection has been declared a global pandemic by the World Health Organization WHO The clinical presentation of SARS CoV 2 infection depends on the severity of the disease and may range from an asymptomatic infection to a severe and lethal illness Fever cough and shortness of breath are among the most common symptoms associated with SARS CoV 2 infection Accumulating evidence indicates that COVID 19 patients commonly develop neurological symptoms such as headache altered mental status anosmia and myalgia In this comprehensive literature review we have summarized the most common neurological complications and reported neurological case studies associated with COVID 19 and neurological side effects associated with COVID 19 treatments Additionally the post acute COVID 19 syndrome and long term neurological complications were discussed We also explained the proposed mechanisms that are involved in the pathogenesis of these neurological complications

Long COVID a comprehensive systematic scoping review To find out what is known from literature about Long COVID until January 30 2021 We undertook a four step search with no language restriction A preliminary search was made to identify the keywords A search strategy of all electronic databases resulted in 66 eligible studies A forward and backward search of the references and citations resulted in additional 54 publications Non English language articles were translated using Google Translate We conducted our scoping review based on the PRISMA ScR Checklist Of 120 papers we found only one randomized clinical trial Of the 67 original studies 22 were cohort and 28 were cross sectional studies Of the total 120 publications 49 1 focused on signs and symptoms 23 3 on management and 10 8 on pathophysiology Ten publications focused on imaging studies The results are also presented extensively in a narrative synthesis in separated sections nomenclature diagnosis pathophysiology risk factors signs symptoms management The controversies in its definition have impaired proper recognition and management The predominant symptoms were fatigue breathlessness arthralgia sleep difficulties and chest pain Recent reports also point to the risk of long term sequela with cutaneous respiratory cardiovascular musculoskeletal mental health neurologic and renal involvement in those who survive the acute phase of the illness

sup 18 sup F FDG brain PET hypometabolism in patients with long COVID In the context of the worldwide outbreak of severe acute respiratory syndrome coronavirus 2 SARS CoV 2 some patients report functional complaints after apparent recovery from COVID 19 This clinical presentation has been referred as long COVID We here present a retrospective analysis of sup 18 sup F FDG brain PET of long COVID patients from the same center with a biologically confirmed diagnosis of SARS CoV 2 infection and persistent functional complaints at least 3 weeks after the initial infection PET scans of 35 patients with long COVID were compared using whole brain voxel based analysis to a local database of 44 healthy subjects controlled for age and sex to characterize cerebral hypometabolism The individual relevance of this metabolic profile was evaluated to classify patients and healthy subjects Finally the PET abnormalities were exploratory compared with the patients characteristics and functional complaints In comparison to healthy subjects patients with long COVID exhibited bilateral hypometabolism in the bilateral rectal orbital gyrus including the olfactory gyrus the right temporal lobe including the amygdala and the hippocampus extending to the right thalamus the bilateral pons medulla brainstem the bilateral cerebellum p voxel 0 001 uncorrected p cluster 0 05 FWE corrected These metabolic clusters were highly discriminant to distinguish patients and healthy subjects 100 correct classification These clusters of hypometabolism were significantly associated with more numerous functional complaints brainstem and cerebellar clusters and all associated with the occurrence of certain symptoms hyposmia anosmia memory cognitive impairment pain and insomnia p 0 05 In a more preliminary analysis the metabolism of the frontal cluster which included the olfactory gyrus was worse in the 7 patients treated by ACE drugs for high blood pressure p 0 032 and better in the 3 patients that had used nasal decongestant spray at the infectious stage p 0 001 This study demonstrates a profile of brain PET hypometabolism in long COVID patients with biologically confirmed SARS CoV 2 and persistent functional complaints more than 3 weeks after the initial infection symptoms involving the olfactory gyrus and connected limbic paralimbic regions extended to the brainstem and the cerebellum These hypometabolisms are associated with patients symptoms with a biomarker value to identify and potentially follow these patients The hypometabolism of the frontal cluster which included the olfactory gyrus seems to be linked to ACE drugs in patients with high blood pressure with also a better metabolism of this olfactory region in patients using nasal decongestant spray suggesting a possible role of ACE receptors as an olfactory gateway for this neurotropism

The psychopathological impact of the SARS CoV 2 epidemic on subjects suffering from different mental disorders An observational retrospective study SARS CoV 2 infection causes a pulmonary disease COVID 19 which spread worldwide generating fear anxiety depression in the general population as well as among subjects affected by mental disorders Little is known about which different psychopathological changes the pandemic caused among individuals affected by different psychiatric disorders which represents the aim of the present study Specific psychometric scales were administered at three time points T0 as outbreak of pandemic T1 as lockdown period T2 as reopening Descriptive analyses and linear regression models were performed A total of 166 outpatients were included Overall psychometric scores showed a significant worsening at T1 with a mild improvement at T2 Only psychopathology in schizophrenia SKZ patients and obsessive compulsive OC symptoms did not significantly improve at T2 Subjects affected by personality disorders PDs resulted to be more compromised in terms of general psychopathology than depressed and anxiety OC ones and showed more severe anxiety symptoms than SKZ patients In conclusion subjects affected by PDs require specific clinical attention during COVID 19 pandemic Moreover the worsening of SKZ and OC symptoms should be strictly monitored by clinicians as these aspects did not improve with the end of lockdown measures Further studies on larger samples are needed to confirm our results ClinicalTrials gov Identifier NCT04694482

Cardiac MRI in Patients with Prolonged Cardiorespiratory Symptoms after Mild to Moderate COVID 19 Infection Background Myocardial injury and inflammation on cardiac MRI in patients suffering from coronavirus disease 19 COVID 19 have been described in recent publications Concurrently a chronic COVID 19 syndrome CCS after COVID 19 infection has been observed manifesting with symptoms like fatigue and exertional dyspnea Purpose To explore the relationship between CCS and myocardial injury and inflammation as an underlying cause of the persistent complaints in previously healthy individuals Materials and Methods In this prospective study from January 2021 to April 2021 study participants without known cardiac or pulmonary diseases prior to COVID 19 infection with persisting CCS symptoms like fatigue or exertional dyspnea after convalescence and healthy control participants underwent cardiac MRI Cardiac MRI protocol included T1 and T2 relaxation times extracellular volume ECV T2 signal intensity ratio and late gadolinium enhancement LGE Student i t i test Mann Whitney U test and χ sup 2 sup test were used for statistical analysis Results 41 participants with CCS 39 13 years 18 men and 42 control participants 39 16 years 26 men were evaluated Median time between initial mild to moderate COVID 19 disease without hospitalization and cardiac MRI was 103 days interquartile range 88 158 Troponin T levels were normal Parameters indicating myocardial inflammation and edema were comparable between participants with CCS and control participants T1 relaxation time 978 23 ms vs 971 25 ms P 17 T2 relaxation time 53 2 ms vs 52 2 ms P 47 T2 signal intensity ratio 1 6 0 2 vs 1 6 0 3 P 10 Visible myocardial edema was present in none of the participants Three of 41 7 participants with CCS demonstrated non ischemic LGE compared to none in the control group 0 of 42 0 P 07 None of the participants fulfilled the 2018 Lake Louise criteria for the diagnosis of myocarditis Conclusion Individuals without hospitalization for COVID 19 and with CCS did not demonstrate signs of active myocardial injury or inflammation on cardiac MRI See also the editorial by Lima and Bluemke

Will Nothing Be the Same Again Changes in Lifestyle during COVID 19 Pandemic and Consequences on Mental Health Social isolation caused by the COVID 19 pandemic has drastically affected lifestyles from sedentary behaviors to reduced physical activity from disrupted sleep patterns to altered dietary habits As a consequence serious mental and emotional responses have been registered There was a significant decline in physical and other meaningful activities of daily living leisure social activity and education In children collateral effects of the pandemic include inadequate nutrition with a risk of both overweight and underweight addiction to screens lack of schooling and psychosocial difficulties Older adults are frequently unable to adapt to lockdown measures and suffer from depression and cognitive complaints Recent studies focusing on changes in lifestyle during the Covid 19 pandemic and consequences on mental health have been identified in PubMed Medline Scopus Embase and ScienceDirect All the available literature has been retrospectively reviewed The results of the present narrative review suggest that mental distress caused by social isolation seems to be linked not only to personality characteristics but also to several lifestyle components sleep disruption altered eating habits reduced physical activity This review aims to explore major changes in the lifestyle and quality of life and the impact of these changes on mental health and to inform clinicians and policymakers about elements that may reduce the negative psychological effects of the quarantine period imposed during this worldwide crisis There is an urgent need for tailored preventive diagnostic and therapeutic mental health interventions for the general population and for higher risk groups

Autoantibodies stabilize neutrophil extracellular traps in COVID 19 The release of neutrophil extracellular traps b NETs b by hyperactive neutrophils is recognized to play an important role in the thromboinflammatory milieu inherent to severe presentations of COVID 19 At the same time a variety of functional autoantibodies have been observed in individuals with severe COVID 19 where they likely contribute to immunopathology Here we aimed to determine the extent to which autoantibodies might target NETs in COVID 19 and if detected to elucidate their potential functions and clinical associations We measured anti NET antibodies in 328 individuals hospitalized with COVID 19 alongside 48 healthy controls We found high anti NET activity in the IgG and IgM fractions of 27 and 60 of patients respectively There was a strong correlation between anti NET IgG and anti NET IgM r 0 4 p 0 0001 Both anti NET IgG and IgM tracked with high levels of circulating NETs impaired oxygenation efficiency and high circulating D dimer Furthermore patients who required mechanical ventilation had a greater burden of anti NET antibodies than did those not requiring oxygen supplementation Levels of anti NET IgG and to a lesser extent anti NET IgM demonstrated an inverse correlation with the efficiency of NET degradation by COVID sera Furthermore purified IgG from COVID sera with high levels of anti NET antibodies impaired the ability of healthy control serum to degrade NETs In summary many individuals hospitalized with COVID 19 have anti NET antibodies which likely impair NET clearance and may potentiate SARS CoV 2 mediated thromboinflammation

Corneal confocal microscopy identifies corneal nerve fibre loss and increased dendritic cells in patients with long COVID Long COVID is characterised by a range of potentially debilitating symptoms which develop in at least 10 of people who have recovered from acute SARS CoV 2 infection This study has quantified corneal sub basal nerve plexus morphology and dendritic cell DC density in patients with and without long COVID Forty subjects who had recovered from COVID 19 and 30 control participants were included in this cross sectional comparative study undertaken at a university hospital All patients underwent assessment with the National Institute for Health and Care Excellence NICE long COVID Douleur Neuropathique 4 DN4 and Fibromyalgia questionnaires and corneal confocal microscopy CCM to quantify corneal nerve fibre density CNFD corneal nerve branch density CNBD corneal nerve fibre length CNFL and total mature and immature DC density The mean time after the diagnosis of COVID 19 was 3 7 1 5 months Patients with neurological symptoms 4 weeks after acute COVID 19 had a lower CNFD p 0 032 CNBD p 0 020 and CNFL p 0 012 and increased DC density p 0 046 compared with controls while patients without neurological symptoms had comparable corneal nerve parameters but increased DC density p 0 003 There were significant correlations between the total score on the NICE long COVID questionnaire at 4 and 12 weeks with CNFD ρ 0 436 p 0 005 ρ 0 387 p 0 038 respectively and CNFL ρ 0 404 p 0 010 ρ 0 412 p 0 026 respectively Corneal confocal microscopy identifies corneal small nerve fibre loss and increased DCs in patients with long COVID especially those with neurological symptoms CCM could be used to objectively identify patients with long COVID

The Rise of Wearable Devices during the COVID 19 Pandemic A Systematic Review The COVID 19 pandemic has wreaked havoc globally and still persists even after a year of its initial outbreak Several reasons can be considered people are in close contact with each other i e at a short range 1 m and the healthcare system is not sufficiently developed or does not have enough facilities to manage and fight the pandemic even in developed countries such as the USA and the U K and countries in Europe There is a great need in healthcare for remote monitoring of COVID 19 symptoms In the past year a number of IoT based devices and wearables have been introduced by researchers providing good results in terms of high accuracy in diagnosing patients in the prodromal phase and in monitoring the symptoms of patients i e respiratory rate heart rate temperature etc In this systematic review we analyzed these wearables and their need in the healthcare system The research was conducted using three databases IEEE Xplore sup sup Web of Science sup sup and PubMed Central sup sup between December 2019 and June 2021 This article was based on the PRISMA guidelines Initially 1100 articles were identified while searching the scientific literature regarding this topic After screening ultimately 70 articles were fully evaluated and included in this review These articles were divided into two categories The first one belongs to the on body sensors wearables their types and positions and the use of AI technology with ehealth wearables in different scenarios from screening to contact tracing In the second category we discuss the problems and solutions with respect to utilizing these wearables globally This systematic review provides an extensive overview of wearable systems for the remote management and automated assessment of COVID 19 taking into account the reliability and acceptability of the implemented technologies

Pediatric bronchoscopy recent advances and clinical challenges b Introduction b During the last 40 years equipment has been improved with smaller instruments and sufficient size working channels This has ensured that bronchoscopy offers therapeutic and interventional options b Areas covered b We provide a review of recent advances and clinical challenges in pediatric bronchoscopy This includes single use bronchoscopes endobronchial ultrasound and cryoprobe Bronchoscopy in persistent preschool wheezing and asthma is included The indications for interventional bronchoscopy have amplified and included balloon dilatation endoscopic intubation the use of airway stents whole lung lavage closing of fistulas and air leak as well as an update on removal of foreign bodies Others include the use of laser and microdebrider in airway surgery Experience with bronchoscope during the COVID 19 pandemic has been included in this review PubMed was searched for articles on pediatric bronchoscopy including rigid bronchoscopy as well as interventional bronchoscopy with a focus on reviewing literature in the past 5 years b Expert opinion b As the proficiency of pediatric interventional pulmonologists continues to grow more interventions are being performed There is a scarcity of published evidence in this field Courses for pediatric interventional bronchoscopy need to be developed The COVID 19 experience resulted in safer bronchoscopy practice for all involved

SARS CoV 2 infection and paediatric endocrine disorders Risks and management considerations Coronavirus 19 COVID 19 is a disease caused by the SARS CoV 2 virus the seventh coronavirus identified as causing disease in humans The SARS CoV 2 virus has multiple potential pathophysiologic interconnections with endocrine systems potentially causing disturbances in glucose metabolism hypothalamic and pituitary function adrenal function and mineral metabolism A growing body of data is revealing both the effects of underlying endocrine disorders on COVID 19 disease outcome and the effects of the SARS CoV 2 virus on endocrine systems However comprehensive assessment of the relationship to endocrine disorders in children has been lacking In this review we present the effects of SARS CoV 2 infection on endocrine systems and review the current literature on complications of COVID 19 disease in underlying paediatric endocrine disorders We provide recommendations on management of endocrinopathies related to SARS CoV 2 infection in this population With the surge in COVID 19 cases worldwide it is important for paediatric endocrinologists to be aware of the interaction of SARS CoV 2 with the endocrine system and management considerations for patients with underlying disorders who develop COVID 19 disease While children and adults share some risk factors that influence risk of complications in SARS CoV 2 infection it is becoming clear that responses in the paediatric population are distinct and outcomes from adult studies cannot be extrapolated Evidence emerging from paediatric studies provides some guidance but highlights the need for more research in this area

Virtual CROI 2020 Highlights of Epidemiology Public Health and Prevention Research At the 2020 Conference on Retroviruses and Opportunistic Infections held virtually as a result of the emerging COVID 19 pandemic trends in the HIV epidemic were highlighted with decreasing HIV incidence reported across several countries although key regions remain heavily impacted including the US South Adolescent girls and young women men who have sex with men MSM transgender persons and people who inject drugs continue to experience a high burden of new infections Sexually transmitted infections during pregnancy can lead to a number of adverse outcomes in infants novel strategies to detect and treat these infections are needed Innovative HIV testing strategies including self testing and assisted partner services are expanding the reach of testing however linkage to care can be improved Novel preexposure prophylaxis PrEP delivery strategies are increasing uptake of PrEP in different groups although adherence and persistence remain a challenge Use of on demand PrEP is increasing among MSM in the US Strategies are needed to address barriers to PrEP uptake and persistence among cis and transgender women Several novel regimens for postexposure prophylaxis show promise

The use of head helmets to deliver noninvasive ventilatory support a comprehensive review of technical aspects and clinical findings A helmet comprising a transparent hood and a soft collar surrounding the patients head can be used to deliver noninvasive ventilatory support both as continuous positive airway pressure and noninvasive positive pressure ventilation NPPV the latter providing active support for inspiration In this review we summarize the technical aspects relevant to this device particularly how to prevent CO sub 2 sub rebreathing and improve patient ventilator synchrony during NPPV Clinical studies describe the application of helmets in cardiogenic pulmonary oedema pneumonia COVID 19 postextubation and immune suppression A section is dedicated to paediatric use In summary helmet therapy can be used safely and effectively to provide NIV during hypoxemic respiratory failure improving oxygenation and possibly leading to better patient centred outcomes than other interfaces

Late Conditions Diagnosed 1 4 Months Following an Initial Coronavirus Disease 2019 COVID 19 Encounter A Matched Cohort Study Using Inpatient and Outpatient Administrative Data United States 1 March 30 June 2020 Late sequelae of COVID 19 have been reported however few studies have investigated the time course or incidence of late new COVID 19 related health conditions post COVID conditions after COVID 19 diagnosis Studies distinguishing post COVID conditions from late conditions caused by other etiologies are lacking Using data from a large administrative all payer database we assessed type association and timing of post COVID conditions following COVID 19 diagnosis Using the Premier Healthcare Database Special COVID 19 Release release date 20 October 2020 data during March June 2020 27 589 inpatients and 46 857 outpatients diagnosed with COVID 19 case patients were 1 1 matched with patients without COVID 19 through the 4 month follow up period control patients by using propensity score matching In this matched cohort study adjusted ORs were calculated to assess for late conditions that were more common in case patients than control patients Incidence proportion was calculated for conditions that were more common in case patients than control patients during 31 120 days following a COVID 19 encounter During 31 120 days after an initial COVID 19 inpatient hospitalization 7 0 of adults experienced 1 of 5 post COVID conditions Among adult outpatients with COVID 19 7 7 experienced 1 of 10 post COVID conditions During 31 60 days after an initial outpatient encounter adults with COVID 19 were 2 8 times as likely to experience acute pulmonary embolism as outpatient control patients and also more likely to experience a range of conditions affecting multiple body systems eg nonspecific chest pain fatigue headache and respiratory nervous circulatory and gastrointestinal symptoms than outpatient control patients These findings add to the evidence of late health conditions possibly related to COVID 19 in adults following COVID 19 diagnosis and can inform healthcare practice and resource planning for follow up COVID 19 care

Metabolomics in the Diagnosis and Prognosis of COVID 19 Coronavirus disease 2019 COVID 19 pandemic triggered an unprecedented global effort in developing rapid and inexpensive diagnostic and prognostic tools Since the genome of SARS CoV 2 was uncovered detection of viral RNA by RT qPCR has played the most significant role in preventing the spread of the virus through early detection and tracing of suspected COVID 19 cases and through screening of at risk population However a large number of alternative test methods based on SARS CoV 2 RNA or proteins or host factors associated with SARS CoV 2 infection have been developed and evaluated The application of metabolomics in infectious disease diagnostics is an evolving area of science that was boosted by the urgency of COVID 19 pandemic Metabolomics approaches that rely on the analysis of volatile organic compounds exhaled by COVID 19 patients hold promise for applications in a large scale screening of population in point of care POC setting On the other hand successful application of mass spectrometry to detect specific spectral signatures associated with COVID 19 in nasopharyngeal swab specimens may significantly save the cost and turnaround time of COVID 19 testing in the diagnostic microbiology and virology laboratories Active research is also ongoing on the discovery of potential metabolomics based prognostic markers for the disease that can be applied to serum or plasma specimens Several metabolic pathways related to amino acid lipid and energy metabolism were found to be affected by severe disease with COVID 19 In particular tryptophan metabolism via the kynurenine pathway were persistently dysregulated in several independent studies suggesting the roles of several metabolites of this pathway such as tryptophan kynurenine and 3 hydroxykynurenine as potential prognostic markers of the disease However standardization of the test methods and large scale clinical validation are necessary before these tests can be applied in a clinical setting With rapidly expanding data on the metabolic profiles of COVID 19 patients with varying degrees of severity it is likely that metabolomics will play an important role in near future in predicting the outcome of the disease with a greater degree of certainty

More than 50 long term effects of COVID 19 a systematic review and meta analysis COVID 19 can involve persistence sequelae and other medical complications that last weeks to months after initial recovery This systematic review and meta analysis aims to identify studies assessing the long term effects of COVID 19 LitCOVID and Embase were searched to identify articles with original data published before the 1st of January 2021 with a minimum of 100 patients For effects reported in two or more studies meta analyses using a random effects model were performed using the MetaXL software to estimate the pooled prevalence with 95 CI PRISMA guidelines were followed A total of 18 251 publications were identified of which 15 met the inclusion criteria The prevalence of 55 long term effects was estimated 21 meta analyses were performed and 47 910 patients were included age 17 87 years The included studies defined long COVID as ranging from 14 to 110 days post viral infection It was estimated that 80 of the infected patients with SARS CoV 2 developed one or more long term symptoms The five most common symptoms were fatigue 58 headache 44 attention disorder 27 hair loss 25 and dyspnea 24 Multi disciplinary teams are crucial to developing preventive measures rehabilitation techniques and clinical management strategies with whole patient perspectives designed to address long COVID 19 care

In vivo evidence of systemic endothelial vascular dysfunction in COVID 19 Endothelial dysfunction is one of the underlying mechanisms to vascular and cardiac complications in patients with COVID 19 We sought to investigate the systemic vascular endothelial function and its temporal changes in COVID 19 patients from a non invasive approach with reactive hyperemia peripheral arterial tonometry PAT This is a prospective observational case control and blinded study The population was comprised by 3 groups patients investigated during acute COVID 19 group 1 patients investigated during past COVID 19 group 2 and controls 1 1 matched to COVID 19 patients by demographics and cardiovascular risk factors group 3 The natural logarithmic scaled reactive hyperemia index LnRHI a measure of endothelium mediated dilation of peripheral arteries was obtained in all the participants and compared between study groups 144 participants were enrolled 72 COVID 19 patients and 72 matched controls Median time from COVID 19 symptoms to PAT assessment was 9 5 and 101 5 days in groups 1 and 2 respectively LnRHI was significantly lower in group 2 compared to both group 1 and controls 0 53 0 23 group 2 vs 0 72 0 26 group 1 p 0 0043 and 0 79 0 23 in group 3 p 0 0001 In addition within group 1 it was observed a markedly decrease in LnRHI from acute COVID 19 to post infection stage 0 73 0 23 vs 0 42 0 26 p 0 0042 This study suggests a deleterious effect of SARS CoV 2 infection on systemic vascular endothelial function These findings open new venues to investigate the clinical implication and prognostic role of vascular endothelial dysfunction in COVID 19 patients and post COVID syndrome using non invasive techniques

Evidence for impaired chronotropic responses to and recovery from 6 minute walk test in women with post acute COVID 19 syndrome What is the central question of this study Are chronotropic responses to a 6 minute walk test different in women with post acute coronavirus disease 2019 COVID 19 syndrome compared with control subjects What is the main finding and its importance Compared with control subjects the increase in heart rate was attenuated and recovery delayed after a 6 minute walk test in participants after infection with severe acute respiratory syndrome coronavirus 2 SARS CoV 2 Women reporting specific symptoms at time of testing had greater impairments compared with control subjects and SARS CoV 2 participants not actively experiencing these symptoms Such alterations have potential to constrain not only exercise tolerance but also participation in free living physical activity in women during post acute recovery from COVID 19 The short term cardiopulmonary manifestations of severe acute respiratory syndrome coronavirus 2 SARS CoV 2 are well defined However the implications of cardiopulmonary sequelae persisting beyond acute illness on physical function are largely unknown Herein we characterized heart rate responses to and recovery from a 6 minute walk test 6MWT in women 3 months after mild to moderate SARS CoV 2 infection compared with non infected control subjects Forty five women n 29 SARS CoV 2 n 16 controls age 56 11 years body mass index 25 8 6 0 kg m sup 2 sup completed pulmonary function testing and a 6MWT The SARS CoV 2 participants demonstrated reduced total lung capacity 84 8 vs 93 13 P 0 006 vital capacity 87 10 vs 93 10 P 0 040 functional residual capacity 75 16 vs 88 16 P 0 006 and residual volume 76 18 vs 93 22 P 0 001 compared with control subjects No between group differences were observed in 6MWT distance P 0 194 however the increase in heart rate with exertion was attenuated among SARS CoV 2 participants compared with control subjects 52 20 vs 65 18 beats min P 0 029 The decrease in heart rate was also delayed for minutes 1 5 of recovery among SARS CoV 2 participants all P 0 05 Women reporting specific symptoms at the time of testing had greater impairments compared with control subjects and SARS CoV 2 participants not actively experiencing these symptoms Our findings provide evidence for marked differences in chronotropic responses to and recovery from a 6MWT in women several months after acute SARS CoV 2 infection

Echocardiographic Indicators Associated with Adverse Clinical Course and Cardiac Sequelae in Multisystem Inflammatory Syndrome in Children with Coronavirus Disease 2019 Multisystem inflammatory syndrome in children MIS C associated with coronavirus disease 2019 causes significant cardiovascular involvement which can be a determinant of clinical course and outcome The aim of this study was to investigate whether echocardiographic measures of ventricular function were independently associated with adverse clinical course and cardiac sequelae in patients with MIS C In a longitudinal observational study of 54 patients with MIS C mean age 6 8 4 4 years 46 male 56 African American measures of ventricular function and morphometry at initial presentation predischarge and at a median of 3 and 10 week follow up were retrospectively analyzed and were compared with those in 108 age and gender matched normal control subjects The magnitude of strain is expressed as an absolute value Risk stratification for adverse clinical course and outcomes were analyzed among the tertiles of clinical and echocardiographic data using analysis of variance and univariate and multivariate regression Median left ventricular apical four chamber peak longitudinal strain LVA4LS and left ventricular global longitudinal strain LVGLS at initial presentation were significantly decreased in patients with MIS C compared with the normal cohort 16 2 and 15 1 vs 22 3 and 22 0 respectively P 01 Patients in the lowest LVA4LS tertile 13 had significantly higher C reactive protein and high sensitivity troponin need for intensive care and need for mechanical life support as well as longer hospital length of stay compared with those in the highest tertile 18 5 P 01 Initial LVA4LS and LVGLS were normal in 13 of 54 and 10 of 39 patients respectively There was no mortality In multivariate regression only LVA4LS was associated with both the need for intensive care and length of stay At median 10 week follow up to date seven of 36 patients 19 and six of 25 patients 24 had abnormal LVA4LS and LVGLS respectively Initial LVA4LS 16 2 indicated abnormal LVA4LS at follow up with 100 sensitivity Impaired LVGLS and LVA4LS at initial presentation independently indicate a higher risk for adverse acute clinical course and persistent subclinical left ventricular dysfunction at 10 week follow up suggesting that they could be applied to identify higher risk children with MIS C

SARS CoV 2 detection in nasopharyngeal swabs performance characteristics of a real time RT qPCR and a droplet digital RT PCR assay based on the exonuclease region ORF1b nsp 14 The emergence and spread of SARS CoV 2 has led to a compelling request for accurate diagnostic tests The aim of this study was assessing the performance of a real time RT qPCR rt RT qPCR assay and of a droplet digital RT PCR dd RT PCR targeting the nsp14 genome region for the detection of SARS CoV 2 in nasopharyngeal swabs A total of 258 nasopharyngeal swabs were analyzed with the nsp14 assays and for comparison with a reference assay targeting the RdRp and E genes Conflicting results were further investigated by two additional protocols the Centers for Disease Control and Prevention CDC real time targeting N1 N2 and a nested RT PCR for the spike region Agreement of results was achieved on 226 samples 156 positive and 70 negative 8 samples were positive in the reference assay and in the nsp14 rt RT qPCR but negative with the dd RT PCR and 24 samples provided different combinations of results with the three assays Sensitivity specificity and accuracy 95 C I of the nsp14 assays were 100 0 97 4 100 0 98 7 92 1 100 0 and 99 6 97 5 100 0 for the rt RT qPCR 92 4 87 4 95 6 100 0 94 2 100 0 and 94 7 91 1 97 0 for the dd RT PCR The results of the study support the use of the nsp14 real time RT qPCR and ddPCR for the detection of SARS CoV 2 in nasopharyngeal swabs

Surveillance and prevalence of antimicrobial resistant bacteria from public settings within urban built environments Challenges and opportunities for hygiene and infection control Antimicrobial resistant AMR bacteria present one of the biggest threats to public health this must not be forgotten while global attention is focussed on the COVID 19 pandemic Resistant bacteria have been demonstrated to be transmittable to humans in many different environments including public settings in urban built environments where high density human activity can be found including public transport sports arenas and schools However in comparison to healthcare settings and agriculture there is very little surveillance of AMR in the built environment outside of healthcare settings and wastewater In this review we analyse the existing literature to aid our understanding of what surveillance has been conducted within different public settings and identify what this tells us about the prevalence of AMR We highlight the challenges that have been reported and make recommendations for future studies that will help to fill knowledge gaps present in the literature

Glasgow Early Treatment Arm Favirpiravir GETAFIX for adults with early stage COVID 19 A structured summary of a study protocol for a randomised controlled trial The GETAFIX trial will test the hypothesis that favipiravir is a more effective treatment for COVID 19 infection in patients who have early stage disease compared to current standard of care This study will also provide an important opportunity to investigate the safety and tolerability of favipiravir the pharmacokinetic and pharmacodynamic profile of this drug and mechanisms of resistance in the context of COVID 19 infection as well as the effect of favipiravir on hospitalisation duration and the post COVID 19 health and psycho social wellbeing of patients recruited to the study GETAFIX is an open label parallel group two arm phase II III randomised trial with 1 1 treatment allocation ratio Patients will be randomised to one of two arms and the primary endpoint will assess the superiority of favipiravir plus standard treatment compared to standard treatment alone This trial will recruit adult patients with confirmed positive valid COVID 19 test who are not pregnant or breastfeeding and have no prior major co morbidities This is a multi centre trial patients will be recruited from in patients and outpatients from three Glasgow hospitals Royal Alexandra Hospital Queen Elizabeth University Hospital and the Glasgow Royal Infirmary Patients must meet all of the following criteria 1 Age 16 or over at time of consent 2 Exhibiting symptoms associated with COVID 19 3 Positive for SARS CoV 2 on valid COVID 19 test 4 Point 1 2 3 or 4 on the WHO COVID 19 ordinal severity scale at time of randomisation Asymptomatic with positive valid COVID 19 test Symptomatic Independent Symptomatic assistance needed Hospitalized with no oxygen therapy 5 Have 10 risk of death should they be admitted to hospital as defined by the ISARIC4C risk index https isaric4c net risk 6 Able to provide written informed consent 7 Negative pregnancy test women of childbearing potential 8 Able to swallow oral medication Patients will be excluded from the trial if they meet any of the following criteria 1 Renal impairment requiring or likely to require dialysis or haemofiltration 2 Pregnant or breastfeeding 3 Of child bearing potential women or with female partners of child bearing potential men who do not agree to use adequate contraceptive measures for the duration of the study and for 3 months after the completion of study treatment 4 History of hereditary xanthinuria 5 Other patients judged unsuitable by the Principal Investigator or sub Investigator 6 Known hypersensitivity to favipiravir its metabolites or any excipients 7 Severe co morbidities including patients with severe hepatic impairment defined as greater than Child Pugh grade A AST or ALT 5 x ULN AST or ALT 3 x ULN and Total Bilirubin 2xULN 8 More than 96 hours since first positive COVID 19 test sample was taken 9 Unable to discontinue contra indicated concomitant medications This is a multi centre trial patients will be recruited from in patients and outpatients from three Glasgow hospitals Royal Alexandra Hospital Queen Elizabeth University Hospital and the Glasgow Royal Infirmary Patients randomised to the experimental arm of GETAFIX will receive standard treatment for COVID 19 at the discretion of the treating clinician plus favipiravir These patients will receive a loading dose of favipiravir on day 1 of 3600mg 1800mg 12 hours apart On days 2 10 patients in the experimental arm will receive a maintenance dose of favipiravir of 800mg 12 hours apart total of 18 doses Patients randomised to the control arm of the GETAFIX trial will receive standard treatment for COVID 19 at the discretion of the treating clinician The primary outcome being assessed in the GETAFIX trial is the efficacy of favipiravir in addition to standard treatment in patients with COVID 19 in reducing the severity of disease compared to standard treatment alone Disease severity will be assessed using WHO COVID 10 point ordinal severity scale at day 15 48 hours All randomised participants will be followed up until death or 60 days post randomisation whichever is sooner Patients will be randomised 1 1 to the experimental versus control arm using computer generated random sequence allocation A minimisation algorithm incorporating a random component will be used to allocate patients The factors used in the minimisation will be site age 16 50 51 70 71 history of hypertension or currently obsess BMI 30 or obesity clinically evident yes no 7 days duration of symptoms yes no unknown sex male female WHO COVID 19 ordinal severity score at baseline 1 2or 3 4 No blinding will be used in the GETAFIX trial Both participants and those assessing outcomes will be aware of treatment allocation In total 302 patients will be randomised to the GETAFIX trial 151 to the control arm and 151 to the experimental arm There will be an optional consent form for patients who may want to contribute to more frequent PK and PD sampling The maximum number of patients who will undergo this testing will be sixteen eight males and eight females This option will be offered to all patients who are being treated in hospital at the time of taking informed consent however only patients in the experimental arm of the trial will be able to undergo this testing The current GETAFIX protocol is version 4 0 12 sup th sup September 2020 GETAFIX opened to recruitment on 26 sup th sup October 2020 and will recruit patients over a period of approximately six months GETAFIX was registered on the European Union Drug Regulating Authorities Clinical Trials EudraCT Database on 15 sup th sup April 2020 Reference number 2020 001904 41 https www clinicaltrialsregister eu ctr search trial 2020 001904 41 GB GETAFIX was registered on ISRCTN on 7 sup th sup September 2020 Reference number ISRCTN31062548 https www isrctn com ISRCTN31062548 The full protocol is attached as an additional file accessible from the Trials website Additional file 1 In the interest in expediting dissemination of this material the familiar formatting has been eliminated this Letter serves as a summary of the key elements of the full protocol The study protocol has been reported in accordance with the Standard Protocol Items Recommendations for Clinical Interventional Trials SPIRIT guidelines see Additional file 2

Characteristics of pediatric multi system inflammatory syndrome PMIS associated with COVID 19 a meta analysis and insights into pathogenesis There was an outbreak of pediatric multisystem inflammation syndrome PMIS was observed in multiple countries recently and this syndrome was suspected to be associated with SARS CoV 2 infection At present there is still no standardized diagnostic criteria and treatment regimen for PMIS while the etiology and pathogenesis still remain unclear We performed a systematic review on PubMed and Embase from the time of inception to June 24th 2020 in order to find relevant cases There are seven studies included and 80 of patients suffered persistent fever and 90 appeared gastrointestinal symptoms IgG antibody against SARS CoV 2 was positive on 81 of patients while 37 of the patients were nucleic acid positive C reactive protein IL 6 and PCT were elevated and intravenous immunoglobulin was a routine treatment for PMIS There were more than half of patients required inotropic supports and mechanical ventilation were applied to 33 of patients The median length of hospital stay was 10 66 days and 74 had admitted to accept intensive care Our study documented three common types of PMIS clinical presentation persistent fever and gastrointestinal symptoms shocked with heart dysfunction and Kawasaki disease like syndrome PMIS patients proved with a marked inflammatory state were possibly associated with SARS CoV 2 infection

Multisystem inflammatory syndrome in children MIS C a mini review Multisystem inflammatory syndrome in children MIS C is a novel life threatening hyperinflammatory condition that develops in children a few weeks after infection with severe acute respiratory syndrome coronavirus 2 SARS CoV 2 This disease has created a diagnostic challenge due to overlap with Kawasaki disease KD and KD shock syndrome The majority of patients with MIS C present with the involvement of at least four organ systems and all have evidence of a marked inflammatory state Most patients show an increase in the level of at least four inflammatory markers C reactive protein neutrophil count ferritin procalcitonin fibrinogen interleukin 6 and triglycerides Therapy is primarily with immunomodulators suggesting that the disease is driven by post infectious immune dysregulation Most patients even those with severe cardiovascular involvement recover without sequelae Since coronary aneurysms have been reported echocardiographic follow up is needed Further study is needed to create uniform diagnostic criteria therapy and follow up protocols

Acute disseminated encephalomyelitis and COVID 19 A systematic synthesis of worldwide cases Acute disseminated encephalomyelitis ADEM has been reported after coronavirus disease 2019 COVID 19 In this review we systematically included worldwide reported cases on this association We included 30 case reports pediatric and adults and explored epidemiological and clinical evidence We described time to diagnosis clinical imaging and laboratory features response to treatment regimens and differences regarding severity Also an original case report was presented Neurologists must be alert to the occurrence of multifocal neurological symptoms with or without encephalopathy in patients recovered from COVID 19 Timely MRI studies should be performed to establish the diagnosis and to consider early corticosteroid based treatment

Review of Cardiac Involvement in Multisystem Inflammatory Syndrome in Children Coronavirus disease 2019 COVID 19 is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 SARS CoV 2 with substantial cardiovascular implications Although infection with SARS CoV 2 is usually mild in children some children later develop a severe inflammatory disease that can have manifestations similar to toxic shock syndrome or Kawasaki disease This syndrome has been defined by the US Centers for Disease Control and Prevention as multisystem inflammatory syndrome in children Although the prevalence is unknown 600 cases have been reported in the literature Multisystem inflammatory syndrome in children appears to be more common in Black and Hispanic children in the United States Multisystem inflammatory syndrome in children typically occurs a few weeks after acute infection and the putative etiology is a dysregulated inflammatory response to SARS CoV 2 infection Persistent fever and gastrointestinal symptoms are the most common symptoms Cardiac manifestations are common including ventricular dysfunction coronary artery dilation and aneurysms arrhythmia and conduction abnormalities Severe cases can present as vasodilatory or cardiogenic shock requiring fluid resuscitation inotropic support and in the most severe cases mechanical ventilation and extracorporeal membrane oxygenation Empirical treatments have aimed at reversing the inflammatory response using immunomodulatory medications Intravenous immunoglobulin steroids and other immunomodulatory agents have been used frequently Most patients recover within days to a couple of weeks and mortality is rare although the medium and long term sequelae particularly cardiovascular complications are not yet known This review describes the published data on multisystem inflammatory syndrome in children focusing on cardiac complications and provides clinical considerations for cardiac evaluation and follow up

Physical and mental health complications post COVID 19 Scoping review Several long lasting health complications have been reported in previous coronavirus infections Therefore the aim of this study was to review studies that evaluated physical and mental health problems post COVID 19 Articles for inclusion in this scoping review were identified by searching the PubMed Scopus Web of Science and Google Scholar databases for items dated from 1 January to 7 November 2020 Observational studies evaluating physical health musculoskeletal symptoms functional status or mental health status with a follow up period longer than 1 month after discharge or after the onset of symptoms were included This scoping review included 34 studies with follow up periods of up to 3 months post COVID 19 The most commonly reported physical health problems were fatigue range 28 to 87 pain myalgia 4 5 to 36 arthralgia 6 0 to 27 reduced physical capacity six minute walking test range 180 to 561 m and declines in physical role functioning usual care and daily activities reduced in 15 to 54 of patients Common mental health problems were anxiety range 6 5 to 63 depression 4 to 31 and post traumatic stress disorder 12 1 to 46 9 Greater fatigue pain anxiety and depression were reported in female patients and individuals admitted to intensive care An overall lower quality of life was seen up to 3 months post COVID 19 This review highlights the presence of several physical and mental health problems up to 3 months post COVID 19 The findings point to the need for comprehensive evaluation and rehabilitation post COVID 19 to promote quality of life

Circular economy approach in solid waste management system to achieve UN SDGs Solutions for post COVID recovery The COVID 19 pandemic and the ensuing socioeconomic crisis has impeded progress towards the UN Sustainable Development Goals UN SDGs This paper investigates the impact of COVID 19 on the progress of the SDGs and provides insight into how green recovery stimulus driven by circular economy CE based solid waste management SWM could assist in attaining the intended targets of UN SDG It was understood in this review that the guiding principles of the UN SDGs such as public health environmental concerns resource value and economic development are similar to those that have driven the growth of waste management activities thus in order to achieve the goals of UN SDG a circular economy approach in solid waste management system should be prioritized in the post COVID economic agenda However policy technology and public involvement issues may hinder the shift to the CE model therefore niche growth might come from developing distinctive waste management driven green jobs formalizing informal waste pickers and by focusing in education and training of informal worker The review also emphasized in creating green jobs by investing in recycling infrastructure which would enable us to address the climate change related concerns which is one of the key target of UN SDG The CE based product designs and business models would emphasize multifunctional goods extending the lifespan of products and their parts and intelligent manufacturing to help the public and private sectors maximise product utility thus reducing waste generation while providing long term economic and environmental benefits The study also recommended strong policies that prioritized investments in decentralization of solid waste systems localization of supply chains recycling and green recovery information sharing and international collaboration in order to achieve the UN SDGs

Cardiac manifestations in SARS CoV 2 associated multisystem inflammatory syndrome in children a comprehensive review and proposed clinical approach Initial reports on COVID 19 described children as largely spared from severe manifestations with only 2 6 of children requiring intensive care treatment However since mid April 2020 clusters of pediatric cases of severe systemic hyperinflammation and shock epidemiologically linked with COVID 19 have been reported This condition was named as SARS Cov 2 associated multisystem inflammatory syndrome in children and showed similarities to Kawasaki disease Here we present a narrative review of cases reported in literature and we discuss the clinical acute and follow up management of these patients Patients with SARS Cov 2 associated multisystem inflammatory syndrome frequently presented with persistent fever gastrointestinal symptoms polymorphic rash conjunctivitis and mucosal changes Elevated inflammatory markers and evidence of cytokine storm were frequently observed A subset of these patients also presented with hypotension and shock 20 100 from either acute myocardial dysfunction or systemic hyperinflammation vasodilation Coronary artery dilation or aneurysms have been described in 6 24 and arrhythmias in 7 60 Cardiac support immunomodulation and anticoagulation are the key aspects for the management of the acute phase Long term structured follow up of these patients is required due to the unclear prognosis and risk of progression of cardiac manifestations Conclusion Multisystem inflammatory syndrome is a novel syndrome related to SARS CoV 2 infection Evidence is still scarce but rapidly emerging in the literature Cardiac manifestations are frequent including myocardial and coronary involvement and need to be carefully identified and monitored over time What is Known Multisystem inflammatory syndrome in children MIS C has been described associated with SARS CoV 2 What is New Patients with MIS C often present with fever gastrointestinal symptoms and shock Cardiac involvement is found in a high proportion of these patients including ventricular dysfunction coronary artery dilation or aneurysm and arrhythmias Management is based on expert consensus and includes cardiac support immunomodulatory agents and anticoagulation Long term follow up is required due to the unclear prognosis and risk of progression of cardiac manifestation

SARS CoV 2 nosocomial infection acquired in a French university hospital during the 1st wave of the Covid 19 pandemic a prospective study In healthcare facilities nosocomial transmissions of respiratory viruses are a major issue SARS CoV 2 is not exempt from nosocomial transmission Our goals were to describe COVID 19 nosocomial cases during the first pandemic wave among patients in a French university hospital and compliance with hygiene measures We conducted a prospective observational study in Grenoble Alpes University Hospital from 01 03 2020 to 11 05 2020 We included all hospitalised patients with a documented SARS CoV 2 diagnosis Nosocomial case was defined by a delay of 5 days between hospitalisation and first symptoms Hygiene measures were evaluated between 11 05 2020 and 22 05 2020 Lockdown measures were effective in France on 17 03 2020 and ended on 11 05 2020 Systematic wearing of mask was mandatory for all healthcare workers HCW and visits were prohibited in our institution from 13 03 2021 and for the duration of the lockdown period Among 259 patients included 14 5 4 were considered as nosocomial COVID 19 Median time before symptom onset was 25 days interquartile range 12 42 Eleven patients 79 had risk factors for severe COVID 19 Five died 36 including 4 deaths attributable to COVID 19 Two clusters were identified The first cluster had 5 cases including 3 nosocomial acquisitions and no tested HCWs were positive The second cluster had 3 cases including 2 nosocomial cases and 4 HCWs were positive Surgical mask wearing and hand hygiene compliance were adequate for 95 and 61 of HCWs respectively The number of nosocomial COVID 19 cases in our hospital was low Compliance regarding mask wearing hand hygiene and lockdown measures drastically reduced transmission of the virus Monitoring of nosocomial COVID 19 cases during the first wave enabled us to determine to what extent the hygiene measures taken were effective and patients protected Trial registration Study ethics approval was obtained retrospectively on 30 September 2020 CECIC Rhône Alpes Auvergne Clermont Ferrand IRB 5891

Characteristics of viral pneumonia in the COVID 19 era an update Influenza virus rhinovirus and adenovirus frequently cause viral pneumonia an important cause of morbidity and mortality especially in the extreme ages of life During the last two decades three outbreaks of coronavirus associated pneumonia namely Severe Acute Respiratory Syndrome Middle East Respiratory Syndrome and the ongoing Coronavirus Infectious Disease 2019 COVID 19 were reported The rate of diagnosis of viral pneumonia is increasingly approaching 60 among children identified as having community acquired pneumonia CAP Clinical presentation ranges from mild to severe pneumonitis complicated by respiratory failure in severe cases The most vulnerable patients the elderly and those living with cancer report a relevant mortality rate No clinical characteristics can be useful to conclusively distinguish the different etiology of viral pneumonia However accessory symptoms such as anosmia or ageusia together with respiratory symptoms suggest COVID 19 An etiologic based treatment of viral pneumonia is possible in a small percentage of cases only Neuraminidase inhibitors have been proven to reduce the need for ventilatory support and mortality rate while only a few data support the large scale use of other antivirals A low middle dose of dexamethasone and heparin seems to be effective in COVID 19 patients but data regarding their possible efficacy in viral pneumonia caused by other viruses are conflicting In conclusion viral pneumonia is a relevant cause of CAP whose interest is increasing due to the current COVID 19 outbreak To set up a therapeutic approach is difficult because of the low number of active molecules and the conflicting data bearing supportive treatments such as steroids

Role of rehabilitation amidst the COVID 19 pandemic a review COVID 19 remains globally a highly infectious disease targeting multiple organs Rehabilitation is increasingly valued among the supportive care fields to combat COVID 19 as currently definitive curative treatment remains largely absent This narrative review is to address rehabilitation related topics associated with the treatment of COVID 19 patients Nosocomial spread remains a high risk for healthcare workers with comparable high ratios of exposed workers suffering from the disease with more severe clinical course Primary principle of rehabilitation is to protect rehabilitation physicians and cover all person to person interactions Translating perspectives are encouraged through each multidisciplinary approach Rehabilitation for the outpatient remains a potential beneficial approach Artificial intelligence can potentially provide aid and possible answers to important problems that may emerge involving COVID 19 The real value of rehabilitation in COVID 19 may be very impactful and beneficial for patients physical and mental health

Battery for deep brain stimulation depletion in Parkinsons Disease and dystonia patients a systematic review Deep brain stimulation DBS therapy for Parkinsons Disease PD and dystonia is associated with the possibility of both minor and major complications One possible side effect is the depletion of implantable pulse generator IPG battery and the associated sudden recurrence of PD or dystonia symptoms which can be potentially life threatening Delayed or postponed outpatient visits due to COVID 19 may be a risk factor of battery end of life consequences To analyse the clinical outcomes in reported PD and dystonia patients treated with DBS who as a result of the sudden depletion of the neurostimulator battery developed life threatening symptoms The databases of PubMed Scopus EMBASE and Google Scholar were searched using pre established criteria A total of 244 articles was found of which 12 met the adopted criteria Selected papers presented a total of 17 case reports of DBS treated patients 11 with PD and six with dystonia who had depleted IPG batteries and due to rapid worsening of PD dystonia symptoms required urgent hospital admission IPG battery replacement was the only effective treatment in the majority of cases IPG battery depletion can result in fatal outcomes Sudden recurrence of PD or dystonia symptoms in patients treated by DBS can be potentially life threatening so scheduling the replacement of a discharged IPG battery should not be postponed The COVID 19 pandemic should alert staff at emergency neurology and movement disorders wards not to postpone the visits of patients with an implanted DBS system

COVID 19 and post traumatic stress disorder The perfect storm for mental health Review Since its outbreak in December 2019 in the Chinese city of Wuhan coronavirus disease 2019 COVID 19 caused by severe acute respiratory syndrome coronavirus 2 SARS CoV 2 has evolved into an ongoing global pandemic Due to the novel antigenic properties of this virus the world population could not develop immunity effectively and this led to the subsequent spread of COVID 19 This caused an unprecedented emergency situation with significant negative effects on health and well being both on an individual and societal level Apart from health economic and social consequences the impact of this pandemic on mental health is increasingly being reported in the scientific literature The present review aimed to provide a comprehensive discussion of the possible neurological and neuropsychiatric manifestations of SARS CoV 2 together with the related underlying molecular pathways In addition the present review focused on populations which are at a higher risk of developing psychiatric disturbances due to the COVID 19 pandemic and discussed possible routes of clinical management and therapeutics to minimize the burden associated with psychiatric disorders Moreover research findings exploring the prevalence of COVID 19 related post traumatic stress disorder PTSD symptoms across vulnerable groups including children adolescents and COVID 19 survivors are presented with particular emphasis on those with severe disease who required hospitalization and or intensive care unit admission Based on the available literature the identification of potential determinants associated with PTSD across the different populations is underlined Lessons learnt from the pandemics across the globe together with the ongoing research on COVID 19 and its impact on mental health highlight the utmost importance for evidence based proactive and targeted interventions in high risk groups aiming to mitigate the risks and manage vulnerabilities

Challenges of modeling and analysis in cybermanufacturing a review from a machine learning and computation perspective In Industry 4 0 smart manufacturing is facing its next stage cybermanufacturing founded upon advanced communication computation and control infrastructure Cybermanufacturing will unleash the potential of multi modal manufacturing data and provide a new perspective called computation service as a part of service oriented architecture SOA where on demand computation requests throughout manufacturing operations are seamlessly satisfied by data analytics and machine learning However the complexity of information technology infrastructure leads to fundamental challenges in modeling and analysis under cybermanufacturing ranging from information poor datasets to a lack of reproducibility of analytical studies Nevertheless existing reviews have focused on the overall architecture of cybermanufacturing SOA or its technical components e g communication protocol rather than the potential bottleneck of computation service with respect to modeling and analysis In this paper we review the fundamental challenges with respect to modeling and analysis in cybermanufacturing Then we introduce the existing efforts in computation pipeline recommendation which aims at identifying an optimal sequence of method options for data analytics machine learning without time consuming trial and error We envision computation pipeline recommendation as a promising research field to address the fundamental challenges in cybermanufacturing We also expect that computation pipeline recommendation can be a driving force to flexible and resilient manufacturing operations in the post COVID 19 industry

Enhancing Teaching Recovery Techniques TRT with Parenting Skills RCT of TRT Parenting with Trauma Affected Syrian Refugees in Lebanon Utilising Remote Training with Implications for Insecure Contexts and COVID 19 Child psychosocial recovery interventions in humanitarian contexts often overlook the significant effect that caregivers can have on improving childrens future trajectory We enhanced the well established evidenced based child trauma recovery programme Teaching Recovery Techniques TRT intervention with parenting sessions i e TRT Parenting TRT P which aims to improve parent mental health and their ability to support their childrens mental health We describe the findings of a three arm randomised controlled trial comparing enhanced TRT P vs TRT and waitlist The primary aim was to test if children in the enhanced arm of the programme show improved child and caregiver mental health We recruited 119 Syrian refugee children and one of their caregivers in Beqaa Valley in Lebanon They were randomised to the TRT TRT P or waitlist control group Data were collected at baseline and 2 weeks and 12 weeks post intervention Training of facilitators was via remote training from the United Kingdom Results showed a highly consistent pattern with children in the enhanced TRT P group showing the greatest levels of improvement in behavioural and emotional difficulties compared to children in the TRT or waitlist control groups Caregivers in the TRT P group also reported significant reductions in depression anxiety and stress Findings indicate that the addition of the evidence based parenting skills components has the potential to enhance the effects of interventions designed to improve childrens mental health in contexts of trauma conflict and displacement Implications for COVID 19 remote learning are also discussed

A Rapid Review on the Influence of COVID 19 Lockdown and Quarantine Measures on Modifiable Cardiovascular Risk Factors in the General Population Preceding coronavirus outbreaks resulted in social isolation which in turn is associated with cardiovascular consequences Whether the current COVID 19 pandemic negatively impacts cardiovascular health is unclear The aim of the rapid review was to investigate whether COVID 19 lockdown influences modifiable cardiovascular risk factors i e physical inactivity sedentary behaviour smoking alcohol use unhealthy diet obesity bad blood lipids and hypertension in the general population Medline and EMBASE were searched until March 2021 Title abstracts and full texts were screened by one reviewer and 20 by a second reviewer Only studies using probability sampling were included in order to ensure the representativeness of the target population Data extraction and critical appraisal were done by one reviewer and double checked by another reviewer We identified 32 studies that fulfilled our inclusion criteria Findings show that physical activity decreased and sedentary behaviour increased among all age groups during the COVID 19 lockdown Among adults alcohol consumption increased dietary quality worsened and the amount of food intake increased Some adults reported weight gain Studies on children and adolescents were sparse This rapid review found a high number of epidemiological studies on the impact of COVID 19 lockdown measures on modifiable cardiovascular risk factors but only a few used probability sampling methods

Long COVID postural tachycardia syndrome an American Autonomic Society statement COVID 19 is a global pandemic that has had a devastating effect on the health and economy of much of human civilization While the acute impacts of COVID 19 were the initial focus of concern it is becoming clear that in the wake of COVID 19 many patients are developing chronic symptoms that have been called Long COVID Some of the symptoms and signs include those of postural tachycardia syndrome POTS Understanding and managing long COVID POTS will require a significant infusion of health care resources and a significant additional research investment In this document from the American Autonomic Society we outline the scope of the problem and the resources and research needed to properly address the impact of Long COVID POTS

Long COVID 19 Syndrome A Comprehensive Review of Its Effect on Various Organ Systems and Recommendation on Rehabilitation Plans The majority of people infected with SARS CoV 2 fully recovered within a few weeks However a considerable number of patients of different ages still suffer from long lasting problems similar to the multi organ damage in its acute phase of infection or experience symptoms continuously for a longer term after the recovery The severity of the primary infection seems not to be associated with the possibility and severity of long term symptoms Various unresolved symptoms have been reported in COVID 19 survivors months after hospital discharge Long COVID 19 Syndrome refers to survivors 4 months after initial symptoms onset It is important to understand the systemic effects of Long COVID 19 Syndrome its presentations and the need for rehabilitations to restore functional recovery in survivors Government healthcare workers and survivor groups should collaborate to establish a self sustaining system to facilitate follow up and rehabilitations with prioritization of resources to more severely Long COVID 19 Syndrome survivors This review looks into the systemic effects of Long COVID 19 Syndrome in various aspects respiratory cardiovascular hematological renal gastrointestinal neurological and metabolic effects of Long COVID 19 Syndromes Recommendations for follow up and rehabilitations details have been explored to cope with the tremendous Long COVID 19 Syndrome patients

Assessment of the Frequency and Variety of Persistent Symptoms Among Patients With COVID 19 A Systematic Review Infection with COVID 19 has been associated with long term symptoms but the frequency variety and severity of these complications are not well understood Many published commentaries have proposed plans for pandemic control that are primarily based on mortality rates among older individuals without considering long term morbidity among individuals of all ages Reliable estimates of such morbidity are important for patient care prognosis and development of public health policy To conduct a systematic review of studies examining the frequency and variety of persistent symptoms after COVID 19 infection A search of PubMed and Web of Science was conducted to identify studies published from January 1 2020 to March 11 2021 that examined persistent symptoms after COVID 19 infection Persistent symptoms were defined as those persisting for at least 60 days after diagnosis symptom onset or hospitalization or at least 30 days after recovery from the acute illness or hospital discharge Search terms included COVID 19 SARS CoV 2 coronavirus 2019 nCoV long term after recovery long haul persistent outcome symptom follow up and longitudinal All English language articles that presented primary data from cohort studies that reported the prevalence of persistent symptoms among individuals with SARS CoV 2 infection and that had clearly defined and sufficient follow up were included Case reports case series and studies that described symptoms only at the time of infection and or hospitalization were excluded A structured framework was applied to appraise study quality A total of 1974 records were identified of those 1247 article titles and abstracts were screened After removal of duplicates and exclusions 92 full text articles were assessed for eligibility 47 studies were deemed eligible and 45 studies reporting 84 clinical signs or symptoms were included in the systematic review Of 9751 total participants 5266 54 0 were male 30 of 45 studies reported mean or median ages younger than 60 years Among 16 studies most of which comprised participants who were previously hospitalized the median proportion of individuals experiencing at least 1 persistent symptom was 72 5 interquartile range IQR 55 0 80 0 Individual symptoms occurring most frequently included shortness of breath or dyspnea 26 studies median frequency 36 0 IQR 27 6 50 0 fatigue or exhaustion 25 studies median frequency 40 0 IQR 31 0 57 0 and sleep disorders or insomnia 8 studies median 29 4 IQR 24 4 33 0 There were wide variations in the design and quality of the studies which had implications for interpretation and often limited direct comparability and combinability Major design differences included patient populations definitions of time zero ie the beginning of the follow up interval follow up lengths and outcome definitions including definitions of illness severity This systematic review found that COVID 19 symptoms commonly persisted beyond the acute phase of infection with implications for health associated functioning and quality of life Current studies of symptom persistence are highly heterogeneous and future studies need longer follow up improved quality and more standardized designs to reliably quantify risks

The clinical spectrum of SARS CoV 2 infection in Gaucher disease Effect of both a pandemic and a rare disease that disrupts the immune system The impact of SARS CoV 2 in rare disease populations has been underreported Gaucher disease GD is a prototype rare disease that shares with SARS CoV 2 a disruption of the lysosomal pathway Retrospective analysis of 11 patients with Type 1 GD who developed COVID 19 between March 2020 and March 2021 Seven male and 4 female patients with Type 1 GD developed COVID 19 One was a pediatric patient 8 years old while the remainder were adults median age of 44 years old range 21 to 64 years old Two patients required hospitalization though none required intensive care or intubation All 11 patients recovered from COVID 19 and there were no reported deaths Our case series suggests that GD patients acquired COVID 19 at a similar frequency as the general population though experienced a milder overall course despite harboring underlying immune system dysfunction and other known co morbidities that confer high risk of adverse outcomes from SARS CoV 2 infection

Case report and systematic review suggest that children may experience similar long term effects to adults after clinical COVID 19 Persistent symptoms in adults after COVID 19 are emerging and the term long COVID is increasingly appearing in the literature However paediatric data are scarce This paper contains a case report of five Swedish children and the long term symptoms reported by their parents It also includes a systematic literature review of the MEDLINE EMBASE and Web of Science databases and the medRxiv bioRxiv pre print servers up to 2 November 2020 The five children with potential long COVID had a median age of 12 years range 9 15 and four were girls They had symptoms for 6 8 months after their clinical diagnoses of COVID 19 None were hospitalised at diagnosis but one was later admitted for peri myocarditis All five children had fatigue dyspnoea heart palpitations or chest pain and four had headaches difficulties concentrating muscle weakness dizziness and sore throats Some had improved after 6 8 months but they all suffered from fatigue and none had fully returned to school The systematic review identified 179 publications and 19 of these were deemed relevant and read in detail None contained any information on long COVID in children Children may experience similar long COVID symptoms to adults and females may be more affected

A systematic review of pathological findings in COVID 19 a pathophysiological timeline and possible mechanisms of disease progression Since the outbreak of the COVID 19 pandemic much has been learned regarding its clinical course prognostic inflammatory markers disease complications and mechanical ventilation strategy Clinically three stages have been identified based on viral infection pulmonary involvement with inflammation and fibrosis Moreover low and high elastance phenotypes can be distinguished in mechanically ventilated patients based on lung mechanics ventilation to perfusion ratio and CT scans these two phenotypes have presumed differences in their underlying pathophysiology Although essential for therapeutic guidance the pathophysiology of COVID 19 is poorly understood Here we systematically reviewed published case reports and case series in order to increase our understanding of COVID 19 pathophysiology by constructing a timeline and correlating histopathological findings with clinical stages of COVID 19 Using PRISMA IPD guidelines 42 articles reporting 198 individual cases were included in our analysis In lung samples n 131 cases we identified three main histological patterns epithelial n 110 85 with reactive epithelial changes and DAD vascular n 76 59 with microvascular damage micro thrombi and acute fibrinous and organizing pneumonia and fibrotic n 28 22 with interstitial fibrosis The epithelial and vascular patterns can present in all stages of symptomatic COVID 19 whereas the fibrotic pattern presents starting at 3 weeks Moreover patients can present with more than one pattern either simultaneously or consecutively These findings are consistent with knowledge regarding clinical patterns of viral infection development of hyperinflammation and hypercoagulability and fibrosis Close collaboration among medical staff is necessary in order to translate this knowledge and classification of pathophysiological mechanisms into clinical stages of disease in individual patients Moreover further research including histopathological studies is warranted in order to develop reliable clinically relevant biomarkers by correlating these pathological findings with laboratory results and radiological findings thus increasing our understanding of COVID 19 and facilitating the move to precision medicine for treating patients

Long Term Non invasive Ventilation in Children Current Use Indications and Contraindications This review focuses on the delivery of non invasive ventilation i e intermittent positive pressure ventilation in children lasting more than 3 months Several recent reviews have brought to light a dramatic escalation in the use of long term non invasive ventilation in children over the last 30 years This is due both to the growing number of children receiving care for complex and severe diseases necessitating respiratory support and to the availability of LT NIV equipment that can be used at home While significant gaps in availability persist for smaller children and especially infants home LT NIV for children with chronic respiratory insufficiency has improved their quality of life and decreased the overall cost of care While long term NIV is usually delivered during sleep it can also be delivered 24 h a day in selected patients Close collaboration between the hospital complex care team the home LT NIV program and family caregivers is of the utmost importance for successful home LT NIV Long term NIV is indicated for respiratory disorders responsible for chronic alveolar hypoventilation with the aim to increase life expectancy and maximize quality of life LT NIV is considered for conditions that affect respiratory muscle performance alterations in central respiratory drive or neuromuscular function and or impose an excessive respiratory load airway obstruction lung disease or chest wall anomalies Relative contraindications for LT NIV include the inability of the local medical infrastructure to support home LT NIV and poor motivation or inability of the patient caregivers to cooperate or understand recommendations Anatomic abnormalities that interfere with interface fitting inability to protect the lower airways due to excessive airway secretions and or severely impaired swallowing or failure of LT NIV to support respiration can lead to considering invasive ventilation via tracheostomy Of note providing home LT NIV during the COVID 19 pandemic has become more challenging This is due both to the disruption of medical systems and the fear of contaminating care providers and family with aerosols generated by a patient positive for SARS CoV 2 during NIV Delay in initiating LT NIV decreased frequency of home visits by the home ventilation program and decreased availability of polysomnography and oximetry transcutaneous PCO sub 2 sub monitoring are observed Teleconsultations and telemonitoring are being developed to mitigate these challenges

Clinical features and follow up of pediatric patients hospitalized for COVID 19 This report summarizes the clinical features and 1 month follow up observations for pediatric patients who were hospitalized with coronavirus disease 2019 COVID 19 in Wuhan Women and Childrens Hospital The 1 month follow up data included clinical manifestations and results from serum severe acute respiratory syndrome coronavirus 2 SARS CoV 2 IgG and IgM tests reverse transcription polymerase chain reaction RT PCR for SARS CoV 2 lung computed tomography CT scans and laboratory tests Between January 20 and March 15 2020 127 patients aged 0 15 years were hospitalized for COVID 19 treatment including 3 severe cases and 124 mild or moderate cases The main therapies included inhalation of aerosolized interferon α 122 127 and additional antiviral drugs 28 127 Among the 81 patients who had pneumonia at admission 35 with right lobe pneumonia had the longest hospital stay mean 14 5 7 days 17 with left lobe pneumonia had the highest creatine kinase 154 106 U L and creatine kinase myocardial band CK MB 43 48 U L levels and 29 with bilateral pneumonia had the highest white blood cell counts 8 3 4 10 sup 9 sup L Among the 46 patients who were successfully followed up 1 month after discharge two notable findings were right lobe pneumonia in 22 95 confidence interval CI 11 37 of patients and persistently elevated serum creatine kinase and CK MB levels The median duration of elevated CK MB was 45 days The mean concentrations of serum SARS CoV 2 IgG and IgM in 41 patients were 8 0 7 5 and 98 40 ng ml respectively At follow up four patients retested positive for SARS CoV 2 The involvement of different lung lobes in patients with COVID 19 was associated with variations in the persistence of pneumonia and elevation of CK MB levels and body temperature

Response strategies for promoting gender equality in public health emergencies a rapid scoping review The COVID 19 pandemic threatens to widen existing gender inequities worldwide A growing body of literature assesses the harmful consequences of public health emergencies PHEs for women and girls however evidence of what works to alleviate such impacts is limited To inform viable mitigation strategies we reviewed the evidence on gender based interventions implemented in PHEs including disease outbreaks and natural disasters We conducted a rapid scoping review to identify eligible studies by systematically searching the databases MEDLINE Global Health and Web of Science with the latest search update on 28 May 2021 We used the Sustainable Development Goals as a guiding framework to identify eligible outcomes of gender in equality Out of 13 920 records 16 studies met our eligibility criteria These included experimental 3 cohort 2 case control 3 and cross sectional 9 studies conducted in the context of natural disasters earthquakes droughts and storms or epidemics Zika Ebola and COVID 19 Six studies were implemented in Asia seven in North Central America and three in Africa Interventions included economic empowerment programmes 5 health promotion largely focused on reproductive health 10 and a postearthquake resettlement programme 1 Included studies assessed gender based outcomes in the domains of sexual and reproductive health equal opportunities access to economic resources violence and health There was a dearth of evidence for other outcome domains relevant to gender equity such as harmful practices sanitation and hygiene practices workplace discrimination and unpaid work Economic empowerment interventions showed promise in promoting womens and girls economic and educational opportunities as well as their sexual and reproductive health during PHEs However some programme beneficiaries may be at risk of experiencing unintended harms such as an increase in domestic violence Focused reproductive health promotion may also be an effective strategy for supporting womens sexual and reproductive health although additional experimental evidence is needed This study identified critical evidence gaps to guide future research on approaches to alleviating gender inequities during PHEs We further highlight that interventions to promote gender equity in PHEs should take into account possible harmful side effects such as increased gender based violence DOI 10 17605 OSF IO 8HKFD

Kidney Outcomes in Long COVID COVID 19 is associated with increased risk of post acute sequelae involving pulmonary and extrapulmonary organ systems referred to as long COVID However a detailed assessment of kidney outcomes in long COVID is not yet available We built a cohort of 1 726 683 US Veterans identified from March 1 2020 to March 15 2021 including 89 216 patients who were 30 day survivors of COVID 19 and 1 637 467 non infected controls We examined risks of AKI eGFR decline ESKD and major adverse kidney events MAKE MAKE was defined as eGFR decline 50 ESKD or all cause mortality We used inverse probability weighted survival regression adjusting for predefined demographic and health characteristics and algorithmically selected high dimensional covariates including diagnoses medications and laboratory tests Linear mixed models characterized intra individual eGFR trajectory Beyond the acute illness 30 day survivors of COVID 19 exhibited a higher risk of AKI aHR 1 94 95 CI 1 86 to 2 04 eGFR decline 30 aHR 1 25 95 CI 1 14 to 1 37 eGFR decline 40 aHR 1 44 95 CI 1 37 to 1 51 eGFR decline 50 aHR 1 62 95 CI 1 51 to 1 74 ESKD aHR 2 96 95 CI 2 49 to 3 51 and MAKE aHR 1 66 95 CI 1 58 to 1 74 Increase in risks of post acute kidney outcomes was graded according to the severity of the acute infection whether patients were non hospitalized hospitalized or admitted to intensive care Compared with non infected controls 30 day survivors of COVID 19 exhibited excess eGFR decline 95 CI of 3 26 3 58 to 2 94 5 20 6 24 to 4 16 and 7 69 8 27 to 7 12 ml min per 1 73 m sup 2 sup per year respectively in non hospitalized hospitalized and those admitted to intensive care during the acute phase of COVID 19 infection Patients who survived COVID 19 exhibited increased risk of kidney outcomes in the post acute phase of the disease Post acute COVID 19 care should include attention to kidney disease

Gamification as Online Teaching Strategy During COVID 19 A Mini Review The ongoing pandemic caused by coronavirus disease 2019 COVID 19 has enforced a shutdown of educative institutions of all levels including high school and university students and has forced educators and institutions to adapt teaching strategies in a hasty way This work reviews the use of gamification based teaching during the pandemic lockdown through a search in Scopus PsycINFO ERIC and Semantic Scholar databases A total of 11 papers from Chemistry Business Computer Science Biology and Medical areas have been identified and included in the present work All of them analyzed the use of gamification strategies during the COVID 19 pandemic and assessed students learning and motivation outcomes In general students reported that gamification was innovative engaging and an efficient strategy to deliver curricula material moreover it was perceived as a fun activity Some students reported that gamified videoconferences aided to connect with their classmates during isolation time providing effective social support However some students reported a bad physical or psychological condition as consequence of the confinement and did not get involved in the activity Some weaknesses of the reviewed studies are the small sample size and its homogeneity which makes it difficult to generalize their results to other scenarios and academic areas Furthermore although there is a feeling of learning during the activity this result is mainly based on subjective perceptions and any of the studies demonstrated that superior learning was achieved in comparison with traditional teaching strategies Nevertheless gamification can be implemented together with traditional lectures and can be a valuable instrument during post COVID times

Post covid 19 pulmonary fibrosis Is it real threat After the COVID 19 outbreak increasing number of patients worldwide who have survived COVID 19 continue to battle the symptoms of the illness long after they have been clinically tested negative for the disease As we battle through this pandemic the challenging part is to manage COVID 19 sequelae which may vary from fatigue and body aches to lung fibrosis This review addresses underlying mechanism risk factors course of disease and treatment option for post covid pulmonary fibrosis Elderly patient who require ICU care and mechanical ventilation are at the highest risk to develop lung fibrosis Currently no fully proven options are available for the treatment of post inflammatory COVID 19 pulmonary fibrosis

Awake Rhinology Surgery in Response to the COVID 19 Pandemic in Europe European health care systems are faced with a backlog of surgical procedures following the suspension of routine surgery during the COVID 19 crisis Routine rhinology surgery under general anaesthetic GA is now faced with significant challenges which include limited theatre capacity the negative ramifications of surgical prioritization reduced patient throughput in secondary care and additional personal protective equipment requirements Delayed surgery in rhinology particularly with regards to chronic rhinosinusitis has previously been shown to have poorer surgical outcomes a detrimental effect on quality of life and long term negative health socio economic effects Awake rhinology surgery under local anaesthetic LA provides an ideal alternative to GA It provides a means of operating on patients in a setting alternative to currently oversubscribed main theatres by utilizing satellite facilities while ensuring identical surgical outcomes for patients who may otherwise have been forced to wait a long time for their procedure It also confers additional benefits in terms of shorter recovery time and hospital stay for patients We have developed a set of recommendations that are intended to help support clinicians and managers to better adopt LA rhinology protocols and minimize the risk to the patient and health care professionals involved International roundtable forums were conducted and supplemented by individual interviews The international board consisted of 12 rhinologists experienced in awake rhinology surgery Feedback was analysed and shared to develop a consensus of best practice Local and national guidelines need to be adhered to with specific focus on patient and clinician safety When performing awake rhinology procedures in the COVID 19 recovery process consider implementing specific safety measures and workflow practices to safeguard patients and staff and minimize the risk of infection Awake surgery potentially provides quicker access to routine rhinology surgery in the post COVID 19 recovery phase ensuring patients are treated in a timely matter thereby avoiding higher downstream costs and improving outcomes

Preparing for the 2020 2021 influenza season The COVID 19 pandemic has altered health seeking behaviors and has increased attention to non pharmaceutical interventions that reduce the risk of transmission of respiratory viruses including SARS CoV 2 and influenza While the potential impact of the COVID 19 pandemic on influenza is not fully known in the Southern hemisphere influenza infection rates appear to be very low Influenza vaccine efficacy for 2019 2020 season was comparable to prior season and influenza vaccine recommendations for pediatric immunizations remain similar to prior years Influenza treatments continue to include neuraminidase inhibitors as well as baloxavir for treatment and in some instances prophylaxis

A further plot twist will long COVID have an impact on dentistry and the dental workforce COVID 19 has dominated our lives since the start of the pandemic in 2020 as well as greatly impacting dentistry its patients and the dental profession A new and potentially further problematic phenomenon is that of long COVID a term used to describe the effects of COVID 19 that continue for weeks or even months beyond the initial illness It is characterised by debilitating symptoms including extreme fatigue shortness of breath insomnia heart palpitations and prolonged high temperature With one in ten people in the UK suffering from long COVID there will undoubtedly be a considerable impact on dentistry provision there will be ramifications not only for patients but also the workforce both physically and mentally The aim of this article is to explore the obstacles we will face due to long COVID examining possible challenges but also possible solutions

Lasting Changes to Circulating Leukocytes in People with Mild SARS CoV 2 Infections Survivors of severe SARS CoV 2 infections frequently suffer from a range of post infection sequelae Whether survivors of mild or asymptomatic infections can expect any long term health consequences is not yet known Herein we investigated lasting changes to soluble inflammatory factors and cellular immune phenotype and function in individuals who had recovered from mild SARS CoV 2 infections i n i 22 compared to those that had recovered from other mild respiratory infections i n i 11 Individuals who had experienced mild SARS CoV 2 infections had elevated levels of C reactive protein 1 3 months after symptom onset and changes in phenotype and function of circulating T cells that were not apparent in individuals 6 9 months post symptom onset Markers of monocyte activation and expression of adherence and chemokine receptors indicative of altered migratory capacity were also higher at 1 3 months post infection in individuals who had mild SARS CoV 2 but these were no longer elevated by 6 9 months post infection Perhaps most surprisingly significantly more T cells could be activated by polyclonal stimulation in individuals who had recently experienced a mild SARS CoV 2 infection compared to individuals with other recent respiratory infections These data are indicative of prolonged immune activation and systemic inflammation that persists for at least three months after mild or asymptomatic SARS CoV 2 infections

SARS CoV 2 associated multisystem inflammatory syndrome in children MIS C A single centers experience SARS CoV 2 related multisystem inflammatory syndrome in children MIS C is a newly defined clinical entity in pediatric ages resembles Kawasaki Disease or toxic shock syndrome Here we aimed to raise awareness about this SARS CoV 2 related syndrome Children diagnosed with MIS C and followed in Pediatric Clinic between November 2020 and January 2021 were included in study Data about patients demographic characteristics clinical and laboratory findings treatment and outcomes were collected from medical records The median age of 20 children with MIS C was 80 5 months 11 of them were male The most common symptoms at admission were fever 100 abdominal pain 70 myalgia 50 and rash 50 Lymphopenia elevated inflammatory markers and cardiac enzymes were their main laboratory findings Cardiac involvement 90 consisted of myopericarditis valvulitis left ventricular dysfunction and coronary arteritis Symptoms mimicking acute appendicitis and ileus were due to gastrointestinal involvement 50 Macular rash on the trunk erythema on upper eyelids were striking Empiric antibiotics and intravenous immunoglobulin were used in all patients glucocorticoids 90 anti thrombotic 65 and vasoactive 45 agents were used according to severity of disease Response to IVIG treatment was poor whereas glucocorticoids have dramatic affect Seven patients 35 were monitored in intensive care unit none of them required intubation mechanic ventilation or ECMO The median recovery time that is the period when fever subside and inflammatory markers returned to normal was 9 5 days Glucocorticoids has critical role in treatment of MIS C early recognition and treatment may decrease need for intensive care by providing rapid recovery

Long term clinical follow up of patients suffering from moderate to severe COVID 19 infection a monocentric prospective observational cohort study Various symptoms and considerable organ dysfunction persist following infection with severe acute respiratory syndrome coronavirus 2 SARS CoV 2 Uncertainty remains about the potential mid and long term health sequelae This prospective study of patients hospitalized with coronavirus disease 2019 COVID 19 in Liège University Hospital Belgium aimed to determine the persistent consequences of COVID 19 Patients admitted to the University Hospital of Liège with moderate to severe confirmed COVID 19 discharged between 2 March and 1 October 2020 were recruited prospectively Follow up at 3 and 6 months after hospital discharge included demographic and clinical data biological data pulmonary function tests PFTs and high resolution computed tomography CT scans of the chest In total 199 individuals were included in the analysis Most patients received oxygen supplementation 80 4 Six months after discharge 47 and 32 of patients still had exertional dyspnoea and fatigue PFTs at 3 month follow up revealed a reduced diffusion capacity of carbon monoxide mean 71 6 18 6 and this increased significantly at 6 month follow up P 0 0001 Chest CT scans showed a high prevalence 68 9 of the cohort of persistent abnormalities mainly ground glass opacities Duration of hospitalization intensive care unit admission and mechanical ventilation were not associated with the persistence of symptoms 3 months after discharge The prevalence of persistent symptoms following hospitalization with COVID 19 is high and stable for up to 6 months after discharge However biological functional and iconographic abnormalities improved significantly over time

SARS CoV 2 plays a pivotal role in inducing hyperthyroidism of Graves disease Coronavirus disease 2019 COVID 19 advances to affect every part of the globe and remains a challenge to the human race Severe acute respiratory syndrome coronavirus 2 SARS CoV 2 was shown to affect many organs and organ systems including the thyroid gland as these parts highly express angiotensin converting enzyme 2 ACE2 protein which functions as a receptor for initially entering the virus into the cells Furthermore some categories of the population including older people and persons with comorbidities are prone to be more vulnerable to COVID 19 and its complications Recent reports showed that SARS CoV 2 infection could cause Graves disease autoimmune hyperthyroidism in post COVID 19 patients Factors that may boost the mortality risk of COVID 19 patients are not completely known yet and a clear perception of the group of vulnerable people is also essential This review briefly summarizes the features of Graves disease such as symptoms risk factors including environmental genetic immunological and other factors associated disorders and therapeutic options It comprehensively describes the recent advances in SARS CoV 2 induced Graves disease and the pivotal role of autoimmune factors in inducing the disease The review also discusses the possible risks of SARS CoV 2 infection and associated COVID 19 in people with hyperthyroidism Furthermore it explains thyroid disease and its association with the severity of COVID 19

Changes in undergraduate medical education due to COVID 19 a systematic review This study aims to provide medical educators with insights into the current status and prospects of undergraduate medical education which has been affected by the COVID 19 pandemic We conducted a database search of PubMed Embase and ERIC and identified articles on COVID 19 related undergraduate medical education We independently reviewed titles and abstracts and extracted data on the geographic location of the study area of specialty phase in medical school preclinical year clerkship year etc type of paper and the main content of the study A total of 49 articles published across multiple countries were included in this study These were categorized as dealing with either 1 curriculum changes in undergraduate medical education due to COVID 19 or 2 student led educational activities related to COVID 19 The 41 articles in the first category showed two main trends replacing in person lectures with online classes in the preclinical years and adopting various remote educational methods to compensate for the discontinued or truncated clerkship in the clinical years The eight articles in the second category showcased various student educational activities that were conducted to meet the publics medical needs during the pandemic This review summarized the essential changes in undergraduate medical education worldwide and reflected on the various teaching methods adopted by medical schools In preparation for the post COVID era a comprehensive online curriculum and evaluation tools are needed which require the development of necessary infrastructure and adequate resources Education aimed at helping students be more socially aware and responsible as medical professionals must be promoted

The impact of artificial intelligence and digital style on industry and energy post COVID 19 pandemic The SARS CoV 2 virus caused crises in social economic and energy areas and medical life worldwide throughout 2020 This crisis had many direct and indirect effects on all areas of society In the meantime the digital and artificial intelligence industry can be used as a professional assistant to manage and control the outbreak of the virus The present articles objective is to investigate the effects of COVID 19 on each of the various fields of medicine industry and energy What sets this article apart is studying the impact of artificial intelligence and digital style on reducing the damage of this fatal virus Energy and related industries are of the areas affected by the SARS CoV 2 virus The most exciting approach in this article is to encourage countries with economies based on non renewable energy to develop solar and wind energies Renewable energies can operate well in the event of another phenomenon such as COVID 19 and reduce the viruss destructive effects and lead to economic prosperity

Old wine in a new bottle post COVID 19 infection central serous chorioretinopathy and the steroids Corona virus disease COVID 19 pandemic can cause myriad of ocular manifestations We report a case of unilateral multi focal central serous retinopathy post COVID 19 infection in an Asian Indian female A 42 year old female presented to us with unilateral blurring in the right eye OD 12 days after COVID 19 infection She had fever chills shortness of breath and cough with tiredness and was COVID RT PCR positive She was administered intravenous and oral antibiotics with injection heparin remdesivir during her 7 day stay at the hospital She was also on steroid inhalers She had no systemic history of note On ocular evaluation her corrected distance visual acuity was 20 40 in OD and 20 20 in left eye OS Anterior segment was normal Anterior vitreous was clear Fundus examination of the OD showed central serous retinopathy CSCR with OS being normal CSCR can occur post COVID 19 due to steroid administration and physicians administering it should be aware of this and refer the patients to an ophthalmologist earlier

Fibromyalgia a new facet of the post COVID 19 syndrome spectrum Results from a web based survey Postacute COVID 19 syndrome PACS is an emerging entity characterised by a large array of manifestations including musculoskeletal complaints fatigue and cognitive or sleep disturbances Since similar symptoms are present also in patients with fibromyalgia FM we decided to perform a web based cross sectional survey aimed at investigating the prevalence and predictors of FM in patients who recovered from COVID 19 Data were anonymously collected between 5 and 18 April 2021 The collection form consisted of 28 questions gathering demographic information features and duration of acute COVID 19 comorbid diseases and other individuals attributes such as height and weight The American College of Rheumatology ACR Survey Criteria and the Italian version of the Fibromyalgia Impact Questionnaire completed the survey A final sample of 616 individuals 77 4 women filled the form 6 3 months after the COVID 19 diagnosis Of these 189 30 7 satisfied the ACR survey criteria for FM 56 6 women A multivariate logistic regression model including demographic and clinical factors showed that male gender OR 9 95 95 CI 6 02 to 16 43 p 0 0001 and obesity OR 41 20 95 CI 18 00 to 98 88 p 0 0001 were the strongest predictors of being classified as having post COVID 19 FM Hospital admission rate was significantly higher in men 15 8 vs 9 2 p 0 001 and obese 19 2 vs 10 8 p 0 016 respondents Our data suggest that clinical features of FM are common in patients who recovered from COVID 19 and that obesity and male gender affect the risk of developing post COVID 19 FM

Refining Long COVID by a Prospective Multimodal Evaluation of Patients with Long Term Symptoms Attributed to SARS CoV 2 Infection COVID 19 long haulers also decribed as having long COVID or post acute COVID 19 syndrome represent 10 of COVID 19 patients and remain understudied In this prospective study we recruited 30 consecutive patients seeking medical help for persistent symptoms 30 days attributed to COVID 19 All reported a viral illness compatible with COVID 19 The patients underwent a multi modal evaluation including clinical psychologic virologic and specific immunologic assays and were followed longitudinally A group of 17 convalescent COVID 19 individuals without persistent symptoms were included as a comparison group The median age was 40 interquartile range 35 54 years and 18 60 were female At a median time of 152 102 164 days after symptom onset fever cough and dyspnea were less frequently reported compared with the initial presentation but paresthesia and burning pain emerged in 18 60 and 13 43 patients respectively The clinical examination was unremarkable in all patients although the median fatigue and pain visual analog scales were 7 5 8 and 5 2 6 respectively Extensive biologic studies were unremarkable and multiplex cytokines and ultra sensitive interferon α2 measurements were similar between long haulers and convalescent COVID 19 individuals without persistent symptoms Using SARS CoV 2 serology and IFN γ ELISPOT we found evidence of a previous SARS CoV 2 infection in 50 15 30 of patients with evidence of a lack of immune response or a waning immune response in two patients Finally psychiatric evaluation showed that 11 36 7 13 43 3 and 9 30 patients had a positive screening for anxiety depression and post traumatic stress disorder respectively Half of patients seeking medical help for post acute COVID 19 syndrome lack SARS CoV 2 immunity The presence of SARS CoV 2 immunity or not had no consequence on the clinical or biologic characteristics of post acute COVID 19 syndrome patients all of whom reported severe fatigue altered quality of life and psychologic distress

Not the great equalizers Covid 19 1918 20 influenza and the need for a paradigm shift in pandemic preparedness Despite common perceptions to the contrary pandemic diseases do not affect populations indiscriminately In this paper we review literature produced by demographers historians epidemiologists and other researchers on disparities during the 1918 20 influenza pandemic and the Covid 19 pandemic Evidence from these studies demonstrates that lower socio economic status and minority stigmatized race or ethnicity are associated with higher morbidity and mortality However such research often lacks theoretical frameworks or appropriate data to explain the mechanisms underlying these disparities fully We suggest using a framework that considers proximal and distal factors contributing to differential exposure susceptibility and consequences as one way to move this research forward Further current pandemic preparedness plans emphasize medically defined risk groups and epidemiological approaches Therefore we conclude by arguing in favour of a transdisciplinary paradigm that recognizes socially defined risk groups includes input from the social sciences and humanities and other diverse perspectives and contributes to the reduction of health disparities before a pandemic hits

Association of COVID 19 Mitigation Measures With Changes in Cardiorespiratory Fitness and Body Mass Index Among Children Aged 7 to 10 Years in Austria Previous studies have shown reductions in self reported physical activity levels in children associated with implementation of COVID 19 mitigation measures and data on objectively assessed health parameters are limited To examine the association of COVID 19 mitigation measures with changes in cardiorespiratory fitness CRF measures and body mass index BMI among primary schoolchildren This cohort study included children aged 7 to 10 years from 12 randomly selected primary schools in urban and rural districts of Klagenfurt Austria Baseline CRF and BMI measurements were obtained in September 2019 before COVID 19 mitigation measures were implemented and follow up measurements were obtained in June and September 2020 COVID 19 mitigation measures Cardiorespiratory fitness was measured with a 6 minute endurance run test Height and weight were objectively measured Standard deviation scores were calculated for CRF and BMI Changes over time were analyzed using analyses of variance Secondary analyses were performed for subgroups stratified by sex A total of 764 children 383 girls 50 1 aged 7 to 10 years had all measurements completed From September 2019 to September 2020 CRF SD scores changed by 1 06 95 CI 1 13 to 1 00 with a similar decrease in both boys and girls Body mass index SD scores had increased by 0 12 95 CI 0 06 0 16 in June 2020 and by 0 16 95 CI 0 12 0 20 in September 2020 compared with September 2019 The increase in BMI SD scores from September 2019 to September 2020 was greater among boys 0 23 95 CI 0 18 0 29 than among girls 0 09 95 CI 0 04 0 15 During the 1 year period the percentage of children with overweight or obesity increased from 20 3 155 children to 24 1 184 children difference 3 8 29 children In this cohort study of children in Austria COVID 19 mitigation measures were associated with decreases in CRF measures and increases in BMI The findings suggest that collaborative efforts are needed to reverse these changes in childrens health to prevent long term negative health outcomes

Long COVID and breathlessness an overview This article offers a review of what is known so far about post acute covid 19 and the underlying pathophysiology related to this condition The main focus will be on the respiratory symptoms It will then explore how community nurses can monitor and support patients with symptoms of breathlessness with a supporting discussion of the current recommendations for the management and treatment of patients presenting with symptoms of breathlessness Palliation of symptoms will be highlighted but managing the supportive care needs for patients affected by COVID 19 and nearing the end of life is outside the scope of this article

Comparison of Clinical Features and Outcome of Dengue Fever and Multisystem Inflammatory Syndrome in Children Associated With COVID 19 MIS C To identify clinical and laboratory features that differentiate dengue fever patients from MIS C patients and determine their outcomes This comparative cross sectional study was done at a tertiary care teaching institute We enrolled all hospitalized children aged 1 month 18 years and diagnosed with either MIS C and or dengue fever according to WHO criteria between June and December 2020 Clinical and laboratory features and outcomes were recorded on a structured proforma During the study period 34 cases of MIS C and 83 cases of Dengue fever were enrolled Mean age of MIS C cases male 86 3 was 7 89 4 61 years MIS C with shock was seen in 15 cases 44 MIS C without shock in 17 cases 50 and Kawasaki disease like presentation in 2 cases 6 Patients of MIS C were younger as compared to dengue fever P 0 002 Abdominal pain and erythematous rash were more common in dengue fever Of the inflammatory markers mean C reactive protein was higher in MIS C patients 100 2 85 1 vs 16 9 29 3 mg dL P 0 001 In contrast serum ferritin levels were higher in dengue fever patients P 0 03 Mean hospital stay patient days was longer in MIS C compared to dengue fever 8 6 vs 6 5 days P 0 014 Clinical and laboratory features can give important clues to differentiate dengue fever and MIS C and help initiate specific treatment

Possible Adrenal Involvement in Long COVID Syndrome i Background i A significant number of patients with COVID 19 experience prolonged symptoms known as Long COVID The most frequent symptoms are fatigue and cognitive dysfunction We describe a patient suffering from Long COVID in whom adrenal involvement was highlighted i Methods i The patient described Long COVID symptoms that persist 3 months after the negativization of the molecular swab test The main symptoms were weakness brain fog dizziness and muscular and joint pain All routine lab panels for inflammation anemia and thyroid and liver function were conducted Moreover salivary cortisol and DHEA S determinations were used to compute the adrenal stress index ASI i Results i All tests were negative except the ASI that showed very low levels of free cortisol The patient started hydrocortisone acetate supplementation i Conclusion i Long COVID symptoms could be explained by an adrenal involvement due to a COVID 19 action on adrenal glands and by a iatrogenic side effect of high glucocorticoid therapy during the COVID 19 infection Salivary cortisol determination is effective for establishing a correct recovery plan

Staying tuned for post COVID 19 syndrome looking for new research to sniff out Post COVID 19 syndrome was defined as a persistent and protracted illness which follows acute COVID 19 infection This condition continues for more than 12 weeks and cannot be attributed to other clinical situations Researchers and clinicians are allied in unraveling the molecular pathogenetic mechanisms and the clinical development of this unexpected SARS CoV 2 infectious evolution Anosmia dysgeusia fatigue dyspnea and brain fog are common symptoms observed in the Post COVID 19 syndrome depicting a multiorgan involvement associated with injuries involving mainly cardiovascular pulmonary musculoskeletal and neuropsychiatric systems This commentary analyzes the state of the art of Post COVID 19 interdisciplinary studies confirming that we are facing a truly intricate biomedicine story

Public health consequences after ten years of the Syrian crisis a literature review Ten years of the Syrian war had a devastating effect on Syrian lives including millions of refugees and displaced people enormous destruction in the infrastructure and the worst economic crisis Syria has ever faced The health sector was hit hard by this war up to 50 of the health facilities have been destroyed and up to 70 of the healthcare providers fled the country seeking safety which increased the workload and mental pressure for the remaining medical staff Five databases were searched and 438 articles were included according to the inclusion criteria the articles were divided into categories according to the topic of the article Through this review the current health status of the Syrian population living inside Syria whether under governmental or opposition control was reviewed and also the health status of the Syrian refugees was examined according to each host country Public health indicators were used to summarize and categorize the information This research reviewed mental health children and maternal health oral health non communicable diseases infectious diseases occupational health and the effect of the COVID 19 pandemic on the Syrian healthcare system The results of the review are irritating as still after ten years of war and millions of refugees there is an enormous need for healthcare services and international organization has failed to respond to those needs The review ended with the current and future challenges facing the healthcare system and suggestions about rebuilding the healthcare system Through this review the major consequences of the Syrian war on the health of the Syrian population have been reviewed and highlighted Considerable challenges will face the future of health in Syria which require the collaboration of the health authorities to respond to the growing needs of the Syrian population This article draws an overview about how the Syrian war affected health sector for Syrian population inside and outside Syria after ten years of war which makes it an important reference for future researchers to get the main highlight of the health sector during the Syrian crisis

Practice patterns in surgical neuro oncology among low and middle income countries during the coronavirus 19 pandemic A scoping review and situational report from the Philippines The coronavirus disease 2019 COVID 19 pandemic has negatively impacted the outcomes of surgical neuro oncology patients worldwide We aimed to review the practice patterns in surgical neuro oncology in low and middle income countries LMICs We also present a situational report from our own country A scoping review was performed following the Preferred Reporting Items for Systematic reviews and Meta Analyses Extension for Scoping Reviews Guidelines Twelve studies were included in the review Most of the studies were from Asia India China Iran Turkey and one was from Brazil Quantitative reports showed a decrease in the number of surgical neuro oncology operations between pre and post COVID 19 time frames but similar proportions of neuro oncology procedures Qualitative review showed similar practice patterns between LMICs and high income countries HICs except for limitations in resources such as negative pressure operating rooms and intensive care units and maintenance of face to face consults despite the adoption of telemedicine Limited data on adjuvant therapy was available in LMICs In our review we found that the practice patterns in surgical neuro oncology in LMICs during the COVID 19 pandemic are similar to those in HICs except for a few modifications due to resource limitation and patient preferences

Building resilient societies after COVID 19 the case for investing in maternal neonatal and child health Resilient societies respond rapidly and effectively to health challenges and the associated economic consequences and adapt to be more responsive to future challenges Although it is only possible to recognise resilience retrospectively the COVID 19 pandemic has occurred at a point in human history when uniquely sufficient knowledge is available on the early life determinants of health to indicate clearly that a focus on maternal neonatal and child health MNCH will promote later resilience This knowledge offers an unprecedented opportunity to disrupt entrenched strategies and to reinvest in MNCH in the post COVID 19 so called new normal Furthermore analysis of the short term medium term and longer term consequences of previous socioeconomic shocks provides important insights into those domains of MNCH such as neurocognitive development and nutrition for which investment will generate the greatest benefit Such considerations apply to high income countries HICs and low income and middle income countries LMICs However implementing appropriate policies in the post COVID 19 recovery period will be challenging and requires political commitment and public engagement

Post COVID 19 syndrome epidemiology diagnostic criteria and pathogenic mechanisms involved Many patients with mild or severe COVID 19 do not make a full recovery and have a wide range of chronic symptoms for weeks or months after infection often of a neurological cognitive or psychiatric nature The epidemiological evidence diagnostic criteria and pathogenesis of post COVID 19 syndrome are reviewed Post COVID 19 syndrome is defined by persistent clinical signs and symptoms that appear while or after suffering COVID 19 persist for more than 12 weeks and cannot be explained by an alternative diagnosis The symptoms can fluctuate or cause relapses It is a heterogeneous condition that includes post viral chronic fatigue syndrome sequelae in multiple organs and the effects of severe hospitalisation post intensive care syndrome It has been reported in patients with mild or severe COVID 19 and irrespective of the severity of the symptoms in the acute phase Between 10 and 65 of survivors who had mild moderate COVID 19 present symptoms of post COVID 19 syndrome for 12 weeks or more At six months subjects report an average of 14 persistent symptoms The most common symptoms are fatigue dyspnoea anxiety depression and impaired attention concentration memory and sleep The underlying biological mechanisms are unknown although an abnormal or excessive autoimmune and inflammatory response may play an important role Clinical manifestations are diverse fluctuating and variable although fatigue and neurocognitive complaints predominate There is no defined consensus on post COVID 19 syndrome and its diagnostic criteria have not been subjected to adequate psychometric evaluation

Post COVID Syndrome An Insight on Its Pathogenesis Post COVID syndrome is increasingly recognized as a new clinical entity in the context of SARS CoV 2 infection Symptoms persisting for more than three weeks after the diagnosis of COVID 19 characterize the post COVID syndrome Its incidence ranges from 10 to 35 however rates as high as 85 have been reported among patients with a history of hospitalization Currently there is no consensus on the classification of post COVID syndrome We reviewed the published information on post COVID syndrome putting emphasis on its pathogenesis The pathogenesis of post COVID syndrome is multi factorial and more than one mechanism may be implicated in several clinical manifestations Prolonged inflammation has a key role in its pathogenesis and may account for some neurological complications cognitive dysfunction and several other symptoms A multisystem inflammatory syndrome in adults MIS A of all ages has been also described recently similarly to multisystem inflammatory syndrome in children MIS C The post infectious inflammatory pathogenetic mechanism of MIS A is supported by the fact that its diagnosis is established through serology in up to one third of cases Other pathogenetic mechanisms that are implicated in post COVID syndrome include immune mediated vascular dysfunction thromboembolism and nervous system dysfunction Although the current data are indicating that the overwhelming majority of patients with post COVID syndrome have a good prognosis registries to actively follow them are needed in order to define the full clinical spectrum and its long term outcome A consensus based classification of post COVID syndrome is essential to guide clinical diagnostic and therapeutic management Further research is also imperative to elucidate the pathogenesis of post COVID syndrome

Long COVID syndrome associated brain fog and chemofog Luteolin to the rescue COVID 19 leads to severe respiratory problems but also to long COVID syndrome associated primarily with cognitive dysfunction and fatigue Long COVID syndrome symptoms especially brain fog are similar to those experienced by patients undertaking or following chemotherapy for cancer chemofog or chemobrain as well in patients with myalgic encephalomyelitis chronic fatigue syndrome ME CFS or mast cell activation syndrome MCAS The pathogenesis of brain fog in these illnesses is presently unknown but may involve neuroinflammation via mast cells stimulated by pathogenic and stress stimuli to release mediators that activate microglia and lead to inflammation in the hypothalamus These processes could be mitigated by phytosomal formulation in olive pomace oil of the natural flavonoid luteolin

Long COVID and Myalgic Encephalomyelitis Chronic Fatigue Syndrome ME CFS A Systemic Review and Comparison of Clinical Presentation and Symptomatology i Background and Objectives i Long COVID defines a series of chronic symptoms that patients may experience after resolution of acute COVID 19 Early reports from studies with patients with long COVID suggests a constellation of symptoms with similarities to another chronic medical illness myalgic encephalomyelitis chronic fatigue syndrome ME CFS A review study comparing and contrasting ME CFS with reported symptoms of long COVID may yield mutualistic insight into the characterization and management of both conditions i Materials and Methods i A systemic literature search was conducted in MEDLINE and PsycInfo through to 31 January 2021 for studies related to long COVID symptomatology The literature search was conducted in accordance with PRISMA methodology i Results i Twenty one studies were included in the qualitative analysis Long COVID symptoms reported by the included studies were compared to a list of ME CFS symptoms compiled from multiple case definitions Twenty five out of 29 known ME CFS symptoms were reported by at least one selected long COVID study i Conclusions i Early studies into long COVID symptomatology suggest many overlaps with clinical presentation of ME CFS The need for monitoring and treatment for patients post COVID is evident Advancements and standardization of long COVID research methodologies would improve the quality of future research and may allow further investigations into the similarities and differences between long COVID and ME CFS

A dermatologic perspective on multisystem inflammatory syndrome in children As of May 2020 an emerging immune mediated syndrome primarily affecting children has been detected primarily in Europe and the United States The incidence of this syndrome appears to mirror the initial infectious assault with a delay of several weeks This syndrome has been termed multisystem inflammatory syndrome in children MIS C and is observed in association with the coronavirus disease 2019 The phenotypes of presentation include several characteristic features including prolonged fever skin eruptions neck stiffness and gastrointestinal manifestations with pronounced abdominal pain Shock and organ dysfunction on presentation are frequent but inconsistent whereas respiratory distress is typically and notably absent We have reviewed the recent published data aiming to better understand MIS C with a focus on its mucocutaneous manifestations

Insight into the emerging role of SARS CoV 2 nonstructural and accessory proteins in modulation of multiple mechanisms of host innate defense Coronavirus disease 19 COVID 19 is an extremely infectious disease caused by severe acute respiratory syndrome coronavirus 2 SARS CoV 2 that has become a major global health concern The induction of a coordinated immune response is crucial to the elimination of any pathogenic infection However SARS CoV 2 can modulate the host immune system to favor viral adaptation and persistence within the host The virus can counteract type I interferon IFN I production attenuating IFN I signaling pathway activation and disrupting antigen presentation Simultaneously SARS CoV 2 infection can enhance apoptosis and the production of inflammatory mediators which ultimately results in increased disease severity SARS CoV 2 produces an array of effector molecules including nonstructural proteins NSPs and open reading frames ORFs accessory proteins We describe the complex molecular interplay of SARS CoV 2 NSPs and accessory proteins with the hosts signaling mediating immune evasion in the current review In addition the crucial role played by immunomodulation therapy to address immune evasion is discussed Thus the current review can provide new directions for the development of vaccines and specific therapies

Rapid implementation of a cohort for the study of post acute sequelae of SARS CoV 2 infection COVID 19 As the coronavirus disease 2019 COVID 19 pandemic continues and millions remain vulnerable to infection with severe acute respiratory syndrome coronavirus 2 SARS CoV 2 attention has turned to characterizing post acute sequelae of SARS CoV 2 infection PASC From April 21 to December 31 2020 we assembled a cohort of consecutive volunteers who a had documented history of SARS CoV 2 RNA positivity b were 2 weeks past onset of COVID 19 symptoms or if asymptomatic first test for SARS CoV 2 and c were able to travel to our site in San Francisco Participants learned about the study by being identified on medical center based registries and being notified or by responding to advertisements At 4 month intervals we asked participants about physical symptoms that were new or worse compared to the period prior to COVID 19 mental health symptoms and quality of life We described 4 time periods 1 acute illness 0 3 weeks 2 early recovery 3 10 weeks 3 late recovery 1 12 20 weeks and 4 late recovery 2 28 36 weeks Blood and oral specimens were collected at each visit We have to date enrolled 179 adults During acute SARS CoV 2 infection 10 had been asymptomatic 125 symptomatic but not hospitalized and 44 symptomatic and hospitalized In the acute phase the most common symptoms were fatigue fever myalgia cough and anosmia dysgeusia During the post acute phase fatigue shortness of breath concentration problems headaches trouble sleeping and anosmia dysgeusia were the most commonly reported symptoms but a variety of others were endorsed by at least some participants Some experienced symptoms of depression anxiety and post traumatic stress as well as difficulties with ambulation and performance of usual activities The median visual analogue scale value rating of general health was lower at 4 and 8 months 80 interquartile range IQR 70 90 and 80 IQR 75 90 compared to prior to COVID 19 85 IQR 75 90 Biospecimens were collected at nearly 600 participant visits Among a cohort of participants enrolled in the post acute phase of SARS CoV 2 infection we found many with persistent physical symptoms through 8 months following onset of COVID 19 with an impact on self rated overall health The presence of participants with and without symptoms and ample biological specimens will facilitate study of PASC pathogenesis Similar evaluations in a population representative sample will be needed to estimate the population level prevalence of PASC

Persistent Post COVID 19 Interstitial Lung Disease An Observational Study of Corticosteroid Treatment b Rationale b The natural history of recovery from severe acute respiratory syndrome coronavirus 2 SARS CoV 2 remains unknown Because fibrosis with persistent physiological deficit is a previously described feature of patients recovering from similar coronaviruses treatment represents an early opportunity to modify the disease course potentially preventing irreversible impairment b Objectives b Determine the incidence of and describe the progression of persistent inflammatory interstitial lung disease ILD following SARS CoV 2 when treated with prednisolone b Methods b A structured assessment protocol screened for sequelae of SARS CoV 2 pneumonitis Eight hundred thirty seven patients were assessed by telephone 4 weeks after discharge Those with ongoing symptoms had outpatient assessment at 6 weeks Thirty patients diagnosed with persistent interstitial lung changes at a multidisciplinary team meeting were reviewed in the interstitial lung disease service and offered treatment These patients had persistent nonimproving symptoms b Results b At 4 weeks after discharge 39 of patients reported ongoing symptoms 325 837 and were assessed Interstitial lung disease predominantly organizing pneumonia with significant functional deficit was observed in 35 837 survivors 4 8 Thirty of these patients received steroid treatment resulting in a mean relative increase in transfer factor following treatment of 31 6 standard deviation SD 27 6 i P i 0 001 and forced vital capacity of 9 6 SD 13 0 i P i 0 014 with significant symptomatic and radiological improvement b Conclusions b Following SARS CoV 2 pneumonitis a cohort of patients are left with both radiological inflammatory lung disease and persistent physiological and functional deficit Early treatment with corticosteroids was well tolerated and associated with rapid and significant improvement These preliminary data should inform further study into the natural history and potential treatment for patients with persistent inflammatory ILD following SARS CoV 2 infection

Some patients complain of persisting symptoms after acute COVID 19 There is no universal definition yet for these post acute sequelae also termed Long COVID Although their prevalence remains to be established a delayed recovery seems to be more common than after other acute infectious diseases Common complaints include fatigue with exercise intolerance dyspnea on exertion chest pain and neuropsychiatric symptoms Female sex comorbidities and severity of the acute disease have been identified as risk factors for persisting symptoms It is however important to highlight that they are not limited to patients after severe COVID 19 Whilst their pathogenesis and prognosis is largely unknown diagnostic evaluation should focus on exclusion of objective organ dysfunctions Due to the variable presentation management is interdisciplinary and may include physiotherapy rehabilitation programmes and psychological support This article aims to summarize the current limited evidence on persisting symptoms after COVID 19

Molecular Pathophysiology of Cardiac Injury and Cardiac Microthrombi in Fatal COVID 19 Insights from Clinico histopathologic and Single Nuclei RNA Sequencing Analyses Cardiac injury is associated with critical COVID 19 yet its etiology remains debated To elucidate the pathogenic mechanisms of COVID 19 associated cardiac injury we conducted a single center prospective cohort study of 69 COVID 19 decedents Of six cardiac histopathologic features microthrombi was the most commonly detected n 48 70 We tested associations of cardiac microthrombi with biomarkers of inflammation cardiac injury and fibrinolysis and with in hospital antiplatelet therapy therapeutic anticoagulation and corticosteroid treatment while adjusting for multiple clinical factors including COVID 19 therapies Higher peak ESR and CRP during hospitalization were independently associated with higher odds of microthrombi Using single nuclei RNA sequence analysis we discovered an enrichment of pro thrombotic anti fibrinolytic extracellular matrix remodeling and immune potentiating signaling amongst cardiac fibroblasts in microthrombi positive COVID 19 hearts relative to microthrombi negative COVID 19 Non COVID 19 non failing hearts were used as reference controls Our cumulative findings identify the specific transcriptomic changes in cardiac fibroblasts as salient features of COVID 19 associated cardiac microthrombi

Post COVID 19 multisystem inflammatory syndrome in children The effect of acute coronavirus disease 2019 COVID 19 on morbidity and mortality in children has been relatively small If a child presents to my office with persistent fever and systemic hyperinflammation but no known exposure to COVID 19 how likely are they to have multisystem inflammatory syndrome in children MIS C What is currently known about MIS C and what is the prognosis for children affected by it Amid the COVID 19 pandemic the emergence of a novel condition presents yet another challenge to clinicians public health professionals and the pediatric population Multisystem inflammatory syndrome in children is a rare but potentially severe condition seen in children with evidence of COVID 19 approximately 2 to 6 weeks before symptom onset Common signs and symptoms include persistent fever systemic hyperinflammation gastrointestinal symptoms eg abdominal pain vomiting diarrhea mucocutaneous changes eg rash conjunctivitis headache or cardiac dysfunction As many children present as asymptomatic or with mild symptoms of COVID 19 the development of MIS C can seem sudden and surprising to families and providers Although children with MIS C usually require hospitalization the outcomes are largely favourable with prompt recognition and intense therapy

Inflammation type dysbiosis of the oral microbiome associates with the duration of COVID 19 symptoms and long COVID In the COVID 19 pandemic caused by SARS CoV 2 many individuals experience prolonged symptoms termed long lasting COVID 19 symptoms long COVID Long COVID is thought to be linked to immune dysregulation due to harmful inflammation with the exact causes being unknown Given the role of the microbiome in mediating inflammation we aimed to examine the relationship between the oral microbiome and the duration of long COVID symptoms Tongue swabs were collected from patients presenting with COVID 19 symptoms Confirmed infections were followed until resolution of all symptoms Bacterial composition was determined by metagenomic sequencing We used random forest modeling to identify microbiota and clinical covariates that are associated with long COVID symptoms Of the patients followed 63 developed ongoing symptomatic COVID 19 and 37 went on to long COVID Patients with prolonged symptoms had significantly higher abundances of microbiota that induced inflammation such as members of the genera Prevotella and Veillonella which of note are species that produce LPS The oral microbiome of patients with long COVID was similar to that of patients with chronic fatigue syndrome Altogether our findings suggest an association with the oral microbiome and long COVID revealing the possibility that dysfunction of the oral microbiome may have contributed to this draining disease

Assessment of tryptophan and kynurenine as prognostic markers in patients with SARS CoV 2 Immune dysregulation and inflammation in patients with SARS CoV 2 is associated with a poor clinical outcome We investigated the value of the inflammatory markers tryptophan and kynurenine in predicting the survival outcome of patients with SARS CoV 2 The study included 252 inpatients with a SARS CoV 2 infection hospitalized between August 2020 and April 2021 Two groups were generated based on disease survival survival group n 199 deceased group n 53 Plasma concentrations of tryptophan kynurenine and interleukin 6 IL 6 were measured on admission In a subset of patients n 105 81 survivors and 24 deceased concentrations of tryptophan and kynurenine were checked 7 days after admission The kynurenine tryptophan ratio TRP KYN ratio was calculated On admission the deceased group showed significantly higher concentrations of kynurenine and a significantly higher KYN TRP ratio compared to the survival group p values 0 001 Kynurenine and the KYN TRP ratio significantly correlated with IL 6 ρ 0 441 and 0 448 p values 0 001 In the survival group kynurenine and the KYN TRP ratio were significantly lower after seven days p values 0 001 In the deceased group no significant differences were found between the measurements Kynurenine and the KYN TRP ratio are potentially useful parameters in predicting the survival outcome in SARS CoV 2 positive patients

Prevalence of childhood mental disorders in high income countries a systematic review and meta analysis to inform policymaking Mental disorders typically start in childhood and persist causing high individual and collective burdens To inform policymaking to address childrens mental health in high income countries we aimed to identify updated data on disorder prevalence We identified epidemiological studies reporting mental disorder prevalence in representative samples of children aged 18 years or younger including a range of disorders and ages and assessing impairment searching January 1990 through February 2021 We extracted associated service use data where studies assessed this We conducted meta analyses using a random effects logistic model using R metafor package Fourteen studies in 11 countries met inclusion criteria published from 2003 to 2020 with a pooled sample of 61 545 children aged 4 18 years including eight reporting service use All data were collected pre COVID 19 Overall prevalence of any childhood mental disorder was 12 7 95 CI 10 1 to 15 9 I sup 2 sup 99 1 Significant heterogeneity pertained to diagnostic measurement and study location Anxiety 5 2 attention deficit hyperactivity 3 7 oppositional defiant 3 3 substance use 2 3 conduct 1 3 and depressive 1 3 disorders were the most common Among children with mental disorders only 44 2 95 CI 37 6 to 50 9 received any services for these conditions An estimated one in eight children have mental disorders at any given time causing symptoms and impairment therefore requiring treatment Yet even in high income countries most children with mental disorders are not receiving services for these conditions We discuss the implications particularly the need to substantially increase public investments in effective interventions We also discuss the policy urgency given the emerging increases in childhood mental health problems since the onset of the COVID 19 pandemic PROSPERO CRD42020157262

Post Ebola sequelae among Ebola child survivors in Sierra Leone There are limited data regarding the long term health effects of child survivors of the 2013 2016 West African Ebola virus disease EVD outbreak Here we assess post Ebola sequelae among EVD child survivors by comparing the self reported symptoms between EVD child survivors and their close household contacts over one year after the end of the outbreak EVD child survivors n 159 and their close contacts n 303 were enrolled in Western and Eastern Sierra Leone Demographics and self reported symptoms data were collected using an interviewer administered questionnaire We compared a list of self reported symptoms between EVD child survivors and their close household contacts using backward stepwise logistic regression EVD child survivors were more likely to be orphans compared to their close contacts Musculoskeletal ocular auditory and neurological symptoms were more prevalent among Ebola child survivors than their close contacts p 0 001 Joint pain and headache were the most common self reported symptoms in EVD child survivors and their close contacts Joint pain AOR 2 633 95 CI 1 31 5 28 p 0 006 eye pain AOR 4 56 95 CI 2 16 9 64 p 0 001 hearing loss AOR 3 85 95 CI 1 15 12 87 p 0 029 memory impairment AOR 7 76 0 95 CI 1 34 45 01 p 0 022 mood changes AOR 5 07 95 CI 2 35 10 94 p 0 001 were more common among survivors than their contacts Our data suggest that EVD child survivors have higher odds than their close contacts of suffering from musculoskeletal ophthalmic auditory and neurological impairment more than a year after the end of the EVD outbreak Routine screening treatment and monitoring of these symptoms is required to prevent long term disability among EVD child survivors

Gastrointestinal Perspective of Coronavirus Disease 2019 in Children An Updated Review Gastrointestinal symptoms are common findings in children with severe acute respiratory syndrome coronavirus 2 infection including vomiting diarrhoea abdominal pain and difficulty in feeding although these symptoms tend to be mild The hepato biliary system and the pancreas may also be involved usually with a mild elevation of transaminases and rarely pancreatitis In contrast a late hyper inflammatory phenomenon termed multisystem inflammatory syndrome MIS C is characterized by more frequent gastrointestinal manifestations with greater severity sometimes presenting as peritonitis Gastrointestinal and hepato biliary manifestations are probably related to a loss in enterocyte absorption capability and microscopic mucosal damage caused by a viral infection of intestinal epithelial cells hepatocytes and other cells through the angiotensin conversion enzyme 2 receptor resulting in immune cells activation with subsequent release of inflammatory cytokines Specific conditions such as inflammatory bowel disease IBD and liver transplantation may pose a risk for the more severe presentation of coronavirus disease 2019 COVID 19 but as adult data accumulate paediatric data is still limited The aim of this review is to summarize the current evidence about the effect of COVID 19 on the gastrointestinal system in children with emphasis on the emerging MIS C and specific considerations such as patients with IBD and liver transplant recipients

The effects of school closures on SARS CoV 2 among parents and teachers To reduce the transmission of severe acute respiratory syndrome coronavirus 2 SARS CoV 2 most countries closed schools despite uncertainty if school closures are an effective containment measure At the onset of the pandemic Swedish upper secondary schools moved to online instruction while lower secondary schools remained open This allows for a comparison of parents and teachers differently exposed to open and closed schools but otherwise facing similar conditions Leveraging rich Swedish register data we connect all students and teachers in Sweden to their families and study the impact of moving to online instruction on the incidence of SARS CoV 2 and COVID 19 We find that among parents exposure to open rather than closed schools resulted in a small increase in PCR confirmed infections odds ratio OR 1 17 95 CI CI95 1 03 to 1 32 Among lower secondary teachers the infection rate doubled relative to upper secondary teachers OR 2 01 CI95 1 52 to 2 67 This spilled over to the partners of lower secondary teachers who had a higher infection rate than their upper secondary counterparts OR 1 29 CI95 1 00 to 1 67 When analyzing COVID 19 diagnoses from healthcare visits and the incidence of severe health outcomes results are similar for teachers but weaker for parents and teachers partners The results for parents indicate that keeping lower secondary schools open had minor consequences for the overall transmission of SARS CoV 2 in society The results for teachers suggest that measures to protect teachers could be considered

Implementation of post intensive care outpatient clinic I POINT for critically ill COVID 19 survivors Although we have enough and cumulative information about acute effects of COVID 19 our knowledge is extremely limited about long term consequences of COVID 19 in terms of its impacts and burdens on patients families and the health system Considering the underlying pathophysiological mechanisms affecting all of the organ systems in critically ill COVID 19 patients who are admitted to intensive care units the development of post intensive care syndrome PICS is inevitable This situation brings along the development of long COVID These patients should be followed regarding cognitive physical and psychiatric aspects and necessary specialist referrals should be carried out In this article we are presenting the experience and recommendations of our center as a guide for the establishment process of post intensive care outpatient clinics for the critically ill patients who required intensive care admission due to COVID 19 and could be discharged

Psychological Impact of COVID 19 on Children and Adolescents A Systematic Review The outbreak of COVID 19 led to a significant psychological impact on individuals particularly those belonging to vulnerable groups This study aimed to synthesize literature on the psychological impact of COVID 19 among children and adolescents Electronic search engines were used to identify studies till March 2021 that reported symptoms of psychological origin in children and adolescents Information was extracted using a predefined template and qualitative analysis was conducted using STROBE One hundred and two relevant papers were identified Most of the studies were conducted online or telephonically The study designs were primarily single group cross sectional though a few prospective retrospective designs were also identified Studies assessing emotional distress showed variable levels of anxiety and depressive symptoms in the study population with greater severity of anxiety symptoms among females and older adolescents Reduced physical activity delayed sleep time increased sleep duration screen time internet use and sedentary habits poor quality of life were other notable findings often correlating with anxiety depression Efforts to address bias discussion on generalizability of their results and sample size calculation were not reported in most studies Psychological impact on children adolescents is significant either due to the fear of the illness or social isolation related to COVID 19 One may focus on improving sleep habits and physical activity and regulating internet use for maintaining psychological well being

Caring for refugees and newcomers in the post COVID 19 era Evidence review and guidance for FPs and health providers To guide clinicians working in a range of primary care clinical settings on how to provide effective care and support for refugees and newcomers during and after the coronavirus disease 2019 COVID 19 pandemic The described approach integrates recommendations from evidence based clinical guidelines on refugee health and COVID 19 practical lessons learned from Canadian Refugee Health Network clinicians working in a variety of primary care settings and contributions from persons with lived experience of forced migration The COVID 19 pandemic has amplified health and social inequities for refugees asylum seekers undocumented migrants transient migrant workers and other newcomers Refugees and newcomers face front line exposure risks difficulties accessing COVID 19 testing exacerbation of mental health concerns and challenges accessing health care social and settlement supports Existing guidelines for clinical care of refugees are useful but creative case by case strategies must be employed to overcome additional barriers in the context of COVID 19 and new care environments such as the need for virtual interpretation and digital literacy skills Clinicians can address inequities and advocate for improved services in collaboration with community partners The COVID 19 pandemic is amplifying structural inequities Refugees and newcomers require and deserve effective health care and support during this challenging time This article outlines practical approaches and advocacy priorities for providing care in the COVID 19 context

Critical analysis of acute kidney injury in pediatric COVID 19 patients in the intensive care unit COVID 19 is responsible for the 2019 novel coronavirus disease pandemic Despite the vast research about the adult population there has been little data collected on acute kidney injury AKI epidemiology associated risk factors treatments and mortality in pediatric COVID 19 patients admitted to the ICU AKI is a severe complication of COVID 19 among children and adolescents A comprehensive literature search was conducted in PubMed MEDLINE and Cochrane Center Trials to find all published literature related to AKI in COVID 19 patients including incidence and outcomes Twenty four studies reporting the outcomes of interest were included Across all studies the overall sample size of COVID positive children was 1 247 and the median age of this population was 9 1 years old Among COVID positive pediatric patients there was an AKI incidence of 30 51 with only 0 56 of these patients receiving KRT The mortality was 2 55 among all COVID positive pediatric patients The incidence of multisystem inflammatory syndrome in children MIS C among COVID positive patients was 74 29 AKI has shown to be a negative prognostic factor in adult patients with COVID 19 and now also in the pediatric cohort with high incidence and mortality rates Additionally our findings show a strong comparison in epidemiology between adult and pediatric COVID 19 patients however they need to be confirmed with additional data and studies

Incomplete Systemic Recovery and Metabolic Phenoreversion in Post Acute Phase Nonhospitalized COVID 19 Patients Implications for Assessment of Post Acute COVID 19 Syndrome We present a multivariate metabotyping approach to assess the functional recovery of nonhospitalized COVID 19 patients and the possible biochemical sequelae of Post Acute COVID 19 Syndrome colloquially known as long COVID Blood samples were taken from patients ca 3 months after acute COVID 19 infection with further assessment of symptoms at 6 months Some 57 of the patients had one or more persistent symptoms including respiratory related symptoms like cough dyspnea and rhinorrhea or other nonrespiratory symptoms including chronic fatigue anosmia myalgia or joint pain Plasma samples were quantitatively analyzed for lipoproteins glycoproteins amino acids biogenic amines and tryptophan pathway intermediates using Nuclear Magnetic Resonance NMR spectroscopy and mass spectrometry Metabolic data for the follow up patients i n i 27 were compared with controls i n i 41 and hospitalized severe acute respiratory syndrome SARS CoV 2 positive patients i n i 18 with multiple time points Univariate and multivariate statistics revealed variable patterns of functional recovery with many patients exhibiting residual COVID 19 biomarker signatures Several parameters were persistently perturbed e g elevated taurine i p i 3 6 10 sup 3 sup versus controls and reduced glutamine glutamate ratio i p i 6 95 10 sup 8 sup versus controls indicative of possible liver and muscle damage and a high energy demand linked to more generalized tissue repair or immune function Some parameters showed near complete normalization e g the plasma apolipoprotein B100 A1 ratio was similar to that of healthy controls but significantly lower i p i 4 2 10 sup 3 sup than post acute COVID 19 patients reflecting partial reversion of the metabolic phenotype phenoreversion toward the healthy metabolic state Plasma neopterin was normalized in all follow up patients indicative of a reduction in the adaptive immune activity that has been previously detected in active SARS CoV 2 infection Other systemic inflammatory biomarkers such as GlycA and the kynurenine tryptophan ratio remained elevated in some but not all patients Correlation analysis principal component analysis PCA and orthogonal partial least squares discriminant analysis O PLS DA showed that the follow up patients were as a group metabolically distinct from controls and partially comapped with the acute phase patients Significant systematic metabolic differences between asymptomatic and symptomatic follow up patients were also observed for multiple metabolites The overall metabolic variance of the symptomatic patients was significantly greater than that of nonsymptomatic patients for multiple parameters χ sup 2 sup i p i 0 014 Thus asymptomatic follow up patients including those with post acute COVID 19 Syndrome displayed a spectrum of multiple persistent biochemical pathophysiology suggesting that the metabolic phenotyping approach may be deployed for multisystem functional assessment of individual post acute COVID 19 patients

SARS CoV 2 and the Brain What Do We Know about the Causality of Cognitive COVID The second year of the COVID 19 coronavirus disease pandemic has seen the need to identify and assess the long term consequences of a SARS CoV 2 infection on an individuals overall wellbeing including adequate cognitive functioning Cognitive COVID is an informal term coined to interchangeably refer to acute changes in cognition during COVID 19 and or cognitive sequelae with various deficits following the infection These may manifest as altered levels of consciousness encephalopathy like symptoms delirium and loss of various memory domains Dysexecutive syndrome is a peculiar manifestation of Cognitive COVID as well In the previous major outbreaks of viruses like SARS CoV MERS CoV and Influenza There have been attempts to understand the underlying mechanisms describing the causality of similar symptoms following SARS CoV 2 infection This review therefore is attempting to highlight the current understanding of the various direct and indirect mechanisms focusing on the role of neurotropism of SARS CoV 2 the general pro inflammatory state and the pandemic associated psychosocial stressors in the causality of Cognitive COVID Neurotropism is associated with various mechanisms including retrograde neuronal transmission via olfactory pathway a general hematogenous spread and the virus using immune cells as vectors The high amounts of inflammation caused by COVID 19 compounded with potential intubation are associated with a deleterious effect on the cognition as well Finally the pandemics unique psychosocial impact has raised alarm due to its possible effect on cognition Furthermore with surfacing reports of post COVID vaccination cognitive impairments after vaccines containing mRNA encoding for spike glycoprotein of SARS CoV 2 we hypothesize their causality and ways to mitigate the risk The potential impact on the quality of life of an individual and the fact that even a minor proportion of COVID 19 cases developing cognitive impairment could be a significant burden on already overwhelmed healthcare systems across the world make it vital to gather further evidence regarding the prevalence presentation correlations and causality of these events and reevaluate our approach to accommodate early identification management and rehabilitation of patients exhibiting cognitive symptoms

COVID 19 pandemic and reasons to prioritize the needs of the health care system to ensure its sustainability A scoping review from January to October 2020 Review The worldwide spread of severe acute respiratory syndrome coronavirus 2 SARS CoV 2 led the World Health Organization to characterize the pandemic as a public health emergency of international concern National health care systems in countries during the initial surge of the pandemic were unable to handle the sanitarian crisis that had emerged Thus the prevention and control of future global health emergencies must be a priority The present scoping review aimed to retrieve articles that summarize the current experience on issues related to historical knowledge and epidemiology clinical features and overall burden of SARS CoV 2 on health care services In summary a comprehensive overview of the information that has been learnt during this period is presented in the current review Furthermore taking into account the global experience the need for planning cohesive and functional health services before similar pandemic events occur in the future is highlighted The next public health issue should be prevented rather than treated In spite of the vaccination benefits a number of sporadic cases of SARS CoV 2infections will persist Information collected remains relevant for appraising how similar threats can be faced in the future Overall collaborative health care plans need to be rethought to increase preparedness

COVID 19 and the Blitz compared mental health outcomes in the UK The Blitz narrative of resilience stands in contrast to the mental health risks identified as consequences of the COVID 19 pandemic Although evidence from then classified studies of World War 2 showed that most people managed the stress of bombing those vulnerable and exposed to substantial trauma had lasting or severe mental illness Studies of different towns and occupational groups identified the proportion of people killed and wounded the percentage of housing destroyed and the loss of paid employment as risk factors for psychological breakdown Mothers and children suffered not only with evacuation but also from the trauma of bombing and damage to schools A general association between civilian physical and psychological casualties suggests that population groups with high rates of infection and mortality might be susceptible to mental illness as a result of the pandemic Lockdown and distancing measures contrast with the wartime sense of belonging and shared identity reinforced by community networks and social activities

Visualizing in deceased COVID 19 patients how SARS CoV 2 attacks the respiratory and olfactory mucosae but spares the olfactory bulb Anosmia the loss of smell is a common and often the sole symptom of COVID 19 The onset of the sequence of pathobiological events leading to olfactory dysfunction remains obscure Here we have developed a postmortem bedside surgical procedure to harvest endoscopically samples of respiratory and olfactory mucosae and whole olfactory bulbs Our cohort of 85 cases included COVID 19 patients who died a few days after infection with SARS CoV 2 enabling us to catch the virus while it was still replicating We found that sustentacular cells are the major target cell type in the olfactory mucosa We failed to find evidence for infection of olfactory sensory neurons and the parenchyma of the olfactory bulb is spared as well Thus SARS CoV 2 does not appear to be a neurotropic virus We postulate that transient insufficient support from sustentacular cells triggers transient olfactory dysfunction in COVID 19 Olfactory sensory neurons would become affected without getting infected

Incidence and risk factors for persistent symptoms in adults previously hospitalized for COVID 19 The long term sequalae of COVID 19 remain poorly characterized We assessed persistent symptoms in previously hospitalized patients with COVID 19 and assessed potential risk factors Data were collected from patients discharged from 4 hospitals in Moscow Russia between 8 April and 10 July 2020 Participants were interviewed via telephone using an ISARIC Long term Follow up Study questionnaire 2 649 of 4755 56 discharged patients were successfully evaluated at median 218 IQR 200 236 days post discharge COVID 19 diagnosis was clinical in 1291 and molecular in 1358 Most cases were mild but 902 34 required supplemental oxygen and 68 2 6 needed ventilatory support Median age was 56 years IQR 46 66 and 1 353 51 1 were women Persistent symptoms were reported by 1247 47 1 participants with fatigue 21 2 shortness of breath 14 5 and forgetfulness 9 1 the most common symptoms and chronic fatigue 25 and respiratory 17 2 the most common symptom categories Female sex was associated with any persistent symptom category OR 1 83 95 CI 1 55 to 2 17 with association being strongest for dermatological 3 26 2 36 to 4 57 symptoms Asthma and chronic pulmonary disease were not associated with persistent symptoms overall but asthma was associated with neurological 1 95 1 25 to 2 98 and mood and behavioural changes 2 02 1 24 to 3 18 and chronic pulmonary disease was associated with chronic fatigue 1 68 1 21 to 2 32 Almost half of adults admitted to hospital due to COVID 19 reported persistent symptoms 6 to 8 months after discharge Fatigue and respiratory symptoms were most common and female sex was associated with persistent symptoms

Acute and post acute neurological manifestations of COVID 19 present findings critical appraisal and future directions Acute and post acute neurological symptoms signs and diagnoses have been documented in an increasing number of patients infected by the Severe Acute Respiratory Syndrome Coronavirus 2 SARS CoV 2 which causes Coronavirus Disease 2019 COVID 19 In this review we aimed to summarize the current literature addressing neurological events following SARS CoV 2 infection discuss limitations in the existing literature and suggest future directions that would strengthen our understanding of the neurological sequelae of COVID 19 The presence of neurological manifestations symptoms signs or diagnoses both at the onset or during SARS CoV 2 infection is associated with a more severe disease as demonstrated by a longer hospital stay higher in hospital death rate or the continued presence of sequelae at discharge Although biological mechanisms have been postulated for these findings evidence based data are still lacking to clearly define the incidence range of characteristics and outcomes of these manifestations particularly in non hospitalized patients In addition data from low and middle income countries are scarce leading to uncertainties in the measure of neurological findings of COVID 19 with reference to geography ethnicity socio cultural settings and health care arrangements As a consequence at present a specific phenotype that would specify a post COVID or long COVID neurological syndrome has not yet been identified