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Blood Cytokine Analysis Suggests That SARS CoV 2 Infection Results in a Sustained Tumour Promoting Environment in Cancer Patients Cytokines chemokines and angiogenic growth factors CCGs have been shown to play an intricate role in the progression of both solid and haematological malignancies Recent studies have shown that SARS CoV 2 infection leads to a worse outcome in cancer patients especially in haematological malignancy patients Here we investigated how SARS CoV 2 infection impacts the already altered CCG levels in solid or haematological malignancies specifically whether there is a protective effect or rather a potentially higher risk for major COVID 19 complications in cancer patients due to elevated CCGs linked to cancer progression Serially analysing immune responses with 55 CCGs in cancer patients under active treatment with or without SARS CoV 2 infection we first showed that cancer patients without SARS CoV 2 infection i n i 54 demonstrate elevated levels of 35 CCGs compared to the non cancer non infected control group of health care workers i n i 42 Of the 35 CCGs 19 were common to both the solid and haematological malignancy groups and comprised previously described cytokines such as IL 6 TNF α IL 1Ra IL 17A and VEGF but also several less well described cytokines chemokines such as Fractalkine Tie 2 and T cell chemokine CTACK Importantly we show here that 7 CCGs are significantly altered in SARS CoV 2 exposed cancer patients i n i 52 Of these TNF α IFN β TSLP and sVCAM 1 identified to be elevated in haematological cancers are also known tumour promoting factors Longitudinal analysis conducted over 3 months showed persistence of several tumour promoting CCGs in SARS CoV 2 exposed cancer patients These data demonstrate a need for increased vigilance for haematological malignancy patients as a part of long COVID follow up

Adolescent Dental Fear and Anxiety Background Assessment and Nonpharmacologic Behavior Guidance Adolescence the period from 11 to 21 years of age bridges the chasm between childhood and adulthood Adolescence can be challenging as bodies cognition and personality go through major transformations but it is also a time of great joy as confident adults with a clear identity develop Dentists need to be knowledgeable about the developmental characteristics of this group because some of the cognitive and emotional changes make adolescents vulnerable to new fears Dentists must tailor behavior guidance to this developing psyche in a way that respects independence and promotes confidence to foster lifelong positive views of dentistry

Confronting COVID 19 associated cough and the post COVID syndrome role of viral neurotropism neuroinflammation and neuroimmune responses Cough is one of the most common presenting symptoms of COVID 19 along with fever and loss of taste and smell Cough can persist for weeks or months after SARS CoV 2 infection often accompanied by chronic fatigue cognitive impairment dyspnoea or pain a collection of long term effects referred to as the post COVID syndrome or long COVID We hypothesise that the pathways of neurotropism neuroinflammation and neuroimmunomodulation through the vagal sensory nerves which are implicated in SARS CoV 2 infection lead to a cough hypersensitivity state The post COVID syndrome might also result from neuroinflammatory events in the brain We highlight gaps in understanding of the mechanisms of acute and chronic COVID 19 associated cough and post COVID syndrome consider potential ways to reduce the effect of COVID 19 by controlling cough and suggest future directions for research and clinical practice Although neuromodulators such as gabapentin or opioids might be considered for acute and chronic COVID 19 cough we discuss the possible mechanisms of COVID 19 associated cough and the promise of new anti inflammatories or neuromodulators that might successfully target both the cough of COVID 19 and the post COVID syndrome

Whats New in Neuraxial Labor Analgesia This article provides an update of recent practice trends in neuraxial labor analgesia It reviews available evidence regarding management of labor pain in obstetric patients with COVID 19 serious adverse events in obstetric anesthesia to help inform risk benefit decisions and increasingly popular neuraxial labor analgesia techniques and adjuvants State of the art modes of epidural drug delivery are also discussed There has recently been a focus on several considerations specific to obstetric anesthesia such as anesthetic management of obstetric patients with COVID 19 platelet thresholds for the safe performance of neuraxial analgesia in obstetric patients with thrombocytopenia and drug delivery modes for initiation and maintenance of neuraxial labor analgesia Neuraxial labor analgesia via standard epidural dural puncture epidural and combined spinal epidural techniques is the most effective therapy to alleviate the pain of childbirth SARS CoV 2 infection is not in and of itself a contraindication to neuraxial labor analgesia or cesarean delivery anesthesia Early initiation of neuraxial labor analgesia in patients with COVID 19 is recommended if not otherwise contraindicated as it may reduce the need for general anesthesia should emergency cesarean delivery become necessary Consensus regarding platelet thresholds for safe initiation of neuraxial procedures has historically been lacking Recent studies have concluded that the risk of spinal epidural hematoma formation after neuraxial procedures is likely low at or above an imprecise range of platelet count of 70 75 000 10 sup 6 sup L Thrombocytopenia has been reported in obstetric patients with COVID 19 but severe thrombocytopenia precluding initiation of neuraxial anesthesia is extremely rare High neuraxial blockade has emerged as one of the most common serious complications of neuraxial analgesia and anesthesia in obstetric patients Growing awareness of factors that contribute to failed conversion of epidural labor analgesia to cesarean delivery anesthesia may help avoid the risks associated with performance of repeat neuraxial techniques and induction of general anesthesia after failed epidural blockade Dural puncture techniques to alleviate the pain of childbirth continue to become more popular as do adjuvant drugs to enhance or prolong neuraxial analgesia Novel techniques for epidural drug delivery have become more widely disseminated

sup 18 sup F FDG brain PET hypometabolism in post SARS CoV 2 infection substrate for persistent delayed disorders Several brain complications of SARS CoV 2 infection have been reported It has been moreover speculated that this neurotropism could potentially cause a delayed outbreak of neuropsychiatric and neurodegenerative diseases of neuroinflammatory origin A propagation mechanism has been proposed across the cribriform plate of the ethmoid bone from the nose to the olfactory epithelium and possibly afterward to other limbic structures and deeper parts of the brain including the brainstem Review of clinical examination and whole brain voxel based analysis of sup 18 sup F FDG PET metabolism in comparison with healthy subjects p voxel 0 001 p cluster 0 05 uncorrected of two patients with confirmed diagnosis of SARS CoV 2 explored at the post viral stage of the disease Hypometabolism of the olfactory rectus gyrus was found on the two patients especially one with 4 week prolonged anosmia Additional hypometabolisms were found within amygdala hippocampus parahippocampus cingulate cortex pre post central gyrus thalamus hypothalamus cerebellum pons and medulla in the other patient who complained of delayed onset of a painful syndrome These preliminary findings reinforce the hypotheses of SARS CoV 2 neurotropism through the olfactory bulb and the possible extension of this impairment to other brain structures sup 18 sup F FDG PET hypometabolism could constitute a cerebral quantitative biomarker of this involvement Post viral cohort studies are required to specify the exact relationship between such hypometabolisms and the possible persistent disorders especially involving cognitive or emotion disturbances residual respiratory symptoms or painful complaints

Long COVID And the fire rages on With the increasing cohort of COVID 19 survivors worldwide we now realize the proportionate rise in post COVID 19 syndrome In this review article we try to define summarize and classify this syndrome systematically This would help clinicians to identify and manage this condition more efficiently We propose a tool kit that might be useful in recording follow up data of COVID 19 survivors

Development of ACE2 autoantibodies after SARS CoV 2 infection Activation of the immune system is implicated in the Post Acute Sequelae after SARS CoV 2 infection PASC but the mechanisms remain unknown Angiotensin converting enzyme 2 ACE2 cleaves angiotensin II Ang II resulting in decreased activation of the AT1 receptor and decreased immune system activation We hypothesized that autoantibodies against ACE2 may develop after SARS CoV 2 infection as anti idiotypic antibodies to anti spike protein antibodies We tested plasma or serum for ACE2 antibodies in 67 patients with known SARS CoV 2 infection and 13 with no history of infection None of the 13 patients without history of SARS CoV 2 infection and 1 of the 20 outpatients that had a positive PCR test for SARS CoV 2 had levels of ACE2 antibodies above the cutoff threshold In contrast 26 32 81 in the convalescent group and 14 15 93 of patients acutely hospitalized had detectable ACE2 antibodies Plasma from patients with antibodies against ACE2 had less soluble ACE2 activity in plasma but similar amounts of ACE2 protein compared to patients without ACE2 antibodies We measured the capacity of the samples to inhibit ACE2 enzyme activity Addition of plasma from patients with ACE2 antibodies led to decreased activity of an exogenous preparation of ACE2 compared to patients that did not have antibodies Many patients with a history of SARS CoV 2 infection have antibodies specific for ACE2 Patients with ACE2 antibodies have lower activity of soluble ACE2 in plasma Plasma from these patients also inhibits exogenous ACE2 activity These findings are consistent with the hypothesis that ACE2 antibodies develop after SARS CoV 2 infection and decrease ACE2 activity This could lead to an increase in the abundance of Ang II which causes a proinflammatory state that triggers symptoms of PASC

Long COVID or Post acute Sequelae of COVID 19 PASC An Overview of Biological Factors That May Contribute to Persistent Symptoms The novel virus severe acute respiratory syndrome coronavirus 2 SARS CoV 2 has caused a pandemic of coronavirus disease 2019 COVID 19 Across the globe a subset of patients who sustain an acute SARS CoV 2 infection are developing a wide range of persistent symptoms that do not resolve over the course of many months These patients are being given the diagnosis Long COVID or Post acute sequelae of COVID 19 PASC It is likely that individual patients with a PASC diagnosis have different underlying biological factors driving their symptoms none of which are mutually exclusive This paper details mechanisms by which RNA viruses beyond just SARS CoV 2 have be connected to long term health consequences It also reviews literature on acute COVID 19 and other virus initiated chronic syndromes such as post Ebola syndrome or myalgic encephalomyelitis chronic fatigue syndrome ME CFS to discuss different scenarios for PASC symptom development Potential contributors to PASC symptoms include consequences from acute SARS CoV 2 injury to one or multiple organs persistent reservoirs of SARS CoV 2 in certain tissues re activation of neurotrophic pathogens such as herpesviruses under conditions of COVID 19 immune dysregulation SARS CoV 2 interactions with host microbiome virome communities clotting coagulation issues dysfunctional brainstem vagus nerve signaling ongoing activity of primed immune cells and autoimmunity due to molecular mimicry between pathogen and host proteins The individualized nature of PASC symptoms suggests that different therapeutic approaches may be required to best manage care for specific patients with the diagnosis

Long COVID Syndrome A Study on the Persistence of Neurological Psychological and Physiological Symptoms Emerging aspects of the Covid 19 clinical presentation are its long term effects which are characteristic of the so called long COVID The aim of the present study was to investigate the prevalence of physical psychological and sleep disturbances and the quality of life in the general population during the ongoing pandemic This study based on an online survey collected demographic data information related to COVID 19 sleep disturbances and quality of life data from 507 individuals The level of sleep disturbances and quality of life was assessed through the Insomnia Severity Index ISI and the EuroQol 5D EQ 5D respectively In total 507 individuals M 91 and F 416 women completed the online survey The main symptoms associated with long COVID were headache fatigue muscle aches myalgia articular pains cognitive impairment loss of concentration and loss of smell Additionally the subjects showed significant levels of insomnia i p i 0 05 and an overall reduced quality of life i p i 0 05 The results of the study appear in line with recent publications but uncertainty regarding the definition and specific features of long COVID remains Further studies are needed in order to better define the clinical presentation of the long COVID condition and related targeted treatments

Care of the postcoronavirus disease 2019 patient In under a year coronavirus disease 2019 COVID 19 has taken the lives of hundreds of thousands of Americans leaving millions of survivors in its wake The enormous number of people who survived acute illness but continue to have symptoms has highlighted the need for standardized evaluation of the post COVID 19 patient This review based on the current literature and our experience aims to guide the care of patients who have survived COVID 19 The literature on this topic is rapidly expanding and covers both pulmonary and nonpulmonary complications of COVID 19 Pulmonary complications include dyspnea with normoxia organizing pneumonia and pulmonary fibrosis Nonpulmonary complications include neurologic cardiac and thromboembolic disease Special consideration should be taken for COVID 19 survivors of intensive care The current review outlines the major clinical findings in post COVID 19 patients and provides a guidelines to the evaluation and management of prolonged symptoms

Admission of a minor to a psychiatric hospital under Polish law Part I Within the scope of mental health protection numerous practical problems arise concerning the issue of providing health services to a minor Admission of a minor to a psychiatric hospital is associated in practice with numerous doubts This part of the article describes the conditions of admission to hospital with the consent of the patient It distinguishes and accurately describes situations where a minor is under or over 16 years of age In addition it explains situations where there is a contradiction of declarations of will by legal guardians in relation to admission their inability to perform legal acts or a contradiction of the statements of the minor and guardian It also addresses the aspect of receiving written consent during the COVID 19 epidemic

The interplay of DAMPs TLR4 and proinflammatory cytokines in pulmonary fibrosis Pulmonary fibrosis is a chronic debilitating condition characterized by progressive deposition of connective tissue leading to a steady restriction of lung elasticity a decline in lung function and a median survival of 4 5 years The leading causes of pulmonary fibrosis are inhalation of foreign particles such as silicosis and pneumoconiosis infections such as post COVID 19 autoimmune diseases such as systemic autoimmune diseases of the connective tissue and idiopathic pulmonary fibrosis The therapeutics currently available for pulmonary fibrosis only modestly slow the progression of the disease This review is centered on the interplay of damage associated molecular pattern DAMP molecules Toll like receptor 4 TLR4 and inflammatory cytokines such as TNF α IL 1β and IL 17 as they contribute to the pathogenesis of pulmonary fibrosis and the possible avenues to develop effective therapeutics that disrupt this interplay

Challenges and Opportunities of Preclinical Medical Education COVID 19 Crisis and Beyond COVID 19 pandemic has disrupted face to face teaching in medical schools globally The use of remote learning as an emergency measure has affected students faculty support staff and administrators The aim of this narrative review paper is to examine the challenges and opportunities faced by medical schools in implementing remote learning for basic science teaching in response to the COVID 19 crisis We searched relevant literature in PubMed Scopus and Google Scholar using specific keywords e g COVID 19 pandemic preclinical medical education online learning remote learning challenges and opportunities The pandemic has posed several challenges to premedical education e g suspension of face to face teaching lack of cadaveric dissections and practical laboratory sessions but has provided many opportunities as well such as the incorporation of online learning in the curriculum and upskilling and reskilling in new technologies To date many medical schools have successfully transitioned their educational environment to emergency remote teaching and assessments During COVID 19 crisis the preclinical phase of medical curricula has successfully introduced the novel culture of online home learning using technology oriented innovations which may extend to post COVID era to maintain teaching and learning in medical education However the lack of hands on training in the preclinical years may have serious implications on the training of the current cohort of students and they may struggle later in the clinical years The use of emergent technology e g artificial intelligence for adaptive learning virtual simulation and telehealth for education is most likely to be indispensable components of the transformative change and post COVID medical education

Long Term Impact of COVID 19 A Systematic Review of the Literature and Meta Analysis The long term impact of COVID 19 is still unknown This study aimed to explore post COVID 19 effects on patients chest computed tomography CT lung function respiratory symptoms fatigue functional capacity health related quality of life HRQoL and the ability to return to work beyond 3 months post infection A systematic search was performed on PubMed Web of Science and Ovid MEDLINE on 22 May 2021 to identify studies that reported persistent effects of COVID 19 beyond 3 months follow up Data on the proportion of patients who had the outcome were collected and analyzed using a one group meta analysis Data were extracted from 24 articles that presented information on a total of 5323 adults post infection between 3 to 6 months after symptom onset or hospital discharge The pooled prevalence of CT abnormalities was 59 95 CI 44 73 I sup 2 sup 96 abnormal lung function was 39 95 CI 24 55 I sup 2 sup 94 fatigue was 38 95 CI 27 49 I sup 2 sup 98 dyspnea was 32 95 CI 24 40 I sup 2 sup 98 chest paint tightness was 16 95 CI 12 21 I sup 2 sup 94 and cough was 13 95 CI 9 17 I sup 2 sup 94 Decreased functional capacity and HRQoL were found in 36 95 CI 22 49 I sup 2 sup 97 and 52 95 CI 33 71 I sup 2 sup 94 respectively On average 8 out of 10 of the patients had returned to work or reported no work impairment Post COVID 19 patients may experience persistent respiratory symptoms fatigue decreased functional capacity and decreased quality of life up to 6 months after infection Further studies are needed to establish the extent to which post COVID 19 effects continue beyond 6 months how they interact with each other and to clarify their causes and their effective management

Raising the bar to ultradisciplinary collaborations in management of chronic thromboembolic pulmonary hypertension Chronic thromboembolic pulmonary hypertension is an underdiagnosed and potentially fatal subgroup of pulmonary hypertension if left untreated Clinical signs include exertional dyspnea and non specific symptoms Diagnosis requires multimodality imaging and heart catheterization Pulmonary endarterectomy an open heart surgery is the gold standard treatment of choice in selected patients in specialized centers Targeted medical therapy and balloon pulmonary angioplasty can be effective in high risk patients with significant comorbidities distal pulmonary vascular obstructions or recurrent persistent pulmonary hypertension after pulmonary endarterectomy Currently there is a limited number of data regarding novel coronavirus 2019 infection in patients with chronic thromboembolic pulmonary hypertension and the changing spectrum of the disease during the pandemic Challenging times during this outbreak due to healthcare crisis and relatively higher case fatality rates require convergence that is an ultradisciplinary collaboration which crosses disciplinary and sectorial boundaries to develop integrated knowledge and new paradigms Management strategies for the new normal such as virtual care preparedness for further threats redesigned standards and working conditions reevaluation of specific recommendations and online collaborations for optimal decisions for chronic thromboembolic pulmonary hypertension patients may change the poor outcomes

COVID Related Stress and Work Intentions in a Sample of US Health Care Workers To evaluate relationships between coronavirus disease 2019 COVID 19 related stress and work intentions in a sample of US health care workers Between July 1 and December 31 2020 health care workers were surveyed for fear of viral exposure or transmission COVID 19 related anxiety or depression work overload burnout and intentions to reduce hours or leave their jobs Among 20 665 respondents at 124 institutions median organizational response rate 34 intention to reduce hours was highest among nurses 33 7 n 776 physicians 31 4 n 2914 and advanced practice providers APPs 28 9 n 608 while lowest among clerical staff 13 6 n 242 and administrators 6 8 n 50 all i P i 001 Burnout odds ratio OR 2 15 95 CI 1 93 to 2 38 fear of exposure COVID 19 related anxiety depression and workload were independently related to intent to reduce work hours within 12 months all i P i 01 Intention to leave ones practice within 2 years was highest among nurses 40 0 n 921 APPs 33 0 n 694 other clinical staff 29 4 n 718 and physicians 23 8 n 2204 while lowest among administrators 12 6 n 93 all i P i 001 Burnout OR 2 57 95 CI 2 29 to 2 88 fear of exposure COVID 19 related anxiety depression and workload were predictors of intent to leave Feeling valued by ones organization was protective of reducing hours OR 0 65 95 CI 0 59 to 0 72 and intending to leave OR 0 40 95 CI 0 36 to 0 45 all i P i 01 Approximately 1 in 3 physicians APPs and nurses surveyed intend to reduce work hours One in 5 physicians and 2 in 5 nurses intend to leave their practice altogether Reducing burnout and improving a sense of feeling valued may allow health care organizations to better maintain their workforces postpandemic

Impact of HIV Infection on COVID 19 Outcomes Among Hospitalized Adults in the U S Whether HIV infection is associated with differences in clinical outcomes among people hospitalized with COVID 19 is uncertain To evaluate the impact of HIV infection on COVID 19 outcomes among hospitalized patients Using the American Heart Associations COVID 19 Cardiovascular Disease registry we used hierarchical mixed effects models to assess the association of HIV with in hospital mortality accounting for patient demographics and comorbidities and clustering by hospital Secondary outcomes included major adverse cardiac events MACE severity of illness and length of stay LOS The registry included 21 528 hospitalization records of people with confirmed COVID 19 from 107 hospitals in 2020 including 220 people living with HIV PLWH PLWH were younger 56 0 13 0 versus 61 3 17 9 years old and more likely to be male 72 3 vs 52 7 Non Hispanic Black 51 4 vs 25 4 on Medicaid 44 5 vs 24 5 and active tobacco users 12 7 versus 6 5 Of the study population 36 PLWH 16 4 had in hospital mortality compared with 3 290 15 4 without HIV Risk ratio 1 06 95 CI 0 79 1 43 risk difference 0 9 95 CI 4 2 to 6 1 p 0 71 After adjustment for age sex race and insurance HIV was not associated with in hospital mortality aOR 1 13 95 CI 0 77 1 6 p 0 54 even after adding body mass index and comorbidities aOR 1 15 95 CI 0 78 1 70 p 0 48 HIV was not associated with MACE aOR 0 99 95 CI 0 69 1 44 p 0 91 severity of illness aOR 0 96 95 CI 0 62 1 50 p 0 86 or LOS aOR 1 03 95 CI 0 76 1 66 p 0 21 HIV was not associated with adverse outcomes of COVID 19 including in hospital mortality MACE or severity of illness We studied 21 528 patients hospitalized with COVID 19 at 107 hospitals in AHAs COVID 19 registry to examine the association between HIV and COVID 19 outcomes More patients with HIV were younger male non Hispanic Black on Medicaid and current smokers HIV was not associated with worse COVID 19 in hospital mortality Risk ratio 1 06 95 CI 0 79 1 43 p 0 71 even after adjustment aOR 1 15 95 CI 0 78 1 70 p 0 48 HIV was also not associated with MACE aOR 0 99 95 CI 0 69 1 44 p 0 91 or severity of illness aOR 0 96 95 CI 0 62 1 50 p 0 86 Our findings do not support that HIV is a major risk factor for adverse COVID 19 outcomes

Investigation of Long COVID Prevalence and Its Relationship to Epstein Barr Virus Reactivation Coronavirus disease 2019 COVID 19 patients sometimes experience long term symptoms following resolution of acute disease including fatigue brain fog and rashes Collectively these have become known as long COVID Our aim was to first determine long COVID prevalence in 185 randomly surveyed COVID 19 patients and subsequently to determine if there was an association between occurrence of long COVID symptoms and reactivation of Epstein Barr virus EBV in 68 COVID 19 patients recruited from those surveyed We found the prevalence of long COVID symptoms to be 30 3 56 185 which included 4 initially asymptomatic COVID 19 patients who later developed long COVID symptoms Next we found that 66 7 20 30 of long COVID subjects versus 10 2 20 of control subjects in our primary study group were positive for EBV reactivation based on positive titers for EBV early antigen diffuse EA D IgG or EBV viral capsid antigen VCA IgM The difference was significant i p i 0 001 Fishers exact test A similar ratio was observed in a secondary group of 18 subjects 21 90 days after testing positive for COVID 19 indicating reactivation may occur soon after or concurrently with COVID 19 infection These findings suggest that many long COVID symptoms may not be a direct result of the SARS CoV 2 virus but may be the result of COVID 19 inflammation induced EBV reactivation

Attributes and predictors of long COVID Reports of long lasting coronavirus disease 2019 COVID 19 symptoms the so called long COVID are rising but little is known about prevalence risk factors or whether it is possible to predict a protracted course early in the disease We analyzed data from 4 182 incident cases of COVID 19 in which individuals self reported their symptoms prospectively in the COVID Symptom Study app sup 1 sup A total of 558 13 3 participants reported symptoms lasting 28 days 189 4 5 for 8 weeks and 95 2 3 for 12 weeks Long COVID was characterized by symptoms of fatigue headache dyspnea and anosmia and was more likely with increasing age and body mass index and female sex Experiencing more than five symptoms during the first week of illness was associated with long COVID odds ratio 3 53 2 76 4 50 A simple model to distinguish between short COVID and long COVID at 7 days total sample size n 2 149 showed an area under the curve of the receiver operating characteristic curve of 76 with replication in an independent sample of 2 472 individuals who were positive for severe acute respiratory syndrome coronavirus 2 This model could be used to identify individuals at risk of long COVID for trials of prevention or treatment and to plan education and rehabilitation services

Vaccine induced immune thrombotic thrombocytopenia and cerebral venous sinus thrombosis post COVID 19 vaccination a systematic review The common reported adverse effects of COVID 19 vaccination consist of the injection sites local reaction followed by several non specific flu like symptoms However rare cases of vaccine induced immune thrombotic thrombocytopenia VITT and cerebral venous sinus thrombosis CVST after viral vector vaccines ChAdOx1 nCoV 19 vaccine Ad26 COV2 vaccine have been reported Herein we systemically reviewed the reported cases of CVST and VITT following the COVID 19 vaccination This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta Analyses PRISMA statement We searched PubMed until May 19 2021 and the following Keywords were used COVID Vaccine Neurology AstraZeneca COVID vaccine ChAdOx1 nCoV 19 COVID vaccine AZD1222 COVID vaccine Janssen COVID vaccine Johnson Johnson COVID vaccine Ad26 COV2 COVID vaccine The authors evaluated the abstracts and titles of each article for screening and inclusion English reports about post vaccine CVST and VITT in humans were collected Until May 19 we found 877 articles with the searched terms We found 12 articles which overall present clinical features of 36 patients with CVST and VITT after the ChAdOx1 nCoV 19 vaccine Moreover two articles were noted which present 13 patients with CVST and VITT after Ad26 COV2 vaccine The majority of the patients were females Symptom onset occurred within one week after the first dose of vaccination Range 4 19 days Headache was the most common presenting symptom Intracerebral hemorrhage ICH and or Subarachnoid hemorrhage SAH were reported in 49 of the patients The platelet count of the patients was between 5 and 127 cells 10 sup 9 sup l PF4 IgG Assay and d Dimer were positive in the majority of the reported cases Among 49 patients with CVST at least 19 patients died 39 due to complications of CVST and VITT Health care providers should be familiar with the clinical presentations pathophysiology diagnostic criteria and management consideration of this rare but severe and potentially fatal complication of the COVID 19 vaccination Early diagnosis and quick initiation of the treatment may help to provide patients with a more favorable neurological outcome

Pulmonary fibrosis secondary to COVID 19 a narrative review b Introduction b Coronavirus disease 2019 COVID 19 is still increasing worldwide and as a result the number of patients with pulmonary fibrosis secondary to COVID 19 will expand over time Risk factors histopathological characterization pathophysiology prevalence and management of post COVID 19 pulmonary fibrosis are poorly understood and few studies have addressed these issues b Areas covered b This article reviews the current evidence regarding post COVID 19 pulmonary fibrosis with an emphasis on the potential risk factors histopathology pathophysiology functional and tomographic features and potential therapeutic modalities A search on the issue was performed in the MEDLINE Embase and SciELO databases and the Cochrane library between 1 December 2019 and 25 January 2021 Studies were reviewed and relevant topics were incorporated into this narrative review b Expert opinion b Pulmonary sequelae may occur secondary to COVID 19 which needs to be included as a potential etiology in the current differential diagnosis of pulmonary fibrosis Therefore serial clinical tomographic and functional screening for pulmonary fibrosis is recommended after COVID 19 mainly in patients with pulmonary involvement in the acute phase of the disease Further studies are necessary to determine the risk factors markers pathophysiology and appropriate management of post COVID 19 pulmonary fibrosis

The Long COVID Syndrome a New Clinical Picture after COVID 19 Infection The Long COVID Syndrome a New Clinical Picture after COVID 19 Infection b Abstract b Long term consequences are increasingly reported in the current literature after COVID 19 infections Some patients suffer from persistent pulmonary and extrapulmonary symptoms even months after the acute infection Pulmonary impairment but also dysregulation and effects on immune system cardiovascular system neurological system skin and kidney are described or anticipated This mini review gives a short update to the practitioner about the current knowledge about Long COVID

Kidney in the net of acute and long haul coronavirus disease 2019 a potential role for lipid mediators in causing renal injury and fibrosis Severe COVID 19 disease is often complicated by acute kidney injury AKI which may transition to chronic kidney disease CKD Better understanding of underlying mechanisms is important in advancing therapeutic approaches SARS CoV 2 induced endothelial injury initiates platelet activation platelet neutrophil partnership and release of neutrophil extracellular traps The resulting thromboinflammation causes ischemia reperfusion I R injury to end organs Severe COVID 19 induces a lipid mediator storm with massive increases in thromboxane A2 TxA2 and PGD2 which promote thromboinflammation and apoptosis of renal tubular cells respectively and thereby enhance renal fibrosis COVID 19 associated AKI improves rapidly in the majority However 15 30 have protracted renal injury raising the specter of transition from AKI to CKD In COVID 19 the lipid mediator storm promotes thromboinflammation ischemia reperfusion injury and cytotoxicity The thromboxane A2 and PGD2 signaling presents a therapeutic target with potential to mitigate AKI and transition to CKD Ramatroban the only dual antagonist of the thromboxane A2 TPr and PGD2 DPr2 signaling could potentially mitigate renal injury in acute and long haul COVID Urgent studies targeting the lipid mediator storm are needed to potentially reduce the heavy burden of kidney disease emerging in the wake of the current pandemic

Paediatric Liver Transplantation During COVID 19 Pandemic Lessons Learned and Unanswered Questions COVID 19 pandemic has imposed many challenges on paediatric liver transplantation PLT services and has necessitated several adaptations in different stages of the process to ensure transplant centres can still deliver the proposed services in addition to protecting patients and staff against infection This review article digs through the current literature to clarify the challenges imposed by SARS CoV2 on PLT centres globally It provides an overview of current practice as well as suggestions from experts in the field to overcome multiple obstacles In paediatrics the reaction to SARS CoV2 may be less severe than that seen in the adult population but this can change in view of newly discovered virus strains Response of transplant centres to the current pandemic was variable depending on the anticipated risk and available resources Telemedicine has helped PLT programmes to continue their activities while protecting patients as well as staff against the risk of SARS CoV2 virus Further studies are needed to guide immunosuppression management in post transplant infected candidates answering this critical question will help PLT centres solve this dilemma

Post acute COVID 19 syndrome Severe acute respiratory syndrome coronavirus 2 SARS CoV 2 is the pathogen responsible for the coronavirus disease 2019 COVID 19 pandemic which has resulted in global healthcare crises and strained health resources As the population of patients recovering from COVID 19 grows it is paramount to establish an understanding of the healthcare issues surrounding them COVID 19 is now recognized as a multi organ disease with a broad spectrum of manifestations Similarly to post acute viral syndromes described in survivors of other virulent coronavirus epidemics there are increasing reports of persistent and prolonged effects after acute COVID 19 Patient advocacy groups many members of which identify themselves as long haulers have helped contribute to the recognition of post acute COVID 19 a syndrome characterized by persistent symptoms and or delayed or long term complications beyond 4 weeks from the onset of symptoms Here we provide a comprehensive review of the current literature on post acute COVID 19 its pathophysiology and its organ specific sequelae Finally we discuss relevant considerations for the multidisciplinary care of COVID 19 survivors and propose a framework for the identification of those at high risk for post acute COVID 19 and their coordinated management through dedicated COVID 19 clinics

Patient electronic communication data in clinical care what is known and what is needed The novel coronavirus COVID 19 and physical distancing guidelines around the world have resulted in unprecedented changes to normal routine and increased smartphone use to maintain social relationships and support Reports of depressive and anxiety symptom are on the rise contributing to suffering among people especially adolescents and young adults with pre existing mental health conditions Psychiatric care has shifted primarily to telehealth limiting the important patient nonverbal communication that has been part of in person clinical sessions Supplementing clinical care with patient electronic communication EC data may provide valuable information and influence treatment decision making Research in the impact of patient EC data on managing psychiatric symptoms is in its infancy This review aims to identify how patient EC has been used in clinical care and its benefits in psychiatry and research We discuss smartphone applications used to gather different types of EC data how data have been integrated into clinical care and implications for clinical care and research

sup 18 sup F FDG PET CT in SARS CoV 2 infection and its sequelae In recent months much of the scientific efforts have focused on research on SARSCoV 2 infection and its consequences in humans Still many aspects remain unknown It is known that the damage caused by SARS CoV 2 is multifactorial and that its extension goes beyond lung inflammation and the acute phase with the appearance of numerous complications and sequelae To date knowledge about the usefulness of sup 18 sup F FDG PET CT in the acute phase has been limited to the incidental detection of SARS CoV 2 unsuspected pneumonia Recent studies have been appearing collecting the findings of sup 18 sup F FDG PET CT in long COVID 19 or persistent COVID 19 state as well as the alterations caused after mass vaccination of the population in the metabolic studies This work aims to review the existing literature focusing on these three issues and to briefly present our own preliminary experience

Post Acute Sequelae of COVID 19 and Cardiovascular Autonomic Dysfunction What Do We Know Post acute sequelae of SARS CoV 2 PASC or long COVID syndrome is emerging as a major health issue in patients with previous SARS CoV 2 infection Symptoms commonly experienced by patients include fatigue palpitations chest pain dyspnea reduced exercise tolerance and brain fog Additionally symptoms of orthostatic intolerance and syncope suggest the involvement of the autonomic nervous system Signs of cardiovascular autonomic dysfunction appear to be common in PASC and are similar to those observed in postural orthostatic tachycardia syndrome and inappropriate sinus tachycardia In this review we report on the epidemiology of PASC discuss current evidence and possible mechanisms underpinning the dysregulation of the autonomic nervous system and suggest nonpharmacological and pharmacological interventions to treat and relieve symptoms of PASC associated dysautonomia

Post COVID 19 exacerbation of fibrodysplasia ossificans progressiva with multiple flare ups and extensive heterotopic ossification in a 45 year old female patient Fibrodyplasia ossificans progressiva FOP is a rare hereditary disease which has a variable course characterized by occasional flare ups of heterotopic ossification HO in soft tissues that are followed by swelling stiffness pain and warmth Here we report for the first time a case of a 45 year old female patient with known FOP recovering from COVID 19 with disease progression potentially linked with the viral illness In December 2020 the patient contracted a mild form of COVID 19 infection without need for hospital admission Since January 2021 the patient felt unwell with occasional abdominal pain which progressively intensified In March 2021 she presented with new onset of HO complaining of pain swelling and thickening sensation in the lower abdomen and left part of the neck Computerized tomography CT and cytokine analysis were performed CT scan revealed new heterotopic bone formation in multiple soft tissue areas of the neck indicating clear radiological progression Radiotherapy which has proven to be an efficient tool to control HO in this patient was not able to halt HO formation after COVID 19 infection Cytokine analysis of a plasma sample obtained during a flare up after COVID 19 infection showed a significantly elevated pro inflammatory cytokines compared to a flare up panel prior to infection Of the 23 analyzed levels of cytokines a staggering number of 21 were above normal levels This case is the first confirmation of uncontrolled post COVID 19 effects in a FOP patient which manifested with flare ups followed by progressive HO possibly caused by a thus far never described form of post COVID syndrome

Severe acute respiratory syndrome coronavirus 2 related multisystem inflammatory syndrome in children mimicking Kawasaki disease The severe acute respiratory syndrome coronavirus 2 SARS CoV 2 pandemic has been characterized by high transmission rates and high mortality in adults with predisposing factors including age 70 years obesity diabetes systemic hypertension and other underlying diseases During the second week of viral pneumonia acute respiratory distress syndrome can occur and carries high mortality Unlike most common respiratory viruses children seem to be less susceptible to SARS CoV 2 infection and generally develop mild disease with low mortality However clusters of severe shock associated with high levels of cardiac biomarkers and unusual vasoplegia requiring inotropes vasopressors and volume loading have recently been described Both the clinical symptoms i e high and persistent fever gastrointestinal disorders skin rash conjunctival injection and dry cracked lips and the biological signs e g elevated C reactive protein procalcitonin and high levels of ferritinaemia mimicked Kawasaki disease In most cases intravenous immunoglobin therapy improved cardiac function and led to full recovery within a few days Adjunctive steroid therapy and sometimes biotherapy e g anti interleukin 1Ra and anti interleukin 6 monoclonal antibodies were often necessary Although almost all children fully recovered within a week some of them later developed coronary artery dilation or aneurysm Thus a new multisystem inflammatory syndrome in children related to SARS CoV 2 has recently been described Similarities with Kawasaki disease and the physiopathology of this syndrome still need further exploration

Characterizing the COVID 19 illness experience to inform the study of post acute sequelae and recovery a qualitative study We aimed to characterize the variability in the illness experience and recovery process from COVID 19 We conducted in depth individual interviews with participants enrolled in the Long term Immunological Impact of Novel Coronavirus LIINC cohort study in San Francisco California from June through October of 2020 Participants were adults who had a previously confirmed positive SARV CoV 2 nucleic acid amplification test result had recovered or were recovering from acute infection and underwent serial evaluations at our clinical research center We purposefully sampled 24 English and Spanish speaking adults with asymptomatic mild and severe symptomatic infection including those who were hospitalized and those with HIV co infection Half of our sample 50 0 identified as Latinx Hispanic and most of the participants were men 62 5 We used thematic analysis to characterize the illness experience recovery process and mental health impact of experiencing COVID 19 and present clinical data for each participant Emergent themes were 1 across symptom profiles and severity experiencing COVID 19 was associated with psychological distress 2 among participants with symptomatic infection the illness experience was characterized by uncertainty in terms of managing symptoms and recovery and 3 despite wide ranging illness experiences participants shared many common characteristics including health information seeking behavior facilitated by access to medical care and uncertainty regarding the course of their illness and recovery COVID 19 was associated with elevated levels of psychological distress regardless of symptoms

COVID 19 potential therapeutics for pediatric patients The global spread of COVID 19 has imparted significant economic medical and social burdens Like adults children are affected by this pandemic However milder clinical symptoms are often experienced by them Only a minimal proportion of the affected patients may develop severe and complicated COVID 19 Supportive treatment is recommended in all patients Antiviral and immunomodulatory medications are spared for hospitalized children with respiratory distress or severe to critical disease Up till now remdesivir is the only USFDA approved anti COVID 19 medication indicated in the majority of symptomatic patients with moderate to severe disease Dexamethasone is solely recommended in patients with respiratory distress maintained on oxygen or ventilatory support The use of these medications in pediatric patients is founded on evidence deriving from adult studies No randomized controlled trials RCTs involving pediatric COVID 19 patients have assessed these medications efficacy and safety among others Similarly three novel monoclonal anti SARS CoV 2 spike protein antibodies bamlanivimab casirivimab and imdevimab have been recently authorized by the USFDA Nonetheless their efficacy has not been demonstrated by multiple RCTs In this review we aim to dissect the various potential therapeutics used in children with COVID 19 We aspire to provide a comprehensive review of the available evidence and display the mechanisms of action and the pharmacokinetic properties of the studied therapeutics Our review offers an efficient and practical guide for treating children with COVID 19

Long COVID 19 A Primer for Cardiovascular Health Professionals on Behalf of the CCS Rapid Response Team It is now widely recognized that COVID 19 illness can be associated with significant intermediate and potentially longer term physical limitations The term long COVID 19 is used to define any patient with persistent symptoms after acute COVID 19 infection ie after 4 weeks It is postulated that cardiac injury might be linked to symptoms that persist after resolution of acute infection as part of this syndrome The Canadian Cardiovascular Society Rapid Response Team has generated this document to provide guidance to health care providers on the optimal management of patients with suspected cardiac complications of long COVID 19

Coronasomnia promoting resilience through insomnia treatment The term coronasomnia is used in popular science to describe sleep disorders associated with the COVID 19 pandemic These disorders may also affect part of the population in the aftermath of the pandemic Early scientific evidence suggests that COVID 19 associated insomnia and insomniac symptoms can become chronic and will continue to preoccupy the sleep medicine community even after the pandemic has ended A literature review was conducted in Medline and Google Scholar using the following combination of keywords insomnia and COVID 19 insomnia and long COVID insomnia PTSD and COVID 19 and fatigue and insomnia in long COVID In addition the authors reviewed several recent articles published by members of the European Insomnia Network Studies on insomnia and COVID 19 show significant associations between acute infection and insomnia in affected individuals The prevalence of insomnia symptoms in COVID 19 affected individuals was 36 to 88 which is significantly higher than the estimated 10 to 40 prevalence of insomnia in the general population Digital therapy as a current treatment option for insomnia can be offered to patients regardless of physical distance Accordingly not only early approval of therapy apps but also person led digital therapy options for insomnia would be recommended The inclusion of personalised and sleep coaching measures in the area of occupational health management is encouraged

Probiotics as Adjuvants in Vaccine Strategy Is There More Room for Improvement It has been recognized that microbiota plays a key role in shaping immune system maturation and activity Since probiotic administration influences the microbiota composition and acts as a biological response modifier the efficacy of an adjuvant for boosting vaccine specific immunity is investigated A review of the literature was performed starting from the mechanisms to laboratory and clinical evidence The mechanisms and in vitro and animal models provide biological plausibility for microbiota use Probiotics have been investigated as adjuvants in farm conditions and as models to understand their potential in human vaccinations with promising results In human studies although probiotics were effective in ameliorating seroconversion to vaccines for influenza rotavirus and other micro organisms the results for clinical use are still controversial especially in particular settings such as during the last trimester of pregnancy Although this topic remains controversial the use of probiotics as adjuvant factors in vaccination represents a strategic key for different applications The available data are deeply influenced by heterogeneity among studies in terms of strains timing and duration of administration and patients Although these do not allow us to draw definitive conclusions probiotics as adjuvants in vaccination should be considered in future studies especially in the elderly and in children where vaccine effectiveness and duration of immunization really matter

Sequelae persistent symptomatology and outcomes after COVID 19 hospitalization the ANCOHVID multicentre 6 month follow up study Long term effects of COVID 19 also called Long COVID affect more than 10 of patients The most severe cases i e those requiring hospitalization present a higher frequency of sequelae but detailed information on these effects is still lacking The objective of this study is to identify and quantify the frequency and outcomes associated with the presence of sequelae or persistent symptomatology SPS during the 6 months after discharge for COVID 19 Retrospective observational 6 month follow up study conducted in four hospitals of Spain A cohort of all 969 patients who were hospitalized with PCR confirmed SARS CoV 2 from March 1 to April 15 2020 was included We collected all the SPS during the 6 months after discharge reported by patients during follow up from primary care records Cluster analyses were performed to validate the measures The main outcome measures were return to the Emergency Services hospital readmission and post discharge death Surviving patients outcomes were collected through clinical histories and primary care reports Multiple logistic regression models were applied The 797 82 2 patients who survived constituted the sample followed while the rest died from COVID 19 The mean age was 63 0 years 53 7 of them were men and 509 63 9 reported some sequelae during the first 6 months after discharge These sequelae were very diverse but the most frequent were respiratory 42 0 systemic 36 1 neurological 20 8 mental health 12 2 and infectious 7 9 SPS with some differences by sex Women presented higher frequencies of headache and mental health SPS among others A total of 160 20 1 patients returned to the Emergency Services 35 4 4 required hospital readmission and 8 1 0 died during follow up The main factors independently associated with the return to Emergency Services were persistent fever dermatological SPS arrythmia or palpitations thoracic pain and pneumonia COVID 19 cases requiring hospitalization during the first wave of the pandemic developed a significant range of mid to long term SPS A detailed list of symptoms and outcomes is provided in this multicentre study Identification of possible factors associated with these SPS could be useful to optimize preventive follow up strategies in primary care for the coming months of the pandemic

Safe Pulmonary Scintigraphy in the Era of COVID 19 One of the major effects of the COVID 19 pandemic within nuclear medicine was to halt performance of lung ventilation studies due to concern regarding spread of contaminated secretions into the ambient air A number of variant protocols for performing lung scintigraphy emerged in the medical literature which minimized or eliminated the ventilation component due to the persistent need to provide this critical diagnostic service without compromising the safety of staff and patients We have summarized and reviewed these protocols many of which are based on concepts developed earlier in the history of lung scintigraphy It is possible that some of these interim remedies may gain traction and earn a more permanent place in the ongoing practice of nuclear medicine

Is the Endothelium the Missing Link in the Pathophysiology and Treatment of COVID 19 Complications Patients with COVID 19 present a wide spectrum of disease severity from asymptomatic cases in the majority to serious disease leading to critical care and even death Clinically four different scenarios occur within the typical disease timeline first an incubation and asymptomatic period second a stage with mild symptoms due mainly to the virus itself third in up to 20 of the patients a stage with severe symptoms where a hyperinflammatory response with a cytokine storm driven by host immunity induces acute respiratory distress syndrome and finally a post acute sequelae PASC phase which present symptoms that can range from mild or annoying to actually quite incapacitating Although the most common manifestation is acute respiratory failure of the lungs other organs are also frequently involved The clinical manifestations of the COVID 19 infection support a key role for endothelial dysfunction in the pathobiology of this condition The virus enters into the organism via its interaction with angiotensin converting enzyme 2 receptor that is present prominently in the alveoli but also in endothelial cells which can be directly infected by the virus Cytokine release syndrome can also drive endothelial damage independently Consequently a distinctive feature of SARS CoV 2 infection is vascular harm with severe endothelial injury widespread thrombosis microangiopathy and neo angiogenesis in response to endothelial damage Therefore endothelial dysfunction seems to be the pathophysiological substrate for severe COVID 19 complications Biomarkers of endothelial injury could constitute strong indicators of disease progression and severity In addition the endothelium could represent a very attractive target to both prevent and treat these complications To establish an adequate therapy the underlying pathophysiology and corresponding clinical stage should be clearly identified In this review the clinical features of COVID 19 the central role of the endothelium in COVID 19 and in other pathologies and the potential of specific therapies aimed at protecting the endothelium in COVID 19 patients are addressed

Assessment of activities of daily living in patients post COVID 19 a systematic review Coronavirus disease has provoked much discussion since its first appearance Despite it being widely studied all over the world little is known about the impact of the disease on functional ability related to performing activities of daily living ADL in patients post COVID 19 infection To understand the impact of COVID 19 on ADL performance of adult patients and to describe the common scales used to assess performance of ADL on patients post COVID 19 A systematic review was conducted We included studies that applied a physical capacity test in COVID 19 patients post infection Two independent reviewers analyzed the studies extracted the data and assessed the quality of the evidence A total of 1 228 studies were included after removing duplicates 1 005 abstracts were screened and of those 983 were excluded A final number of nine studies which met the eligibility criteria were included The findings revealed worsening of physical function and ADL performance in all patients post COVID 19 infection All included studies found a reduction of ADL beyond the test or scale used revealing a vital worsening of functional ability in ADL performance and consequently loss of independence in COVID 19 patients after the acute phase of infection Functional ability status previous to COVID 19 is crucial for predicting the severity of the disease and mortality Barthel Index and ADL score were the most used assessment tools across subjects with different intrinsic capacity and context levels

Erythema Multiforme and COVID 19 What Do We Know i Background i Erythema multiforme EM is an acute cutaneous eruption often associated with infections and more rarely with drugs This review aimed to evaluate the association between erythema multiforme and coronavirus disease 2019 COVID 19 i Methods i A systematic search of PubMed MEDLINE Scimago Scopus and ISI Web of Science was performed Original articles case series or case reports were evaluated and selected i Results i Fourteen articles were selected describing a total of 70 patients EM is a cutaneous eruption rarely occurring in COVID 19 and is in most cases associated with a hypersensitivity reaction to the virus In these cases EM seems to affect patients younger than 30 years or older than 55 years Infrequently some drugs used in the management of COVID 19 may induce EM especially hydroxychloroquine The three groups of patients seem to have different clinical characteristics and courses i Conclusions i From these data it is possible to preliminarily propose that EM or EM like eruptions linked to COVID 19 might be divided into three types the virus related juvenile type affecting patients 30 year old the virus related older type affecting patients 55 years and the drug induced type The occurrence of a skin rash does not seem to be related to the severity and clinical course of COVID 19

Long term sequelae are highly prevalent one year after hospitalization for severe COVID 19 Many coronavirus disease 2019 Covid 19 survivors show symptoms months after acute illness The aim of this work is to describe the clinical evolution of Covid 19 one year after discharge We performed a prospective cohort study on 238 patients previously hospitalized for Covid 19 pneumonia in 2020 who already underwent clinical follow up 4 months post Covid 19 200 consented to participate to a 12 months clinical assessment including pulmonary function tests with diffusing lung capacity for carbon monoxide DLCO post traumatic stress PTS symptoms evaluation by the Impact of Event Scale IES motor function evaluation by Short Physical Performance Battery and 2 min walking test chest Computed Tomography CT After 366 363 369 days 79 patients 39 5 reported at least one symptom A DLCO 80 was observed in 96 patients 49 0 Severe DLCO impairment 60 was reported in 20 patients 10 2 related to extent of CT scan abnormalities Some degree of motor impairment was observed in 25 8 of subjects 37 200 patients 18 5 showed moderate to severe PTS symptoms In the time elapsed from 4 to 12 months after hospital discharge motor function improves while respiratory function does not being accompanied by evidence of lung structural damage Symptoms remain highly prevalent one year after acute illness

An environmental scan of impacts and interventions for women with methamphetamine use in pregnancy and their children Indigenous women are overrepresented among people who use PWU methamphetamine MA due to colonialism and intergenerational trauma Prenatal methamphetamine exposure PME is increasing as the number of PWUMA of childbearing age grows Yet impacts of MA in pregnancy and effective interventions are not yet well understood We conducted an environmental scan of published and grey literature 2010 2020 to determine effects of MA use in pregnancy for mothers and their offspring effective interventions and implications for Indigenous women A strategic search of Ovid Medline Embase ProQuest Public Health and CINAHL databases identified academic literature while Google and ProQuest Public Health identified grey literature Article selection was based on titles abstracts and keywords The time frame captured recent MA composition and excluded literature impacted by coronavirus disease 2019 Data extracted from 80 articles identified 463 results related to 210 outcomes and seven interventions Analysis focused on six categories maternal neonatal infant cognitive behavioral neurological and interventions Maternal outcomes were more congruent than child outcomes The most prevalent outcomes were general neonatal infant outcomes A lack of Indigenous specific research on PME and interventions highlights a need for future research that incorporates relevant historical and sociocultural contexts

Application of the PCR number of cycle threshold value Ct in COVID 19 The SARS CoV 2 pandemic persists with all its virulence despite 650 382 819 doses of COVID vaccine worldwide The reference test for infection identification is reverse transcription polymerase chain reaction RT qPCR The usefulness of this test may be diminished by simplifying its result as positive or negative Determining the number of cycles Ct in positive RT qPCR tests can assist in decision making when interpreted in the clinical context of patients

Investigating the association between mass transit adoption and COVID 19 infections in US metropolitan areas Urbanization introduces the threat of increased epidemic disease transmission resulting from crowding on mass transit The coronavirus disease 2019 COVID 19 pandemic which has directly led to over 600 000 deaths in the US as of July 2021 triggered mass social distancing policies to be enacted as a key deterrent of widespread infections Social distancing can be challenging in confined spaces required for transportation such as mass transit systems Little is published regarding the degree to which mass transit system adoption effects impacted the rise of the COVID 19 pandemic in urban centers Taking an ecological approach where areal data are the unit of observation this national scale study aims to measure the association between the adoption of mass transit and COVID 19 spread through confirmed cases in US metropolitan areas National survey based transit adoption measures are entered in a negative binomial regression model to evaluate differences between areas The model results demonstrate that mass transit adoption in US metropolitan areas was associated with the magnitude of outbreaks Higher incidence of COVID 19 early in the pandemic was associated with survey results conveying higher transit use Increasing weekly bus transit usage in metropolitan statistical areas by one scaled unit was associated with a 1 38 95 CI 1 25 1 90 times increase in incidence rate of COVID 19 a 10 increase in weekly train transit usage was associated with an increase in incidence rate of 1 54 95 CI 1 42 2 07 times These conclusions should inform early action practices in urban centers with busy transit systems in the event of future infectious disease outbreaks Deeper understanding of these observed associations may also benefit modeling efforts by allowing researchers to include mathematical adjustments or better explain caveats to results when communicating with decision makers and the public in the crucial early stages of an epidemic

Neural and Self report Measures of Sensitivity to Uncertainty as Predictors of COVID Related Negative Affect The COVID 19 pandemic has been a period of unprecedented uncertainty Research indicates individuals differ in their response to uncertainty and these differences are mediated by anterior insula aINS function Those most sensitive to uncertainty are likely vulnerable to negative affect in the context of the pandemic The current study was designed to directly test this question using both neural and self reported measures of sensitivity to uncertainty Fifty nine volunteers completed a task designed to probe neural response to anticipation of predictable P and unpredictable U threat of electric shock during functional magnetic resonance imaging and a self report measure of intolerance of uncertainty IU Approximately two years later during the peak of the pandemic participants reported their emotional reactions to the COVID 19 crisis Multilevel mixed models revealed that greater aINS activation to U threat and greater self reported IU were independent predictors of increased COVID related negative affect These findings were significant when adjusting for biological sex and depression and anxiety symptom severity The results add to a growing literature demonstrating that individual differences in response to uncertainty have a robust impact on mood and functioning Results also highlight that individuals highly sensitive to uncertainty may be at increased risk for poor mental health during the ongoing pandemic

The BEMED study BMJ 2016 352 DOI 10 1136 was designed as multi centric double blind plaebo controlled study in patients with Menières disease It should compare a low level 2 24 mg d vs high level 3 48 mg d betahstine intake vs placebo The primary endpoint was the number of vertigo attacks lasting longer than 20 min as documented in a patients diary The main finding of the study was that betahistine did not significantly better reduced the number of vertigo attacks than placebo Therefore the BEMED study should be critically discussed in the present paper

Postacute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 Infection A State of the Art Review The vast majority of patients 99 with severe acute respiratory syndrome coronavirus 2 survive immediate infection but remain at risk for persistent and or delayed multisystem This review of published reports through May 31 2021 found that manifestations of postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection PASC affect between 33 and 98 of coronavirus disease 2019 survivors and comprise a wide range of symptoms and complications in the pulmonary cardiovascular neurologic psychiatric gastrointestinal renal endocrine and musculoskeletal systems in both adult and pediatric populations Additional complications are likely to emerge and be identified over time Although data on PASC risk factors and vulnerable populations are scarce evidence points to a disproportionate impact on racial ethnic minorities older patients patients with preexisting conditions and rural residents Concerted efforts by researchers health systems public health agencies payers and governments are urgently needed to better understand and mitigate the long term effects of PASC on individual and population health

Case Report Rhino orbital Mucormycosis Related to COVID 19 A Case Series Exploring Risk Factors There has been a surge of rhino orbital mucormycosis cases in India in the wake of the second wave of the COVID 19 pandemic It has been widely suggested that dysglycemia resulting from diabetes which is a common comorbidity in COVID 19 patients and indiscriminate steroid use has resulted in this surge We report a series of 13 cases of rhino orbital mucormycosis in COVID 19 patients admitted to our center between mid April and early June 2021 The cases showed a male preponderance two patients had loss of vision and four of them showed intracranial extension of disease Twelve patients had received steroids and 12 had preexisting or newly diagnosed diabetes both steroid use and diabetes being the most common identified risk factors Considering other possible risk factors immunosuppressed state antiviral or ayurvedic Indian traditional medications and oxygen therapy were not associated with a definite risk of mucormycosis because they were not present uniformly in the patients We propose that COVID 19 itself through molecular mechanisms predisposes to mucormycosis with other factors such as dysglycemia or steroid use increasing the risk

Long COVID and Health Inequities The Role of Primary Care Policy Points An estimated 700 000 people in the United States have long COVID that is symptoms of COVID 19 persisting beyond three weeks COVID 19 and its long term sequelae are strongly influenced by social determinants such as poverty and by structural inequalities such as racism and discrimination Primary care providers are in a unique position to provide and coordinate care for vulnerable patients with long COVID Policy measures should include strengthening primary care optimizing data quality and addressing the multiple nested domains of inequity

Factors associated with COVID 19 preventive health behaviors among the general public in Mexico City and the State of Mexico To evaluate factors associated with COVID 19 preventive health behaviors among adults in Mexico City and the State of Mexico We conducted a cross sectional survey from June to October 2020 through a structured internet based questionnaire in a non probabilistic sample of adults 18 years living in Mexico City and the State of Mexico The independent variables included sociodemographic and clinical factors health literacy access to COVID 19 information and perception of COVID 19 risk and of preventive measures effectiveness The dependent variable was COVID 19 preventive health behaviors defined as the number of preventive actions adopted by participants The data were analyzed through multivariate negative binomial regression analysis The survey was completed by 1 030 participants Most participants were women 70 7 had a high school or above level of education 98 8 and had adequate health literacy and access to COVID 19 information Only 18 perceived having a high susceptibility to COVID 19 though 83 8 recognized the diseases severity and 87 1 the effectiveness of preventive measures The median number of COVID 19 preventive actions was 13 5 range 0 19 The factors associated with preventive health behavior were being female of older age a professional worker a homemaker or a retiree engaging in regular physical exercise having high health literacy and access to COVID 19 information sources and perceiving COVID 19 as severe and preventive measures as effective People with high education and internet access in Mexico City and the State of Mexico reported significant engagement in COVID 19 preventive actions during the first wave of the COVID 19 pandemic

SARS CoV 2 Nucleocapsid protein attenuates stress granules and interacts with mRNAs to impair host stress response Severe acute respiratory syndrome coronavirus 2 SARS CoV 2 nucleocapsid N protein is essential for viral replication making it a promising target for antiviral drug and vaccine development SARS CoV 2 infected patients exhibit an uncoordinated immune response however the underlying mechanistic details of this imbalance remain obscure Here starting from a functional proteomics workflow we catalogued the protein protein interactions of SARS CoV 2 proteins including an evolutionarily conserved specific interaction of N with the stress granule resident proteins G3BP1 and G3BP2 N localizes to stress granules and sequesters G3BPs away from their typical interaction partners thus attenuating stress granule formation We found that N binds directly to host mRNAs in cells with a preference for 3 UTRs and modulates target mRNA stability We show that the N protein rewires the G3BP1 mRNA binding profile and suppresses the physiological stress response of host cells which may explain the imbalanced immune response observed in SARS CoV 2 infected patients

Pathophysiology of COVID 19 Why Children Fare Better than Adults The world is facing Coronavirus Disease 2019 COVID 19 pandemic which is causing a large number of deaths and burden on intensive care facilities It is caused by Severe Acute Respiratory Syndrome coronavirus 2 SARS CoV 2 originating in Wuhan China It has been seen that fewer children contract COVID 19 and among infected children have less severe disease Insights in pathophysiological mechanisms of less severity in children could be important for devising therapeutics for high risk adults and elderly Early closing of schools and day care centers led to less frequent exposure and hence lower infection rate in children The expression of primary target receptor for SARS CoV 2 i e angiotensin converting enzyme 2 ACE 2 decreases with age ACE 2 has lung protective effects by limiting angiotensin 2 mediated pulmonary capillary leak and inflammation Severe COVID 19 disease is associated with high and persistent viral loads in adults Children have strong innate immune response due to trained immunity secondary to live vaccines and frequent viral infections leading to probably early control of infection at the site of entry Adult patients show suppressed adaptive immunity and dysfunctional over active innate immune response in severe infections which is not seen in children These could be related to immune senescence in elderly Excellent regeneration capacity of pediatric alveolar epithelium may be contributing to early recovery from COVID 19 Children less frequently have risk factors such as co morbidities smoking and obesity But young infants and children with pre existing illnesses could be high risk groups and need careful monitoring Studies describing immune pathogenesis in COVID 19 are lacking in children and need urgent attention

Identification of homologous human miRNAs as antivirals towards COVID 19 genome The COVID 19 fatality rate is 57 worldwide The investigation of possible antiviral therapy using host microRNA miRNA to inhibit viral replication and transmission is the need of the hour Computational techniques were used to predict the hairpin precursor miRNA pre miRNAs of COVID 19 genome with high homology towards human host miRNA Top 21 host miRNAs with 80 homology towards 18 viral pre miRNAs were identified The Gibbs free energy ΔG between host miRNAs and viral pre miRNAs hybridization resulted in the best 5 host miRNAs having the highest base pair complementarity miR 4476 had the strongest binding with viral pre miRNA ΔG 21 8 kcal mol due to maximum base pairing in the seed sequence Pre miR 651 secondary structure was most stable due to the 1 least minimum free energy ΔG 24 4 kcal mol energy frequency and noncanonical base pairing and 2 maximum number of stem base pairing and small loop size Host miRNAs viral mRNAs interaction can effectively inhibit viral transmission and replication Furthermore miRNAs gene network and gene ontology studies indicate top 5 host miRNAs interaction with host genes involved in transmembrane receptor signaling cell migration RNA splicing nervous system formation and tumor necrosis factor mediated signaling in respiratory diseases This study identifies host miRNA virus pre miRNAs strong interaction structural stability and their gene network analysis provides strong evidence of host miRNAs as antiviral COVID 19 agents

SARS CoV 2 Neuronal Invasion and Complications Potential Mechanisms and Therapeutic Approaches Clinical reports suggest that the coronavirus disease 19 COVID 19 pandemic caused by severe acute respiratory syndrome SARS coronavirus 2 CoV 2 has not only taken millions of lives but has also created a major crisis of neurologic complications that persist even after recovery from the disease Autopsies of patients confirm the presence of the coronaviruses in the CNS especially in the brain The invasion and transmission of SARS CoV 2 in the CNS is not clearly defined but because the endocytic pathway has become an important target for the development of therapeutic strategies for COVID 19 it is necessary to understand endocytic processes in the CNS In addition mitochondria and mechanistic target of rapamycin mTOR signaling pathways play a critical role in the antiviral immune response and may also be critical for endocytic activity Furthermore dysfunctions of mitochondria and mTOR signaling pathways have been associated with some high risk conditions such as diabetes and immunodeficiency for developing severe complications observed in COVID 19 patients However the role of these pathways in SARS CoV 2 infection and spread are largely unknown In this review we discuss the potential mechanisms of SARS CoV 2 entry into the CNS and how mitochondria and mTOR pathways might regulate endocytic vesicle mitochondria interactions and dynamics during SARS CoV 2 infection The mechanisms that plausibly account for severe neurologic complications with COVID 19 and potential treatments with Food and Drug Administration approved drugs targeting mitochondria and the mTOR pathways are also addressed

What is the recovery rate and risk of long term consequences following a diagnosis of COVID 19 A harmonised global longitudinal observational study protocol Very little is known about possible clinical sequelae that may persist after resolution of acute COVID 19 A recent longitudinal cohort from Italy including 143 patients followed up after hospitalisation with COVID 19 reported that 87 had at least one ongoing symptom at 60 day follow up Early indications suggest that patients with COVID 19 may need even more psychological support than typical intensive care unit patients The assessment of risk factors for longer term consequences requires a longitudinal study linked to data on pre existing conditions and care received during the acute phase of illness The primary aim of this study is to characterise physical and psychosocial sequelae in patients post COVID 19 hospital discharge This is an international open access prospective observational multisite study This protocol is linked with the International Severe Acute Respiratory and emerging Infection Consortium ISARIC and the WHOs Clinical Characterisation Protocol which includes patients with suspected or confirmed COVID 19 during hospitalisation This protocol will follow up a subset of patients with confirmed COVID 19 using standardised surveys to measure longer term physical and psychosocial sequelae The data will be linked with the acute phase data Statistical analyses will be undertaken to characterise groups most likely to be affected by sequelae of COVID 19 The open access follow up survey can be used as a data collection tool by other follow up studies to facilitate data harmonisation and to identify subsets of patients for further in depth follow up The outcomes of this study will inform strategies to prevent long term consequences inform clinical management interventional studies rehabilitation and public health management to reduce overall morbidity and improve long term outcomes of COVID 19 The protocol and survey are open access to enable low resourced sites to join the study to facilitate global standardised longitudinal data collection Ethical approval has been given by sites in Colombia Ghana Italy Norway Russia the UK and South Africa New sites are welcome to join this collaborative study at any time Sites interested in adopting the protocol as it is or in an adapted version are responsible for ensuring that local sponsorship and ethical approvals in place as appropriate The tools are available on the ISARIC website www isaric org PROTOCOL REGISTRATION NUMBER osf io c5rw3 PROTOCOL VERSION 3 August 2020 EUROQOL ID 37035

Persistent symptoms and decreased health related quality of life after symptomatic pediatric COVID 19 A prospective study in a Latin American tertiary hospital To prospectively evaluate demographic anthropometric and health related quality of life HRQoL in pediatric patients with laboratory confirmed coronavirus disease 2019 COVID 19 This was a longitudinal observational study of surviving pediatric post COVID 19 patients n 53 and pediatric subjects without laboratory confirmed COVID 19 included as controls n 52 was performed The median duration between COVID 19 diagnosis n 53 and follow up was 4 4 months 0 8 10 7 Twenty three of 53 43 patients reported at least one persistent symptom at the longitudinal follow up visit and 12 53 23 had long COVID 19 with at least one symptom lasting for 12 weeks The most frequently reported symptoms at the longitudinal follow up visit were headache 19 severe recurrent headache 9 tiredness 9 dyspnea 8 and concentration difficulty 4 At the longitudinal follow up visit the frequencies of anemia 11 versus 0 p 0 030 lymphopenia 42 versus 18 p 0 020 C reactive protein level of 30 mg L 35 versus 0 p 0 0001 and D dimer level of 1000 ng mL 43 versus 6 p 0 0004 significantly reduced compared with baseline values Chest X ray abnormalities 11 versus 2 p 0 178 and cardiac alterations on echocardiogram 33 versus 22 p 0 462 were similar at both visits Comparison of characteristic data between patients with COVID 19 at the longitudinal follow up visit and controls showed similar age p 0 962 proportion of male sex p 0 907 ethnicity p 0 566 family minimum monthly wage p 0 664 body mass index p 0 601 and pediatric pre existing chronic conditions p 1 000 The Pediatric Quality of Live Inventory 4 0 scores median physical score 69 0 100 versus 81 34 100 p 0 012 and school score 60 15 100 versus 70 15 95 p 0 028 were significantly lower in pediatric patients with COVID 19 at the longitudinal follow up visit than in controls Pediatric patients with COVID 19 showed a longitudinal impact on HRQoL parameters particularly in physical school domains reinforcing the need for a prospective multidisciplinary approach for these patients These data highlight the importance of closer monitoring of children and adolescents by the clinical team after COVID 19

Consequences of visiting restrictions during the COVID 19 pandemic An integrative review During the COVID 19 pandemic visiting restrictions of different extents have been implemented However despite the long history of visiting restrictions in health care systems little is known about their effects This review sought to explore the consequences of visitor restrictions in health care services during the COVID 19 pandemic A systematic integrative review was conducted in accordance with the PRISMA guidelines based on a systematic search in PubMed CHINAL full plus Web of Science PsychInfo Scopus and the Cochrane Library A total of 17 scientific papers covering intensive care pediatric care general medical care hospital care palliative care and nursing home settings were included Although appreciation for the technical solutions enabling remote meetings was reported visiting restrictions had several consequences mainly negative for the patients health the health and wellbeing of family members and the provision of care Among physical health consequences reduced nutrition intake decreased activities of daily living and increased physical pain and symptoms were reported Among mental health consequences for the patient loneliness depressive symptoms agitation aggression reduced cognitive ability and overall dissatisfaction were observed For family members worry anxiety and uncertainty occurred and they reported an increased need for information from care providers Family members of neonatal intensive care unit patients reported less bonding with their child and family relation disturbances due to the restrictions For care providers visiting restrictions added the burdens of ethical dilemmas learning new technical means to enable social interaction and an increased demand for communication with families and providing social support to both family members and patients When implementing visiting restrictions in health care services decision makers and nurses need to be aware of their potential negative effects and adapt the provision of care to compensate for such effects Nurses in all sectors should be aware that visiting restrictions may affect patients families and health care services for longer than the actual pandemic Since the level of evidence regarding effect from visiting restrictions is low further studies is strongly needed

The need for gentle medicine in a post Covid 19 world As it has historically been the case with many pandemics the Covid 19 experience will induce many philosophers to reconsider the value of medical practice This should be a good opportunity to critically scrutinize the way medical research and medical interventions are carried out For much of its history medicine has been very inefficient But even in its contemporary forms a review of common protocols in medical research and medical interventions reveal many shortcomings especially related to methodological flaws and more importantly conflicts of interests due to profit incentives In the face of these problems we propose a program of gentle medicine This term originally formulated by philosopher Jacob Stegenga describes a form of medicine in which physicians intervene less than they currently do As part of this general program we advance a series of reform recommendations that could be enacted both by medical staff in their everyday practice but also by public health officials and policymakers

Could Probiotics and Postbiotics Function as Silver Bullet in the Post COVID 19 Era We are currently experiencing the realities of the most severe pandemic within living memory with major impacts on the health and economic well being of our planet The scientific community has demonstrated an unprecedented mobilization capability with the rapid development of vaccines and drugs targeting the protection of human life and palliative measures for infected individuals However are we adequately prepared for ongoing defense against COVID 19 and its variants in the post pandemic world Moreover are we equipped to provide a satisfactory quality of life for individuals who are recovering from COVID 19 disease What are the possibilities for the acceleration of the recovery process Here we give special consideration to the potential and already demonstrated role of probiotics and traditional medical approaches to the management of current and potential future encounters with our major virus adversaries

Evolution of Human Memory B Cells From Childhood to Old Age High quality medical assistance and preventive strategies including pursuing a healthy lifestyle result in a progressively growing percentage of older people The population and workforce is aging in all countries of the world It is widely recognized that older individuals show an increased susceptibility to infections and a reduced response to vaccination suggesting that the aged immune system is less able to react and consequently protect the organism The SARS CoV 2 pandemic is dramatically showing us that the organism reacts to novel pathogens in an age dependent manner The decline of the immune system observed in aging remains unclear We aimed to understand the role of B cells We analyzed peripheral blood from children 4 18 years young people 23 60 years and elderly people 65 91 years by flow cytometry We also measured antibody secretion by ELISA following a T independent stimulation Here we show that the elderly have a significant reduction of CD27 sup dull sup memory B cells a population that bridges innate and adaptive immune functions In older people memory B cells are mostly high specialized antigen selected CD27 sup bright sup Moreover after i in vitro i stimulation with CpG B cells from older individuals produced significantly fewer IgM and IgA antibodies compared to younger individuals Aging is a complex process characterized by a functional decline in multiple physiological systems The immune system of older people is well equipped to react to often encountered antigens but has a low ability to respond to new pathogens

Mental health problems in Indonesian internship doctors during the COVID 19 pandemic All new graduate medical doctors in Indonesia will work in government healthcare facilities for one year as internship doctors Problems such as the shortage of PPE no specific treatment guidelines and inadequate support from authorities contributed to mental health problems This study aimed to determine mental health problems and associated demographics and concerns of Indonesian internship doctors in the COVID 19 pandemic era This cross sectional study was performed from 1 31 Januari 2021 via Google Form questionnaire to collect data Logistic regression analysis was used to identify the association between demographic data concerns in internship doctors working place and mental health using Depression Anxiety Stress Scale 21 Depression anxiety and stress in internship doctors were 32 6 44 1 and 19 5 consecutively Multivariate analysis showed that the only demographic factor associated with depression was female sex Concerns of internship doctors were the most factors associated with mental health Working in triage was associated with depression and stress Donning and doffing training of PPE difficulty to practice physical distancing and hesitancy to attend patients were associated with depression and anxiety Difficulty to practice physical distancing in hospital w associated with anxiety and stress Firstly some difficulties in data collection Secondly the self reported tools of mental health are not always aligned with the psychiatric assessment Lastly possibility of recall biases from each batch To minimize mental health problems of internship doctors their concerns must be tackled Medical schools have an important role to manage concerns of these internship doctors

Long term SARS CoV 2 specific immune and inflammatory responses in individuals recovering from COVID 19 with and without post acute symptoms We describe severe acute respiratory syndrome coronavirus 2 SARS CoV 2 specific T cell responses soluble markers of inflammation and antibody levels and neutralization capacity longitudinally in 70 individuals with PCR confirmed SARS CoV 2 infection Participants represent a spectrum of illness and recovery including some with persistent viral shedding in saliva and many experiencing post acute sequelae of SARS CoV 2 infection PASC T cell responses remain stable for up to 9 months Whereas the magnitude of early CD4 sup sup T cell immune responses correlates with severity of initial infection pre existing lung disease is independently associated with higher long term SARS CoV 2 specific CD8 sup sup T cell responses Among participants with PASC 4 months following coronavirus disease 2019 COVID 19 symptom onset we observe a lower frequency of CD8 sup sup T cells expressing CD107a a marker of degranulation in response to Nucleocapsid N peptide pool stimulation and a more rapid decline in the frequency of N specific interferon γ producing CD8 sup sup T cells Neutralizing antibody levels strongly correlate with SARS CoV 2 specific CD4 sup sup T cell responses

The Importance of Listening in Treating Invisible Illness and Long Haul COVID 19 Primary and specialty care clinicians strive to base diagnoses and treatment on specific measurable abnormalities Yet those with invisible controversial illnesses such as myalgic encephalomyelitis chronic fatigue syndrome ME CFS often have symptoms not explained by standard laboratory values For instance one of the cardinal features of ME CFS is postexertional malaise the exacerbation of symptoms fatigue pain cognitive dysfunction following exertion which contradicts studies showing the health benefits of exercise In these cases overly physicalist approaches to caring for patients are not likely to be helpful and a clinicians willingness to listen to a patients experience of illness becomes essential

Post Acute Sequelae of SARS CoV 2 Infection Among Adults Aged 18 Years Long Beach California April 1 December 10 2020 Post acute sequelae of COVID 19 also known as long COVID is used to describe the long term symptoms that might be experienced weeks to months after primary infection with SARS CoV 2 the virus that causes COVID 19 Among persons with a previous COVID 19 diagnosis estimates of the prevalence of sequelae range from 5 among nonhospitalized persons to 80 among hospitalized persons 1 2 Studies have analyzed the aftereffects of COVID 19 but few have assessed the demographic characteristics associated with long COVID 3 4 Health disparities resulting from pervasive structural and socioeconomic barriers in the U S health care system might contribute to differences in these effects and might continue to exacerbate existing inequities 5 To identify trends in post acute sequelae the Long Beach Department of Health and Human Services LBDHHS interviewed a random sample of 366 persons aged 18 years who received a positive SARS CoV 2 test result during April 1 December 10 2020 One third of the persons interviewed reported having at least one symptom 2 months after their positive test result with higher odds of sequelae among persons aged 40 54 years females and those with preexisting conditions Black or African American Black participants had higher odds of reporting dyspnea and myalgia arthralgia compared with other racial ethnic groups Persons who were aged 40 years female Black or who reported known preexisting conditions also reported higher numbers of distinct sequelae As the number of recovered COVID 19 patients increases monitoring the prevalence of post acute sequelae among larger cohorts in diverse populations will be necessary to understand and manage this condition Identification of groups disproportionately affected by post acute COVID 19 sequelae can help develop efforts to prioritize preventions and treatment strategies including vaccination of groups at higher risk for these long term sequelae and access to testing and care for post acute sequelae

Model for utilizing distance learning post COVID 19 using PACT a cross sectional qualitative study COVID 19 pandemic pressured medical schools globally to shift to Distance learning DL as an alternative way to ensure that the content delivered is satisfactory for student progression This work aims at mapping priorities for post COVID planning for better balance between distance learning and face to face learning This qualitative study aimed to develop a model for utilizing DL using The Polarity Approach for Continuity and Transformation PACT A virtual mapping session was held with 79 faculty from 19 countries They worked in small groups to determine upsides and downsides of face to face and DL subsequently An initial polarity map was generated identifying five tension areas Faculty Students Curriculum Social aspects and Logistics A 63 item assessment tool was generated based on this map piloted and then distributed as a self administered assessment The outcomes of this assessment were utilized for another mapping session to discuss warning signs and action steps to maintain upsides and avoid downsides of each pole Participants agreed that face to face teaching allows them to inspire students and have meaningful connections with them They also agreed that DL provides a good environment for most students However students with financial challenges and special needs may not have equal opportunities to access technology As regards social issues participants agreed that face to face learning provides a better chance for professionalism through enhanced team work Cognitive communication and clinical skills are best achieved in face to face Participants agreed that logistics for conducting DL are much more complicated when compared to face to face learning Participants identified around 10 warning signs for each method that need to be continuously monitored in order to minimize the drawbacks of over focusing on one pole at the expense of the other Action steps were determined to ensure optimized use of in either method In order to plan for the future we need to understand the dynamics of education within the context of polarities Educators need to understand that the choice of DL although was imposed as a no alternative solution during the COVID era yet it has always existed as a possible alternative and will continue to exist after this era The value of polarity mapping and leveraging allows us to maximize the benefit of each method and guide educators decisions to minimize the downsides for the good of the learning process

Burdens of post acute sequelae of COVID 19 by severity of acute infection demographics and health status The Post Acute Sequelae of SARS CoV 2 infection PASC have been characterized however the burden of PASC remains unknown Here we used the healthcare databases of the US Department of Veterans Affairs to build a cohort of 181 384 people with COVID 19 and 4 397 509 non infected controls and estimated that burden of PASC defined as the presence of at least one sequela in excess of non infected controls was 73 43 72 10 74 72 per 1000 persons at 6 months Burdens of individual sequelae varied by demographic groups age race and sex but were consistently higher in people with poorer baseline health and in those with more severe acute infection In sum the burden of PASC is substantial PASC is non monolithic with sequelae that are differentially expressed in various population groups Collectively our results may be useful in informing health systems capacity planning and care strategies of people with PASC

A narrative review on characterization of acute respiratory distress syndrome in COVID 19 infected lungs using artificial intelligence COVID 19 has infected 77 4 million people worldwide and has caused 1 7 million fatalities as of December 21 2020 The primary cause of death due to COVID 19 is Acute Respiratory Distress Syndrome ARDS According to the World Health Organization WHO people who are at least 60 years old or have comorbidities that have primarily been targeted are at the highest risk from SARS CoV 2 Medical imaging provides a non invasive touch free and relatively safer alternative tool for diagnosis during the current ongoing pandemic Artificial intelligence AI scientists are developing several intelligent computer aided diagnosis CAD tools in multiple imaging modalities i e lung computed tomography CT chest X rays and lung ultrasounds These AI tools assist the pulmonary and critical care clinicians through a faster detection of the presence of a virus b classifying pneumonia types and c measuring the severity of viral damage in COVID 19 infected patients Thus it is of the utmost importance to fully understand the requirements of for a fast and successful and timely lung scans analysis This narrative review first presents the pathological layout of the lungs in the COVID 19 scenario followed by understanding and then explains the comorbid statistical distributions in the ARDS framework The novelty of this review is the approach to classifying the AI models as per the by school of thought SoTs exhibiting based on segregation of techniques and their characteristics The study also discusses the identification of AI models and its extension from non ARDS lungs pre COVID 19 to ARDS lungs post COVID 19 Furthermore it also presents AI workflow considerations of for medical imaging modalities in the COVID 19 framework Finally clinical AI design considerations will be discussed We conclude that the design of the current existing AI models can be improved by considering comorbidity as an independent factor Furthermore ARDS post processing clinical systems must involve include i the clinical validation and verification of AI models ii reliability and stability criteria and iii easily adaptable and iv generalization assessments of AI systems for their use in pulmonary critical care and radiological settings

Retinal nerve fibre layer and ganglion cell layer changes in children who recovered from COVID 19 a cohort study To investigate the optic nerve and macular parameters of children who recovered from COVID 19 compared with healthy children using optical coherence tomography OCT Cohort study Hospital Clinico San Carlos Madrid Children between 6 and 18 years old who recovered from COVID 19 with laboratory confirmed SARS CoV 2 infection and historical controls were included All patients underwent an ophthalmological examination including macular and optic nerve OCT Demographic data medical history and COVID 19 symptoms were noted Peripapillary retinal nerve fibre layer thickness macular retinal nerve fibre layer thickness macular ganglion cell layer thickness and retinal thickness 90 patients were included 29 children who recovered from COVID 19 and 61 controls Patients with COVID 19 presented an increase in global peripapillary retinal nerve fibre layer thickness mean difference 7 7 95 CI 3 4 to 12 1 temporal superior mean difference 11 0 95 CI 3 3 to 18 6 temporal inferior mean difference 15 6 95 CI 6 5 to 24 7 and nasal mean difference 9 8 95 CI 2 9 to 16 7 sectors Macular retinal nerve fibre layer analysis showed decreased thickness in the nasal outer p 0 011 and temporal inner p 0 036 sectors in patients with COVID 19 while macular ganglion cell layer thickness increased in these sectors p 0 001 and p 0 015 respectively No differences in retinal thickness were noted Children with recent history of COVID 19 present significant changes in peripapillary and macular OCT analyses

Planning for disposal of COVID 19 pandemic wastes in developing countries a review of current challenges The health sector is critical to the well being of any country but developing countries have several obstacles that prevent them from providing adequate health care This became an even larger concern after the COVID 19 outbreak left millions of people dead worldwide and generated huge amounts of infected or potentially infected wastes The management and disposal of medical wastes during and post COVID 19 represent a major challenge in all countries but this challenge is particularly great for developing countries that do not have robust waste disposal infrastructure The main problems in developing countries include inefficient treatment procedures limited capacity of healthcare facilities and improper waste disposal procedures The management of medical wastes in most developing countries was primitive prior to the pandemic The improper treatment and disposal of these wastes in our current situation may further speed COVID 19 spread creating a serious risk for workers in the medical and sanitation fields patients and all of society Therefore there is a critical need to discuss emerging challenges in handling treating and disposing of medical wastes in developing countries during and after the COVID 19 outbreak There is a need to determine best disposal techniques given the conditions and limitations under which developing countries operate Several open questions need to be investigated concerning this global issue such as to what extent developing countries can control the expected environmental impacts of COVID 19 particularly those related to medical wastes What are the projected management scenarios for medical wastes under the COVID 19 outbreak And what are the major environmental risks posed by contaminated wastes related to COVID 19 treatment Studies directed at the questions above careful planning the use of large capacity mobile recycling facilities and following established guidelines for disposal of medical wastes should reduce risk of COVID 19 spread in developing countries

The impact of COVID 19 lockdown on child and adolescent mental health systematic review COVID 19 was declared a pandemic in March 2020 resulting in many countries worldwide calling for lockdowns This study aimed to review the existing literature on the effects of the lockdown measures established as a response to the COVID 19 pandemic on the mental health of children and adolescents Embase Ovid Global Health PsycINFO Web of Science and pre print databases were searched in this PRISMA compliant systematic review PROSPERO CRD42021225604 We included individual studies reporting on a wide range of mental health outcomes including risk and protective factors conducted in children and adolescents aged 19 years exposed to COVID 19 lockdown Data extraction and quality appraisal were conducted by independent researchers and results were synthesised by core themes 61 articles with 54 999 children and adolescents were included mean age 11 3 years 49 7 female Anxiety symptoms and depression symptoms were common in the included studies and ranged 1 8 49 5 and 2 2 63 8 respectively Irritability range 16 7 73 2 and anger range 30 0 51 3 were also frequently reported by children and adolescents Special needs and the presence of mental disorders before the lockdown alongside excessive media exposure were significant risk factors for anxiety Parent child communication was protective for anxiety and depression The COVID 19 lockdown has resulted in psychological distress and highlighted vulnerable groups such as those with previous or current mental health difficulties Supporting the mental health needs of children and adolescents at risk is key Clinical guidelines to alleviate the negative effects of COVID 19 lockdown and public health strategies to support this population need to be developed

Post COVID 19 assessment in a specialist clinical service a 12 month single centre prospective study in 1325 individuals Post COVID 19 complications require simultaneous characterisation and management to plan policy and health system responses We describe the 12 month experience of the first UK dedicated post COVID 19 clinical service to include hospitalised and non hospitalised patients In a single centre observational analysis we report the demographics symptoms comorbidities investigations treatments functional recovery specialist referral and rehabilitation of 1325 individuals assessed at the University College London Hospitals post COVID 19 service between April 2020 and April 2021 comparing by referral route posthospitalised PH non hospitalised NH and post emergency department PED Symptoms associated with poor recovery or inability to return to work full time were assessed using multivariable logistic regression 1325 individuals were assessed PH 547 41 3 PED 212 16 NH 566 42 7 Compared with the PH and PED groups the NH group were younger median 44 6 35 6 52 8 years vs 58 3 47 0 67 7 years and 48 5 39 4 55 7 years more likely to be female 68 2 43 0 and 59 9 less likely to be of ethnic minority 30 9 52 7 and 41 0 or seen later after symptom onset median IQR 194 118 298 days 69 51 111 days and 76 55 128 days all p 0 0001 All groups had similar rates of onward specialist referral NH 18 7 PH 16 1 and PED 18 9 p 0 452 and were more likely to require support for breathlessness 23 7 5 5 and 15 1 p 0 001 and fatigue 17 8 4 8 and 8 0 p 0 001 Hospitalised patients had higher rates of pulmonary emboli persistent lung interstitial abnormalities and other organ impairment 716 54 0 individuals reported 75 optimal health median 70 IQR 55 85 Less than half of employed individuals could return to work full time at first assessment Post COVID 19 symptoms were significant in PH and NH patients with significant ongoing healthcare needs and utilisation Trials of interventions and patient centred pathways for diagnostic and treatment approaches are urgently required

Paediatric dental care during and post COVID 19 era Changes and challenges ahead COVID 19 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 SARS CoV 2 The virus is transmitted through respiratory droplets and by physical contact from contaminated surfaces to the mucosa Its route of transmission has caused a significant challenge in medical and dental healthcare This article aims to review the literature and information available on the provision of paediatric dental treatment during and post pandemic and to provide specific recommendations on the safe provision of paediatric dental care Children infected by SARS CoV 2 have no or milder COVID 19 symptoms and are potential vectors in spreading the disease Routine dental treatment is suspended in many countries because of the increased risk of cross infection in dental practices Only emergency dental care is provided for urgent conditions It is necessary to gradually reinstate regular dental care to paediatric patients and maintain their good oral health To control the disease transmission and maintain the oral health of the population minimally intervention techniques that minimise or eliminate aerosol generation plus comprehensive oral health preventive measures should be practised to safeguard safety at dental practices in this unprecedented time Robust infection control guidelines should be implemented in dental clinics to minimise the risk of infection and to ensure the safety of patients and staff during the pandemic Three levels of preventive care should be practised to prevent oral diseases and improve childrens oral health in this COVID 19 era Treatment should be prioritized to patients in urgent needs and aerosol generating procedures should be minimized

Immunomodulation and immunotherapeutics of COVID 19 Severe acute respiratory syndrome coronavirus 2 causes coronavirus disease 2019 a pandemic which was originated from Wuhan city of China The pandemic has affected millions of people worldwide The pathogenesis of SARS CoV 2 is characterized by a cytokine storm in the blood cytokinemia and tissues especially the lungs One of the major repercussions of this inflammatory process is the endothelial injury causing intestinal bleeding coagulopathy and thromboembolism which result in various sudden and unexpected post COVID complications including kidney failure myocardial infarction or multiorgan failure In this review we have summarized the immune responses biochemical changes and inflammatory responses in the human body after infection with the SARS CoV 2 virus The increased amount of inflammatory cytokines chemokines and involvement of complement proteins in inflammatory reaction increase the risk of occurrence of disease

Hospitalizations Associated with COVID 19 Among Children and Adolescents COVID NET 14 States March 1 2020 August 14 2021 Although COVID 19 associated hospitalizations and deaths have occurred more frequently in adults sup sup COVID 19 can also lead to severe outcomes in children and adolescents 1 2 Schools are opening for in person learning and many prekindergarten children are returning to early care and education programs during a time when the number of COVID 19 cases caused by the highly transmissible B 1 617 2 Delta variant of SARS CoV 2 the virus that causes COVID 19 is increasing sup sup Therefore it is important to monitor indicators of severe COVID 19 among children and adolescents This analysis uses Coronavirus Disease 2019 Associated Hospitalization Surveillance Network COVID NET sup sup data to describe COVID 19 associated hospitalizations among U S children and adolescents aged 0 17 years During March 1 2020 August 14 2021 the cumulative incidence of COVID 19 associated hospitalizations was 49 7 per 100 000 children and adolescents The weekly COVID 19 associated hospitalization rate per 100 000 children and adolescents during the week ending August 14 2021 1 4 was nearly five times the rate during the week ending June 26 2021 0 3 among children aged 0 4 years the weekly hospitalization rate during the week ending August 14 2021 was nearly 10 times that during the week ending June 26 2021 During June 20 July 31 2021 the hospitalization rate among unvaccinated adolescents aged 12 17 years was 10 1 times higher than that among fully vaccinated adolescents Among all hospitalized children and adolescents with COVID 19 the proportions with indicators of severe disease such as intensive care unit ICU admission after the Delta variant became predominant June 20 July 31 2021 were similar to those earlier in the pandemic March 1 2020 June 19 2021 Implementation of preventive measures to reduce transmission and severe outcomes in children is critical including vaccination of eligible persons universal mask wearing in schools recommended mask wearing by persons aged 2 years in other indoor public spaces and child care centers sup sup and quarantining as recommended after exposure to persons with COVID 19 sup sup

Children with long covid Almost half of children who contract covid 19 may have lasting symptoms which should factor into decisions on reopening schools reports b Helen Thomson b

Renin Angiotensin System RAS and Immune System Profile in Specific Subgroups with COVID 19 The identification of vulnerable subgroups and risk factors associated with the susceptibility to severe acute respiratory syndrome coronavirus 2 SARS CoV 2 infection and coronavirus disease 2019 COVID 19 is of utmost importance in a pandemic scenario Potential interactions between renin angiotensin system RAS immune markers and COVID 19 play a role in disease outcome in specific groups of patients This review aimed to describe the particularities of the RAS and the immune system profile of particular subgroups of patients This non systematic review summarizes evidence on SARS CoV 2 infection in specific subgroups of patients and possible relationships between immune system RAS and the pathophysiology of COVID 19 The RAS and the immune system exert a role in the pathogenesis and prognosis of COVID 19 mainly in cases of hypertension diabetes obesity and other chronic diseases The overactivation of the ACE Ang II AT1R axis and the enhancement of inflammation contribute to deleterious effects of COVID 19 Likewise pregnant women and elderly patients usually display immune responses that are less effective in withstanding exposition to viruses while children are relatively protected against severe complications of COVID 19 Women conversely exhibit stronger antiviral responses and are less sensitive to the effects of increased Ang II Future Perspectives The recognition of vulnerable subgroups and risk factors for disease severity is essential to better understand the pandemic Precision medicine tools including proteomics and metabolomics approaches identified metabolic patterns of the severe form of disease and might be the alternative to diagnose evaluate and predict the prognosis and the efficiency of therapies

Hyperventilation A Possible Explanation for Long Lasting Exercise Intolerance in Mild COVID 19 Survivors Since the outbreak of the coronavirus COVID 19 pandemic most attention has focused on containing transmission and addressing the surge of critically ill patients in acute care settings As we enter the second phase of the pandemic emphasis must evolve to post acute care of COVID 19 survivors Persisting cardiorespiratory symptoms have been reported at several months after the onset of the infection Information is lacking on the pathophysiology of exercise intolerance after COVID 19 Previous outbreaks of coronaviruses have been associated with persistent dyspnea muscle weakness fatigue and reduced quality of life The extent of Covid 19 sequelae remains to be evaluated but persisting cardiorespiratory symptoms in COVID 19 survivors can be described as two distinct entities The first type of post Covid symptoms are directly related to organ injury in the acute phase or the complications of treatment The second type of persisting symptoms can affect patients even with mild initial disease presentation without evidence of organ damage The mechanisms are still poorly qualified to date There is a lack of correlation between initial symptom severity and residual symptoms at exertion We report exercise hyperventilation as a major limiting factor in COVID 19 survivors The origin of this hyperventilation may be related to an abnormality of ventilatory control by either hyperactivity of activator systems automatic and cortical ventilatory control peripheral afferents and sensory cortex or failure of inhibitory systems endorphins in the aftermath of pulmonary infection Hyperventilation induced hypocapnia can cause a multitude of extremely disabling symptoms such as dyspnea tachycardia chest pain fatigue dizziness and syncope at exertion

A clinical primer for the expected and potential post COVID 19 syndromes In late 2019 a novel coronavirus SARS CoV 2 COVID 19 spread unchecked across the worlds population With tens of millions infected the long term consequences of COVID 19 infection will be a major health care focus for years after the contagion subsides Most complications stem from direct viral invasion provoking an over exuberant inflammatory response driven by innate immune cells and activation of the clotting cascade causing thrombosis Injury to individual organs and their protective linings are frequent presentations in respiratory cardiovascular and neurological systems Reviewing the historical context of postviral fatiguing symptoms seems relevant to understanding reports of uneven recoveries and persistent symptoms that are emerging as long haul COVID 19 The pandemic is also an unprecedented sociocultural event transforming how people consider their health gather in groups and navigate their daily lives The unprecedented sociocultural stresses of the pandemic will have an invisible ubiquitous and predictable impact on neurologic endocrine and immune functioning even in people untouched by the virus COVID 19 may also have a surprise or two in store with unique clinical presentations and novel mechanisms of injury which are yet to clearly emerge Although challenging and unfortunate these times also represent a unique opportunity to start to unravel the physiology that underlie how viruses may trigger cancers neurological disease and postviral fatiguing syndromes

Vaccination boosts protective responses and counters SARS CoV 2 induced pathogenic memory B cells Much is to be learned about the interface between immune responses to SARS CoV 2 infection and vaccination We monitored immune responses specific to SARS CoV 2 Spike Receptor Binding Domain RBD in convalescent individuals for eight months after infection diagnosis and following vaccination Over time neutralizing antibody responses which are predominantly RBD specific generally decreased while RBD specific memory B cells persisted RBD specific antibody and B cell responses to vaccination were more vigorous than those elicited by infection in the same subjects or by vaccination in infection naïve comparators Notably the frequencies of double negative B memory cells which are dysfunctional and potentially pathogenic increased in the convalescent subjects over time Unexpectedly this effect was reversed by vaccination Our work identifies a novel aspect of immune dysfunction in mild moderate COVID 19 supports the practice of offering SARS CoV 2 vaccination regardless of infection history and provides a potential mechanistic explanation for the vaccination induced reduction of Long COVID symptoms

Pediatric COVID toes and fingers The emergence of the coronavirus disease 2019 COVID 19 worldwide pandemic has been associated with a new constellation of cutaneous features in children Among the unusual dermatologic presentations are the so called COVID toes inflammatory nodules of the feet and toes sometimes involving the hands and fingers These lesions mimic acral pernio the synonym being chilblains Unlike adult patients with COVID toes children are less likely to manifest symptomatic COVID 19 Although a few studies have found some linkage to COVID 19 through the serum IgA or IgG severe acute respiratory syndrome coronavirus 2 SARS CoV 2 spike protein other studies have no demonstrable linkage suggesting that barefoot children in cold weather develop such lesions It appears that the chilblain like lesions related to the period of the COVID 19 pandemic may reflect a brisk immune response portending a good prognosis and perhaps some form of innate immunity The possible need to screen for coagulopathy is unclear but this has been suggested in one report Until we fully understand the pattern of immune response to COVID 19 questions may persist as to how disease manifestations are linked to SARS CoV 2 exposures

Long COVID Distinction between Organ Damage and Deconditioning 1 Background Long COVID syndrome refers to long term sequelae of the novel viral disease which occur even in patients with initially mild disease courses However there is still little evidence of the actual organic consequences and their frequency and there is no standardized workup to diagnose long COVID syndrome yet In this study we aim to determine the efficiency of a stepwise diagnostic approach for reconvalescent COVID 19 patients with cardiopulmonary symptoms 2 Methods The diagnostic workup for long COVID syndrome included three steps In the first step the focus was on broad applicability e g blood tests and body plethysmography In the second step cardiopulmonary exercise testing CPET and cardiac MRI CMR were used The third step was tailored to the individual needs of each patient The observation period lasted from 22 February to 14 May 2021 3 Results We examined 231 patients in our long COVID unit mean SD age 47 8 14 9 132 57 1 women Acute illness occurred a mean SD of 121 77 days previously Suspicious findings in the first visit were seen in 80 34 6 patients prompting further diagnostics Thirty six patients were further examined with CPET and CMR Of those 16 44 4 had pathological findings The rest had functional complaints without organ damage functional long COVID Cardiopulmonary sequelae were found in asymptomatic as well as severe courses of the initial COVID 19 disease 4 Conclusions A structured diagnostic pathway for the diagnosis of long COVID syndrome is practicable and rational in terms of resource allocation With this approach manifest organ damage can be accurately and comprehensively diagnosed and distinguished from functional complaints

Myocarditis and Pericarditis Following mRNA COVID 19 Vaccination What Do We Know So Far This is a cross sectional study of 29 published cases of acute myopericarditis following COVID 19 mRNA vaccination The most common presentation was chest pain within 1 5 days after the second dose of mRNA COVID 19 vaccination All patients had an elevated troponin Cardiac magnetic resonance imaging revealed late gadolinium enhancement consistent with myocarditis in 69 of cases All patients recovered clinically rapidly within 1 3 weeks Most patients were treated with non steroidal anti inflammatory drugs for symptomatic relief and 4 received intravenous immune globulin and corticosteroids We speculate a possible causal relationship between vaccine administration and myocarditis The data from our analysis confirms that all myocarditis and pericarditis cases are mild and resolve within a few days to few weeks The bottom line is that the risk of cardiac complications among children and adults due to severe acute respiratory syndrome coronavirus 2 SARS CoV 2 infection far exceeds the minimal and rare risks of vaccination related transient myocardial or pericardial inflammation

Severe Fatigue in Long COVID Web Based Quantitative Follow up Study in Members of Online Long COVID Support Groups Fatigue is the most commonly reported symptom in patients with persistent complaints following COVID 19 ie long COVID Longitudinal studies examining the intensity of fatigue and differentiating between physical and mental fatigue are lacking The objectives of this study were to 1 assess the severity of fatigue over time in members of online long COVID peer support groups and 2 assess whether members of these groups experienced mental fatigue physical fatigue or both A 2 wave web based follow up study was conducted in members of online long COVID peer support groups with a confirmed diagnosis approximately 3 and 6 months after the onset of infectious symptoms Demographics COVID 19 diagnosis received health care from medical professionals or allied health care professionals fatigue Checklist Individual Strength subscale subjective fatigue CIS Fatigue 8 56 points and physical and mental fatigue self constructed questions 3 21 points were assessed Higher scores indicated more severe fatigue A CIS Fatigue score 36 points was used to qualify patients as having severe fatigue A total of 239 patients with polymerase chain reaction computed tomography confirmed COVID 19 completed the survey 10 weeks SD 2 and 23 weeks SD 2 after onset of infectious symptoms respectively T1 and T2 Of these 239 patients 198 82 8 were women 142 59 4 had no self reported pre existing comorbidities 208 87 self reported being in good health before contracting COVID 19 and 62 25 9 were hospitalized during acute infection The median age was 50 years IQR 39 56 The vast majority of patients had severe fatigue at T1 and T2 n 204 85 4 and n 188 78 7 respectively No significant differences were found in the prevalence of normal mild and severe fatigue between T1 and T2 P 12 The median CIS Fatigue score was 48 points IQR 42 53 at T1 and it decreased from T1 to T2 median change 2 points IQR 7 to 3 P 001 At T1 a median physical fatigue score of 19 points IQR 16 20 and a median mental fatigue score of 15 points IQR 10 17 were reported these scores were lower at T2 for physical but not for mental fatigue median change for physical fatigue 1 point IQR 3 to 0 P 001 median change for mental fatigue 0 points IQR 3 to 3 P 52 At the time of completing the follow up survey 194 239 81 2 and 164 239 68 6 of all patients had received care from at least one medical professional and one allied health care professional respectively Fatigue in members of online long COVID support groups with a confirmed COVID 19 diagnosis decreases from 10 to 23 weeks after onset of symptoms Despite this severe fatigue remains highly prevalent Both physical and mental fatigue are present It remains unclear whether and to what extent fatigue will resolve spontaneously in the longer term Netherlands Trial Register NTR8705 https www trialregister nl trial 8705

Clinical Nutrition Research and the COVID 19 Pandemic A Scoping Review of the ASPEN COVID 19 Task Force on Nutrition Research The purpose of this scoping review by the American Society for Parenteral and Enteral Nutrition ASPEN Coronavirus Disease 2019 COVID 19 Nutrition Task Force was to examine nutrition research applicable to the COVID 19 pandemic The rapid pace of emerging scientific information has prompted this activity to discover research knowledge gaps This methodology adhered with recommendations from the Joanna Briggs Institute There were 2301 citations imported Of these there were 439 articles fully abstracted with 23 main topic areas identified across 24 article types and sourced across 61 countries and 51 specialties in 8 settings and among 14 populations Epidemiological mechanistic relationships between nutrition and COVID 19 were reviewed and results mapped to the Population Intervention Comparator Outcome and Time PICO T questions The aggregated data were analyzed by clinical stage pre COVID 19 acute COVID 19 and chronic post COVID 19 Research gaps were discovered for all PICO T questions Nutrition topics meriting urgent research included food insecurity societal infrastructure and transcultural factors pre COVID 19 cardiometabolic based chronic disease pediatrics nutrition support and hospital infrastructure acute COVID 19 registered dietitian nutritionist counseling chronic post COVID 19 and malnutrition and management all stages The paucity of randomized controlled trials RCTs was particularly glaring Knowledge gaps were discovered for PICO T questions on pediatrics micronutrients bariatric surgery and transcultural factors pre COVID 19 enteral nutrition protein energy requirements and glycemic control with nutrition acute COVID 19 and home enteral and parenteral nutrition support chronic post COVID 19 In conclusion multiple critical areas for urgent nutrition research were identified particularly using RCT design to improve nutrition care for patients before during and after COVID 19

Characteristics and predictors of acute and chronic post COVID syndrome A systematic review and meta analysis A significant proportion of individuals experience lingering and debilitating symptoms following acute COVID 19 infection The National Institute for Health and Care Excellence NICE have coined the persistent cluster of symptoms as post COVID syndrome This has been further sub categorised into acute post COVID syndrome for symptoms persisting three weeks beyond initial infection and chronic post COVID syndrome for symptoms persisting beyond twelve weeks The aim of this review was to detail the prevalence of clinical features and identify potential predictors for acute and chronic post COVID syndrome A systematic literature search with no language restrictions was performed to identify studies detailing characteristics and outcomes related to survivorship of post COVID syndrome The last search was performed on 6 March 2021 and all pre dating published articles included A means of proportion meta analysis was performed to quantify characteristics of acute and chronic post COVID syndrome Study quality was assessed with a specific risk of bias tool PROSPERO Registration CRD42020222855 A total of 43 studies met the eligibility criteria of which 38 allowed for meta analysis Fatigue and dyspnoea were the most prevalent symptoms in acute post COVID 0 37 and 0 35 and fatigue and sleep disturbance in chronic post COVID syndrome 0 48 and 0 44 respectively The available evidence is generally of poor quality with considerable risk of bias and are of observational design In conclusion this review highlights that flaws in data capture and interpretation noted in the uncertainty within our meta analysis affect the applicability of current knowledge Policy makers and researchers must focus on understanding the impact of this condition on individuals and society with appropriate funding initiatives and global collaborative research

Myocarditis With COVID 19 mRNA Vaccines Myocarditis has been recognized as a rare complication of coronavirus disease 2019 COVID 19 mRNA vaccinations especially in young adult and adolescent males According to the US Centers for Disease Control and Prevention myocarditis pericarditis rates are 12 6 cases per million doses of second dose mRNA vaccine among individuals 12 to 39 years of age In reported cases patients with myocarditis invariably presented with chest pain usually 2 to 3 days after a second dose of mRNA vaccination and had elevated cardiac troponin levels ECG was abnormal with ST elevations in most and cardiac MRI was suggestive of myocarditis in all tested patients There was no evidence of acute COVID 19 or other viral infections In 1 case a cardiomyopathy gene panel was negative but autoantibody levels against certain self antigens and frequency of natural killer cells were increased Although the mechanisms for development of myocarditis are not clear molecular mimicry between the spike protein of severe acute respiratory syndrome coronavirus 2 SARS CoV 2 and self antigens trigger of preexisting dysregulated immune pathways in certain individuals immune response to mRNA and activation of immunologic pathways and dysregulated cytokine expression have been proposed The reasons for male predominance in myocarditis cases are unknown but possible explanations relate to sex hormone differences in immune response and myocarditis and also underdiagnosis of cardiac disease in women Almost all patients had resolution of symptoms and signs and improvement in diagnostic markers and imaging with or without treatment Despite rare cases of myocarditis the benefit risk assessment for COVID 19 vaccination shows a favorable balance for all age and sex groups therefore COVID 19 vaccination is recommended for everyone 12 years of age

A Paradigm for Post Covid 19 Fatigue Syndrome Analogous to ME CFS A significant proportion of COVID 19 patients are suffering from prolonged Post COVID 19 Fatigue Syndrome with characteristics typically found in Myalgic Encephalomyelitis Chronic Fatigue Syndrome ME CFS However no clear pathophysiological explanation as yet has been provided A novel paradigm for a Post COVID 19 Fatigue Syndrome is developed here from a recent unifying model for ME CFS Central to its rationale SARS CoV 2 in common with the triggers viral and non viral of ME CFS is proposed to be a physiologically severe i stressor i which could be targeting a i stress integrator i within the brain the hypothalamic paraventricular nucleus PVN It is proposed that inflammatory mediators released at the site of COVID 19 infection would be transmitted as i stress signals via i humoral and neural pathways which overwhelm this i stress center i In genetically susceptible people an intrinsic i stress threshold i is suggested to be exceeded causing ongoing dysfunction to the hypothalamic PVNs complex neurological circuitry In this compromised state the hypothalamic PVN might then be hyper sensitive to a wide range of lifes ongoing physiological i stressors i This could result in the reported post exertional malaise episodes and more severe relapses in common with ME CFS that perpetuate an ongoing disease state When a certain i stress tolerance level i is exceeded the hypothalamic PVN can become an epicenter for microglia induced activation and neuroinflammation affecting the hypothalamus and its proximal limbic system which would account for the range of reported ME CFS like symptoms A model for Post COVID 19 Fatigue Syndrome is provided to stimulate discussion and critical evaluation Brain scanning studies incorporating increasingly sophisticated imaging technology should enable chronic neuroinflammation to be detected even at a low level in the finite detail required thus helping to test this model while advancing our understanding of Post COVID 19 Fatigue Syndrome pathophysiology

Home and Community Based Physical Therapist Management of Adults With Post Intensive Care Syndrome More than 4 million adults survive a stay in the intensive care unit each year with many experiencing new or worsening physical disability mental health problems and or cognitive impairments known as post intensive care syndrome PICS Given the prevalence and magnitude of physical impairments after critical illness many survivors including those recovering from COVID 19 could benefit from physical therapist services after hospital discharge However due to the relatively recent recognition and characterization of PICS there may be limited awareness and understanding of PICS among physical therapists practicing in home health care and community based settings This lack of awareness may lead to inappropriate and or inadequate rehabilitation service provision While this perspective article provides information relevant to all physical therapists it is aimed toward those providing rehabilitation services outside of the acute and postacute inpatient settings This article reports the prevalence and clinical presentation of PICS and provides recommendations for physical examination and outcomes measures plan of care and intervention strategies The importance of providing patient and family education coordinating community resources including referring to other health care team members and community based rehabilitation service options is emphasized Finally this perspective article discusses current challenges for optimizing outcomes for people with PICS and suggests future directions for research and practice

COVID 19 cardiac injury Implications for long term surveillance and outcomes in survivors Up to 20 30 of patients hospitalized with coronavirus disease 2019 COVID 19 have evidence of myocardial involvement Acute cardiac injury in patients hospitalized with COVID 19 is associated with higher morbidity and mortality There are no data on how acute treatment of COVID 19 may affect the convalescent phase or long term cardiac recovery and function Myocarditis from other viral pathogens can evolve into overt or subclinical myocardial dysfunction and sudden death has been described in the convalescent phase of viral myocarditis This raises concerns for patients recovering from COVID 19 Some patients will have subclinical and possibly overt cardiovascular abnormalities Patients with ostensibly recovered cardiac function may still be at risk of cardiomyopathy and cardiac arrhythmias Screening for residual cardiac involvement in the convalescent phase for patients recovered from COVID 19 associated cardiac injury is needed The type of testing and therapies for post COVID 19 myocardial dysfunction will need to be determined Therefore now is the time to plan for appropriate registries and clinical trials to properly assess these issues and prepare for long term sequelae of post COVID 19 cardiac syndrome

Coronavirus occurrence surveillance and persistence in wastewater The coronavirus disease COVID 19 outbreak reported in China in December 2019 has spread throughout the world The WHO declared it as a pandemic in March 2020 The pandemic severely affected public health and the global economy Many studies conducted on the coronavirus have helped us to elucidate its pathogenicity and pathophysiology However it is important to study the behavior of the pathogen in the environment to develop effective control measures While studying the persistence and transmission of viruses in drinking water and wastewater systems a low concentration of coronavirus and its nucleic acids have been detected in municipal wastewaters This could be due to their high susceptibilities to degradation in aqueous environments Epidemiological study on coronaviruses in wastewater will serve two purposes i e in early detection of outbreak and in identifying asymptomatic carriers In such cases the epidemiological study will help in early detection of the presence of the virus in the community Secondly it will help in knowing if there are asymptomatic carriers as such people do not show any signs of symptoms but shed the viruses in feces The present review focuses on the epidemiological surveillance of wastewater for coronaviruses as in recent years these are increasingly causing global pandemics In this review we have discussed the four pertinent areas of coronavirus study 1 occurrence of coronavirus in wastewater 2 wastewater based epidemiological surveillance of coronaviruses 3 epidemiological surveillance tools used for detection of coronaviruses in sewage and 4 persistence and sustainability of coronaviruses in wastewater

Use of Cardiopulmonary Stress Testing for Patients With Unexplained Dyspnea Post Coronavirus Disease The authors used cardiopulmonary exercise testing CPET to define unexplained dyspnea in patients with post acute sequelae of severe acute respiratory syndrome coronavirus 2 SARS CoV 2 infection PASC We assessed participants for criteria to diagnose myalgic encephalomyelitis chronic fatigue syndrome ME CFS Approximately 20 of patients who recover from coronavirus disease COVID remain symptomatic This syndrome is named PASC Its etiology is unclear Dyspnea is a frequent symptom The authors performed CPET and symptom assessment for ME CFS in 41 patients with PASC 8 9 3 3 months after COVID All patients had normal pulmonary function tests chest X ray and chest computed tomography scans Peak oxygen consumption peak VO sub 2 sub slope of minute ventilation to CO sub 2 sub production VE VCO sub 2 sub slope and end tidal pressure of CO sub 2 sub PetCO sub 2 sub were measured Ventilatory patterns were reviewed with dysfunctional breathing defined as rapid erratic breathing Eighteen men and 23 women average age 45 13 years were studied Left ventricular ejection fraction was 59 9 Peak VO sub 2 sub averaged 20 3 7 mL kg min 77 21 predicted VO sub 2 sub VE VCO sub 2 sub slope was 30 7 PetCO sub 2 sub at rest was 33 5 4 5 mm Hg Twenty four patients 58 5 had a peak VO sub 2 sub 80 predicted All patients with peak VO sub 2 sub 80 had a circulatory limitation to exercise Fifteen of 17 patients with normal peak VO sub 2 sub had ventilatory abnormalities including peak respiratory rate 55 n 3 or dysfunctional breathing n 12 For the whole cohort 88 of patients n 36 had ventilatory abnormalities with dysfunctional breathing n 26 increased VE VCO sub 2 sub n 17 and or hypocapnia PetCO sub 2 sub 35 n 25 Nineteen patients 46 met criteria for ME CFS Circulatory impairment abnormal ventilatory pattern and ME CFS are common in patients with PASC The dysfunctional breathing resting hypocapnia and ME CFS may contribute to symptoms CPET is a valuable tool to assess these patients

Metabolic Reprogramming in COVID 19 Plenty of research has revealed virus induced alternations in metabolic pathways which is known as metabolic reprogramming Studies focusing on COVID 19 have uncovered significant changes in metabolism resulting in the perspective that COVID 19 is a metabolic disease Reprogramming of amino acid glucose cholesterol and fatty acid is distinctive characteristic of COVID 19 infection These metabolic changes in COVID 19 have a critical role not only in producing energy and virus constituent elements but also in regulating immune response offering new insights into COVID 19 pathophysiology Remarkably metabolic reprogramming provides great opportunities for developing novel biomarkers and therapeutic agents for COVID 19 infection Such novel agents are expected to be effective adjuvant therapies In this review we integrate present studies about major metabolic reprogramming in COVID 19 as well as the possibility of targeting reprogrammed metabolism to combat virus infection

Emergent Crisis of COVID 19 Pandemic Mental Health Challenges and Opportunities Mental health is a fundamental human right and is part of the well being of society The public health burden of mental health disorders affects peoples social and economic status around the world Coronaviruss COVID 19 negative impact on the economy and mental health worldwide is concerning This is a worldwide emergency and there is an urgent need for research about this topic to prevent long lasting adverse effects on the population Unpreparedness and inconsistencies in guidelines lockdowns containment strategies unemployment financial losses physical distancing isolation chaos and uncertainty are among factors that lead to a rise in emotional distress anxiety and depression Governments decisions affect the socioeconomic status of a country and the psychological well being of the people COVID 19 pandemic exposed disparities in multiple mental health care systems by having adverse mental health effects in people with pre existing mental health disorders and previously healthy individuals Aggregation of concurrent or cumulative comorbid risk factors for COVID 19 disease and its psychosocial sequelae could provide invaluable information for the public health stakeholders This review aims to address the burden and the psychosocial impact of the COVID 19 pandemic the challenges and opportunities facing mental health systems and proposes new strategies to improve the mental health outcomes in the post COVID era

Lung Transplantation of COVID 19 Patients How I Do It The COVID 19 pandemic has caused acute lung injury in millions of individuals worldwide Some patients develop COVID related acute respiratory distress syndrome CARDS and cannot be liberated from mechanical ventilation Others may develop post COVID fibrosis resulting in substantial disability and need for long term supplemental oxygen In both of these situations treatment teams often inquire about the possibility of lung transplantation In fact lung transplantation has been successfully employed for both CARDS and post COVID fibrosis in a limited number of patients worldwide Lung transplantation after COVID infection presents a number of unique challenges that transplant programs must consider In those with severe CARDS the inability to conduct proper psychosocial evaluation and pretransplantation education marked deconditioning from critical illness and infectious concerns regarding viral reactivation are major hurdles In those with post COVID fibrosis our limited knowledge about the natural history of recovery after COVID 19 infection is problematic Increased knowledge of the likelihood and degree of recovery after COVID 19 acute lung injury is essential for appropriate decision making with regard to transplantation Transplant physicians must weigh the risks and benefits of lung transplantation differently in a post COVID fibrosis patient who is likely to remain stable or gradually improve in comparison with a patient with a known progressive fibrosing interstitial lung disease fILD Clearly lung transplantation can be a life saving therapeutic option for some patients with severe lung injury from COVID 19 infection In this review we discuss how lung transplant providers from a number of experienced centers approach lung transplantation for CARDS or post COVID fibrosis

Post COVID syndrome A reflection and opinion paper A high proportion of people who have suffered from COVID 19 report after recovery from the acute phase of the disease clinical manifestations both subjective and objective that continue beyond 3 weeks or even 3 months after the original clinical disease There is still no agreed nomenclature to refer to this condition but perhaps the most commonly used is post COVID syndrome The Scientific Committee on COVID of the Madrid College of Physicians ICOMEM has discussed this problem with a multidisciplinary approach in which internists infectious disease specialists psychiatrists pneumologists surgeons geriatricians pediatricians microbiologists family physicians and other specialists have participated trying to gather the existing information and discussing it in the group The clinical manifestations are very variable and range from simple fatigue to persistent fibrosing lung lesions with objective alterations of pulmonary function Post COVID syndrome seems to be particularly frequent and severe in adults who have required admission to Intensive Care Units and has a peculiar behavior in a very small group of children The post COVID syndrome which undoubtedly exists is at first sight not clearly distinguishable from clinical manifestations that which occur after other acute viral diseases and after prolonged stays in ICUs due to other diseases Therefore it offers excellent research opportunities to clarify its pathogenesis and possibly that of other related entities It is possible that progressively there will be an increased demand for care among the millions of people who have suffered and overcome acute COVID for which the health authorities should design mechanisms for the agile management of care that will possibly require well coordinated multidisciplinary groups This paper structured in questions on different aspects of the post COVID syndrome attempts to stage the current state of this problem

Vaccines for COVID 19 Where do we stand in 2021 As of July 2021 over 3 billion doses of a COVID 19 vaccines have been administered globally and there are now 19 COVID 19 vaccines approved for use in at least one country Several of these have been shown to be highly effective both in clinical trials and real world observational studies some of which have included special populations of interest A small number of countries have approved a COVID 19 vaccine for use in adolescents or children These are laudable achievements but the global vaccination effort has been challenged by inequitable distribution of vaccines predominantly to high income countries with only 0 9 of people in low income countries having received at least one dose of a COVID 19 vaccine Addressing this inequity is of critical importance and will result in better control of SARS CoV 2 globally Other challenges include the reduced protection from COVID 19 vaccines against some strains of SARS CoV 2 necessitating the development of variant specific vaccines and uncertainties around the duration of protection from vaccine induced immunity

Guidance for Health Care Leaders During the Recovery Stage of the COVID 19 Pandemic A Consensus Statement The COVID 19 pandemic is the greatest global test of health leadership of our generation There is an urgent need to provide guidance for leaders at all levels during the unprecedented preresolution recovery stage To create an evidence and expertise informed framework of leadership imperatives to serve as a resource to guide health and public health leaders during the postemergency stage of the pandemic A literature search in PubMed MEDLINE and Embase revealed 10 910 articles published between 2000 and 2021 that included the terms leadership and variations of emergency crisis disaster pandemic COVID 19 or public health Using the Standards for Quality Improvement Reporting Excellence reporting guideline for consensus statement development this assessment adopted a 6 round modified Delphi approach involving 32 expert coauthors from 17 countries who participated in creating and validating a framework outlining essential leadership imperatives The 10 imperatives in the framework are 1 acknowledge staff and celebrate successes 2 provide support for staff well being 3 develop a clear understanding of the current local and global context along with informed projections 4 prepare for future emergencies personnel resources protocols contingency plans coalitions and training 5 reassess priorities explicitly and regularly and provide purpose meaning and direction 6 maximize team organizational and system performance and discuss enhancements 7 manage the backlog of paused services and consider improvements while avoiding burnout and moral distress 8 sustain learning innovations and collaborations and imagine future possibilities 9 provide regular communication and engender trust and 10 in consultation with public health and fellow leaders provide safety information and recommendations to government other organizations staff and the community to improve equitable and integrated care and emergency preparedness systemwide Leaders who most effectively implement these imperatives are ideally positioned to address urgent needs and inequalities in health systems and to cocreate with their organizations a future that best serves stakeholders and communities

Thrombotic risk in children with COVID 19 infection A systematic review of the literature Coagulation and inflammatory parameters are mildly altered in children with SARS CoV 2 COVID 19 infection and laboratory evidence of a proinflammatory and procoagulant state has been noted in multisystem inflammatory syndrome in children MIS C It is not clear whether this pediatric condition is related to thrombotic events With this study we reviewed the literature for thrombotic complications in children with COVID 19 infection and MIS C We searched the Medline PubMed Advanced Search Builder Scopus Web Of Science and Google Scholar electronic databases until 1 January 2021 using the medical subject headings MeSH terms and text words their combinations and truncated synonyms THROMBOSIS OR THROMBOPHILIA AND CHILD OR CHILDREN OR INFANT AND COVID 19 OR SARS CoV 2 Inclusion criteria were children with COVID 19 or SARS COV 2 infection The search was limited to articles published in English Exclusion criteria were reviews of published studies studies published only as abstracts letters or conference proceedings discussion papers animal studies or editorials After screening for duplicates the initial search yielded 86 records 12 were case reports involving 19 children comorbidities were absent or mild in 73 7 The most common site of thrombosis the lung 21 the most often used drug was heparin 42 Two studies were an international survey n 337 patients and a large multicenter study n 186 patients with MIS C The risk of ischemic stroke in SARS CoV 2 infection 0 82 and deep venous thrombosis in MIS C 4 3 was lower in children than in adults Thrombodic or thromboembolic events are rare in pediatric patients with COVID 19 infection and MIS C Nonetheless as in adults a high index of suspicion should be maintained in children with COVID 19 infection or MIS C particularly in those with comorbidities predisposing to thrombotic events

Post COVID 19 Tachycardia Syndrome A Distinct Phenotype of Post Acute COVID 19 Syndrome In this paper we highlight the presence of tachycardia in post acute COVID 19 syndrome by introducing a new label for this phenomenon post COVID 19 tachycardia syndrome and argue that this constitutes a phenotype or sub syndrome in post acute COVID 19 syndrome We also discuss epidemiology putative mechanisms treatment options and future research directions in this novel clinical syndrome

Identification of a Vulnerable Group for Post Acute Sequelae of SARS CoV 2 PASC People with Autoimmune Diseases Recover More Slowly from COVID 19 Evidence is emerging that a significant percentage of COVID 19 cases experience symptom persistence beyond 30 days and go on to develop post acute sequelae Our objective was to compare the risk for COVID 19 symptom persistence by self reported use of medications for autoimmune disease among participants of an on line COVID 19 registry A community based online survey collected weekly data on COVID 19 symptom presentation Participants who completed informed consent online reported a positive COVID 19 test result within 14 days prior to enrollment and also reported demographics underlying illnesses and medication use were included Symptom presence and severity were evaluated weekly after enrollment and compared between participants reporting use of medications for autoimmune conditions and all others Logistic regression was used to evaluate the odds of more severe acute illness and symptom persistence approximately 30 days after enrollment A total of 1 518 COVID 19 positive participants were included Participants reporting use of medications for autoimmune disease n 70 were more likely to have experienced symptoms at all time points over a 30 day time period and were more likely to report more severe presentation of COVID 19 during acute illness adjusted OR 95 CI 1 32 0 76 2 29 compared to those reporting not taking medications for autoimmune disease At about 30 days after enrollment users of medications for autoimmune disease were more than twice as likely to report three or more symptoms adjusted OR 95 CI 2 53 1 21 5 29 In particular their risk of persistent shortness of breath and fatigue was elevated adjusted OR 95 CI 2 66 1 15 6 18 and 4 73 2 17 10 34 respectively Individuals with underlying autoimmune conditions appear to be particularly vulnerable to post acute sequelae from COVID 19 early intervention might be considered