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SARS-CoV-2 proteins

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    Changes in the rate of cardiometabolic and pulmonary events during the COVID-19 pandemic MESHD

    Authors: Alex J Walker; John Tazare; George Hickman; Christopher T Rentsch; Elizabeth J Williamson; Krishnan Bhaskaran; David Evans; Kevin Wing; Rohini Mathur; Angel YS Wong; Anna Schultze; Sebastian CJ Bacon; Christopher Bates; Caroline E Morton; Helen J Curtis; Emily Nightingale; Helen I McDonald; Amir Mehrkar; Peter Inglesby; Brian MacKenna; Jonathan Cockburn; William J Hulme; Harriet Forbes; Caroline Minassian; Richard Croker; John Parry; Frank Hester; Sam Harper; Rosalind M Eggo; Stephen JW Evans; Liam Smeeth; Ian J Douglas; Laurie Tomlinson; Ben Goldacre

    doi:10.1101/2021.02.17.21251812 Date: 2021-02-19 Source: medRxiv

    BackgroundThere has been extensive speculation about the relationship between COVID-19 MESHD and various cardiometabolic and pulmonary conditions. This a complex question: COVID-19 MESHD may cause a cardiometabolic or respiratory event; admission for a clinical event may result in hospital-acquired SARS-CoV-2 infection MESHD; both may contribute to a patient surpassing the threshold for presenting to services; and the presence of a pandemic may change whether patients present to services at all. To inform analysis of these questions, we set out to describe the overall rate of various key clinical events over time, and their relationship with COVID-19 MESHD. MethodsWorking on behalf of NHS England, we used data from the OpenSAFELY platform containing data from approximately 40% of the population of England. We selected the whole adult population of 17m patients and within this identified two further mutually exclusive groups: patients who tested positive for SARS-CoV-2 in the community; and patients hospitalised with COVID-19 MESHD. We report counts of death MESHD, DVT, PE, ischaemic stroke MESHD, MI MESHD, heart failure MESHD, AKI and diabetic ketoacidosis MESHD in each month between February 2019 and October 2020 within each of: the general population, community SARS-CoV-2 cases, and hospitalised patients with COVID-19 MESHD. Outcome events were defined using hospitalisations, GP records and cause of death data. ResultsFor all outcomes except death there was a lower count of events in April 2020 compared to April 2019. For most outcomes the minimum count of events was in April 2020, where the decrease compared to April 2019 in events ranged from 5.9% (PE) to 40.0% ( heart failure MESHD). Despite hospitalised COVID-19 MESHD patients making up just 0.14% of the population in April 2020, these patients accounted for an extremely high proportion of cardiometabolic and respiratory events in that month (range of proportions 10.3% (DVT) to 33.5% (AKI)). InterpretationWe observed a substantial drop in the incidence of cardiometabolic and pulmonary events in the non- COVID-19 MESHD general population, but high occurrence of COVID-19 MESHD among patients with these events. Shortcomings in routine NHS secondary care data, especially around the timing and order of events, make causal interpretations challenging. We caution that the intermediate findings reported here should be used to inform the design and interpretation of any studies using a general population comparator to evaluate the relationship between COVID-19 MESHD and other clinical events.

    Mapping of SARS-CoV-2 Brain Invasion and Histopathology in COVID-19 Disease MESHD

    Authors: Geidy E Serrano; Jessica E. Walker; Richard Arce; Michael J Glass; Daisy Vargas; Lucia Sue; Anthony J Intorcia; Courtney M. Nelson; Javon Oliver; Jaclyn Papa; Aryck Russell; Katsuko E. Suszczewicz; Claryssa Borja; Christine Belden; Danielle Goldfarb; David Shprecher; Alireza Atri; Charles H. Adler; Holly A Shill; Erika Driver-Dunckley; Shyamal H. Mehta; Benjamin Readhead; Matthew J Huentelman; Joseph L. Peters; Christian Bimi; Joseph P. Mizgerd; Eric M. Reiman; Thomas J. Montine; Marc Desforges; James L. Zehnder; Malaya K. Sahoo; Haiyu Zhang; Daniel Solis; Benjamin A. Pinsky; Michael Deture; Dennis W. Dickson; Thomas G. Beach

    doi:10.1101/2021.02.15.21251511 Date: 2021-02-18 Source: medRxiv

    The coronavirus SARS-CoV-2 (SCV2) causes acute respiratory distress MESHD, termed COVID-19 MESHD disease, with substantial morbidity and mortality. As SCV2 is related to previously-studied coronaviruses that have been shown to have the capability for brain invasion, it seems likely that SCV2 may be able to do so as well. To date, although there have been many clinical and autopsy-based reports that describe a broad range of SCV2-associated neurological conditions, it is unclear what fraction of these have been due to direct CNS invasion versus indirect effects caused by systemic reactions to critical illness. Still critically lacking is a comprehensive tissue-based survey of the CNS presence and specific neuropathology of SCV2 in humans. We conducted an extensive neuroanatomical survey of RT-PCR-detected SCV2 in 16 brain regions from 20 subjects who died of COVID-19 MESHD disease. Targeted areas were those with cranial nerve nuclei, including the olfactory bulb, medullary dorsal motor nucleus of the vagus nerve and the pontine trigeminal nerve nuclei, as well as areas possibly exposed to hematogenous entry, including the choroid plexus MESHD, leptomeninges, median eminence of the hypothalamus MESHD and area postrema of the medulla. Subjects ranged in age from 38 to 97 (mean 77) with 9 females and 11 males. Most subjects had typical age-related neuropathological findings. Two subjects had severe neuropathology, one with a large acute cerebral infarction MESHD and one with hemorrhagic encephalitis MESHD, that was unequivocally related to their COVID-19 MESHD disease while most of the 18 other subjects had non-specific histopathology including focal B-amyloid precursor protein white matter immunoreactivity and sparse perivascular mononuclear cell cuffing. Four subjects (20%) had SCV2 RNA in one or more brain regions including the olfactory bulb, amygdala, entorhinal area, temporal and frontal neocortex, dorsal medulla and leptomeninges. The subject with encephalitis MESHD was SCV2-positive in a histopathologically-affected area, the entorhinal cortex, while the subject with the large acute cerebral infarct MESHD was SCV2-negative in all brain regions. Like other human coronaviruses, SCV2 can inflict acute neuropathology in susceptible patients. Much remains to be understood, including what viral and host factors influence SCV2 brain invasion and whether it is cleared from the brain subsequent to the acute illness.

    COVID-19 MESHD infection and subsequent thromboembolism MESHD: A self-controlled case series analysis of a population cohort

    Authors: Frederick Ho; Kenneth Man; Mark Toshner; Carlos Celis-Morales; Ian Wong; Naveed Sattar; Jill Pell

    doi:10.1101/2021.02.02.21251043 Date: 2021-02-05 Source: medRxiv

    Importance: An unexpectedly large number of people infected with Covid-19 MESHD appear to have experienced ischaemic stroke MESHD or thrombotic MESHD event. Objective: This study aims to assess the risk associations between Covid-19 MESHD infection and thromboembolism MESHD. Design: This is a self-controlled case-series study in Scotland. Their incidence rates during the risk interval (5 days before to 56 days after the positive test) and the control interval (the remaining periods) were compared intra-personally. Setting: Population-based. Participants: Individuals with confirmed (positive test) Covid-19 MESHD and at least one thromboembolic MESHD event between March 2018 and October 2020. Exposure: Covid-19 MESHD test positive. Main Outcomes and Measures: Myocardial infarction MESHD ( MI MESHD), ischaemic stroke MESHD, deep-vein thrombosis MESHD ( DVT MESHD), and pulmonary embolism MESHD ( PE MESHD) hospital admissions and deaths. Results: Across Scotland, 1,449 individuals tested positive for Covid-19 MESHD and experienced a thromboembolic MESHD event. The risk of thromboembolism MESHD was significantly elevated over the whole risk period but highest in the 7 days following the positive test ( IRR HGNC 12.01, 95% CI 9.91-14.56), especially among people >=75 years ( IRR HGNC 22.78, 95% CI 17.58-29.53). Risk of MI MESHD, stroke MESHD, PE MESHD and DVT MESHD were all significantly higher in the week following a positive test. The risk of PE MESHD and DVT MESHD was particularly high and remained significantly elevated even 56 days following the test. Conclusions and relevance: Confirmed Covid-19 MESHD infection was associated with early elevated risk of MI MESHD, ischaemic stroke MESHD, and stronger and long elevations in risk with DVT MESHD and PE MESHD, reinforcing the need to consider monitoring and early diagnosis. Treatment and prevention trials may need to be considered out of hospital on the basis of risk stratification.

    Rates of serious clinical outcomes in survivors of hospitalisation with COVID-19 MESHD: a descriptive cohort study within the OpenSAFELY platform

    Authors: John Tazare; Alex J Walker; Laurie Tomlinson; George Hickman; Christopher T Rentsch; Elizabeth J Williamson; Krishnan Bhaskaran; David Evans; Kevin Wing; Rohini Mathur; Angel YS Wong; Anna Schultze; Sebastian CJ Bacon; Christopher Bates; Caroline E Morton; Helen J Curtis; Emily Nightingale; Helen I McDonald; Amir Mehrkar; Peter Inglesby; Brian MacKenna; Jonathan Cockburn; William J Hulme; Charlotte Warren-Gash; Ketaki Bhate; Emma Powell; Any Mulick; Harriet Forbes; Caroline Minassian; Richard Croker; John Parry; Frank Hester; Sam Harper; Rosalind M Eggo; Stephen JW Evans; Liam Smeeth; Ian J Douglas; Ben Goldacre

    doi:10.1101/2021.01.22.21250304 Date: 2021-01-25 Source: medRxiv

    BackgroundPatients with COVID-19 MESHD are thought to be at higher risk of cardiometabolic and pulmonary complications MESHD, but quantification of that risk is limited. We aimed to describe the overall burden of these complications in survivors of severe COVID-19 MESHD. MethodsWorking on behalf of NHS England we used data from the OpenSAFELY platform linking primary care records to death certificate and hospital data. We constructed two cohorts: a COVID-19 MESHD cohort consisting of patients discharged following hospitalisation with COVID-19 MESHD, and a comparison population of patients discharged following hospitalisation with pneumonia MESHD in 2019. Outcomes included DVT, PE, ischaemic stroke MESHD, MI MESHD, heart failure MESHD, AKI and new type 2 diabetes MESHD diagnosis. Outcome rates from hospital discharge were measured in each cohort, stratified by patient demographics and 30-day period. We fitted Cox regression models to estimate crude and age/sex adjusted hazard ratios comparing outcome rates between the two cohorts. ResultsAmongst the population of 31,569 patients discharged following hospitalisation with COVID-19 MESHD, the highest rates were observed for heart failure MESHD (199.3; 95% CI: 191.8 - 207.1) and AKI (154.5; 95% CI: 147.9 - 161.4). Rates of DVT, heart failure MESHD, ischaemic stroke MESHD, MI MESHD, PE and diabetes MESHD were high over the four months post discharge, especially in the first month. Patterns were broadly similar to those seen in patients discharged with pneumonia MESHD but somewhat higher in the COVID-19 MESHD population for stroke MESHD (adj-HR 1.78; 95% CI: 1.53 - 2.08), PE (adj-HR 1.38; 95% CI: 1.21 - 1.58), MI MESHD (adj-HR 1.46; 95% CI: 1.20 - 1.76), AKI (adj-HR 1.27; 95% CI: 1.19 - 1.36) and T2DM (adj-HR 1.28; 95% CI: 1.08 - 1.50). ConclusionsIn this descriptive study of survivors of severe COVID-19 MESHD, rates of the measured outcomes are at least as high, though in some cases slightly higher, than in patients discharged after hospitalisation with pneumonia MESHD. Further work is needed to identify what characteristics of COVID-19 MESHD patients put them at highest risk of adverse events.

    Six-month Neurological and Psychiatric Outcomes in 236,379 Survivors of COVID-19 MESHD

    Authors: Maxime Taquet; John R Geddes; Masud Husain; Sierra Luciano; Paul J Harrison

    doi:10.1101/2021.01.16.21249950 Date: 2021-01-24 Source: medRxiv

    BackgroundNeurological and psychiatric MESHD sequelae of COVID-19 MESHD have been reported, but there are limited data on incidence rates and relative risks. MethodsUsing retrospective cohort studies and time-to-event analysis, we estimated the incidence of ICD-10 diagnoses in the 6 months after a confirmed diagnosis of COVID-19 MESHD: intracranial haemorrhage MESHD; ischaemic stroke MESHD; Parkinsonism MESHD; Guillain-Barre syndrome MESHD; nerve/nerve root/plexus disorders; myoneural/muscle disease MESHD; encephalitis MESHD; dementia MESHD; mood, anxiety MESHD, and psychotic disorders MESHD; substance misuse; and insomnia MESHD. Data were obtained from the TriNetX electronic health records network (over 81 million patients). We compared incidences with those in propensity score-matched cohorts of patients with influenza or other respiratory infections MESHD using a Cox model. We investigated the effect on incidence estimates of COVID-19 MESHD severity, as proxied by hospitalization and encephalopathy MESHD (including delirium MESHD and related disorders). Findings236,379 patients survived a confirmed diagnosis of COVID-19 MESHD. Among them, the estimated incidence of neurological or psychiatric MESHD sequelae at 6 months was 33.6%, with 12.8% receiving their first such diagnosis. Most diagnostic categories were commoner after COVID-19 MESHD than after influenza or other respiratory infections MESHD (hazard ratios from 1.21 to 5.28), including stroke MESHD, intracranial haemorrhage MESHD, dementia MESHD, and psychotic disorders MESHD. Findings were equivocal for Parkinsonism and Guillain-Barre syndrome MESHD. Amongst COVID-19 MESHD cases, incidences and hazard ratios for most disorders were higher in patients who had been hospitalized, and markedly so in those who had experienced encephalopathy MESHD. Results were robust to sensitivity analyses, including comparisons against an additional four index health events. InterpretationThe study provides evidence for substantial neurological and psychiatric MESHD morbidity following COVID-19 MESHD infection. Risks were greatest in, but not limited to, those who had severe COVID-19 MESHD. The information can help in service planning and identification of research priorities. FundingNational Institute for Health Research (NIHR) Oxford Health Biomedical Research Centre.

    COVID-19 MESHD Associated Cerebral Infarction MESHD in an Elderly Patient: A Case Report

    Authors: Jumin Xie; Changwu Feng; Jie Chen; Zhu Wang

    doi:10.21203/rs.3.rs-139941/v1 Date: 2021-01-03 Source: ResearchSquare

    Background: The 2019 Severe Acute Respiratory Syndrome MESHD Coronavirus (SARS-Cov-2) had been declared an emergency at the beginning and eventually progressing to a pandemic by World Health Organization. To date, more than 78,194,9471 people confirmed infected by SARS-Cov-2 and 1,736,752 dead, globally. Various characteristics were described in the case reports and clinical studies after SARS-Cov-2 hitting the whole world. Case presentation: COVID-19 MESHD cases accompanied with cerebral infraction were hardly reported. Herein, we present a 74-yesrs-old patient who got SARS-Cov-2 infected at the late January and developed cerebral infraction. After accurate treatment, the old patient recovered and discharged from hospital on April 3, 2020. We keep on supervising the patient, after 7 months long physical condition surveillance, the patient live a normal life with on obvious sequelae detected.  Conclusions: In this paper, we present a elder COVID-19 MESHD case associated with cerebral infraction and whole process management in treatment. The elder patients lived a normal life after discharging from Huangshi central hospital which we believed that early introducing of traditional Chinese medicine played important roles in COVID-19 MESHD treatment. We aimed to broaden new cognition towards SARS-Cov-2 infection MESHD and suggest therapy to COVID-19 MESHD cases with cerebral infraction.     

    Neurological Disorders associated with COVID-19 MESHD Hospital Admissions : Experience of a Single Tertiary Healthcare Centre

    Authors: Permesh Singh Dhillon; Robert Dineen; Haley Morris; Radu Tanasescu; Esmaeil Nikfekr; Jonathan Evans; Cris S Constantinescu; Akram A Hosseini

    doi:10.1101/2020.11.22.20235184 Date: 2020-12-11 Source: medRxiv

    BackgroundEarly reports have detailed a range of neurological symptoms MESHD in patients with the SARS-CoV-2 infection MESHD. However, there is a lack of detailed description and incidence of the neurological disorders MESHD amongst hospitalized COVID-19 MESHD patients. We describe a range of neurological disorders MESHD (other than non-specific neurological symptoms), including their clinical, radiological and laboratory findings, encountered in our cohort COVID-19 MESHD patients admitted to a large tertiary institution. MethodsWe reviewed our prospectively collated database of all adult Neurology referrals, Neurology and Stroke MESHD admissions and Neurological multi-disciplinary MESHD team meetings for all hospitalized patients with suspected or proven COVID-19 MESHD from 17 March 2020 to 31 August 2020. ResultsTwenty-nine of 1243 COVID-19 MESHD inpatients (2.3%) presented with COVID-19 MESHD-related neurological disorders MESHD. The mean age was 68.9 +/-13.5(SD) years, age range of 34-97 years, and there were 17 males. 22 patients had confirmed, 5 were probable and 2 had suspected COVID-19 MESHD infection according to the WHO case classification. Eight patients (27%) required critical care admission. Neurological symptoms MESHD at presentation included acute confusion MESHD and delirium MESHD, seizures MESHD, and new focal neurological deficits MESHD. Based on the pre-defined neurological phenotype, COVID-19 MESHD patients were grouped into four main categories. 16 patients had cerebrovascular events (13 with acute ischaemic stroke MESHD and 3 had haemorrhagic features), 7 patients were found to have inflammatory, non-inflammatory and autoimmune encephalopathy MESHD (including 2 with known Multiple Sclerosis MESHD), whilst movement and peripheral nervous system disorders MESHD were diagnosed in 3 patients each. ConclusionAlthough the exact prevalence and aetiology remains unclear, non-sporadic new onset of neurological disorders MESHD, in addition to anosmia MESHD, occurs during the acute COVID-19 MESHD-infection. Longitudinal follow-up of these patients is required to determine the long-term effects, treatment response and outcome of the SARS-CoV-2 infection MESHD.

    Characteristics of Coagulation/Fibrinolysis Abnormalities in Serious Corona Virus Disease 2019 ( COVID-19 MESHD) Patients Complicated with Stroke: Case Series

    Authors: Hiroyasu Ishikura; Junichi Maruyama; Yoshito Izutani; Shinichi Morimoto; Kazushi Takayama; Yuhei Irie; Taisuke Kitamura; Mitsutoshi Iwaasa; Kota Hoshino; Yoshihiko Nakamura

    doi:10.21203/rs.3.rs-100578/v1 Date: 2020-10-30 Source: ResearchSquare

    Background: Not surprisingly, novel coronavirus disease 2019 MESHD ( COVID-19 MESHD) patients are frequently complicated with COVID-19 MESHD associated coagulopathy MESHD (CAC). And cerebrovascular disease MESHD is not uncommon during SARS-CoV-2 infection MESHD, especially in older patients and severe patients with risk factors. This time we treated six patients with serious COVID-19 MESHD, of whom two had a stroke MESHD during ICU admission. Based on our experience, we report some findings on the relationship between CAC pattern and risk of stroke MESHD in patients with serious COVID-19 MESHD.Case presentation: Two patients who subsequently had a stroke MESHD were transferred to our emergency center and underwent veno-venous extracorporeal corporeal membrane oxygenation (V-V ECMO) with unfractionated heparin as an anticoagulant for treatment of severe respiratory failure MESHD. In one patient, the platelet count was 5.7 × 104/mm3 on ICU admission, increased to above 10 × 104/mm3 after 5 days. In the other patient, the platelet count progressed to above 10 × 104/mm3 for the observation period of 8 days. Both prothrombin-international normalized ratio and activated partial thromboplastin time remained almost within the normal ranges throughout the 8-day period. In contrast, the levels of fibrin degradation products, D-dimer, and plasmin alfa2-plasmin inhibitor complex remained above the upper limits of the normal ranges throughout the 8-day period, and the levels in both cases increased markedly around the onset of stroke MESHD.Discussion: From these findings, we gained a strong impression that the pattern of CAC in stroke MESHD patients was not a “suppressed-fibrinolytic type” pattern, but rather an “enhanced-fibrinolytic type” pattern.Conclusions: During the period in which serious COVID-19 MESHD patients undergo V-V ECMO, we need to be aware that these patients with CAC may be complicated with stroke MESHD not only cerebral infarction MESHD, but also cerebral hemorrhage MESHD.

    Continuous extracorporeal treatments in a dialysis patient with COVID-19 MESHD

    Authors: Yoshihito Nihei; Hajime Nagasawa; Yusuke Fukao; Masao Kihara; Seiji Ueda; Tomohito Gohda; Yusuke Suzuki

    doi:10.21203/rs.3.rs-63251/v2 Date: 2020-08-20 Source: ResearchSquare

    The coronavirus disease 2019 MESHD ( COVID-19 MESHD) pandemic is now a major global health threat. More than half a year have passed since the first discovery of severe acute respiratory syndrome coronavirus-2 MESHD (SARS-CoV2), no effective treatment has been established especially in intensive care unit. Inflammatory cytokine storm caused by SARS-CoV-2 infection MESHD has been reported to play a central role in COVID-19 MESHD; therefore, treatments for suppressing cytokines, including extracorporeal treatments, are considered to be beneficial. However, until today the efficacy of removing cytokines by extracorporeal treatments in patients with COVID-19 MESHD is unclear. Herein, we report our experience with a 66-year-old male patient undergoing maintenance peritoneal dialysis who became critically ill with COVID-19 MESHD and underwent several extracorporeal treatment approaches including plasma exchange, direct hemoperfusion using a polymyxin B-immobilized fiber column and continuous hemodiafiltration. Though the patient developed acute respiratory distress syndrome MESHD ( ARDS MESHD) repeatedly and subacute cerebral infarction MESHD and finally died for respiratory failure MESHD on day 30 after admission, these attempts appeared to dampen the cytokine storm based on the observed decline in serum IL-6 HGNC levels and were effective against ARDS MESHD and secondary haemophagocytic lymphohistiocytosis MESHD. This case suggests the significance of timely initiation of extracorporeal treatment approaches in critically ill MESHD patients with COVID-19 MESHD.

    COVID-19 MESHD and Ischemic Stroke

    Authors: Amira Sidig; Khabab Abbasher; Hussien Abbasher; Radi Tofaha Alhusseini; Mohamed Elsayed; Mohammed Abbasher; Sufian Khalid M. N; Khalid Hajnoor; Mohammed Malekaldar; Mutaz F. Digna; Abbasher Hussien; Omer Eladil A. Hamid

    doi:10.21203/rs.3.rs-49338/v1 Date: 2020-07-26 Source: ResearchSquare

    Background: SARS-CoV-2 causes COVID-19 MESHD disease. It was identified in December 2019 and rapidly evolved into a pandemic. During the outbreak of COVID-19 MESHD, researches demonstrated its effect on many systems, including the nervous system. In our clinic, we have reported an impact of SARS-CoV-2, causing the ischaemic stroke MESHD.Case Report: A 62-year-old Sudanese male with some comorbidities brought to the A&E with fever MESHD, chest symptoms MESHD, and acute evolving left-sided hemiplegia MESHD power grade 0/5 MRCS with left upper motor neuron facial palsy MESHD. Investigations: CT brain: right middle cerebral artery MCA infarction MESHD. CT- chest: bilateral ground-glass appearance. COVID-19 MESHD Test was positive. elevated D-dimer and C-reactive protein HGNC.Discussion: A retrospective study of data from the COVID-19 MESHD outbreak in China showed that the incidence of stroke MESHD among hospitalized patients was approximately 5%. The fact that COVID-19 MESHD is an acute inflammatory condition associated with an increased incidence of fatty plaques formation, injury of the vascular wall, and hypercoagulability MESHD, causing brain infarct MESHD can be a reasonable hypothesis.ConclusionPatients with COVID-19 MESHD are at increased risk of thrombo-embolization MESHD, leading to arterial and venous cerebrovascular accident MESHD. This case report enhances the importance of further studies to clarify the relationship between stroke MESHD and COVID-19 MESHD.

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