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SARS-CoV-2 proteins

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    Background rates of hospitalizations and emergency department visits for selected thromboembolic MESHD and coagulation disorders MESHD in Ontario, Canada, 2015 to 2020, to inform COVID-19 MESHD vaccine safety surveillance

    Authors: Sharifa Nasreen; Andrew Calzavara; Maria Sundaram; Shannon E MacDonald; Christiaan Righolt; Menaka Pai; Thalia Field; Lily W Zhou; Sarah Wilson; Jeff Kwong

    doi:10.1101/2021.04.02.21254856 Date: 2021-04-04 Source: medRxiv

    Objective: The objective of this study was to estimate background rates of selected thromboembolic MESHD and coagulation disorders MESHD in Ontario, Canada. Design: Population-based retrospective observational study using linked health administrative databases. Records of hospitalizations and emergency department visits were searched to identify cases using diagnostic codes from the International Statistical Classification of Diseases MESHD and Related Health Problems, Tenth Revision, Canada (ICD-10-CA). Participants: All Ontario residents. Primary outcome measures: Incidence rates of stroke MESHD, deep vein thrombosis MESHD, pulmonary embolism MESHD, idiopathic thrombocytopenia MESHD, disseminated intravascular coagulation MESHD, and cerebral venous thrombosis MESHD during five pre-pandemic years (2015-2019, annually, averaged, and monthly average) and 2020. Results: The average annual population was 14 million with 51% female. The mean annual rates during 2015-2019 were 127.1/100,000 population (95% confidence interval [CI], 126.2, 127.9) for ischemic stroke MESHD, 22.0/100,000 (95%CI, 21.6, 22.3) for intracerebral haemorrhage MESHD, 9.4 (95%CI, 9.2, 9.7) for subarachnoid haemorrhage MESHD, 86.8/100,000 (95%CI, 86.1, 87.5) for deep vein thrombosis MESHD, 63.7/100,000 (95%CI, 63.1, 64.3) for pulmonary embolism MESHD, 6.1/100,000 (95%CI, 5.9, 6.3) for idiopathic thrombocytopenia MESHD, 1.6/100,000 (95%CI, 1.5, 1.7) for disseminated intravascular coagulation MESHD, and 1.5/100,000 (95%CI, 1.4, 1.6) for cerebral venous thrombosis MESHD. Rates were lower in 2020 than during the pre-pandemic years for ischemic stroke MESHD, deep vein thrombosis MESHD, and idiopathic thrombocytopenia MESHD. Rates were generally consistent over time, except for pulmonary embolism MESHD, which increased from 57.1 to 68.5 per 100,000 between 2015 and 2019. Rates were higher for females than males for subarachnoid haemorrhage MESHD, pulmonary embolism MESHD, and cerebral venous thrombosis MESHD, and vice versa for ischemic stroke MESHD and intracerebral haemorrhage MESHD. Rates increased with age for most of these conditions, but idiopathic thrombocytopenia MESHD demonstrated a bimodal distribution with incidence peaks at 0-19 years and [≥]60 years. Conclusions: Our estimated background rates help to contextualize observed events of these potential adverse events of special interest and to detect potential safety signals related to COVID-19 MESHD vaccines.

    Characterizing the incidence of adverse events of special interest for COVID-19 MESHD vaccines across eight countries: a multinational network cohort study

    Authors: Xintong Li; Anna Ostropolets; Rupa Makadia; Azza Shoaibi; Gowtham Rao; Anthony G. Sena; Eugenia Martinez-Hernandez; Antonella Delmestri; Katia Verhamme; Peter Rijnbeek; Talita Duarte-Salles; Marc A Suchard; Patrick B Ryan; George Hripcsak; DANIEL PRIETO-ALHAMBRA

    doi:10.1101/2021.03.25.21254315 Date: 2021-03-26 Source: medRxiv

    As large-scale immunization programs against COVID-19 MESHD proceed around the world, safety signals will emerge that need rapid evaluation.1,2 We report population-based, age- and sex-specific background incidence rates of potential adverse events of special interest (AESI) in eight countries using thirteen databases. This multi-national network cohort study included eight electronic medical record and five administrative claims databases from Australia, France, Germany, Japan, Netherlands, Spain, the United Kingdom and the United States, mapped to a common data model. People observed for at least 365 days before 1 January 2017, 2018, or 2019 were included. We based study outcomes on lists published by regulators: acute myocardial infarction MESHD, anaphylaxis MESHD, appendicitis MESHD, Bell s palsy MESHD, deep vein thrombosis MESHD, disseminated intravascular coagulation MESHD, encephalomyelitis MESHD, Guillain-Barre syndrome MESHD, hemorrhagic MESHD and non-hemorrhagic stroke MESHD, immune thrombocytopenia MESHD, myocarditis/pericarditis MESHD, narcolepsy, pulmonary embolism MESHD, and transverse myelitis MESHD.3 We calculated incidence rates stratified by age, sex, and database. We pooled rates across databases using random effects meta-analyses. We classified meta-analytic estimates into Council of International Organizations of Medical Sciences categories: very common, common, uncommon, rare, or very rare.4 We analyzed 126,661,070 people. Rates varied greatly between databases and by age and sex. Some AESI (e.g., myocardial infarction MESHD, Guillain-Barre syndrome MESHD) increased with age, while others (e.g., anaphylaxis MESHD, appendicitis MESHD) were more common in young people. As a result, AESI were classified differently according to age. For example, myocardial infarction MESHD was very rare in children, rare in women aged 35-54 years, uncommon in men and women aged 55-84 years, and common in those aged [≥]85 years. We report robust baseline rates of prioritized AESI across 13 databases. Age, sex, and variation between databases should be considered if background AESI rates are compared to event rates observed with COVID-19 MESHD vaccines.

    COVID-19 MESHD Neuropathology at Columbia University Irving Medical Center/New York Presbyterian Hospital

    Authors: Kiran Thakur; Emily H Miller; Michael D Glendinning; Osama Al Dalahmah; Matei Banu; Amelia K Boehme; Alex Boubour; Samuel Bruce; Alexander M Chong; Jan Claassen; Phyllis Faust; Gunnar Hargus; Richard Hickman; Sachin Jambawalikar; Alexander Khandji; Carla Kim; Robyn S Klein; Angela Lignelli-Dipple; Chun-Chieh Lin; Yang Liu; Michael Miller; Gul Moonis; Anna Nordvig; Jonathan Overdevest; Morgan Prust; Serge Przedborski; William Roth; Allison Soung; Kurenai Tanji; Andrew Teich; Dritan Agalliu; Anne-Catrin Uhlemann; James E. Goldman; Peter Canoll

    doi:10.1101/2021.03.16.21253167 Date: 2021-03-20 Source: medRxiv

    Many patients with SARS-CoV-2 infection MESHD develop neurological signs and symptoms, though, to date, little evidence exists that primary infection of the brain is a significant contributing factor. We present the clinical, neuropathological, and molecular findings of 41 consecutive patients with SARS-CoV-2 infections MESHD who died and underwent autopsy in our medical center. The mean age was 74 years (38-97 years), 27 patients (66%) were male and 34 (83%) were of Hispanic/Latinx ethnicity. Twenty-four patients (59%) were admitted to the intensive care unit (ICU). Hospital-associated complications were common, including 8 (20%) with deep vein thrombosis MESHD/ pulmonary embolism MESHD (DVT/PE), 7 (17%) patients with acute kidney injury MESHD requiring dialysis, and 10 (24%) with positive blood cultures during admission. Eight (20%) patients died within 24 hours of hospital admission, while 11 (27%) died more than 4 weeks after hospital admission. Neuropathological examination of 20-30 areas from each brain revealed hypoxic/ischemic MESHD changes in all brains, both global and focal; large and small infarcts MESHD, many of which appeared hemorrhagic; and microglial activation with microglial nodules accompanied by neuronophagia, most prominently in the brainstem. We observed sparse T lymphocyte accumulation in either perivascular regions or in the brain parenchyma. Many brains contained atherosclerosis MESHD of large arteries and arteriolosclerosis MESHD, though none had evidence of vasculitis MESHD. Eighteen (44%) contained pathologies of neurodegenerative diseases MESHD, not unexpected given the age range of our patients. We examined multiple fresh frozen and fixed tissues from 28 brains for the presence of viral RNA and protein, using quantitative reverse-transcriptase PCR (qRT- PCR), RNAscope, and immunocytochemistry with primers, probes, and antibodies directed against the spike and nucleocapsid regions. qRT-PCR revealed low to very low, but detectable, viral RNA levels in the majority of brains, although they were far lower than those in nasal epithelia. RNAscope and immunocytochemistry failed to detect viral RNA or protein in brains. Our findings indicate that the levels of detectable virus in COVID-19 MESHD brains are very low and do not correlate with the histopathological alterations. These findings suggest that microglial activation, microglial nodules and neuronophagia, observed in the majority of brains, do not result from direct viral infection of brain parenchyma, but rather likely from systemic inflammation MESHD, perhaps with synergistic contribution from hypoxia/ischemia MESHD. Further studies are needed to define whether these pathologies, if present in patients who survive COVID-19 MESHD, might contribute to chronic neurological problems MESHD.

    An Unusual Presentation of Pyelonephritis MESHD: Is it COVID-19 MESHD Related?

    Authors: Liseanne van 't Hof; Lucy Pellikaan; Darius Soonawala; Hossain Roshani

    doi:10.21203/rs.3.rs-219574/v1 Date: 2021-02-07 Source: ResearchSquare

    IntroductionIn severe cases of COVID-19 MESHD, late complications such as coagulopathy MESHD and organ injury are increasingly described. In milder cases of the disease, the exact time frame and causal path of late onset complications has not yet been determined. Although direct and indirect renal injury MESHD by SARS-CoV-2 has been confirmed, hemorrhagic renal infection MESHD or coagulative problems in the urinary tract have not yet been described.Case PresentationThis case report describes a 35-year-old female without relevant medical history who, five days after having recovered from an infection with SARS-CoV-2, had an unusual course of acute pyelonephritis of the right kidney MESHD and persistent fever MESHD under targeted antibiotic treatment. A hemorrhagic ureteral obstruction MESHD and severe swollen renal parenchyma preceded the onset of fever MESHD and was related to the developing pyelonephritis MESHD. Sudden thrombotic vascular occlusion MESHD in the right eye appeared during admission. Symmetrical paresthesia in de limbs in combination of severe lower back pain MESHD and gastro-intestinal manifestation was documented and not been explained despite of intensive investigation.ConclusionWe present the unusual combination of culture confirmed bacterial hemorrhagic pyelonephritis MESHD with a blood clot in the proximal right ureter, complicated by a retinal venous thrombosis MESHD, in a patient who had recovered from SARS-CoV-2-infection MESHD five days before presentation. The case is suspect of a COVID-19 MESHD related etiology. 

    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.

    Cerebrovascular disease MESHD and coronavirus ( COVID-19 MESHD): a case report

    Authors: Amira Athanasios; Ivy Daley; Abid Ulhaque; Parth Desai

    doi:10.21203/rs.3.rs-158019/v1 Date: 2021-01-27 Source: ResearchSquare

    Background: Novel coronavirus ( COVID-19 MESHD) has been associated with a hypercoagulable state which has led to the following complications: increased risk for deep vein thrombosis MESHD, pulmonary embolism MESHD, acute coronary syndrome MESHD, and acute stroke MESHD. Case presentation: We present the case of a 66-year-old, Hispanic male who was admitted to the intensive care unit for severe respiratory illness MESHD secondary to the COVID-19 MESHD infection. The patient suffered an acute stroke MESHD on day 7 at the hospital. Conclusion: Emerging evidence suggests a coagulation dysfunction MESHD with the COVID-19 MESHD infection particularly in patients with severe illness with or without comorbid conditions. Amidst the current global pandemic, acute stroke MESHD in the setting of respiratory failure MESHD, should prompt suspicion for coronavirus infection MESHD

    COVID-19 MESHD Associated Coagulopathy MESHD Is a Reversible Phenomenon - 3-Month Follow Up Reveals Normalization of Coagulation Status Associated With Complete Venous Recanalization MESHD in Patients After Severe COVID-19 MESHD

    Authors: Abakar Magomedov; Daniel Zickler; Stoyan Karaivanov; Annika Kurreck; Frédéric H Münch; Julian Kamhieh-Milz; Andreas Kahl; Sophie K Piper; Kai-Uwe Eckardt; Thomas Dörner; Jan Matthias Kruse

    doi:10.21203/rs.3.rs-143670/v1 Date: 2021-01-08 Source: ResearchSquare

    Background: COVID 19 is associated with a hypercoagulable state and frequent thromboembolic complications MESHD. For how long this acquired abnormality lasts potentially requiring preventive measures, such as anticoagulation remains to be delineated.Methods: We used viscoelastic rotational thrombelastometry MESHD (ROTEM) in a single center cohort of 13 critical ill patients and performed follow up examinations three months after discharge from ICU.Results: We found clear signs of a hypercoagulable state due to severe hypofibrinolysis and a high rate of thromboembolic complications MESHD during the phase of acute illness MESHD. Three month follow up revealed a normalization of the initial coagulation abnormality MESHD together without evidence of venous thrombosis MESHD in all thirteen patients. Conclusion: In our cohort the coagulation profile was completely normalized three months after COVID-19 MESHD. It thus appears reasonable that anticoagulation can be discontinued beyond this timepoint in patients with complete venous reperfusion.

    Impact of a clinical pharmacist in ultrasound-guided venous thromboembolism screening in hospitalized COVID-19 MESHD patients: a pilot prospective study.

    Authors: Laura Gillespie; Rashid Z. Khan; John E. Stillson; Connor M. Bunch; Faisal Salim Shariff; Jacob Speybroeck; Anne Grisoli; Meredith Wireman Schmidt; Htay Phyu; Jason Jablonski; Byars Wells; Dan H. Fulkerson; Lyndsay Oancea; Abraham Leiser; Mark Walsh

    doi:10.21203/rs.3.rs-113407/v1 Date: 2020-11-21 Source: ResearchSquare

    Background: The recognition, prevention and treatment of venous thromboembolism MESHD ( VTE MESHD) remains a major challenge in the face of the recent SARS-COV-2 pandemic which has been associated with significant cardiovascular, renal, respiratory and hematologic complications related to hypercoagulability MESHD. There has been little literature thus far on the utility of screening ultrasound and role of the clinical pharmacist in treating these patients.Methods: We present a prospective pilot program of thirty-one consecutive SARS-CoV-2 patients who were provided four extremity screening ultrasounds for VTE MESHD on admission. This was coordinated by a clinical pharmacist as part of a multidisciplinary approach. Quantitative and qualitative data were recorded with the goal of describing the utility of the clinical pharmacist in ultrasound screening. Data collected include: demographics, information on clinical symptoms or signs at presentation, and laboratory and radiologic results during the hospitalization from each individual electronic medical record.Results: Nine of the thirty-one patients presented with venous thrombosis MESHD. Of the nine patients, there were twenty-two total clotted vessels, all of which were asymptomatic. The clinical pharmacist, as the coordinator for a multidisciplinary COVID-19 MESHD associated coagulopathy MESHD management team, drafted a screening and treatment protocol for anticoagulation prophylaxis and therapy of VTE MESHD after ultrasound findings.Conclusion: VTE MESHD screening of hospitalized SARS-CoV-2 patients reveals a significant number of asymptomatic VTEs and justifies diagnostic, prophylactic, and treatment measures coordinated by a clinical pharmacist.

    Arterial and Venous Thromboembolic Complications of COVID-19 MESHD Detected by CT Angiogram and Venous Duplex Ultrasound

    Authors: Dr. Edison Lee; Dr. Adam Krajewski; Dr. Cynthia Clarke; Dr. David O’Sullivan; Dr. Timothy Herbst; Dr. Steven Lee

    doi:10.21203/rs.3.rs-105290/v1 Date: 2020-11-09 Source: ResearchSquare

    OBJECTIVE. To investigate the incidence of thromboembolic MESHD events, specifically pulmonary embolism MESHD ( PE MESHD), deep vein thrombosis MESHD ( DVT MESHD), and cerebrovascular accidents MESHD ( CVA MESHD), in patients tested positive for COVID-19 MESHD through RT-PCR in a regional healthcare system in Connecticut.MATERIALS AND METHODS. All CT angiogram (CTA) and venous duplex extremity ultrasound (US) examinations performed on 192 consecutively documented cases of COVID-19 MESHD were retrospectively reviewed at a multi-centered healthcare system. Clinical characteristics and patient outcomes were evaluated and compared between two groups based on the presence or absence of acute thromboembolic MESHD events.RESULTS. Of the 16,264 patients tested for COVID-19 MESHD, 3,727 (23%) were positive. Out of those, 192 patients underwent 245 vascular imaging studies including chest CTA (86), venous duplex ultrasound (134), and CTA head and neck (25). Among those who underwent imaging, 49 (26%) demonstrated acute thromboembolic MESHD events which included 13/86 (15%) with PE MESHD, 34/134 (25%) with DVT MESHD, and 6/25 (24%) with CVA MESHD. One patient had positive results on all 3 examinations and 2 patients had positive results on both chest CTA and venous duplex US. Males were more likely to have a thromboembolic MESHD event than females (33/103 (34%) vs. 14/89 (16%), p=0.009). No significant difference was observed with respect to age, cardiopulmonary comorbidities, malignancy MESHD history, diabetes MESHD, or dialysis.CONCLUSION. Approximately 26% of COVID-19 MESHD patients with positive testing who underwent vascular imaging with CTA or venous duplex ultrasound had thromboembolic MESHD events including PE MESHD, DVT MESHD, and CVA MESHD. This indicates that COVID-19 MESHD patients are at increased risk for thromboembolic complications MESHD.

    Proximal Deep Vein Thrombosis and Pulmonary Embolism in COVID-19 MESHD Patients: A Systematic Review and Meta-Analysis Short Tittle: Venous Thromboembolism in COVID-19 MESHD Patients

    Authors: Gregoire Longchamp; Sara Manzocchi-Besson; Alban Longchamp; Marc Righini; Helia Robert-Ebadi; Marc Blondon

    doi:10.21203/rs.3.rs-104503/v1 Date: 2020-11-07 Source: ResearchSquare

    BACKGROUNG COVID-19 MESHD appears to be associated with a high risk of venous thromboembolism MESHD ( VTE MESHD). We aimed to systematically review and meta-analyze the risk of clinically relevant VTE MESHD in patients hospitalized for COVID-19 MESHD. METHODSThis meta-analysis included original articles in English published from 01/01/2020 to 06/15/2020 in Pubmed/MEDLINE, Embase, Web of science, and Cochrane. Outcomes were major VTE MESHD, defined as any objectively diagnosed pulmonary embolism MESHD ( PE MESHD) and/or proximal deep vein thrombosis MESHD ( DVT MESHD). Primary analysis estimated the risk of VTE MESHD, stratified by acutely and critically ill inpatients. Secondary analyses explored the separate risk of proximal DVT MESHD and of PE MESHD; the risk of major VTE MESHD stratified by screening and by type of anticoagulation. RESULTSIn 33 studies (n=4’009 inpatients) with heterogeneous thrombotic MESHD risk factors, VTE MESHD incidence was 9% (95%CI 5-13%, I2=92.5) overall, and 21% (95%CI 14-28%, I2=87.6%) for patients hospitalized in the ICU. Proximal lower limb DVT incidence was 3% (95%CI 1-5%, I2= 87.0%) and 8% (95%CI 3-14%, I2=87.6%), respectively. PE MESHD incidence was 8% (95%CI 4-13%, I2=92.1%) and 17% (95%CI 11-25%, I2=89.3%), respectively. Screening and absence of anticoagulation were associated with a higher VTE MESHD incidence. When restricting to medically ill inpatients, the VTE MESHD incidence was 2% (95%CI 0-6%).CONCLUSIONSThe risk of major VTE MESHD among COVID-19 MESHD inpatients is high but varies greatly with severity of the disease. These findings reinforce the need for the use of thromboprophylaxis in all COVID-19 MESHD inpatients and for clinical trials testing different thromboprophylaxis regimens in subgroups of COVID-19 MESHD inpatients. TRIAL REGISTRATIONThe review protocol was registered in PROSPERO International Prospective Register of Systematic Reviews (CRD42020193369).

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