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SARS-CoV-2 proteins

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    Prevalence use of nonsteroidal anti-inflammatory drugs in the general population with COVID-19 MESHD and associated COVID-19 MESHD risk, hospitalization, severity, death MESHD, and safety outcomes: A systematic review and meta-analysis

    Authors: huilei zhao; shanshan huang; kaibo mei; wen shao; yuan jiang; wengen zhu; jianyong ma; jing zhang; peng yu; xiao liu

    doi:10.1101/2021.05.01.21256428 Date: 2021-05-05 Source: medRxiv

    Introduction: Recent reports of potential harmful effects of nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with Corona Virus Disease MESHD 2019 ( COVID-19 MESHD) have provoked great concern. Therefore, the safety of NSAIDs is still questioned. Methods: We searched the PubMed, EMBASE, Cochrane Library and Web of Science databases from December 2019 to January 2021 to examine use prevalence for NSAIDs in general, as well as associated COVID-19 MESHD risk and outcomes. This study has been registered with PROSPERO (CRD42019132063) Results: We included 25 studies with a total of 101,215 COVID-19 MESHD patients. The use of NSAIDs in COVID-19 MESHD patients reached 19%. Exposure to NSAIDs was not associated with significantly increased risk of developing COVID-19 MESHD (odds ratio [OR]=0.98, 95% confidence interval [CI]: 0.78-1.24; I2=82%), hospitalization (OR=1.06, 95%CI: 0.76-1.48; I2=81%), mechanical ventilation (OR=0.71, 95%CI: 0.47-1.06; I2=38%), and length of hospital stay. Moreover, use of NSAIDs was significantly associated with better outcomes, including severity of COVID-19 MESHD (OR=0.79, 95%CI: 71-0.89; I2=0%) and death MESHD (OR=0.68, 95%CI: 0.52-0.89; I2=85%) in patients with COVID-19 MESHD. Regarding safety outcomes, exposure to NSAIDs was associated with increased risk of stroke MESHD (OR=2.32, 95%CI: 1.04-5.2; I2=0%), but not with myocardial infraction MESHD (OR=1.49; p=0.66; I2=0%), overt thrombosis MESHD (OR=0.76, p=0.50; I2=28%) and major bleeding MESHD (p=0.61). Conclusion: Based on current evidence, exposure to NSAIDs is not linked to increased odds or exacerbation of COVID-19 MESHD in the general COVID-19 MESHD population. Furthermore, administration of NSAIDs might have better outcomes and survival benefits in the general COVID-19 MESHD population, although potentially increasing the risk of stroke MESHD. Use of NSAIDs might be safe and beneficial in COVID-19 MESHD. Future observational and randomized control trials are needed for further confirmation.

    A systematic review on Multisystem Inflammatory Syndrome in Children ( MIS HGNC-C) with COVID-19 MESHD: Development of a scoring system for clinical diagnosis

    Authors: Dr.Suchitra Vishwambhar Surve; Ms. Shaini Joseph; Dr. Rahul K Gajbhiye; Smita D Mahale; Dr. Deepak N Modi

    doi:10.1101/2021.04.23.21255879 Date: 2021-04-25 Source: medRxiv

    Background There is growing evidence of Multisystem Inflammatory Syndrome MESHD in Children ( MIS HGNC-C) resembling Kawasaki disease in children infected with SARS-CoV-2. The review was undertaken to evaluate the case definition, the spectrum of clinical presentations and current management practices in children with COVID-19 MESHD presenting with or without MIS HGNC-C. Methods The individual patient data from 119 studies accounting for 333 children were analyzed. We devised a scoring system as per WHO criteria to classify the patients as MIS HGNC-C or without MIS HGNC-C. A score of 3 was given for the presence of fever MESHD (>24h) and a score of 1 for lab-confirmed diagnosis of SARS-CoV-2. Additionally, a score of 1 was given for a) rash MESHD or conjunctivitis MESHD or muco-cutaneous inflammation MESHD signs, b) hypotension MESHD or shock, c) diarrhea MESHD, vomiting MESHD or abdominal pain MESHD, d) features of myocardial dysfunction MESHD as determined by abnormal eco-cardiography or elevated Troponin or N-terminal pro b-type natriuretic peptide (NT-proBNP), e) evidence of coagulopathy MESHD as evidenced by elevated levels of prothrombin time PT, partial thromboplastin time PTT or D-dimer, f) laboratory evidence of inflammation MESHD as determined by elevated erythrocyte sedimentation rate (ESR) or C-reactive protein HGNC ( CRP HGNC) or procalcitonin. A negative score of (-3) was given when there was a diagnosis of sepsis MESHD, staphylococcal or streptococcal shock syndrome MESHD. Based on these criteria, a minimum score of 6 was essential to classify the child as MIS HGNC-C. Results Based on this score, 18% (52/289) of cases were identified to be MIS HGNC-C. A greater proportion of children with MIS HGNC-C had cardiac involvement ( MIS HGNC-C 80% vs Non- MIS HGNC-C 20%) and gastrointestinal involvement MESHD ( MIS HGNC-C 71% vs Non- MIS HGNC-C 12%). Lymphopenia MESHD was commonly reported in MIS-C ( MIS HGNC-C 54.2% vs Non- MIS HGNC-C 29.7%). In addition to routine inflammatory markers, significamtly greater proportion of children with MIS-C had elevated Ferritin, LDH, Fibrinogen HGNC and IL-6 HGNC. Children with MIS HGNC-C were less likely to have respiratory symptoms like cough ( MIS HGNC-C 25% vs Non- MIS HGNC-C 75%) and rhinorrhea MESHD ( MIS HGNC-C 4% vs Non- MIS HGNC-C 22.8%). A greater proportion of children with MIS HGNC-C required intensive care and aggressive treatment; and mortality rates were also higher in MIS-C group ( MIS HGNC-C 10% vs Non- MIS HGNC-C 1%). Conclusion The children with COVID-19 MESHD having cardiac and/or gastrointestinal involvement MESHD are more likely to develop MIS HGNC-C. The children with MIS HGNC-C have higher mortality rates. The scoring system developed herein will aid clinicians in patient diagnosis and timely management.

    Clomipramine suppresses ACE2 HGNC-mediated SARS-CoV-2 entry MESHD

    Authors: Yuri Kato; Shigeru Yamada; Kazuhiro Nishiyama; Ayano Satsuka; Suyong Re; Daiki Tomokiyo; Jae Man Lee; Tomohiro Tanaka; Akiyuki Nishimura; Kenzo Yonemitsu; Hiroshi Asakura; Yuko Ibuki; Yumiko Imai; Noriho Kamiya; Kenji Mizuguchi; Takahiro Kusakabe; Yasunari Kanda; Motohiro Nishida

    doi:10.1101/2021.03.13.435221 Date: 2021-03-14 Source: bioRxiv

    Myocardial damage caused by the newly emerged coronavirus ( SARS-CoV-2) infection MESHD is one of key determinants of COVID-19 MESHD severity and mortality. SARS-CoV-2 entry to host cells are initiated by binding with its receptor, angiotensin converting enzyme (ACE) 2 HGNC, and the ACE2 HGNC abundance is thought to reflect the susceptibility to infection. Here, we found that clomipramine, a tricyclic antidepressant, potently inhibits SARS-CoV-2 infection MESHD and metabolic disorder MESHD in human iPS-derived cardiomyocytes. Among 13 approved drugs that we have previously identified as potential inhibitor of doxorubicin-induced cardiotoxicity MESHD, clomipramine showed the best potency to inhibit SARS-CoV-2 spike PROTEIN glycoprotein pseudovirus-stimulated ACE2 HGNC internalization. Indeed, SARS-CoV-2 infection MESHD to human iPS-derived cardiomyocytes (iPS-CMs) and TMPRSS2 HGNC-expressing VeroE6 cells were dramatically suppressed even after treatment with clomipramine. Furthermore, the combined use of clomipramine and remdesivir was revealed to synergistically suppress SARS-CoV-2 infection MESHD. Our results will provide the potentiality of clomipramine for the breakthrough treatment of severe COVID-19 MESHD.

    CD47 HGNC as a potential biomarker for the early diagnosis of severe COVID-19 MESHD

    Authors: Katie-May McLaughlin; Denisa Bojkova; Marco Bechtel; Joshua Kandler; Philipp Reus; Trang Le; Julian UG Wagner; Sandra Ciesek; Mark N Wass; Martin Michaelis; Jindrich N Cinatl Jr.

    doi:10.1101/2021.03.01.433404 Date: 2021-03-01 Source: bioRxiv

    The coronavirus SARS-CoV-2 is the cause of the ongoing COVID-19 pandemic MESHD. Most SARS-CoV-2 infections MESHD SARS-CoV-2 infections MESHD are mild or even asymptomatic. However, a small fraction of infected MESHD individuals develops severe, life-threatening disease, which is caused by an uncontrolled immune response resulting in hyperinflammation. Antiviral interventions are only effective prior to the onset of hyperinflammation. Hence, biomarkers are needed for the early identification and treatment of high-risk patients. Here, we show in a range of model systems and data from post mortem samples that SARS-CoV-2 infection MESHD results in increased levels of CD47 HGNC, which is known to mediate immune escape in cancer MESHD and virus-infected cells. Systematic literature searches also indicated that known risk factors such as older age and diabetes MESHD are associated with increased CD47 HGNC levels. High CD47 HGNC levels contribute to vascular disease MESHD, vasoconstriction, and hypertension MESHD, conditions which may predispose SARS-CoV-2-infected MESHD individuals to COVID-19 MESHD-related complications such as pulmonary hypertension MESHD, lung fibrosis MESHD, myocardial injury MESHD, stroke MESHD, and acute kidney injury MESHD. Hence, CD47 HGNC is a candidate biomarker for severe COVID-19 MESHD. Further research will have to show whether CD47 HGNC is a reliable diagnostic marker for the early identification of COVID-19 MESHD patients requiring antiviral therapy.

    A cannabinoid receptor agonist shows anti-inflammatory and survival properties in human SARS-CoV-2-infected iPSC-derived cardiomyocytes MESHD

    Authors: Luiz Guilherme H.S. Aragao; Julia T Oliveira; Jairo R Temerozo; Mayara A Mendes; Jose Alexandre Salerno; Carolina da S. G. Pedrosa; Teresa Puig-Pijuan; Carla Verissimo; Isis M Ornelas; Thayana Torquato; Gabriela Vitoria; Carolina Q. Sacramento; Natalia Fintelman-Rodrigues; Suelen da Silva Gomes Dias; Vinicius Cardoso Soares; Leticia R. Q. Souza; Karina Karmirian; Livia Goto-Silva; Diogo Biagi; Estela M. Cruvinel; Rafael Dariolli; Daniel R. Furtado; Patricia T. Bozza; Helena L. Borges; Thiago Moreno L. Souza; Marilia Zaluar P. Guimaraes; Stevens Rehen

    doi:10.1101/2021.02.20.431855 Date: 2021-02-21 Source: bioRxiv

    Coronavirus disease 2019 MESHD ( COVID-19 MESHD) is caused by acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), which can infect several organs and lead to loss of vital organ function, especially impacting respiratory capacity. Among the extrapulmonary manifestations of COVID-19 MESHD is myocardial injury MESHD, caused both directly and indirectly by SARS-CoV-2, and which is associated with a high risk of mortality. One of the hallmarks of severe COVID-19 MESHD is the "cytokine storm", at which point the immune system malfunctions, leading to possible organ failure MESHD and death MESHD. Cannabinoids are known to have anti-inflammatory properties by negatively modulating the release of pro-inflammatory cytokines. Herein, we investigated the effects of the cannabinoid agonist WIN 55,212-2 (WIN) on SARS-CoV-2-infected MESHD human iPSC-derived cardiomyocytes (hiPSC-CMs). Although WIN did not modulate angiotensin-converting enzyme II, nor reduced SARS-CoV-2 infection MESHD and replication in hiPSC-CMs at the conditions tested, it had anti-inflammatory and protective effects by reducing the levels of interleukins 6, 8,18 and tumor necrosis factor-alpha HGNC tumor necrosis factor-alpha MESHD ( TNF HGNC-) and lactate dehydrogenase (LDH) activity in these cells without causing hypertrophic cardiac damage MESHD. These findings suggest that cannabinoids should be further investigated as an alternative therapeutic tool for the treatment of COVID-19 MESHD. HighlightsO_LIHuman iPSC-derived cardiomyocytes (hiPSC-CMs) express CB1 HGNC receptor. C_LIO_LIThe cannabinoid receptor agonist, WIN 55,212-2 (WIN), does not influence SARS-CoV-2 infection MESHD in hiPSC-CMs. C_LIO_LIWIN reduces inflammation MESHD and death MESHD in SARS-CoV-2-infected hiPSC-CMs MESHD. C_LI

    The Prognostic Value of Myocardial Injury MESHD in COVID-19 MESHD Patients and Associated Characteristics

    Authors: jian he; Bicheng Zhang; Quan Zhou; Wenjing Yang; Jing Xu; Tingting Liu; Haijun Zhang; Zhiyong Wu; Dong Li; Qing Zhou; Jie Yan; Cuizhen Zhang; Robert G. Weiss; Guanshu Liu; Zhongzhao Teng; Arlene Sirajuddin; Haiyan Qian; Shihua Zhao; Andrew E. Arai; Minjie Lu; Xiaoyang Zhou

    doi:10.21203/rs.3.rs-251810/v1 Date: 2021-02-17 Source: ResearchSquare

    Background: Since December 2019, Coronavirus disease 2019 MESHD ( COVID-19 MESHD) has emerged as an international pandemic. COVID-19 MESHD patients with myocardial injury MESHD might need special attention. However, understanding on this aspect remains unclear. This study aimed to illustrate clinical characteristics and the prognostic value of myocardial injury MESHD to COVID-19 MESHD patients. Methods: This retrospective, single-center study finally included 304 hospitalized COVID-19 MESHD cases confirmed by real-time RT-PCR from January 11 to March 25, 2020. Myocardial injury MESHD was determined by serum high-sensitivity troponin I (Hs-TnI). The primary endpoint was COVID-19 MESHD associated mortality. Results: Of 304 COVID-19 MESHD patients (median age, 65 years; 52.6% males), 88 patients (27.3%) died (61 patients with myocardial injury MESHD, 27 patients without myocardial injury MESHD on admission). COVID-19 MESHD patients with myocardial injury MESHD had more comorbidities ( hypertension MESHD, chronic obstructive pulmonary disease MESHD, cardiovascular disease MESHD, and cerebrovascular disease MESHD); lower lymphocyte counts, higher C-reactive protein HGNC ( CRP HGNC, median, 84.9 vs 28.5 mg/L, p<0.001), procalcitonin levels (median, 0.29 vs 0.06 ng/ml, p<0.001), inflammatory and immune response markers; more frequent need for noninvasive ventilation, invasive mechanical ventilation; and was associated with higher mortality incidence (hazard ratio, HR=7.02, 95% confidence interval, CI, 4.45-11.08, p<0.001) than those without myocardial injury MESHD. Myocardial injury MESHD (HR=4.55, 95% CI, 2.49-8.31, p<0.001), senior age, CRP HGNC levels, and novel coronavirus pneumonia MESHD ( NCP PROTEIN) types on admission were independent predictors to mortality in COVID-19 MESHD patients. Conclusions: COVID patients with myocardial injury MESHD on admission is associated with more severe clinical presentation and biomarkers. Myocardial injury MESHD and higher HsTNI are both strongest independent predictors to COVID related mortality after adjusting confounding factors. In addition, senior age, CRP HGNC levels and NCP PROTEIN types are also associated with mortality. Trial registration: Not applicable.

    Evaluation the relationship of left ventricular global longitudinal strain and laboratory parameters in discharged patients with COVID-19 MESHD: A follow-up study

    Authors: Derya BAYKIZ; Elif AYDUK GOVDELI; Pelin KARACA OZER; Ekrem Bilal KARAAYVAZ; Yunus CATMA; Alpay MEDETALIBEYOGLU; Atahan CAGATAY; Berrin UMMAN; Tufan TUKEK; Zehra BUGRA

    doi:10.21203/rs.3.rs-233011/v1 Date: 2021-02-11 Source: ResearchSquare

    Background The novel coronavirus infection MESHD ( COVID-19 MESHD) disease has spread rapidly and posed a great threat to global public health. The laboratory parameters and clinical outcomes of the disease in discharged patients remain unknown. In this study, we aimed to investigate the laboratory and echocardiographic findings of patients with COVID-19 MESHD after discharge and the relation between left ventricular global longitudinal strain (LVGLS) and inflammatory parameters in discharged patients.Methods A total of 75 patients recovering from COVID-19 MESHD as the study group were prospectively recruited from the COVID-19 MESHD outpatient clinic for their follow-up visits at a median 6 months after discharge. Patients were classified into groups according to pneumonia MESHD severity and impairment in LVGLS. Laboratory findings of patients both at admission and after discharge were evaluated and the relation with pneumonia MESHD severity at admission and LVGLS after discharge were analyzed.Results Serum ferritin, lactate dehydrogenase (LDH) and prohormone B-type natriuretic peptide (pro-BNP) levels after discharge were significantly higher in the study group than the control group (n = 44). Ferritin was found to be related to pneumonia MESHD severity. Serum ferritin and LDH values after discharge were significantly higher in patients with impaired LVGLS than those with preserved. There was a significant correlation between LVGLS, serum ferritin and LDH values after discharge (r = -0.252, p = 0.012; r = -0.268, p = 0.005, respectively).Conclusions Clinicians should pay close attention to the serum ferritin and LDH levels in discharged patients for predicting the severity of COVID-19 MESHD disease and early identification of subclinical left ventricular myocardial dysfunction MESHD.

    Clinical Characteristics of Severe COVID-19 MESHD in China: A Case Series and Meta-analysis

    Authors: Geling Teng; Hua Hu; Xia Wang; Junsheng Wang; Hongmei Zhang; Ying Chen

    doi:10.21203/rs.3.rs-186426/v1 Date: 2021-01-29 Source: ResearchSquare

    Background: There have been inconsistent reports regarding the unique manifestations of severe coronavirus disease 2019 MESHD ( COVID-19 MESHD) occurring in China. This study analyzed the clinical manifestation of 13 severe COVID-19 MESHD cases at a single institution and compared the data to previously reported characteristics of severe COVID-19 MESHD in China. Methods: This retrospective case study included patients with severe COVID-19 MESHD who were admitted to the isolation ward of the Shandong Chest Hospital from January 2020 to February 2020. The clinical signs and symptoms, laboratory examination results, imaging features, treatment strategies, and patient prognoses were summarized. A database search was then conducted for studies published through December 2020 documenting characteristics of severe COVID-19 MESHD cases in China. The pooled results for severe COVID-19 MESHD patients in China were calculated by using the random-effects model.Results: A total of 4 severe and 9 critical patients were included from Shandong Chest Hospital. The average patient age was 55.3 (range 23-88) years, and 61.5% of patients were male. Chest computed tomography for all patients showed multiple lesions as ground-glass shadows in both lungs. All patients presented bacterial infection MESHD and various degrees of liver and myocardial injury MESHD. The treatment strategies for patients included antibiotics, immunoglobulin, and glucocorticoids, and mechanical ventilation was used in all patients for respiratory failure MESHD. Two patients died, and 11 recovered. In the pooled data for severe COVID-19 MESHD patients, the most common comorbidities were hypertension MESHD, diabetes mellitus MESHD, and coronary heart disease MESHD. The common signs in these patients were fever MESHD, cough MESHD, fatigue MESHD, chest tightness MESHD, and a leukocyte count > 10. Conclusions: Older males with hypertension MESHD, diabetes mellitus MESHD, and coronary heart disease MESHD may be at higher risk of developing severe COVID-19 MESHD. Patients should be assessed for concomitant bacterial infections MESHD. Cardiac and liver enzymes, fever MESHD, cough MESHD, fatigue MESHD, chest tightness MESHD, and leukocytosis MESHD should be monitored for signs of disease progression. 

    Findings from Cardiovascular Evaluation of NCAA Division I Collegiate Student-Athletes after Asymptomatic or Mildly Symptomatic SARS-CoV-2 Infection MESHD

    Authors: Calvin E Hwang; Andrea Kussman; Jeffrey W Christle; Victor Froelicher; Matthew T Wheeler; Kegan J Moneghetti

    doi:10.1101/2021.01.07.21249407 Date: 2021-01-08 Source: medRxiv

    ObjectivesThe risk of myocardial damage MESHD after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection MESHD has been controversial. There is an urgent need for data to support the appropriate level of cardiovascular screening for safe return-to-play. The purpose of this study is to report the incidence of abnormal cardiovascular MESHD findings in National Collegiate Athletic Association (NCAA) Division I student-athletes with a history of SARS-CoV-2 infection MESHD. MethodsThis is a case series of student-athletes at a single NCAA Division I institution who tested positive for SARS-CoV-2 by polymerase chain reaction (PCR) or antibody testing (IgG) from 4/15/2020 to 10/31/2020. From 452 athletes who were screened, 5,124 PCR and 452 antibody tests were completed. Student-athletes were followed through 12/31/2020 (median 104 days, range 64-182 days). Cardiac work-up included clinical evaluation, troponin level, electrocardiogram (ECG), and echocardiogram. Additional work-up was ordered as clinically indicated. Results55 student-athletes tested positive for SARS-CoV-2. Of these, 38 (69%) had symptoms of Coronavirus Disease MESHD ( COVID-19 MESHD), 14 (26%) had a positive IgG test, and 41 (74%) had a positive PCR test. Eight abnormal cardiovascular screening evaluations necessitated further testing including cardiac magnetic resonance imaging (cMRI). Two athletes received new cardiac diagnoses, one probable early cardiomyopathy MESHD and one pericarditis MESHD, while the remaining six had normal cardiac MRIs. ConclusionThese data support recent publications which recommend the de-escalation of cardiovascular testing for athletes who have recovered from asymptomatic or mildly symptomatic SARS-CoV-2 infection MESHD. Continued follow-up of these athletes for sequelae of SARS-CoV-2 is critical.

    Prevalence and Prognostic Value of Myocardial Injury MESHD in the Initial Presentation of  SARS-CoV-2 Infection MESHD among Older Adults

    Authors: Isabel Arnau-Barres; Ana Pascual-Dapena; Inmaculada López-Montesinos; Silvia Gómez-Zorrilla; Luisa Sorli; Marta Herrero; Juan Pablo Horcajada; Xavier Nogues; Olga Vazquez; Natalia García-Giralt; Ramon Miralles; Robert Güerri-Fernández

    doi:10.21203/rs.3.rs-134407/v1 Date: 2020-12-22 Source: ResearchSquare

    Myocardial involvement during SARS-CoV-2 infection MESHD has been reported in many prior publications. Data about this condition in older adults is scarce especially its role in clinical prognosis. We aim to study the prevalence and the clinical implications of acute myocardial injury MESHD ( MIN MESHD) during SARS-CoV-2 infection MESHD, particularly in older patients.MethodsLongitudinal observational study where all consecutive adult patients admitted to a COVID-19 MESHD unit between March to April 2020 were included. Those patients aged ≥65 were considered as older patients. MIN MESHD was defined as at least 1 high-sensitive troponin (hs- TnT HGNC) concentration above the 99th percentile upper reference limit with different sex-cutoff.ResultsAmong the 634 patients admitted during the period of observation 365(58%) had evidence of MIN MESHD (hs- TnT HGNC>14 pg/mL), and among those 224(61%) were older adults. Individuals with acute MIN MESHD were more prone to be older, had more comorbidities, more functional decline at admission, and higher inflammatory parameters. Among older adults, MIN MESHD was associated with longer time to recovery compared to those without MIN MESHD [13 days(IQR 6-21) vs 9 days(IQR 5-17);p<0.001 repectively. In-hospital mortality was significantly higher in older adults with MIN MESHD at admission vs those without MIN MESHD [71(31%) vs 11(12%);p<0.001]. In a logistic regression model adjusting by age, sex, severity and Charlson comorbidity index the OR for in-hospital mortality was 2.1 (95% CI:1.02-4.42;p=0.043) among those older adults with MIN MESHD at presentation.ConclusionMIN is frequent in individuals with SARS-CoV-2 infection MESHD, especially in older adults and in patients with pre-existing comorbidities and with higher inflammatory levels. Older adults with acute myocardial injury MESHD had greater time to clinical recovery, more severe presentation of the disease and higher odds of in-hospital mortality.  

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SARS-CoV-2 Proteins


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