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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (12)

ProteinN (5)

NSP5 (4)

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    Network Representation Learning-Based Drug Mechanism Discovery and Anti-Inflammatory Response Against COVID-19 MESHD

    Authors: Wang Xiaoqi; Bin Xin; Zhijian Xu; Kenli LI; Fei Li; Wu Zhong; Weihong Tan; Shaoliang Peng

    doi:10.26434/chemrxiv.12531314.v3 Date: 2021-01-18 Source: ChemRxiv

    Recent studies have been demonstrated that the excessive inflammatory response is an important factor of death in COVID-19 MESHD patients. In this study, we proposed a network representation learning-based methodology, termed AIdrug2cov, to discover drug mechanism and anti-inflammatory response for patients with COVID-19 MESHD. This work explores the multi-hub characteristic of a heterogeneous drug network integrating 8 unique networks. Inspired by the multi-hub characteristic, we design three billion special meta paths to train a deep representation model for learning low-dimensional vectors that integrate long-range structure dependency and complex semantic relation among network nodes. Using the representation vectors, AIdrug2cov identifies 40 potential targets and 22 high-confidence drugs that bind to tumor necrosis factor(TNF)-α HGNC tumor necrosis factor(TNF)-α MESHD or interleukin(IL)-6 HGNC to prevent excessive inflammatory responses in COVID-19 MESHD patients. Finally, we analyze mechanisms of action based on PubMed publications and ongoing clinical trials, and explore the possible binding modes between the new predicted drugs and targets via docking program. In addition, the results in 5 pharmacological application suggested that AIdrug2cov significantly outperforms 5 other state-of-the-art network representation approaches, future demonstrating the availability of AIdrug2cov in drug development field. In summary, AIdrug2cov is practically useful for accelerating COVID-19 MESHD therapeutic development. The source code and data can be downloaded from https://github.com/pengsl-lab/AIdrug2cov.git.

    Detection of SARS-Cov-2 RNA in serum is associated with increased mortality risk in hospitalized COVID-19 MESHD patients.

    Authors: Diego A. Rodriguez Serrano; Emilia Roy-Vallejo; Nelly D. Zurita Cruz; Alexandra Martin Ramirez; Sebastian C. Rodriguez-Garcia; Nuria Arevalillo-Fernandez; Jose Maria Galvan-Roman; Leticia Fontan Garcia-Rodrigo; Lorena Vega Piris; Marta Chicot Llano; David Arribas Mendez; Begona Gonzalez de Marcos; Julia Hernando Santos; Ana Sanchez Azofra; Elena Avalos Perez-Urria; Pablo Rodriguez-Cortes; Laura Esparcia; Ana Marcos-Jimenez; Santiago Sanchez-Alonso; Irene Llorente; Joan B. Soriano; Carmen Suarez Fernandez; Rosario Garcia-Vicuna; Julio Ancochea; Jesus Sanz; Cecilia Munoz-Calleja; Rafael de la Camara; Alfonso Canabal Berlanga; Isidoro Gonzalez-Alvaro; Laura Cardenoso; John R Bradley

    doi:10.1101/2021.01.14.21249372 Date: 2021-01-15 Source: medRxiv

    Background COVID-19 MESHD has overloaded national health services worldwide. Thus, early identification of patients at risk of poor outcomes is critical. Our objective was to analyse SARS-CoV-2 RNA detection in serum as a severity biomarker in COVID-19 MESHD. Methods and FindingsRetrospective observational study including 193 patients admitted for COVID-19 MESHD. Detection of SARS-CoV-2 RNA in serum (CoVemia) was performed with samples collected at 48-72 hours of admission by two techniques from Roche and Thermo Fischer Scientific (TFS). Main outcome variables were mortality and need for ICU admission during hospitalization for COVID-19 MESHD. CoVemia was detected in 50-60% of patients depending on technique. The correlation of Ct in serum between both techniques was good (intraclass correlation coefficient: 0.612; p < 0.001). Patients with CoVemia were older (p = 0.006), had poorer baseline oxygenation (PaO2/FiO2; p < 0.001), more severe lymphopenia MESHD (p < 0.001) and higher LDH (p < 0.001), IL-6 HGNC (p = 0.021), C-reactive protein HGNC ( CRP HGNC; p = 0.022) and procalcitonin (p = 0.002) serum levels. We defined "relevant CoVemia" when detection Ct was < 34 with Roche and < 31 for TFS. These thresholds had 95% sensitivity and 35 % specificity. Relevant CoVemia predicted death during hospitalization (OR 9.2 [3.8 - 22.6] for Roche, OR 10.3 [3.6 - 29.3] for TFS; p < 0.001). Cox regression models, adjusted by age, sex and Charlson index, identified increased LDH serum levels and relevant CoVemia (HR = 9.87 [4.13-23.57] for TFS viremia MESHD and HR = 7.09 [3.3-14.82] for Roche viremia MESHD) as the best markers to predict mortality. ConclusionsCoVemia assessment at admission is the most useful biomarker for predicting mortality in COVID-19 MESHD patients. CoVemia is highly reproducible with two different techniques (TFS and Roche), has a good consistency with other severity biomarkers for COVID-19 MESHD and better predictive accuracy. AUTHOR SUMMARY COVID-19 MESHD shows a very heterogeneous clinical picture. In addition, it has overloaded national health services worldwide. Therefore, early identification of patients with poor prognosis is critical to improve the use of limited health resources. In this work, we evaluated whether baseline SARS-CoV2 RNA detection in blood (CoVemia) is associated with worse outcomes. We studied almost 200 patients admitted to our hospital and about 50-60% of them showed positive CoVemia. Patients with positive CoVemia were older and had more severe disease; CoVemia was also more frequent in patients requiring admission to the ICU. Moreover, we defined "relevant CoVemia", as the amount of viral load that better predicted mortality obtaining 95% sensitivity and 35% specificity. In addition, relevant CoVemia was a better predictor than other biomarkers such as LDH, lymphocyte count, interleukin-6 HGNC, and indexes used in ICU such as qSOFA and CURB65. In summary, detection of CoVemia is the best biomarker to predict death MESHD in COVID-19 MESHD patients. Furthermore, it is easy to be implemented and is reproducible with two techniques (Roche and Thermo Fisher Scientific) that are currently used for diagnosis in nasopharyngeal swabs samples.

    Early immune pathology and persistent dysregulation MESHD characterise severe COVID-19 MESHD

    Authors: Laura Bergamaschi; Federica Mescia; Lorinda Turner; Aimee Hanson; Prasanti Kotagiri; Benjamin J. Dunmore; Helene Ruffieux; Aloka DeSa; Oisin Huhn; Mark R. Wills; Stephen Baker; Rainer Doffinger; Gordon Dougan; Anne Elmer; Ian G Goodfellow; Ravindra K. Gupta; Myra Hosmillo; Kelvin Hunter; Nathalie Kingston; Paul J. Lehner; Nicholas J. Matheson; Jeremy K. Nicholson; Anna M. Petrunkina; Sylvia Richardson; Caroline Saunders; James E.D. Thaventhiran; Erik J.M. Toonen; Michael P. Weekes; - CambridgeInstituteofTherapeuticImmunologyandInfectiousDisease-NationalInstituteofHealthResearch(CITI; Mark Toshner; Christoph Hess; John R. Bradley; Paul A. Lyons; Kenneth G.C. Smith

    doi:10.1101/2021.01.11.20248765 Date: 2021-01-15 Source: medRxiv

    In a study of 207 SARS-CoV2-infected MESHD individuals with a range of severities followed over 12 weeks from symptom onset, we demonstrate that an early robust immune response, without systemic inflammation MESHD, is characteristic of asymptomatic or mild disease. Those presenting to hospital had delayed adaptive responses and systemic inflammation MESHD already evident at around symptom onset. Such early evidence of inflammation MESHD suggests immunopathology may be inevitable in some individuals, or that preventative intervention might be needed before symptom onset. Viral load does not correlate with the development of this pathological response, but does with its subsequent severity. Immune recovery is complex, with profound persistent cellular abnormalities correlating with a change in the nature of the inflammatory response, where signatures characteristic of increased oxidative phosphorylation and reactive-oxygen species-associated inflammation MESHD replace those driven by TNF HGNC and IL-6 HGNC. These late immunometabolic inflammatory changes and unresolved immune cell defects, if persistent, may contribute to "long COVID".

    Preliminary Efficacy of Tocilizumab Treatment in The Patients With COVID-19 MESHD.

    Authors: Yu Chen; Xijing Zhang

    doi:10.21203/rs.3.rs-147574/v1 Date: 2021-01-14 Source: ResearchSquare

    Background: Interleukin-6 HGNC ( IL-6 HGNC) was considered to be with the severity and mortality in COVID-19 MESHD patients, which implies a potential therapeutic target for treatment. We aimed to evaluate the safety and initial efficacy of Tocilizumab treatment for COVID-19 MESHD patients.Methods: In the retrospective study, sixty-one patients with COVID-19 MESHD with the mean age of 69 were enrolled from Feb 27 to Mar 14, 2020 in Wuhan Huoshenshan Hospital. Twenty-nine of them received one dose (400 mg) of add-on Tocilizumab treatment as the treated group and remaining 32 cases served as control group. The clinical manifestations and laboratory examinations were compared between the two groups.Results: The average duration of symptoms to admission was 28.2 days. Compared with the cases in control group, the treated cases exhibited a significant increase of serum IL-6 HGNC on the seventh day since Tocilizumab injection, however, there were no differences in whole blood white cell count, circulating lymphocyte count, serum C-reactive protein HGNC, and respiratory parameters or other clinical manifestations between the treated and control groups. There were no adverse events associated with Tocilizumab treatment in the treated COVID-19 MESHD patients.Conclusions: In the elder moderate and severe patients with COVID-19 MESHD, one dose of Tocilizumab treatment was safe but no clinical benefit was observed on the seventh day in this study.Trial registration: Chinese Clinical Trail Registry, ChiCTR2000033705. Registered June 10, 2020 - Retrospectively registered, http://www.chictr.org.cn/showprojen.aspx?proj=54989.

    Cerebrospinal fluid in COVID-19 MESHD neurological complications: no cytokine storm or neuroinflammation.

    Authors: Maria A. Garcia; Paula V. Barreras; Allie Lewis; Gabriel Pinilla; Lori J. Sokoll; Thomas Kickler; Heba Mostafa; Mario Caturegli; Abhay Moghekar; Kathryn C. Fitzgerald; - Hopkins Neuro-COVID-19 Group; Carlos A Pardo; Sriram Subramaniam; Alyson Ann Ann Kelvin; Mohamed G. Al Kuwari; Hamad Eid Al Romaihi; Mohamed H. Al-Thani; Roberto Bertollini; Abdullatif Al Khal; Laith J Abu-Raddad; Menno D. de Jong; Marije K Bomers

    doi:10.1101/2021.01.10.20249014 Date: 2021-01-12 Source: medRxiv

    BACKGROUND. Neurological complications MESHD occur in COVID-19 MESHD. We aimed to examine cerebrospinal fluid (CSF) of COVID-19 MESHD subjects with neurological complications MESHD and determine presence of neuroinflammatory changes implicated in pathogenesis. METHODS. Cross-sectional study of CSF neuroinflammatory profiles from 18 COVID-19 MESHD subjects with neurological complications categorized by diagnosis ( stroke MESHD, encephalopathy MESHD, headache MESHD) and illness severity (critical, severe, moderate, mild). COVID-19 MESHD CSF was compared with CSF from healthy, infectious and neuroinflammatory disorders MESHD and stroke MESHD controls (n=82). Cytokines ( IL-6 HGNC, TNF-alpha HGNC, IFN-gamma HGNC, IL-10 HGNC, IL-12p70, IL-17A HGNC), inflammation MESHD and coagulation markers (high-sensitivity- C Reactive Protein HGNC [hsCRP], ferritin, fibrinogen HGNC, D-dimer, Factor VIII) and neurofilament light chain ( NF-L HGNC), were quantified. SARS-CoV2 RNA and SARS-CoV2 IgG and IgA antibodies in CSF were tested with RT-PCR and ELISA. RESULTS. CSF from COVID-19 MESHD subjects showed a paucity of neuroinflammatory changes, absence of pleocytosis MESHD or specific increases in pro-inflammatory markers or cytokines ( IL-6 HGNC, ferritin, or D-dimer). Anti-SARS-CoV2 antibodies in CSF of COVID-19 MESHD subjects (77%) were observed despite no evidence of SARS-CoV2 viral RNA. A similar increase of pro-inflammatory cytokines ( IL-6 HGNC, TNF-alpha HGNC;, IL-12p70) and IL-10 HGNC in CSF of COVID-19 MESHD and non- COVID-19 MESHD stroke MESHD subjects was observed compared to controls. CSF-NF-L was elevated in subjects with stroke MESHD and critical COVID-19 MESHD. CSF-hsCRP was present almost exclusively in COVID-19 MESHD cases. CONCLUSION. The paucity of neuroinflammatory changes in CSF of COVID-19 MESHD subjects and lack of SARS-CoV2 RNA do not support the presumed neurovirulence of SARS-CoV2 or neuroinflammation MESHD in pathogenesis of neurological complications in COVID-19 MESHD. Elevated CSF-NF-L indicates neuroaxonal injury MESHD in COVID-19 MESHD cases. The role of CSF SARS-CoV2 IgG antibodies is still undetermined.

    Risk Factors Associated with Disease Severity and Clinical Outcomes for COVID-19 MESHD in Wuhan, China

    Authors: Yun Liu; Hao Wu; Bei Zhu; Yi Yang; Peng Cheng; Chaolin Huang; Wenjuan Wu; Weihong Zhao; Jinsong Zhang

    doi:10.21203/rs.3.rs-143695/v1 Date: 2021-01-08 Source: ResearchSquare

    Background: A new type of pneumonia MESHD caused by severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) appeared in Wuhan, China. However, the risk factors and characteristics related to the severity of the disease and its outcomes need to be further explored.Methods: In this retrospective study, we evaluated COVID-19 MESHD patients with severe disease and those who were critically ill, as diagnosed at Jinyintan Hospital (Wuhan, China). The demographic information, clinical characteristics, complications, and laboratory results for the patients were evaluated. Multivariate logistic regression methods were used to analyze risk factors related to hospital deaths.Results: The 235 COVID-19 MESHD patients included were divided into a severe group of 183 (78%) and a critical group of 52 (22%). Of these patients, 185 (79%) were discharged, and 50 (21%) died during hospitalization. In multivariate logistic analyses, age (OR=1.07, 95% CI 1.02-1.14, P=0.009), critical disease MESHD (OR=48.23, 95% CI 10.91-323.13, P<0.001), low lymphocyte counts (OR=15.48, 95% CI 1.98-176.49, P=0.015), elevated interleukin 6 HGNC ( IL-6 HGNC) (OR=9.11, 95% CI 1.69-67.75, P=0.017), and elevated aspartate aminotransferase ( AST HGNC) (OR=8.46, 95% CI 2.16-42.60, P=0.004) were independent risk factors for adverse outcomes.Conclusions: The results show that advanced age (> 64 years), critical illness, low lymphocyte levels, and elevated IL-6 HGNC and AST HGNC were factors for the risk of death for COVID-19 MESHD patients who had severe disease and those who were critically ill.

    Efficacy and Safety of Tocilizumab in Patients with COVID-19 MESHD: A Systematic Review and Meta-Analysis.

    Authors: Zhenlu Li; Qianqiu Che; Mao Li; Jianping Liu; Rao Du; Chao Yue; Ling Zhang; Hongwei Li; Liming Zhao; Weiming Hu; huimin Lu; Junjie Xiong

    doi:10.21203/rs.3.rs-143693/v1 Date: 2021-01-08 Source: ResearchSquare

    Background Tocilizumab (TCZ) is an anti- interleukin-6 HGNC antibody that has been used to treat patients with 2019 coronavirus disease MESHD ( COVID-19 MESHD). Numerous retrospective studies have shown beneficial treatment efficacy. Several recent randomized clinical trials have questioned the efficacy of TCZ in patients with COVID-19 MESHD. Therefore, we performed an updated systematic review and meta-analysis to explore the effectiveness and safety of tocilizumab recently used for treating patients with COVID-19 MESHD. Methods Randomized clinical trials (RCTs) and comparative studies that compared the outcomes between TCZ and standard of care (SOC) were analysed. PubMed, EMBASE, and the Cochrane Library (inception to November 20, 2020) were systematically searched. Primary outcomes included mortality and the rate of requirement for mechanical ventilation (MV). In addition, several subgroup analyses stratified by disease severity, publication type and TCZ administration were performed. Results Three RCTs, twenty-one cohort studies and nine case-control studies including 11,206 patients were finally included. The TCZ group included 2,794 patients (24.93%) and the SOC group included 8,412 patients (75.07%). The mortality rate (>14 days) of the TCZ group, 29.63% (590/1,991), was lower than the SOC group, 41.51% (2,380/5,734) (OR 0.64, 0.57 to 0.73; p <0.00001). However, no significant difference in-14-day mortality rates was observed between the two groups (13.53% vs 22.92%, p = 0.21). Meanwhile, the rate of MV was significantly decreased in the TCZ group compared with the SOC group (OR 0.42, 0.22 to 0.83; p = 0.01). According to the results of the subgroup analysis stratified by disease severity, TCZ only reduced the mortality rate for critical patients with COVID-19 MESHD compared with SOC (OR 0.60, 0.52 to 0.71; P < 0.00001), particularly for patients in the intensive care unit (ICU) or patients requiring MV. No statistically significant increase was recognized in the rates of secondary infections or thrombosis MESHD between the two groups. Conclusions This systematic review and meta-analysis found that the addition of tocilizumab to the SOC might reduce mortality after 14 days in patients with COVID-19 MESHD, particularly critical patients requiring MV. More extensive RCTs with longer follow-up periods are needed to validate these findings.

    Immunological and Inflammatory Indicators of COVID-19 MESHD Patients With Returned-positive Nucleic Acid Tests During Hospitalization: a Retrospective Cohort Study

    Authors: Yin Wang; Xiaobei Chen; Yi Zhang; Hongyan Chen; Quan Zhou; Dong Li; Zhili Niu; Huidan Yu; Xiaojun Wang; Haijun Zhang; Tingting Liu; Bicheng Zhang; Hui Yu; Xiaochuan Wang; Yuan Jiang; Yalan Dou; Xiaotian Chen; Xiaoyang Zhou; Weili Yan

    doi:10.21203/rs.3.rs-142839/v1 Date: 2021-01-07 Source: ResearchSquare

    Background: COVID-19 MESHD cases with suspected returned-positive SRAS-CoV-2 tests following consecutive negative tests have been reported, but evidence-based explanations for this phenomenon is still lacking. We aimed to describe the clinical and laboratory characteristics of returned-positive COVID-19 MESHD patients during treatment in comparison with other patients.Methods: From January 20 to April 10, 2020, all COVID-19 MESHD inpatient with at least three RT-PCR SARS-CoV-2 tests in Renmin Hospital in Wuhan, China were enrolled. Patients with 2 consecutively negative RT-PCR results followed by a positive result were classified as returned-positive patients, and their characteristics and repeatedly measured laboratory results were compared with the rest of the patients. Linear mixed effects models were performed.Results: A total of 789 COVID-19 MESHD patients were included and 22.8% patients returned positive in RT-PCR SARS-CoV-2 test. No significant differences were found for general characteristics between the returned-positive and the control groups. The trends of inflammatory and immune factors including the third component of complement (C3), C-reactive protein HGNC, procalcitonin (PCT), IL-4 HGNC, IL-6 HGNC, the counts of lymphocyte, CD3+, CD8+, white blood cell and immunoglobulin levels during hospitalization were significantly different between the two groups. During the returned-positive period, C3, PCT, serum IgM, anti-SARS-CoV-2 IgM and anti-SARS-CoV-2 IgG were significantly higher in the returned-positive patients at certain time points.Conclusions: Returned-positive COVID-19 MESHD patients appeared to be more sever at admission, and had periodically higher levels in C3, PCT, serum IgM and two specific antibodies during hospitalization. This suggests that positive return of SARS-COV-2 could not be completely explained by false-negative testing and longer observation of these patients is warranted. 

    COVID-19 MESHD virtual patient cohort reveals immune mechanisms driving disease outcomes

    Authors: Adrianne L. Jenner; Rosemary A. Aogo; Sofia Alfonso; Vivienne Crowe; Amanda P. Smith; Penelope A. Morel; Courtney L. Davis; Amber M. Smith; Morgan Craig; Josep Redon Sr.; Jaime Signes Sr.; David Navarro Sr.; Adrian B McDermott; Ajay K Sethi; Miriam A Shelef; Ann Moormann; Mireya Wessolossky; Vanni Bucci; Ana Maldonado-Contreras; Michael Chiorazzi; Edwin Ruiz Fuentes; - Yale IMPACT Team; Nathan D Grubaugh; Shelli Farhadian; Charles Dela Cruz; Albert Ko; Wade L Schulz; Aaron M Ring; Shuangge Ma; Saad Omer; Anne L Wyllie; Akiko Iwasaki; Andrew J. Page; Robert A. Kingsley; Gibson Mhlanga

    doi:10.1101/2021.01.05.425420 Date: 2021-01-06 Source: bioRxiv

    To understand the diversity of immune responses to SARS-CoV-2 and distinguish features that predispose individuals to severe COVID-19 MESHD, we developed a mechanistic, within-host mathematical model and virtual patient cohort. Our results indicate that virtual patients with low production rates of infected cell derived IFN HGNC subsequently experienced highly inflammatory disease phenotypes, compared to those with early and robust IFN HGNC responses. In these in silico patients, the maximum concentration of IL-6 HGNC was also a major predictor of CD8+ T cell depletion. Our analyses predicted that individuals with severe COVID-19 MESHD also have accelerated monocyte-to-macrophage differentiation that was mediated by increased IL-6 HGNC and reduced type I IFN signalling. Together, these findings identify biomarkers driving the development of severe COVID-19 MESHD and support early interventions aimed at reducing inflammation MESHD.

    Saliva viral load is a dynamic unifying correlate of COVID-19 MESHD severity and mortality

    Authors: Julio Silva; Carolina Lucas; Maria Sundaram; Benjamin Israelow; Patrick Wong; Jon Klein; Maria Tokuyama; Peiwen Lu; Arvind Venkataraman; Feimei Liu; Tianyang Mao; Ji Eun Oh; Annsea Park; arnau Casanovas-Massana; Chantal B.F. Vogels; Catherine M. Muenker; Joseph Zell; John B. Fournier; Melissa Campbell; Michael Chiorazzi; Edwin Ruiz Fuentes; - Yale IMPACT Team; Nathan D Grubaugh; Shelli Farhadian; Charles Dela Cruz; Albert Ko; Wade L Schulz; Aaron M Ring; Shuangge Ma; Saad Omer; Anne L Wyllie; Akiko Iwasaki; Andrew J. Page; Robert A. Kingsley; Gibson Mhlanga

    doi:10.1101/2021.01.04.21249236 Date: 2021-01-06 Source: medRxiv

    While several clinical and immunological parameters correlate with disease severity and mortality in SARS-CoV-2 infection MESHD, work remains in identifying unifying correlates of coronavirus disease 2019 MESHD ( COVID-19 MESHD) that can be used to guide clinical practice. Here, we examine saliva and nasopharyngeal (NP) viral load over time and correlate them with patient demographics, and cellular and immune profiling. We found that saliva viral load was significantly higher in those with COVID-19 MESHD risk factors; that it correlated with increasing levels of disease severity and showed a superior ability over nasopharyngeal viral load as a predictor of mortality over time (AUC=0.90). A comprehensive analysis of immune factors and cell subsets revealed strong predictors of high and low saliva viral load, which were associated with increased disease severity or better overall outcomes, respectively. Saliva viral load was positively associated with many known COVID-19 MESHD inflammatory markers such as IL-6 HGNC, IL-18 HGNC, IL-10 HGNC, and CXCL10 HGNC, as well as type 1 immune response cytokines. Higher saliva viral loads strongly correlated with the progressive depletion of platelets, lymphocytes, and effector T cell subsets including circulating follicular CD4 T cells (cTfh). Anti-spike (S) and anti-receptor binding domain (RBD) IgG levels were negatively correlated with saliva viral load showing a strong temporal association that could help distinguish severity and mortality in COVID-19 MESHD. Finally, patients with fatal COVID-19 MESHD exhibited higher viral loads, which correlated with the depletion of cTfh cells, and lower production of anti-RBD and anti-S IgG levels. Together these results demonstrated that viral load, as measured by saliva but not nasopharyngeal, is a dynamic unifying correlate of disease presentation, severity, and mortality over time.

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HGNC Genes
SARS-CoV-2 Proteins


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