Corpus overview


MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

There are no SARS-CoV-2 protein terms in the subcorpus


SARS-CoV-2 Proteins
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    IL-6 HGNC and D-Dimer at Admission Predicts Cardiac Injury MESHD and Early Mortality during SARS-CoV-2 Infection MESHD

    Authors: Daoyuan Si; Beibei Du; Bo Yang; Lina Jin; Lujia Ni; Qian Zhang; Zhongfan Zhang; Mohammed Ali Azam; Patrick F.H Lai; Stephane Masse; Huan Sun; Xingtong Wang; Slava Epelman; Patrick R Lawler; Ping Yang; Kumaraswamy Nanthakumar

    doi:10.1101/2021.03.22.21254077 Date: 2021-03-29 Source: medRxiv

    BACKGROUND: We recently described mortality of cardiac injury MESHD in COVID-19 MESHD patients. Admission activation of immune, thrombotic MESHD biomarkers and their ability to predict cardiac injury MESHD and mortality patterns in COVID-19 MESHD is unknown. METHODS: This retrospective cohort study included 170 COVID-19 MESHD patients with cardiac injury MESHD at admission to Tongji Hospital in Wuhan from January 29-March 8, 2020. Temporal evolution of inflammatory cytokines, coagulation markers, clinical, treatment and mortality were analyzed. RESULTS: Of 170 patients, 60 (35.3%) died early (<21d) and 61 (35.9%) died after prolonged stay. Admission lab work that correlated with early death MESHD were elevate levels of interleukin 6 HGNC ( IL-6 HGNC) (p<0.0001), Tumor Necrosis Factor-a HGNC Tumor Necrosis Factor-a MESHD ( TNF-a HGNC) (p=0.0025), and C-reactive protein HGNC ( CRP HGNC) (p<0.0001). We observed the trajectory of biomarker changes after admission, and determined that early mortality had a rapidly increasing D-dimer, gradually decreasing platelet and lymphocyte counts. Multivariate and simple linear regression models showed that death risk was determined by immune and thrombotic MESHD pathway activation. Increasing cTnI HGNC levels were associated with those of increasing IL-6 HGNC (p=0.03) and D-dimer (p=0.0021). Exploratory analyses suggested that patients that received heparin has lower early mortality compared to those who did not (p =0.07), despite similar risk profile. CONCLUSIONS: In COVID-19 MESHD patients with cardiac injury MESHD, admission IL-6 HGNC and D-dimer predicted subsequent elevation of cTnI HGNC and early death MESHD, highlighting the need for early inflammatory cytokine-based risk stratification in patients with cardiac injury MESHD.

    Targeting of the NLRP3 HGNC Inflammasome for early COVID-19 MESHD

    Authors: Carlo Marchetti; Kara Mould; Isak W. Tengesdal; William J. Janssen; Charles A. Dinarello

    doi:10.1101/2021.02.24.432734 Date: 2021-02-24 Source: bioRxiv

    Following entry and replication of Severe Acute Respiratory Syndrome-coronavirus MESHD 2 (SARS-CoV-2) into ACE2 expressing cells, the infected cells undergo lysis releasing more virus but also cell contents. In the lung, constitutive cytokines such as IL-1 HGNC are released together with other cell contents. A cascade of inflammatory cytokines ensues, including chemokines and IL-1{beta}, triggering both local as well as systemic inflammation MESHD. This cascade of inflammatory cytokines in patients with COVID-19 MESHD is termed Cytokine Release Syndrome ( CRS MESHD), and is associated with poor outcomes and death MESHD. Many studies reveal that blocking IL-1{beta HGNC} activities in COVID-19 MESHD patients reduces disease severity and deaths MESHD. Here we report highly significant circulating levels of IL-1{beta HGNC}, IL-1 Receptor antagonist HGNC, IL-6 HGNC, TNF HGNC, IL-10 HGNC and soluble urokinase plasminogen activator receptor HGNC in COVID-19 MESHD patients with mild or no symptoms. We also report that in circulating myeloid cells from the same patients, there is increased expression of the NOD-, LRR- and pyrin domain-containing 3 ( NLRP3 HGNC) early in the infection. We observed increased NLRP3 HGNC gene expression in myeloid cells correlated with IL-1{beta HGNC} gene expression and also with elevated circulating IL-1{beta HGNC} levels. We conclude that early in SARS-CoV-2 infection MESHD, NLRP3 HGNC activation takes place and initiates the CRS. Thus, NLRP3 HGNC is a target to reduce the organ damage of inflammatory cytokines of the CRS.

    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

    Efficacy of Doxycycline in treating COVID-19 MESHD Positive Patients: A Case Series

    Authors: Zohreh Akhoundi Meybody; Mohammad Bagher Owlia; Sina Owlia; Seyed Rohollah Mousavinasab

    doi:10.21203/ Date: 2021-01-06 Source: ResearchSquare

    Background: Given the high morbidity and mortality caused by Coronavirus Disease 2019 MESHD ( COVID-19 MESHD), scientific research is necessary to achieve a proper treatment regimen. Since doxycycline is effective in reducing inflammatory factors, including IL-6 HGNC and TNF-alpha HGNC that play an important role in initiating cytokine storms and probably causing death MESHD in patients with COVID-19 MESHD, its use is associated with low side effects and can be used orally, the present study was attempted to evaluate the efficacy of doxycycline in the treatment of inpatients and outpatients with COVID-19 MESHD.Methods: This descriptive and prospective study was performed on inpatients and outpatients were diagnosed with COVID-19 MESHD based on polymerase chain reaction (PCR) test from nasopharyngeal secretions or computerized tomography scan (CT Scan). Patients who met the inclusion criteria received doxycycline at a dose of 100 mg every 12 hours for 7 days and then were evaluated on the baseline day and on days 3, 7, and 14 after admission for cough, Shortness of breath MESHD, temperature and oxygen saturation.Results:  Out of 21 patients, 11 patients were male and 10 patients were female. Cough, SOB, temperature, and O2 sat improved in both of outpatients and inpatients compared to baseline. In general, the results showed that doxycycline was more effective in improving cough, SOB, temperature, and O2 sat in outpatients than inpatients. Conclusion:  It can be concluded that doxycycline with the dose and duration prescribed in our study could play an effective role in the treatment of patients with COVID-19 MESHD

    COVID-19 MESHD cytokines and the hyperactive immune response: Synergism of TNF-α HGNC and IFN-γ HGNC in triggering inflammation, tissue damage, and death

    Authors: Evan Peter Williams; Lillian Zalduondo; Colleen Beth Jonsson; Alex R Schuurman; Jan Verhoeff; Saskia D van Asten; Hetty J Bontkes; Siebe G Blok; Janwillem Duitman; Harm Jan Bogaard; Leo Heunks; Rene Lutter; Tom van der Poll; Juan J Garcia Vallejo; Qiqi Cao; Fangjin Chen; Yuqing Chen; Xuelian Cheng; Guohong Deng; Wenyu Ding; Yingmei Feng; Rui Gan; Chuang Guo; Shuai He; Chen Jiang; Juanran Liang; Yi-Min Li; Jun Lin; Yun Ling; Haofei Liu; Jianwei Liu; Nianping Liu; Yang Liu; Meng Luo; Qiang Ma; Qibing Song; Wujianan Sun; Gaoxiang Wang; Feng Wang; Ying Wang; Xiaofeng Wen; Qian Wu; Xiaowei Xie; Xinxin Xiong; Xudong Xing; Hao Xu; Chonghai Yin; Dongdong Yu; Kezhuo Yu; Biao Zhang; Tong Zhang; Jincun Zhao; Peidong Zhao; Jianfeng Zhou; Wei Zhou; Sujuan Zhong; Xiaosong Zhong; Shuye Zhang; Lin Zhu; Ping Zhu; Bing Zou; Jiahua Zou; Zengtao Zuo; Fan Bai; Xi Huang; Xiuwu Bian; Penghui Zhou; Qinghua Jiang; Zhiwei Huang; Jin-Xin Bei; Lai Wei; Xindong Liu; Tao Cheng; Xiangpan Li; Fu-Sheng Wang; Hongyang Wang; Bing Su; Kun Qu; Xiaoqun Wang; JieKai Chen; Ronghua Jin; Zemin Zhang

    doi:10.1101/2020.10.29.361048 Date: 2020-10-29 Source: bioRxiv

    The COVID-19 MESHD COVID-19 MESHD pandemic has caused significant morbidity and mortality. Currently, there is a critical shortage of proven treatment options and an urgent need to understand the pathogenesis of multi-organ failure MESHD and lung damage MESHD. Cytokine storm is associated with severe inflammation MESHD and organ damage during COVID-19 MESHD. However, a detailed molecular pathway defining this cytokine storm is lacking, and gaining mechanistic understanding of how SARS-CoV-2 elicits a hyperactive inflammatory response is critical to develop effective therapeutics. Of the multiple inflammatory cytokines produced by innate immune cells during SARS-CoV-2 infection MESHD, we found that the combined production of TNF- and IFN-{gamma} specifically induced inflammatory cell death MESHD, PANoptosis, characterized by gasdermin-mediated pyroptosis, caspase-8 HGNC-mediated apoptosis, and MLKL HGNC-mediated necroptosis. Deletion of pyroptosis, apoptosis, or necroptosis mediators individually was not sufficient to protect against cell death. However, cells deficient in both RIPK3 HGNC and caspase-8 HGNC or RIPK3 HGNC and FADD HGNC were resistant to this cell death. Mechanistically, the STAT1 HGNC/ IRF1 HGNC axis activated by TNF- and IFN-{gamma} co-treatment induced iNOS for the production of nitric oxide. Pharmacological and genetic deletion of this pathway inhibited pyroptosis, apoptosis, and necroptosis in macrophages. Moreover, inhibition of PANoptosis protected mice from TNF- and IFN-{gamma}-induced lethal cytokine shock MESHD that mirrors the pathological symptoms of COVID-19 MESHD. In vivo neutralization of both TNF- and IFN-{gamma} in multiple disease models associated with cytokine storm showed that this treatment provided substantial protection against not only SARS-CoV-2 infection MESHD, but also sepsis MESHD, hemophagocytic lymphohistiocytosis MESHD, and cytokine shock models, demonstrating the broad physiological relevance of this mechanism. Collectively, our findings reveal that blocking the COVID-19 MESHD cytokine-mediated inflammatory cell death MESHD signaling pathway identified in this study may benefit patients with COVID-19 MESHD or other cytokine storm-driven syndromes by limiting inflammation MESHD and tissue damage. The findings also provide a molecular and mechanistic description for the term cytokine storm. Additionally, these results open new avenues for the treatment of other infectious and autoinflammatory diseases MESHD and cancers MESHD where TNF- and IFN-{gamma} synergism play key pathological roles.

    Clinical Characteristics and Risk Factors of Disseminated Intravascular Coagulation in Patients with COVID-19 MESHD

    Authors: Meng Jin; Xinying Yue; Shanshan Zhang; Yanan Wang; Zequn Lu; Zhi Yao; Jing Wang; Jun Xiao; Qinglin Li; Cai Liu; Hongyuan Cui; Ke Hu; Xiaofan Wu; Jianbo Tian; Yi Xiao

    doi:10.21203/ Date: 2020-09-07 Source: ResearchSquare

    Background: Coronavirus disease 2019 MESHD ( COVID-19 MESHD) has spread globally. However, the association between COVID-19 MESHD and disseminated intravascular coagulation MESHD (DIC) has been scarcely addressed. We aimed to systematically characterize the clinical features and examine risk factors for DIC development in COVID-19 MESHD patients.Methods: In this single-centered, retrospective, and observational study, all patients with DIC (N=59) and 270 patients without DIC were matched by propensity score matching based on age, sex, and comorbidities. Demographic data, symptoms, radiological, laboratory examinations, and clinical outcomes were compared between patients with and without DIC. Furthermore, univariable and multivariable logistic regression were used to explore the risk factors associated with DIC development in COVID-19 MESHD patients.Results: Higher proportion of patients with DIC and COVID-19 MESHD (54 of 59 [91·53%]) developed into death MESHD than non DIC patients (58 of 270 [21·48%]). Patients with DIC presented aggravated inflammation MESHD responses, liver damage MESHD, and especially coagulation dysfunction MESHD. Moreover, in addition to previously reported coagulation-related markers, such as FDP, D-dimer, and platelet, we also identified several novel risk factors associated with DIC development, including decreased fibrinogen (OR=0·476, 95%CI=0·380-0·596, P<0·0001) and ALB (0·901, 0·845- 0·961, P=0·0015), and elevated IL-6 HGNC (1·010, 1·005-1·015, P=0·00017) and TNF-α HGNC (1·053, 1·016-1·091, P=0·0045).Conclusions: Patients with DIC and COVID-19 MESHD were predisposed to poor clinical outcomes. These risk factors identified may be helpful for early surveillance of disease progression and making standardized treatment strategies.

    Lymphocyte May Be a Reference Index of the Outcome of Cancer Patients in COVID-19 MESHD Infection

    Authors: Xun Yuan; Yuan Gao; Qian Chu

    doi:10.21203/ Date: 2020-08-12 Source: ResearchSquare

    Background: The novel coronavirus ( COVID-19 MESHD)– infected pneumonia MESHD is an international concern as it spreads through human populations and across national and international borders.Methods: In this retrospective study, we consecutively included all cancer MESHD cases who had been identified as having a nucleic acid-confirmed COVID-19 MESHD infection from two designated hospitals in Wuhan, China. Non-cancer MESHD patients were also enrolled for comparison. The clinical data were gathered from the medical recordsfrom Jan 14 to March 12.Results: Among the 117 cancer MESHD patients infected with COVID19 MESHD, the median age was 63 years and 48.7% were male. Male, hematologic cancer MESHD, dyspnea MESHD on admission, and anti- cancer MESHD therapy significantly increased the risk of death MESHD. The amounts of cytokines and immune cells were correlated with the outcomeofcancer patients infected with COVIP-19. However, high level of TNF-a HGNC, IL-2R HGNC, IL-6 HGNC, IL-8 HGNC did not increase the risk of death in non-cancer MESHD patients. Moreover, IL-2R HGNC and IL-6 HGNC markedly decreased in cancer MESHD patients recovered from COVID-19 MESHD.Conclusions: Cancer MESHD patients with COVID-19 MESHD were associated with high mortality (23.9%).The amounts of cytokines and lymphocytes could be utilized as the reference index in predicting the survival outcome of cancer MESHD patients with COVID-19 MESHD.

    Risk factors related to acute respiratory distress syndrome MESHD and death MESHD in patients with COVID-19 MESHD: a retrospective cohort study in Wuhan, China

    Authors: Jing Wang; Lu Wang; Meng Jin; Zequn Lu; Yao Li; Xu Zhang; Zhi Yao; Tianyi Dong; Yanan Wang; Siyuan Niu; Qinglin Li; Cai Liu; Jirong Qi; Jianbo Tian; Ying Wang; Zhihua Wang

    doi:10.21203/ Date: 2020-06-29 Source: ResearchSquare

    Background:The COVID-19 pandemic MESHD has been considered a great threat to global public health. We aimed to clarify the risk factors associated with the development of acute respiratory distress syndrome MESHD ( ARDS MESHD) and progression from ARDS MESHD to death MESHD and construct a risk prediction model.Methods:In this single-centered, retrospective, and observational study, 796 COVID-19 MESHD patients developed ARDS MESHD and 735 COVID-19 MESHD patients without ARDS MESHD were matched by propensity score at an approximate ratio of 1:1 based on age, sex and comorbidities. Demographic data, symptoms, radiological findings, laboratory examinations, and clinical outcomes were compared between those with or without ARDS MESHD. Univariable and multivariable logistic regression models were applied to explore the risk factors for development of ARDS MESHD and progression from ARDS MESHD to death MESHD and establish a comprehensive risk model. Results:Higher SOFA, qSOFA, APACHE II and SIRS scores, elevated inflammatory cytokines, dysregulated multi-organ damage biomarkers, decreased immune cell subsets were associated with higher proportion of death MESHD (34.17% vs 1.22%; P<0.001) and increased risk odds of death MESHD (OR=57.216, 95%CI=28.373-115.378; P<0.001) in COVID-19 MESHD patients with ARDS MESHD. In addition to previous reported risk factors related to ARDS MESHD development and death MESHD, such as neutrophils, IL-6 HGNC, D-Dimer, leukocytes and platelet, we identified elevated  TNF-α HGNC (OR=1.146, 95%CI=1.100-1.194; P<0.001), CK-MB (OR=1.350, 95%CI=1.180-1.545; P<0.001), declined ALB HGNC (OR=0.834, 95%CI=0.799-0.872; P<0.001), CD8 HGNC+ T cells (OR=0.983, 95%CI=0.976-0.990; P<0.001) and CD3-CD19+ B cells (OR=0.992, 95%CI=0.988-0.997; P=0.003) as novel risk factors. Most importantly, the predictive accuracy of the combined model integrating four score systems and these risk factors demonstrated highest among all models for the development of ARDS MESHD (AUC= 0.904) and the progression from ARDS MESHD to death (AUC= 0.959).Conclusion: COVID-19 MESHD patients with ARDS MESHD were more likely to develop into death MESHD. The potential risk factors and the comprehensive prediction model could be helpful to identify patients that are at risk of developing ARDS MESHD with poor prognosis at an early stage, which might help physicians to formulate a timely therapeutic strategy.

    Transcriptional response of signalling pathways to SARS-CoV-2 infection MESHD in normal human bronchial epithelial cells

    Authors: Enes Ak; Pinar Pir

    doi:10.1101/2020.06.20.163006 Date: 2020-06-20 Source: bioRxiv

    SARS-CoV-2 virus, the pathogen that causes Covid-19 MESHD disease, emerged in Wuhan region in China in 2019, infected more than 4M people and is responsible for death MESHD of at least 300K patients globally as of May 2020. Identification of the cellular response mechanisms to viral infection MESHD by SARS-CoV-2 may shed light on progress of the disease, indicate potential drug targets, and make design of new test methods possible. In this study, we analysed transcriptomic response of normal human bronchial epithelial cells (NHBE) to SARS-CoV-2 infection MESHD and compared the response to H1N1 infection. Comparison of transcriptome of NHBE cells 24 hours after mock-infection and SARS-CoV-2 infection MESHD demonstrated that most genes that respond to infection were upregulated (320 genes) rather than being downregulated (115 genes).While upregulated genes were enriched in signalling pathways related to virus response, downregulated genes are related to kidney development. We mapped the upregulated genes on KEGG pathways to identify the mechanisms that mediate the response. We identified canonical NF{kappa}B HGNC, TNF HGNC and IL-17 HGNC pathways to be significantly upregulated and to converge to NF{kappa}B HGNC pathway via positive feedback loops. Although virus entry protein ACE2 HGNC has low expression in NHBE cells, pathogen response pathways are strongly activated within 24 hours of infection. Our results also indicate that immune response system is activated at the early stage of the infection and orchestrated by a crosstalk of signalling pathways. Finally, we compared transcriptomic SARS-CoV-2 response to H1N1 response in NHBE cells to elucidate the virus specificity of the response and virus specific extracellular proteins expressed by NHBE cells.

    An inflammatory cytokine signature helps predict COVID-19 MESHD severity and death

    Authors: Diane Marie Del Valle; Seunghee Kim-schulze; Huang Hsin-hui; Noam D Beckmann; Sharon Nirenberg; Bo Wang; Yonit Lavin; Talia Swartz; Deepu Madduri; Aryeh Stock; Thomas Marron; Hui Xie; Manish Kumar Patel; Oliver van Oekelen; Adeeb Rahman; Patricia Kovatch; Judith Aberg; Eric Schadt; Sundar Jagannath; Madhu Mazumdar; Alexander Charney; Adolfo Firpo-Betancourt; Damodara Rao Mendu; Jeffrey Jhang; David Reich; Keith Sigel; Carlos Cordon-Cardo; Marc Feldmann; Samir Parekh; Miriam Merad; Sacha Gnjatic

    doi:10.1101/2020.05.28.20115758 Date: 2020-05-30 Source: medRxiv

    The COVID-19 MESHD COVID-19 MESHD pandemic caused by infection with Severe Acute Respiratory Syndrome Coronavirus 2 MESHD (SARS-CoV-2) has led to more than 100,000 deaths in the United States. Several studies have revealed that the hyper-inflammatory response induced by SARS-CoV-2 is a major cause of disease severity and death in infected MESHD patients. However, predictive biomarkers of pathogenic inflammation MESHD to help guide targetable immune pathways are critically lacking. We implemented a rapid multiplex cytokine assay to measure serum IL-6 HGNC, IL-8 HGNC, TNF HGNC-, and IL-1{beta HGNC} in hospitalized COVID-19 MESHD patients upon admission to the Mount Sinai Health System in New York. Patients (n=1484) were followed up to 41 days (median 8 days) and clinical information, laboratory test results and patient outcomes were collected. In 244 patients, cytokine measurements were repeated over time, and effect of drugs could be assessed. Kaplan-Meier methods were used to compare survival by cytokine strata, followed by Cox regression models to evaluate the independent predictive value of baseline cytokines. We found that high serum IL-6 HGNC, IL-8 HGNC, and TNF HGNC- levels at the time of hospitalization were strong and independent predictors of patient survival. Importantly, when adjusting for disease severity score, common laboratory inflammation markers, hypoxia MESHD and other vitals, demographics, and a range of comorbidities, IL-6 HGNC and TNF HGNC- serum levels remained independent and significant predictors of disease severity and death MESHD. We propose that serum IL-6 HGNC and TNF HGNC- levels should be considered in the management and treatment of COVID-19 MESHD patients to stratify prospective clinical trials, guide resource allocation and inform therapeutic options. We also propose that patients with high IL-6 HGNC and TNF HGNC- levels should be assessed for combinatorial blockade of pathogenic inflammation MESHD in this disease.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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