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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (14)

NSP5 (4)

ProteinS1 (3)

ProteinN (2)

NSP2 (1)


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    Management of rheumatic diseases in the times of COVID-19 pandemic MESHD COVID-19 pandemic MESHD- perspectives of rheumatology practitioners from India

    Authors: Latika Gupta; Durga Misra; Vishwesh Agarwal; Suma Balan; Vikas Agarwal

    doi:10.1101/2020.04.03.20048389 Date: 2020-04-07 Source: medRxiv

    Background. The Coronavirus disease MESHD 19 ( COVID-19 MESHD) pandemic has led to widespread concerns about the risk of infection in patients with rheumatic diseases MESHD ( RD MESHD) receiving disease modifying ant-rheumatic drugs (DMARDs) and other immunosuppressants (IS). Methods. A SurveyMonkey based electronic survey was conducted amongst members of the Indian Rheumatology Association to understand the need for changes in prevailing practices. Results. Of the 861 invitees, 221 responded. In the wake of the pandemic, 47.5% would reduce biological DMARDs (bDMARDs) while only 12.2% would reduce the use of conventional synthetic DMARDs. 64.2% were likely to defer change in IS, the reluctance being most with rituximab (58.3%) followed by cyclophosphamide (53.3%), anti- tumor MESHD tumor HGNC necrosis MESHD factor alpha agents (52.4%) and Janus kinase inhibitors (34.39%). Hydroxychloroquine was the preferred choice (81.9%) for the treatment of COVID-19 MESHD followed by protease inhibitors (22.1%) and intravenous immunoglobulin (8.1%). Chloroquine was less preferred (19%). More than two-thirds (70.5%) believed that COVID-19 MESHD might trigger macrophage activation syndrome MESHD. Social distancing (98.1%) and hand hygiene (74.6%) were recommended by majority. 62.8% would avoid touch for clinical examination whenever feasible. Conclusion. Most rheumatologists perceived the need to change treatment of RDs during the COVID-19 pandemic MESHD; reduce immunosuppression and defer the usage of rituximab and bDMARDs.

    In silico synergistic drug repurposing for combating novel coronavirus ( COVID-19 MESHD) outbreaks

    Authors: Minjee Kim; Young Bong Kim

    doi:10.21203/rs.3.rs-21849/v1 Date: 2020-04-07 Source: ResearchSquare

    As the number of novel coronavirus ( COVID-19 MESHD) cases continues to rise, there is a global need for rapid drug development. In this study, we propose a systems pharmacology approach to reposition FDA-approved drug candidates for coronavirus, identify targets and suggest a synergistic drug combination using network pharmacology. We collected 67 genes associated with coronavirus, performed an enrichment analysis to obtain coronavirus-associated disease- pathway and constructed protein-protein interaction (PPI) network based on 67 genes. Total 37 significant disease-pathways were retrieved, and associated FDA-approved drugs were listed for drug repurposing candidates. Our PPI network showed 51 targets from 67 genes and identified IL6 HGNC and TNF HGNC as potential targets for coronavirus. From the FDA drug list, we selected four drugs that are experimentally used or studied for coronavirus to construct two- drug combinations. From six drug-drug networks, we identified hydroxychloroquine + ribavirin combination had the highest number of overlapping targets ( IL6 HGNC, IL2 HGNC, IL10 HGNC, CASP3 HGNC, IFNA1 HGNC) from PPI network target list, suggesting a potent synergistic drug combination for coronavirus. With the aim to support the rapid drug development, we suggest a new approach using systems-level drug repurposing for COVID-19 MESHD treatment.

    Atazanavir inhibits SARS-CoV-2 replication and pro-inflammatory cytokine production

    Authors: Natalia Fintelman-Rodrigues; Carolina Q Sacramento; Carlyle Ribeiro Lima; Franklin Souza da Silva; Andre Ferreira; Mayara Mattos; Caroline S. de Freitas; Vinicius Cardoso Soares; Suelen da Silva Gomes Dias; Jairo R. Temerozo; Milene Miranda; Aline R. Matos; Fernando A Bozza; Nicolas Carels; Carlos Roberto Alves; Marilda M Siqueira; Patricia T. Bozza; Thiago Moreno L. Souza

    doi:10.1101/2020.04.04.020925 Date: 2020-04-05 Source: bioRxiv

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is already responsible for far more deaths than previous pathogenic coronaviruses (CoVs) from 2002 and 2012. The identification of clinically approved drugs to be repurposed to combat 2019 CoV disease MESHD ( COVID-19 MESHD) would allow the rapid implementation of potentially life-saving procedures. The major protease ( Mpro) of SARS-CoV-2 PROTEIN is considered a promising target, based on previous results from related CoVs with lopinavir (LPV), an HIV protease inhibitor. However, limited evidence exists for other clinically approved antiretroviral protease inhibitors, such as atazanavir (ATV). ATV is of high interest because of its bioavailability within the respiratory tract. Our results show that ATV could dock in the active site of SARS-CoV-2 Mpro PROTEIN, with greater strength than LPV. ATV blocked Mpro PROTEIN activity. We confirmed that ATV inhibits SARS-CoV-2 replication, alone or in combination with ritonavir (RTV) in Vero cells, human pulmonary epithelial cell line and primary monocytes, impairing virus-induced enhancement of IL-6 HGNC and TNF HGNC- levels. Together, our data strongly suggest that ATV and ATV/RTV should be considered among the candidate repurposed drugs undergoing clinical trials in the fight against COVID-19 MESHD.

    Analysis of factors affected the SARS-CoV-2 viral shedding time of COVID-19 MESHD patients in Anhui, China: a retrospective study

    Authors: You-Hui Tu; Yuan-Yuan Wei; Da-Wei Zhang; Chang-Shan Chen; Xian-Wei Hu; GuangHe Fei

    doi:10.21203/rs.3.rs-20954/v1 Date: 2020-04-02 Source: ResearchSquare

    Background The epidemic of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has spread worldwide, but the factors that may affect the SARS-CoV-2 viral shedding time in coronavirus disease 2019 MESHD ( COVID-19 MESHD) patients were rarely reported. Methods We retrospectively recruited 40 confirmed common COVID-19 MESHD patients and classified them into two groups according to the SARS-CoV-2 viral shedding time (group A (less than 10 days) and group B (10 days or more)). The demographic, laboratory parameters and chest computed tomography (CT) features on admission and the 3 rd day after treatment were analyzed respectively. Results Fourteen patients were in group A and 26 patients in group B, the median SARS-CoV-2 viral shedding time of the two groups was 7 and 16 days respectively. Compared to the group A, the comorbidity, epidemiological risk history, serum glucose and CD4/8 on admission were significantly higher in the group B (P<0.05). On the 3 rd day after treatment, the group B got significantly higher IL-6 HGNC, IL-2R HGNC, TNF-α HGNC and CD4/8, and lower platelet and CD8 HGNC + T lymphocyte counts than group A (P<0.05). Logistic regression analyses revealed that the higher epidemiological risk history, serum glucose and CD4/8 on admission were significantly associated with a longer SARS-CoV-2 viral shedding time (OR=7.5, 11.41, 9.21 respectively, P<0.05), as well as the higher TNF-α HGNC and lower CD8 HGNC + T lymphocytes on the 3 rd day after treatment (OR=2.36, 0.98 respectively, P<0.05). Conclusions Our study provides the evidence that the prolonged SARS-CoV-2 viral shedding time might be correlated with the patients’ epidemiological risk history, as well as the serum glucose and CD4/8 on admission, TNF-α HGNC and CD8 HGNC + T lymphocytes on the 3 rd day after treatment. Our result may help clinicians to distinguish the patients with a prolonged viral shedding time at the early stage.

    COVID-19 MESHD: A Drug Repurposing and Biomarker Identification by Using Comprehensive Gene-Disease Associations through Protein-Protein Interaction Network Analysis

    Authors: Suresh Kumar

    id:10.20944/preprints202003.0440.v1 Date: 2020-03-30 Source: Preprints.org

    COVID-19 MESHD (2019-nCoV) is a pandemic disease MESHD with an estimated mortality rate of 3.4% (estimated by the WHO as of March 3, 2020). Until now there is no antiviral drug and vaccine for COVID-19 MESHD. The current overwhelming situation by COVID-19 MESHD patients in hospitals is likely to increase in the next few months. About 15 percent of patients with serious disease in COVID-19 MESHD require immediate health services. Rather than waiting for new anti-viral drugs or vaccines that take a few months to years to develop and test, several researchers and public health agencies are attempting to repurpose medicines that are already approved for another similar disease and have proved to be fairly effective. This study aims to identify FDA approved drugs that can be used for drug repurposing and identify biomarkers among high- risk and asymptomatic groups. In this study gene-disease association related to COVID-19 MESHD reported mild, severe symptoms and clinical outcomes were determined. The high-risk group was studied related to SARS-CoV-2 viral entry and life cycle by using Disgenet and compared with curated COVID-19 MESHD gene data sets from the CTD database. The overlapped gene sets were enriched and the selected genes were constructed for protein-protein interaction networks. Through interactome, key genes were identified for COVID-19 MESHD and also for high risk and asymptomatic groups. The key hub genes involved in COVID-19 MESHD were VEGFA HGNC, TNF HGNC, IL-6 HGNC, CXCL8 HGNC, IL10 HGNC, CCL2 HGNC, IL1B HGNC, TLR4 HGNC, ICAM1 HGNC, MMP9 HGNC. The identified key genes were used for drug-gene interaction for drug repurposing. The chloroquine, lenalidomide, pentoxifylline, thalidome, sorafenib, pacitaxel, rapamycin, cortisol, statins were proposed to be probable drug repurposing candidates for the treatment of COVID-19 MESHD. However, these predicted drug candidates need to be validated through randomized clinical trials. Also, a key gene involved in high risk and the asymptomatic group were identified, which can be used as probable biomarkers for early identification.

    A Multi-hospital Study in Wuhan, China:Protective Effects of Non-menopause and Female Hormones on SARS-CoV-2 infection MESHD

    Authors: Ting Ding; Jinjin Zhang; Tian Wang; Pengfei Cui; Zhe Chen; Jingjing Jiang; Su Zhou; Jun Dai; Bo Wang; Suzhen Yuan; Wenqing Ma; Lingwei Ma; Yueguang Rong; Jiang Chang; Xiaoping Miao; Xiangyi Ma; Shixuan Wang

    doi:10.1101/2020.03.26.20043943 Date: 2020-03-30 Source: medRxiv

    Objective To determine the correlation between menstruation status/sex hormones and prognosis of COVID-19 MESHD, and to identify potential protective factors for female patients. Design, Setting, and Participants A cross-sectional study of COVID-19 MESHD patients who were hospitalized at Tongji and Mobile Cabin Hospitals from Jan 28, 2020 to March 8, 2020. Sex differences in severity and composite endpoints (admission to intensive care unit (ICU), use of mechanical ventilation, or death MESHD) of COVID-19 MESHD patients were compared. The correlation analysis and cox/logistic regression modeling of menstruation status/sex hormones and prognosis were conducted. Correlation between cytokines related to immunity and inflammation MESHD and disease severity or estradiol (E2) was revealed.Results Chi square test indicated significant differences in distribution of composite endpoints (p<0.01) and disease severity (p=0.05) between male and female patients (n=1902). 435 female COVID-19 MESHD patients with menstruation records were recruited. By the end of Mar 8 HGNC, 111 patients recovered and discharged (25.3%). Multivariate Cox regression model adjusted for age and severity indicated that post-menopausal patients show the greater risk of hospitalization time than non-menopausal patients (relative hazard [RH], 1.91; 95% confidence interval [CI], 1.06-3.46)Logistic regression model showed that higher AMH HGNC as a control for age increases the risk of severity of COVID-19 MESHD (HR=0.146, 95%CI= (0.026-0.824) p=0.029). E2 showed protective effect against disease severity (HR=0.335, 95%CI= (0.105-1.070), p=0.046).In the Mann-Whitney U test, the higher levels of IL6 HGNC and IL8 HGNC were found in severe group (p=0.040, 0.033).The higher levels of IL2R HGNC, IL6 HGNC, IL8 HGNC and IL10 HGNC were also observed in patients with composite end points(p<0.001,<0.001, =0.009, = 0.040).E2 levels were negatively correlated with IL2R HGNC, IL6 HGNC, IL8 HGNC and TNF HGNC in luteal phase (Pearson Correlation=-0.592, -0.558, -0.545, -0.623; p=0.033, 0.048, 0.054, 0.023) and with C3 in follicular phase (Pearson Correlation=-0.651; p=0.030). Conclusions and Relevance Menopause is an independent risk factor for COVID-19 MESHD. E2 and AMH HGNC are negatively correlated with COVID-19 MESHD severity probably due to their regulation of cytokines related to immunity and inflammation MESHD.

    COVID-19 MESHD infection induces readily detectable morphological and inflammation-related phenotypic changes in peripheral blood monocytes, the severity of which correlate with patient outcome

    Authors: Dan Zhang; Rui Guo; Lei Lei; Hongjuan Liu; Yawen Wang; Yili Wang; Tongxin Dai; Tianxiao Zhang; Yanjun Lai; Jingya Wang; Zhiqiang Liu; Aili He; Michael O'Dwyer; Jinsong Hu

    doi:10.1101/2020.03.24.20042655 Date: 2020-03-26 Source: medRxiv

    Background: Excessive monocyte/macrophage activation with the development of a cytokine storm and subsequent acute lung injury MESHD, leading to acute respiratory distress syndrome MESHD ( ARDS MESHD) is a feared consequence of infection with COVID-19 MESHD. The ability to recognize and potentially intervene early in those patients at greatest risk of developing this complication could be of great clinical utility. Methods: We performed detailed flow cytometric analysis of peripheral blood samples from 28 COVID-19 MESHD patients treated at Xian No.8 Hospital and the First Affiliated Hospital of Xian Jiaotong University in early 2020 in an attempt to identify factors that could help predict severity of disease and patient outcome. Findings: While we did not detect significant differences in the number of monocytes between patients with COVID-19 MESHD and normal healthy individuals,we did identify significant morphological and functional differences, which are more pronounced in patients requiring prolonged hospitalization and ICU admission. Patients with COVID-19 MESHD have larger than normal monocytes, easily identified on forward scatter, side scatter analysis by routine flow cytometry,with the presence of a distinct population of monocytes with high forward scatter (FSC-high). On more detailed analysis, these FSC-high monocytes are CD11b HGNC+, CD14 HGNC+, CD16 HGNC+, CD68 HGNC+, CD80 HGNC+, CD163 HGNC+, CD206 HGNC+ and secrete IL-6 HGNC, IL-10 HGNC and TNF-alpha HGNC, consistent with an inflammatory phenotype. Conclusions: The detection and serial monitoring of this subset of inflammatory monocytes using flow cytometry could be of great help in guiding the prognostication and treatment of patients with COVID-19 MESHD and merits further evaluation.

    An Update on SARS-COV-2/ COVID-19 MESHD with Particular Reference on Its Clinical Pathology, Pathogenesis, Immunopathology and Mitigation Strategies – A Review

    Authors: Kuldeep Dhama; Shailesh Kumar Patel; Mamta Pathak; Mohd. Iqbal Yatoo; Ruchi Tiwari; Yashpal Singh Malik; Rajendra Singh; Ranjit Sah; Ali A. Rabaan; D. Katterine Bonilla-Aldana; Alfonso J. Rodriguez-Morales

    id:10.20944/preprints202003.0348.v1 Date: 2020-03-23 Source: Preprints.org

    Coronavirus Disease 2019 MESHD ( COVID-19 MESHD), caused by a novel coronavirus named Severe Acute Respiratory Syndrome MESHD - Coronavirus-2 (SARS-CoV-2), emerged in early December 2019 in China and attained a pandemic situation worldwide by its rapid spread to nearly 167 countries with 287.239 confirmed cases and 11.921 human deaths with a case fatality rate (CFR) of around 4 per cent. Bats were considered as the reservoir host, and the search of a probable intermediate host is still going on. Animals have anticipated culprit of SARS-CoV-2 as of now. The disease is mainly manifested by pneumonia MESHD and related respiratory signs and symptoms, but the involvement of the gastrointestinal system and nervous system is also suggested. The severe form of the disease associated with death MESHD is mainly reported in older and immune-compromised patients with pre-existing disease history. Death MESHD in severe cases is attributed to respiratory failure MESHD associated with hyperinflammation. Cytokine storm syndrome associated with rampant inflammation MESHD in response to SARS-CoV-2 infection MESHD is considered as the leading killer of COVID-19 MESHD patients. COVID-19 MESHD patients were reported with higher levels of many pro-inflammatory cytokines and chemokines like IFN-g HGNC, IL-1b HGNC, IP-10 HGNC, and MCP-1 HGNC. Furthermore, severe cases of COVID-19 MESHD revealed higher levels of TNF-α HGNC, G-CSF HGNC, and MIP-1A HGNC. Blood profile of the COVID-19 MESHD patients exhibits lymphopenia MESHD, leucopenia, thrombocytopenia MESHD and RNAaemia along with increased levels of aspartate aminotransferase. SARS-CoV-2 infection MESHD in pregnant women does not lead to fetus mortalities unlike other zoonotic coronaviruses like SARS-CoV and MERS-CoV, with no evidence of intrauterine transmission to neonates. Rapid and confirmatory diagnostics have been developed, and high efforts are being made to develop effective vaccines and therapeutics. In the absence of any virus-specific therapeutic, internationally health care authorities are recommending adoption of effective prevention and control measures to counter and contain this pandemic virus. This paper is an overview of this virus and the disease with a particular focus on SARS-COV-2 / COVID-19 MESHD clinical pathology, pathogenesis and immunopathology along with a few recent research developments.

    Effect of continuous renal replacement therapy on all-cause mortality in COVID-19 MESHD patients undergoing invasive mechanical ventilation: a retrospective cohort study

    Authors: Yi Yang; Jia Shi; Shuwang Ge; Shuiming Guo; Xue Xing; Yanan Wang; Anying Cheng; Qingquan Liu; Junhua Li; Yong Ning; Fan He; Gang Xu

    doi:10.1101/2020.03.16.20036780 Date: 2020-03-20 Source: medRxiv

    Background: For the coronavirus disease 2019 MESHD (COVID 19), critically ill MESHD patients had a high mortality rate. We aimed to assess the association between prolonged intermittent renal replacement therapy (PIRRT) and mortality in patients with COVID 19 undergoing invasive mechanical ventilation. Methods: In this retrospective cohort study, we included all patients with COVID 19 undergoing invasive mechanical ventilation from February 12nd to March 2nd, 2020. All patients were followed until death MESHD or March 28th, and all survivors were followed for at least 30 days. Results: For 36 hospitalized COVID 19 patients with invasive mechanical ventilation, the mean age was 69.4 (10.8) years, and 30 patients (83.3%) were men. Twenty two (61.1%) patients received PIRRT (PIRRT group) and 14 cases (38.9%) were managed with conventional strategy (non PIRRT group). There were no differences in age, sex, comorbidities, complications, treatments and most of the laboratory findings. During median follow up period of 9.5 (interquartile range 4.3 33.5) days, 13 of 22 (59.1%) patients in the PIRRT group and 11 of 14 (78.6%) patients in the non-PIRRT group died. Kaplan Meier analysis demonstrated prolonged survival in patients in the PIRRT group compared with that in the non PIRRT group (P = 0.042). The association between PIRRT and a reduced risk of mortality remained significant in three different models, with adjusted hazard ratios varying from 0.332 to 0.398. Higher levels of IL2 HGNC receptor, TNFa HGNC, procalcitonin, prothrombin time, and NT proBNP were significantly associated with an increased risk of mortality in patients with PIRRT. Conclusion: PIRRT may be beneficial for the treatment of COVID 19 patients with invasive mechanical ventilation. Further prospective multicenter studies with larger sample sizes are required.

    Clinical Features and Outcome Analysis of Patients Infected with Severe and Critical COVID-19 MESHD Associated Pneumonia

    Authors: Yangmei Xiong; Ying Feng; Mengwei Li; Jing Wang; Xingguo Zhang; Xiangyang Chen; Xin Rao

    doi:10.21203/rs.3.rs-17395/v1 Date: 2020-03-12 Source: ResearchSquare

    Background Until now, information on the clinical characteristics of severe and critical patients with COVID-19 MESHD is extremely limited.The aim of the present study was to analyse the clinical features of these patients and influencing factors of clinical outcome, and explore treatment effects of prone position on COVID-19 MESHD patients with severe ARDS. Methods A retrospective analysis was performed on 55 COVID-19 MESHD patients in the ICU of Zhongnan Hospital of Wuhan University from January 6 to February 15, 2020 in Wuhan, China. Case data from each patient were collected and related clinical outcomes on day 14 of ICU admission were recorded. The follow-up deadline was February 29, 2020. Results Of the 55 patients included, 35 were male (63.6%), with an average age of 63.0 (SD 15.2) years, and 80.0% were patients over 50 years old. The first three symptoms were fever (36 cases, 65.5%), fatigue (13 cases, 23.6%), and cough (11 cases, 20.0%). The rate of invasive mechanical ventilation was 52.7% (29 cases); on the 14th day of ICU admission, 31 patients(56.4%) were improved, and 19 (34.5%) were worsened.  On the 14th day after entering the ICU, a comparative analysis showed that peripheral blood CD4 HGNC, CD8 HGNC, and NK cell counts in deteriorated patients were significantly lower than those in improved patients (P<0.05). Meanwhile, concentrations of IL-10 HGNC, IL-4 HGNC, IL-6 HGNC and TNF-α HGNC in deteriorated patients were higher than those in improved patients (P <0.05). Among  a total of 27 prone position sessions, the oxygenation index (PaO2 / FiO2 ) of 9 prone position sessions(33.3%) improved, and the PaCO2 in arterial blood gas analysis of 5 sessions(18.5%) improved. Conclusion The majority of patients with severe and critical COVID-19 MESHD in the ICU were over 50 years old and male. 52.7% need invasive mechanical ventilation. On the 14th day of admission, 56.4% of the patients improved, 34.5% of the patients deteriorated. The rate of deaths during hospitalization was 21.8%. The worsening of COVID-19 MESHD patients might be related to excessive inflammatory and immune responses. In addition, prone ventilation may improve oxygenation in some COVID-19 MESHD patients with severe ARDS, but a significant mortality benefit with proning was uncertain.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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