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HGNC Genes

SARS-CoV-2 proteins

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NSP5 (1)


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    SARS-CoV-2 infection MESHD in the Syrian hamster model causes inflammation MESHD as well as type I interferon dysregulation MESHD in both respiratory and non-respiratory tissues including the heart and kidney

    Authors: Magen Francis; Una Goncin; Andrea Kroeker; Cynthia Swan; Robyn Ralph; Yao Lu; Athema Etzioni; Darryl Falzarano; Volker Gerdts; Steve Machtaler; Jason Kindrachuk; Alyson Ann Kelvin

    doi:10.1101/2021.04.07.438843 Date: 2021-04-08 Source: bioRxiv

    COVID-19 MESHD ( coronavirus disease 2019 MESHD) caused SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection MESHD is a disease affecting several organ systems. A model that captures all clinical symptoms of COVID-19 MESHD as well as long-haulers disease is needed. We investigated the host responses associated with infection in several major organ systems including the respiratory tract, the heart, and the kidneys after SARS-CoV-2 infection MESHD in Syrian hamsters. We found significant increases in inflammatory cytokines ( IL-6 HGNC, IL-1beta HGNC, and TNF HGNC) and type II interferons whereas type I interferons were inhibited. Examination of extrapulmonary tissue indicated inflammation MESHD in the kidney, liver, and heart which also lacked type I interferon upregulation. Histologically, the heart had evidence of mycarditis and microthrombi while the kidney had tubular inflammation MESHD. These results give insight into the multiorgan disease experienced by people with COVID-19 MESHD and possibly the prolonged disease in people with post-acute sequelae of SARS-CoV-2 (PASC).

    Mast Cells and COVID-19 MESHD: a case report implicating a role of mast cell activation in the prevention and treatment of Covid-19 MESHD

    Authors: Isabelle Brock; Anne Maitland

    doi:10.21203/rs.3.rs-330667/v2 Date: 2021-03-15 Source: ResearchSquare

    Coronavirus disease MESHD ( COVID-19 MESHD) is a heterogeneous syndrome MESHD following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection MESHD of the upper respiratory tract. ln adults, the clinical condition can range from asymptomatic cases to severe acute respiratory syndrome MESHD and multi-organ dysfunction MESHD. Those at risk of developing COVID-19 MESHD related hyperinflammatory syndrome MESHD likely had an ineffective, innate immune response to this novel pathogen. Mast cells are associated with the epithelium, contributing to tissue homeostasis and epithelial barrier defense. Equipped with an array of pathogen receptors, mast cells exhibit distinct cytokine profiles, dependent on the tissue and the triggered pathogen receptors. Following viral infections, mast cells produce pro-inflammatory chemical mediators, such as interleukin-1 (IL-1) and IL-6 HGNC, and these cytokines has been shown to be elevated in severe COVID-19 MESHD cases. Here, we present a case of a patient with a longstanding history of signs and symptoms, worrisome for a mast cell activation syndrome MESHD ( MCAS MESHD), but never had laboratory confirmation of this non-clonal mast cell activation disorder, until she contracted COVID-19 MESHD. This case illustrates the need to recognize the rate of mast cell activation in SARS-CoV-2 infection MESHD, not only to optimize anti-SARS-CoV-2 therapy, including the development of vaccine, but to potentially curb the risk of SARS­ CoV-2 triggered hyperinflammatory syndrome MESHD.

    Soluble angiotensin-converting enzyme 2 HGNC is transiently elevated in COVID-19 MESHD and correlates with specific inflammatory and endothelial markers

    Authors: Annika Lundstrom; Louise Ziegler; Sebastian Havervall; Ann-Sofie Rudberg; Fien Von Meijenfeldt; Ton Lisman; Nigel Mackman; Per Sanden; Charlotte Thalin

    doi:10.1101/2021.03.03.21252841 Date: 2021-03-05 Source: medRxiv

    RationaleAngiotensin-converting enzyme 2 ( ACE2 HGNC) is the main entry receptor of severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), but how SARS-CoV-2 interactions with ACE2 HGNC influences the renin-angiotensin system (RAS) in Coronavirus disease 2019 MESHD ( COVID-19 MESHD) is unknown. ObjectiveTo measure circulating ACE2 HGNC and ACE HGNC levels in COVID-19 MESHD patients and investigate association with risk factors, outcome and inflammatory markers. Methods and resultsSoluble ACE2 HGNC (sACE2) and sACE concentrations were measured by ELISA in plasma samples from 114 hospital-treated COVID-19 MESHD patients and 10 healthy controls. Follow-up samples after four months were available for 58/114 patients. Von Willebrand MESHD Von Willebrand HGNC factor ( VWF HGNC), factor VIII ( fVIII HGNC), D-dimer, interleukin 6 ( IL-6 HGNC), tumor necrosis MESHD factor and plasminogen activator inhibitor 1 ( PAI-1 HGNC) had previously been determined. Levels of sACE2 were higher in COVID-19 MESHD patients than in healthy controls, median 5.0 (interquartile range 2.8-11.8) ng/ml versus 1.4 (1.1-1.6) ng/ml, p < 0.0001. sACE2 was higher in men than women, but were not affected by other risk factors for severe COVID-19 MESHD. sACE 2 decreased to 2.3 (1.6-3.9) ng/ml at follow-up, p < 0.0001, but remained higher than in healthy controls, p=0.012. Follow-up sACE2 levels were higher with increasing age, BMI, total number of comorbidities, for patients with diabetes MESHD and patients on RAS-inhibition. sACE was marginally lower during COVID-19 MESHD compared with at follow-up, 57 (45-70) ng/ml versus 72 (52-87) ng/ml, p=0.008. Levels of sACE2 and sACE did not differ depending on survival or disease severity (care level, respiratory support). sACE2 during COVID-19 MESHD correlated with VWF HGNC, fVIII HGNC and D-dimer, while sACE correlated with IL-6 HGNC, TNF HGNC and PAI-1 HGNC. ConclusionssACE2 was transiently elevated in COVID-19 MESHD, likely due to increased shedding from infected cells. sACE2 and sACE during COVID-19 MESHD differed distinctly in their correlations with markers of inflammation MESHD and endothelial dysfunction, suggesting release from different cell types and/or vascular beds.

    Chyawanprash for the prevention of COVID-19 MESHD infection among healthcare workers: A Randomized Controlled Trial

    Authors: Arun Gupta; Amit Madan; Babita Yadav; Richa Singhal; Pallavi Suresh Mundada; Yogesh Kumar Pandey; Riju Agarwal; Rakesh Rana; Arunabh Tripathi; Bhagwan Sahay Sharma; BCS Rao; Bharti Gupta; Narayanam Srikanth; Kartar Singh Dhiman

    doi:10.1101/2021.02.17.21251899 Date: 2021-02-19 Source: medRxiv

    Background: Coronavirus disease 2019 MESHD ( Covid19 MESHD) occurs after exposure to severe acute respiratory syndrome coronavirus 2 MESHD (SARSCoV2). For persons who are at high risk of exposure, the standard of care is personal protection from getting infected. Whether Ayurvedic rasayana drug like Chyawanprash can prevent symptomatic infection in frontline health care workers is unknown. Objective: To evaluate the effect of the combination of Chyawanprash and Standard Preventive Regimen compared to the use of Standard Preventive Regimen alone on the proportion of RT-PCR confirmed COVID 19 infections among frontline healthcare workers (HCWs). Methods: An open label randomized controlled trial was conducted in the HCWs between 25 to 60 years age currently working in an environment with chance of direct exposure to COVID 19 cases. The interventions to be compared in this trial were Standard Preventive Regimen as per institutional guidelines and based on their roles (Group I) and Ayurvedic Intervention viz., Chyawanprash 12 g twice for 30 days from day of randomization plus Standard Preventive Regimen (Group II). The incidence of RT PCR confirmed COVID19 MESHD cases in both groups, was the primary outcome measure. Evaluation of the safety of the study drug (by any statistically significant change in various biochemical and hematological parameters and occurrence of any adverse drug reactions); incidence of any other infective diseases (bacterial / viral / fungal / etc.) like upper respiratory tract illness during the study period and any change in the immunoglobulins like IgG, IgM and IgE and inflammatory markers like TNF alpha HGNC, IL6 HGNC and IL10 HGNC were the secondary outcome measures. Results: Out of 193 participants who completed the study, no participant in both groups was COVID 19 positive at the end of one month. In post intervention follow up, 4 subjects in Group I and 2 subjects in Group II were COVID 19 positive. No adverse drug reaction or any serious adverse event was reported during the study. No clinically significant change in the safety parameters was observed before and after the study. Statistically significant rise in Serum IgG level was seen in Group II but other inflammatory and immune markers did not show statistically significant difference. Conclusion: Chyawanprash was well tolerated by all the participants in the intervention group but to prove its adaptogenic effect and efficacy as an add-on to the standard care in preventing the occurrence of COVID 19, clinical trial for longer duration with larger sample size is needed. Trial registration: Clinical Trials Registry of India vide CTRI/2020/05/025275 dated 20/05/2020 Date of IEC approval: 19.5.2020 Keywords: Adaptogen, Ayurveda, Health personnel, Prophylaxis, Rasayana, SARS CoV 2

    Dynamics of anti-SARS-CoV-2 IgG Antibodies Post- COVID-19 MESHD in a Brazilian Amazon Population

    Authors: Carlos David Araújo Bichara; Ednelza da Silva Graça Amoras; Gergiane Lopes Vaz; Maria Karoliny da Silva Torres; Maria Alice Freitas Queiroz; Isabella Pinheiro Costa do Amaral; Izaura Maria Vieira Cayres Vallinoto; Cléa Nazaré Carneiro Bichara; Antonio Carlos Rosário Vallinoto

    doi:10.21203/rs.3.rs-228739/v1 Date: 2021-02-10 Source: ResearchSquare

    Background: In this study, the prevalence and persistence of anti-SARS-CoV-2 (severe acute respiratory syndrome-coronavirus MESHD) IgG was evaluated in volunteers 90 days after COVID-19 MESHD ( coronavirus disease 2019 MESHD) diagnosis by correlating response dynamics with clinical conditions, IL-1β HGNC and IL-6 HGNC cytokine levels, epidemiological characteristics, and disease severity. Methods: The study recruited 200 volunteers aged 18 years or older of both sexes diagnosed with COVID-19 MESHD. ELISA testing was performed to detect IgG persistence and cytokine levels in 135 individuals with a previous serological test at the time of COVID-19 MESHD diagnosis.Results: Among the 135 individuals who underwent a previous serological test for anti-SARS-CoV-2 antibody and provided a new blood sample 90 days after the first examination, 125 showed reactivity to IgG (92.6%). Of the 125 individuals with detectable IgG in the first test, 69.6% showed persistence of this antibody after 90 days; however, in 10 (30.4%) individuals, IgG was nonreactive in the second evaluation. The frequency of all reported symptoms was higher in individuals who maintained IgG persistence after 90 days of symptoms, and no relationship with cytokine levels was observed. Conclusions: The results of the present study show a high frequency of loss of anti-SARS-CoV-2 IgG antibodies within three months after COVID-19 MESHD diagnosis in the Brazilian Amazon.

    Neural epidermal growth factor-like 1 HGNC protein variant increases survival and modulates the inflammatory and immune responses in human ACE-2 HGNC transgenic mice infected with SARS-CoV-2

    Authors: Roopa Biswas; Shannon Eaker; Dharmendra Kumar Soni; Swagata Kar; Denae LoBato; Cymbeline Culiat

    doi:10.1101/2021.02.08.430254 Date: 2021-02-08 Source: bioRxiv

    Coronavirus disease 2019 MESHD ( COVID-19 MESHD) is a viral illness caused by the severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) and is a worsening global pandemic. COVID-19 MESHD has caused at least 1.7 million deaths worldwide and over 300,000 in the United States. Recently, two promising vaccines are being administered in several countries. However, there remains an urgent need for a therapeutic treatment for COVID-19 MESHD patients with severe respiratory damage MESHD that can lead to intensive care, prolonged hospitalization, or mortality. Moreover, an increasing population of patients manifest lingering disabling symptoms (called Long Haulers). Here, we tested the efficacy of a recombinant neural epidermal growth factor like 1 protein variant (NELL1-NV1) in a COVID-19 MESHD mouse model, transgenic mice expressing the human angiotensin I-converting enzyme 2 HGNC ( ACE2 HGNC) receptor (tg-mice hACE2 HGNC) infected with SARS-CoV-2. The administration of NELL1-NV1 to SARS-CoV-2-infected MESHD tg-mice hACE2 HGNC significantly improved clinical health score and increased survival. Analyses of bronchoalveolar (BAL) fluid demonstrated decreased levels of several cytokines and chemokines (IFN-{gamma}, IL-10, IL-12 p70, CXCL-10/IP-10, MIG and Rantes), in NV1-treated treated mice compared to controls. Cytokines including IL-1 HGNC, IL-9 HGNC, IL-6 HGNC, LIX/ CXCL5 HGNC, KC/ CXCL1 HGNC, MIP-2 HGNC/ CXCL2 HGNC, MIP-1 HGNC/ CCL3 HGNC, and G-CSF HGNC, critical to immune responses such as neutrophil recruitment, viral clearance and vascularization, were increased compared to controls. Our data suggest the potential of NELL1 HGNC-NV1-based therapy to mitigate the cytokine storm, modulate the abnormal immune response and repair respiratory tissue damage in COVID-19 MESHD patients.

    Clinical utility of Corona Virus Disease MESHD-19 serum IgG, IgM, and neutralizing antibodies and inflammatory markers

    Authors: Ernst J Schaefer; Florence Comite; Latha Dulipsingh; Maxine Lang; Jessica Jimison; Martin M Grajower; Nathan E Lebowitz; Andrew S Geller; Margaret R Diffenderfer; Lihong He; Gary Breton; Michael L Dansinger; Ben Saida; Chong Yuan

    doi:10.1101/2021.01.19.21249604 Date: 2021-01-20 Source: medRxiv

    Most deaths MESHD from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection MESHD occur in older subjects. We assessed age effects and clinical utility of serum SARS-CoV-2 immunoglobulin G (IgG), immunoglobulin M (IgM), and neutralizing antibodies and serum inflammatory markers. Serum IgG, IgM, and neutralizing antibody levels were measured using chemiluminescence assays from Diazyme (Poway, CA), while serum interleukin-6 HGNC ( IL-6 HGNC), C reactive protein HGNC ( CRP HGNC), and ferritin were measured with immunoassays obtained from Roche (Indianapolis, IN). In 79,005 subjects, IgG and IgM levels were positive ([≥]1.0 arbitrary units [AU]/mL) in 5.29% and 3.25% of subjects, respectively. In antibody positive subjects, median IgG levels were 3.93 AU/mL if <45 years of age, 10.18 AU/mL if 45-64 years of age, and 10.85 AU/mL if [≥]65 years of age (p<0.0001). In SARS-CoV-2 RNA positive cases, family members and exposed subjects (n=1,111), antibody testing was found to be valuable for case finding, and persistent IgM levels were associated with chronic symptoms. In non-hospitalized and hospitalized subjects assessed for SARS-CoV-2 RNA (n=278), median IgG levels in AU/mL were 0.05 in negative subjects (n=100), 14.83 in positive outpatients (n=129), and 30.61 in positive hospitalized patients (n=49, p<0.0001). Neutralizing antibody levels correlated significantly with IgG (r=0.875; p<0.0001). Two or more of the criteria of IL-6 HGNC [≥]10 pg/mL, CRP HGNC [≥]10 mg/L, and/or IgM >1.0 AU/mL occurred in 97.7% of inpatients versus 1.8% of outpatients (>50-fold relative risk, C statistic 0.986, p<0.0001). Our data indicate that: 1) IgG levels are significantly higher in positive older subjects, possibly to compensate for decreased cellular immunity with aging; 2) IgG levels are important for case finding in family clusters; 3) IgG levels are significantly correlated with neutralizing antibody levels; 4) persistently elevated IgM levels are associated with chronic disease MESHD; and 5) markedly elevated IL-6 HGNC, hs- CRP HGNC, and/or positive IgM accurately identify SARS-CoV-2 RNA positive subjects requiring hospitalization.

    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.

    Humoral and cell-mediated response in colostrum after exposure to severe acute respiratory syndrome coronavirus 2 MESHD

    Authors: Vignesh Narayanaswamy; Brian Pentecost; Dominique Alfandari; Emily Chin; Kathleen Minor; Alyssa Kastrinakis; Tanya Lieberman; Kathleen F Arcaro; Heidi Leftwich

    doi:10.1101/2021.01.03.20248715 Date: 2021-01-04 Source: medRxiv

    BackgroundColostrum provides an immune sharing between a mother and her infant. The transfer in colostrum of antibodies against SARS-CoV-2 and the elicited cytokines may provide crucial protection to the infant. There is limited literature on the immune response to SARS-CoV-2 present in colostrum. ObjectiveTo evaluate the presence of antibodies specific to SARS-CoV-2 and the associated cytokines in colostrum from women who tested positive for the virus. Study DesignBetween March and September 2020 we obtained bilateral colostrum samples collected on spot cards within 48 hours of delivery from 15 new mothers who had previously tested positive for SARS-CoV-2. Five of these 15 COVID-19 MESHD positive women also provided bilateral liquid colostrum within 1-2 days of providing the spot card samples. Archived bilateral colostrum samples collected from 8 women during 2011-2013 were used as pre- COVID-19 MESHD controls. All samples were tested for reactivity to the Receptor Binding Domain (RBD) of the SARS-CoV-2 spike PROTEIN protein using an ELISA that measures SARS-CoV-2 RBD-specific IgA, IgG, and IgM, and for concentrations of 10 inflammatory cytokines ( IFN{gamma HGNC}, TNF HGNC, IL-1{beta HGNC}, IL-2 HGNC, IL-4 HGNC, IL-6 HGNC, IL-8 HGNC, IL-10 HGNC, IL-12, IL-13 HGNC) using a multiplex electrochemiluminescent sandwich assay. ResultsBilateral colostrum samples from 73%, 73% and 33% of the 15 COVID-19 MESHD mothers exhibited IgA, IgG, and IgM reactivity to RBD respectively. Colostrum samples from two of the 8 pre-pandemic controls showed IgA and IgG reactivity to RBD. Additionally, COVID-19 MESHD mothers had significantly higher levels of 9 of the 10 inflammatory markers (all except IFN{gamma HGNC}) as compared to the pre- COVID-19 MESHD controls. Comparable results were obtained with both the spot card-eluates and liquid samples. ConclusionsA strong humoral immune response is present in the colostrum of women who were infected with SARS-CoV-2 before delivering. High levels of 9 inflammatory markers were also present in the colostrum. The evolution and duration of the antibody response, as well as dynamics of the cytokine response, remain to be determined. Our results also indicate that future large-scale studies can be conducted with milk easily collected on paper spot cards.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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