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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (15)

NSP5 (4)

ProteinS1 (3)

ProteinN (2)

NSP2 (1)


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SARS-CoV-2 Proteins
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    Methotrexate Hampers Immunogenicity to BNT162b2 mRNA COVID-19 MESHD Vaccine in Immune-Mediated Inflammatory Disease

    Authors: Rebecca H Haberman; Ramin Herati; David Simon; Marie Samanovic; Rebecca B. Blank; Michael Tuen; Sergei Koralov; Raja Atreya; Koray Tascilar; Joseph Allen; Rochelle Castillo; Amber Cornelius; Paula Rackoff; Gary Solomon; Samrachana Adhikari; Natalie Azar; Pamela Rosenthal; Peter Izmirly; Jonathan Samuels; Brian Golden; Soumya Reddy; Markus F. Neurath; Steven B. Abramson; Georg Schett; Mark J Mulligan; Jose U Scher

    doi:10.1101/2021.05.11.21256917 Date: 2021-05-12 Source: medRxiv

    Objective: To investigate the humoral and cellular immune response to mRNA COVID-19 MESHD vaccines in patients with immune-mediated inflammatory diseases (IMIDs) on immunomodulatory treatment. Methods: Established patients at NYU Langone Health with IMID (n=51) receiving the BNT162b2 mRNA vaccination were assessed at baseline and after second immunization. Healthy subjects served as controls (n=26). IgG antibody responses to the spike protein PROTEIN were analyzed for humoral response. Cellular immune response to SARS-CoV-2 was further analyzed using high-parameter spectral flow cytometry. A second independent, validation cohort of controls (n=182) and patients with IMID (n=31) from Erlangen, Germany were also analyzed for humoral immune response. Results: Although healthy subjects (n=208) and IMID patients on biologic treatments (mostly on TNF HGNC blockers, n=37) demonstrate robust antibody responses (over 90%), those patients with IMID on background methotrexate (n=45) achieve an adequate response in only 62.2% of cases. Similarly, IMID patients do not demonstrate an increase in CD8+ T cell activation after vaccination. Conclusions: In two independent cohorts of IMID patients, methotrexate, a widely used immunomodulator for the treatment of several IMIDs, adversely affected humoral and cellular immune response to COVID-19 MESHD mRNA vaccines. Although precise cut offs for immunogenicity that correlate with vaccine efficacy are yet to be established, our findings suggest that different strategies may need to be explored in patients with IMID taking methotrexate to increase the chances of immunization efficacy against SARS-CoV-2 as has been demonstrated for augmenting immunogenicity to other viral vaccines.

    Autoantibodies against Progranulin HGNC and IL-1 receptor antagonist HGNC in critically ill COVID-19 MESHD

    Authors: Lorenz Thurner; Natalie Fadle; Moritz Bewarder; Igor Kos; Evi Regitz; Onur Cetin; Bernhard Thurner; Yvan Fischer; Torben Rixecker; Klaus-Dieter Preuss; Claudia Schormann; Frank Neumann; Sylvia Hartmann; Theresa Bock; Dominic Kaddu-Mulindwa; Birgit Bette; Joerg Thomas Bittenbring; Konstantinos Christofyllakis; Angelika Bick; Vadim Lesan; Zanir Abdi; Sebastian Mang; Andre Becker; Carlos Metz; Frederik Seiler; Johannes Lehmann; Philipp Agne; Thomas Adams; Andreas Link; Christian Werner; Angela Thiel-Bodenstaff; Matthias Reichert; Guy Danziger; Cihan Papan; Jan Pilch; Thorsten Pfuhl; Patrick Wuchter; Christian Herr; Stefan Lohse; Hubert Schrezenmeier; Michael Boehm; Frank Langer; Gereon Gaebelein; Bettina Friesenhahn-Ochs; Robert Bals; Frank Lammert; Sixten Koerper; Juergen Rissland; Christian Lensch; Stephan Stilgenbauer; Soeren L. Becker; Sigrun Smola; Marcin Krawczyk; Philipp Lepper

    doi:10.1101/2021.04.23.441188 Date: 2021-04-26 Source: bioRxiv

    INTRODUCTION: Hyperinflammation is frequently observed in patients with severe COVID-19 MESHD. Inadequate and defective IFN type I responses against SARS-CoV-2, caused by autoantibodies in a proportion of patients, lead to severe courses. In addition, hyperactive responses of the humoral immune system have been described so far. RATIONALE: In the current study we investigated a possible role of neutralizing autoantibodies against anti-inflammatory mediators. Plasma from patients with severe and critical COVID-19 MESHD was screened by ELISA for antibodies against PGRN HGNC, IL-10 HGNC, IL-18BP HGNC, IL-22BP HGNC and IL-1-RA HGNC. Autoantibodies were characterized and the antigens were analyzed for immunogenic alterations. RESULTS: PGRN HGNC-autoantibodies were detected with high titers in 11 of 30 (36.7%), and IL 1 HGNC-RA-autoantibodies in 14 of 30 (46.7%) patients of a discovery cohort with severe to critical COVID-19 MESHD. In a validation cohort of 41 patients with critical COVID-19 MESHD high-titered PGRN HGNC-Abs were detected in 12 (29.3%) and IL-1-RA HGNC-Abs in 19 of 41 patients (46.2%). PGRN HGNC-Abs and IL-1-RA HGNC-Abs belonged to IgM and several IgG subclasses. In separate cohorts with non-critical COVID-19 MESHD, PGRN HGNC-Abs and IL-1-RA HGNC-Abs were detected significantly less frequently and at low titers. Neither PGRN HGNC- nor IL-1-RA HGNC-Abs were found in 40 healthy controls vaccinated against SARS-CoV-2. PGRN HGNC-Abs were not cross-reactive against SARS-CoV-2 structural proteins or against IL-1-RA HGNC. Plasma levels of both free PGRN HGNC PGRN MESHD and IL-1-RA HGNC were significantly decreased in autoantibody-positive patients compared to Ab-negative and non-COVID controls. Functionally, PGRN HGNC-Abs from patients reduced PGRN HGNC-dependent inhibition of TNF HGNC- signaling in vitro. The pSer81 hyperphosphorylated PGRN HGNC isoform was exclusively detected in patients with high-titer PGRN HGNC-Abs; likewise, a yet unidentified hyperphosphorylated IL-1-RA HGNC isoform was only found in patients with high-titer IL-1-RA HGNC-Abs. No autoantibodies against IL-10 HGNC, IL-18BP HGNC or IL-22BP HGNC were found. CONCLUSION: To conclude, neutralizing autoantibodies to IL-1-RA HGNC and PGRN HGNC occur in a significant proportion of patients with critical COVID-19 MESHD, with a concomitant decrease in circulating PGRN HGNC and IL-1-RA HGNC, which is indicative of a misdirected, proinflammatory autoimmune response. The break of self-tolerance is likely caused by atypical isoforms of both antigens due to hyperphosphorylation. It remains to be determined whether these secondary modifications are induced by the SARS-CoV-2-infection MESHD itself, or are preexisting and predispose for a critical course.

    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).

    Relative expression of pro-inflammatory molecules in COVID-19 MESHD patients manifested disease severities.

    Authors: Shireen Nigar; SM Tanjil Shah; Ali Ahasan Setu; Sourav Dutta Dip; Habiba Ibnat; M. Touhid Islam; Selina Akter; Iqbal Kabir Jahid; Md. Anwar Hossain

    doi:10.1101/2021.04.01.21254770 Date: 2021-04-07 Source: medRxiv

    Aggressive immune response, due to over-expressed pro-inflammatory molecules, had been characterized in COVID-19 MESHD patients. Some of those mediators have a dual and opposite role on immune-systems to play behind differential disease severities. We investigated the expression of some cytokines and chemokines in COVID-19 MESHD patients in Bangladesh. We diagnosed the patients by detecting SARS-CoV-2 RNA in nasal swab samples by the real-time RT-PCR method. Thirty adult patients were preselected based on their disease severities and grouped into mild, moderate, and severe cases. Nine healthy volunteers participated in this study as control. Relative expression of nine cytokines/chemokine in total leukocytes was semi-quantified in SYBRgreen-based qRT-PCR. We performed statistical tests on transformed log data using SPSS 24.0. At the onset of symptoms (day-1), ACE2 HGNC (P < 0.05) and IL-6 HGNC (P > 0.05) were up-regulated in all COVID-19 MESHD groups, although expression levels did not significantly correlate with disease severities. However, expression of IL-6 HGNC, MCP-1 HGNC, MIP-1 HGNC, TNF- HGNC, RANTES HGNC, and ACE2 HGNC, on day-14, were positively correlated with disease severities. Relative viral load at day-1 showed no significant correlation with cytokine expression but had a significant positive correlation with RANTES HGNC and ACE2 HGNC expression on day-14 (P < 0.05). Male patients had a higher level of IL-6 HGNC than female patients on day-1 (P < 0.05). All COVID-19 MESHD patients showed up-regulated cytokines and chemokines on the day-14 compared to day-1 except TNF HGNC-. Female patients had higher expression of ACE2 HGNC and IL-12 on day-14. Up-regulated cytokines/chemokines at the convalescent stage, especially IL-6 HGNC, may target anti-cytokine therapy in post- COVID-19 MESHD patients management.

    SARS-CoV-2 Vaccines Elicit Durable Immune Responses in Infant Rhesus Macaques

    Authors: Carolina Garrido Garrado; Alan D Curtis; Maria Dennis; Sachi H Pathak; Hongmei Gao; David Montefiori; Mark Tomai; Christopher B Fox; Pamela A Kozlowski; Trevor Scobey; Jennifer E Munt; Michael L Mallory; Pooja T Saha; Michael G Hudgens; Lisa C Lindesmith; Ralph S. Baric; Olubukola M Abiona; Kizzmekia S Corbett; Darin Edwards; Andrea Carfi; Genevieve Fouda; Koen K. A. Van Rompay; Kristina De Paris; Sallie R Permar

    doi:10.1101/2021.04.05.438479 Date: 2021-04-06 Source: bioRxiv

    Early life SARS-CoV-2 vaccination has the potential to provide lifelong protection and achieve herd immunity. To evaluate SARS-CoV-2 infant vaccination, we immunized two groups of 8 infant rhesus macaques (RMs) at weeks 0 and 4 with stabilized prefusion SARS-CoV-2 S-2P spike (S) protein PROTEIN, either encoded by mRNA encapsulated in lipid nanoparticles (mRNA-LNP) or mixed with 3M-052-SE, a TLR7/8 agonist in a squalene emulsion (Protein+3M-052-SE). Neither vaccine induced adverse effects. High magnitude S-binding IgG and neutralizing infectious dose 50 (ID50) >103 were elicited by both vaccines. S-specific T cell responses were dominated by IL-17 HGNC, IFN-g HGNC, or TNF-a HGNC. Antibody and cellular responses were stable through week 22. The S-2P mRNA-LNP and Protein-3M-052-SE vaccines are promising pediatric SARS-CoV-2 vaccine candidates to achieve durable protective immunity.

    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.

    Authors: Natalia G Sampaio; Lise Chauveau; Jonny Hertzog; Anne Bridgeman; Gerissa Fowler; Jurgen P Moonen; Maeva Dupont; Rebecca A Russel; Marko Noerenberg; Jan Rehwinkel

    doi:10.1101/2021.03.26.437180 Date: 2021-03-27 Source: bioRxiv

    Human cells respond to infection by SARS-CoV-2, the virus that causes COVID-19 MESHD, by producing cytokines including type I and III interferons (IFNs) and proinflammatory factors such as IL6 HGNC and TNF HGNC. IFNs can limit SARS-CoV-2 replication but cytokine imbalance contributes to severe COVID-19 MESHD. We studied how cells detect SARS-CoV-2 infection MESHD. We report that the cytosolic RNA sensor MDA5 HGNC was required for type I and III IFN induction in the lung cancer MESHD cell line Calu-3 upon SARS-CoV-2 infection MESHD. Type I and III IFN HGNC induction further required MAVS HGNC and IRF3 HGNC. In contrast, induction of IL6 HGNC and TNF HGNC was independent of the MDA5 HGNC- MAVS HGNC- IRF3 HGNC axis in this setting. We further found that SARS-CoV-2 infection MESHD inhibited the ability of cells to respond to IFNs. In sum, we identified MDA5 HGNC as a cellular sensor for SARS-CoV-2 infection MESHD that induced type I MESHD and III IFNs.

    The polymorphism L412F in TLR3 HGNC inhibits autophagy and is a marker of severe COVID-19 MESHD in males.

    Authors: Susanna Croci; Mary Anna Venneri; Stefania Mantovani; Chiara Fallerini; Elisa Benetti; Nicola Picchiotti; Federica Campolo; Francesco Imperatore; Maria Palmieri; Sergio Daga; Chiara Gabbi; Francesca Montagnani; Giada Beligni; Ticiana D.J. Farias; Miriam L. Carriero; Laura Di Sarno; Diana Alaverdian; Sigrid Aslaksen; Maria Vittoria Cubellis; Ottavia Spiga; Margherita Baldassarri; Francesca Fava; Paul J. Norman; Elisa Frullanti; Andrea M. Isidori; Antonio Amoroso; Francesca Mari; Simone Furini; Mario Mondelli; - GEN-COVID Multicenter Study; Mario Chiariello; Alessandra Renieri; Ilaria Meloni

    doi:10.1101/2021.03.23.21254158 Date: 2021-03-26 Source: medRxiv

    The polymorphism L412F in TLR3 HGNC has been associated with several infectious diseases MESHD. However, the mechanism underlying this association is still unexplored. Here, we show that the L412F polymorphism in TLR3 HGNC is a marker of severity in COVID-19 MESHD. This association increases in the sub-cohort of males. Impaired autophagy and reduced TNF HGNC production was demonstrated in HEK293 cells transfected with TLR3 HGNC-L412F plasmid and stimulated with specific agonist poly(I:C). A statistically significant reduced survival at 28 days was shown in L412F COVID-19 MESHD patients treated with the autophagy-inhibitor hydroxychloroquine (P=0.038). An increased frequency of autoimmune disorders MESHD as co-morbidity was found in L412F COVID-19 MESHD males with specific class II HLA haplotypes prone to autoantigen presentation. Our analyses indicate that L412F polymorphism makes males at risk of severe COVID-19 MESHD and provides a rationale for reinterpreting clinical trials considering autophagy pathways.

    Transcriptome analysis of PBMCs reveals distinct immune response in the asymptomatic and re-detectable positive COVID-19 MESHD patients

    Authors: Jiaqi Zhang; Dongzi Lin; Kui Li; Xiangming Ding; Lin Li; Yuntao Liu; Dongdong Liu; Jing Lin; Xiangyun Teng; Yizhe Li; Ming Liu; Xiaodan Wang; Dan He; Yaling Shi; Dawei Wang; Jianhua Xu

    doi:10.1101/2021.03.16.21251286 Date: 2021-03-24 Source: medRxiv

    The existence of asymptomatic and re-detectable positive COVID-19 MESHD patients presents the disease control challenges of COVID-19 MESHD. Most studies on immune response of COVID-19 MESHD have focused on the moderately or severely symptomatic patients, however little is known about the immune response in asymptomatic and re-detectable positive patients. Here we performed a comprehensive analysis of the transcriptomic profiles of PBMCs from 48 COVID-19 MESHD patients which include 8 asymptomatic, 13 symptomatic, 15 recovering and 12 RP MESHD patients. Our analysis revealed a down-regulation of IFN response and complement activation in the asymptomatic patients compared with the symptomatic, indicating a weaker immune response of the PBMCs in the asymptomatic patients. In addition, we observed a lower expression of the cytokines and chemokines in the PBMC of asymptomatic and symptomatic patients. In contrast, the cytokines and chemokines level in the RP patients are higher than the recovering. GSEA analysis showed the enrichment of TNFa HGNC/ NF-{kappa}B HGNC and influenza infection MESHD in the RP MESHD patients compared with the recovering patients, indicating a flu-like, hyper-inflammatory immune response in the PBMC of RP MESHD patients. Thus our findings could extend our understanding of host immune response during the progression COVID-19 MESHD disease and help the clinical management and the immunotherapy development for COVID-19 MESHD.

    Serological response to COVID-19 MESHD vaccination in IBD MESHD patients receiving biologics

    Authors: Serre-Yu Wong; Rebekah Dixon; Vicky Martinez Pazos; - ICARUS-IBD; Sacha Gnjatic; Jean-Frederic Colombel; Ken Cadwell

    doi:10.1101/2021.03.17.21253848 Date: 2021-03-20 Source: medRxiv

    Objective The impact of medications on COVID-19 MESHD vaccine efficacy in IBD MESHD patients is unknown, as patients with immunosuppressed states and/or treated with immunosuppressants were excluded from vaccine trials. To address this, we evaluated serological responses to COVID-19 MESHD vaccination with the SARS-CoV-2 spike MESHD SARS-CoV-2 spike PROTEIN (S) mRNA BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (NIH-Moderna) vaccines in IBD MESHD patients enrolled in an ongoing SARS-CoV-2 sero-survey at the Icahn School of Medicine at Mount Sinai in New York City. Design We obtained sera from 48 patients who had undergone vaccination with one or two vaccine doses. Sera were tested for SARS-CoV-2 anti-RBD total immunoglobulins and IgG (Siemens COV2T and sCOVG assays), anti-Spike IgG (in-house ELISA), and anti-nucleocapsid antibodies (Roche). Results All IBD MESHD patients (15/15) who completed two-dose vaccine schedules achieved seroconversion to high levels. Two IBD MESHD patients with history of COVID-19 MESHD infections and who were seropositive at baseline seroconverted to high levels after the first dose. Concurrent biologic use was 85% (41/48), including 33% of patients (16) on TNF HGNC antagonist monotherapy, 42% (17) on vedolizumab monotherapy, 6% (3) on vedolizumab combination therapy with thiopurine, and 8% (4) ustekinumab; 1 patient was receiving guselkumab for psoriasis MESHD. Three patients (6%) were on oral steroids at the time of vaccination. Conclusion IBD MESHD patients receiving biologics can seroconvert with robust serological responses after complete Pfizer-BioNTech and NIH-Moderna COVID-19 MESHD vaccination. In IBD-patients with previous SARS-CoV-2 seroconversion, a single dose of either vaccine can induce high index values, mirroring findings from the general population.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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