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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    Effect of Tocilizumab on ventilator free days composite outcome in SARS-CoV-2 patients. A retrospective competing risk analysis.

    Authors: Ahmed F. Mady; Basheer Abdulrahman; Omar E. Ramadan; Shahzad A. Mumtaz; Mohammed A. Al-Odat; Ahmed Kuhail; Rehab Altoraifi; Rayan Alshae; Abdulrahman M. Alharthy; Dimitrios Karakitsos; Waleed Th. Aletreby

    doi:10.1101/2021.04.01.21254794 Date: 2021-04-07 Source: medRxiv

    Background: SARS CoV 2 infection MESHD demonstrates a wide range of severity, the more severe cases demonstrate a cytokine storm with elevated serum interleukin 6, hence IL 6 receptor HGNC antibody Tocilizumab was tried for the management of severe cases. Objectives: The effect of Tocilizumab treatment on the composite outcome of ventilator free days, among critically ill SARS CoV MESHD 2 patients. Method: Retrospective observational propensity score matching study, comparing mechanically ventilated patients upon ICU admission who received Tocilizumab to a control group. Utilizing competing risk analysis method, and reporting subdistributional hazard ratio of a composite outcome of ventilator free days at day 28. Results: 29 patients in the intervention group were compared to 29 patients in the control group. Matched groups were similar at base line. The primary outcome of ventilator free days was higher in the intervention group (SHR 2.7, 95% CI: 1.2 to 6.3; p = 0.02), crude ICU mortality rate was not different between Tocilizumab and control groups (37.9% versus 62% respectively, p = 0.1), actual ventilator free days were significantly longer in Tocilizumab group (mean difference 4.7 days, 95% CI 1.1 to 8.3; p = 0.02). Sensitivity analysis by Cox regression showed a significantly lower hazard ratio of death MESHD in Tocilizumab group (HR 0.49, 95% CI: 0.25 to 0.97; p = 0.04). While there was no difference in grown positive cultures among groups (55.2% in Tocilizumab group versus 34.5% in the control, 95% CI of difference: -7.11% to 54.4%; p = 0.1). Conclusion: Tocilizumab may improve the composite outcome of ventilator free days at day 28 among mechanically ventilated SARS-CoV-2 patients, it is associated with significantly longer actual ventilator free days, and insignificantly lower mortality and superinfection.

    Mapping Systemic Inflammation and Antibody Responses in Multisystem Inflammatory Syndrome in Children (MIS-C)

    Authors: Conor Gruber; Roosheel Patel; Rebecca Trachman; Lauren Lepow; Fatima Amanat; Florian Krammer; Karen M. Wilson; Kenan Onel; Daniel Geanon; Kevin Tuballes; Manishkumar Patel; Konstantinos Mouskas; Nicole Simons; Vanessa Barcessat; Diane Del Valle; Samantha Udondem; Gurpawan Kang; Sandeep Gangadharan; George Ofori-Amanfo; Adeeb Rahman; Seunghee Kim-Schulze; Alexander Charney; Sacha Gnjatic; Bruce Gelb; Miriam Merad; Dusan Bogunovic

    doi:10.1101/2020.07.04.20142752 Date: 2020-07-06 Source: medRxiv

    Initially, the global outbreak of COVID-19 MESHD caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spared children from severe disease. However, after the initial wave of infections, clusters of a novel hyperinflammatory disease MESHD have been reported in regions with ongoing SARS-CoV-2 MESHD epidemics. While the characteristic clinical features are becoming clear, the pathophysiology remains unknown. Herein, we report on the immune profiles of eight Multisystem Inflammatory Syndrome MESHD in Children ( MIS HGNC-C) cases. We document that all MIS HGNC-C patients had evidence of prior SARS-CoV-2 exposure, mounting an antibody response with normal isotype-switching and neutralization capability. We further profiled the secreted immune response by high-dimensional cytokine assays, which identified elevated signatures of inflammation MESHD ( IL-18 HGNC and IL-6 HGNC), lymphocytic and myeloid chemotaxis and activation ( CCL3 HGNC, CCL4 HGNC, and CDCP1 HGNC) and mucosal immune dysregulation ( IL-17A HGNC, CCL20 HGNC, CCL28 HGNC). Mass cytometry immunophenotyping of peripheral blood revealed reductions of mDC1 and non-classical monocytes, as well as both NK- and T- lymphocytes, suggesting extravasation to affected tissues. Markers of activated myeloid function were also evident, including upregulation of ICAM1 HGNC and FcR1 in neutrophil and non-classical monocytes, well-documented markers in autoinflammation MESHD and autoimmunity that indicate enhanced antigen presentation and Fc-mediated responses. Finally, to assess the role for autoimmunity secondary to infection, we profiled the auto-antigen reactivity of MIS HGNC-C plasma, which revealed both known disease-associated autoantibodies (anti-La) and novel candidates that recognize endothelial, gastrointestinal and immune-cell antigens. All patients were treated with anti- IL6R HGNC antibody or IVIG, which led to rapid disease resolution tracking with normalization of inflammatory markers.

    Compassionate Use of Tocilizumab in Severe SARS-CoV2 Pneumonia. When late administration is too late.

    Authors: Miguel Gorgolas; Alfonso Cabello; Laura Prieto Perez; Felipe Villar Alvarez; Beatriz Alvarez Alvarez; Maria Jesus Rodriguez Nieto; Irene Carrillo Acosta; Itziar Fernandez Ormaechea; Aws Al-Hayani; Pilar Carballosa; Silvia Calpena Martinez; Farah Ezzine de Blas; Marina Castellanos Gonzalez; Alba Naya Prieto; Marta Lopez de las Heras; Marcel Jose Rodriguez Guzman; Ana Cordero Guijarro; Antonio Broncano Lavado; Alicia Macias Valcayo; Marta Martin Garcia; Javier Becares Martinez; Ricardo Fernandez Roblas; Miguel A Piris Pinilla; Jose Fortes Alen; Olga Sanchez Pernaute; Fredeswinda Romero Bueno; Sarah Heili Frades; German Peces Barba Romero

    doi:10.1101/2020.06.13.20130088 Date: 2020-06-16 Source: medRxiv

    Introduction Tocilizumab is an interleukin 6 receptor HGNC antagonist which has been used for the treatment of severe SARS-CoV-2 pneumonia MESHD (SSP), aiming to ameliorate the cytokine release syndrome (CRS) -induced acute respiratory distress syndrome MESHD ( ARDS MESHD). However, there is no data about the best moment for its administration along the course of the disease. Methods We provided tocilizumab on a compassionate-use basis to patients with SSP hospitalized (excluding intensive care and intubated cases) who required oxygen support to have a saturation >93%. Primary endpoint was intubation or death MESHD after 24 hours of its administration. Patients received at least one dose of 400 mg intravenous tocilizumab during March 8-2020, through April 20-2020. Findings A total of 207 patients were studied and 186 analysed. The mean age was 65 years and 68% were male. A co-existing condition was present in 68 % of cases. At baseline, 114 (61%) required oxygen support with FiO2 >0.5 % and 72 (39%) <0.5%. Early administration of tocilizumab, when the need of oxygen support was still below FiO2 <0.5%, was significantly more effective than given it in advanced stages (FiO2 >0.5 %), achieving lower rates of intubation or death MESHD (13% vs 37% repectively, p<0.001). Interpretation The benefit of tocilizumab in severe SARS-Cov-2 pneumonia MESHD is only expected when it is administrated before the need of high oxygen support.

    Sarilumab use in severe SARS-CoV-2 pneumonia

    Authors: Elisa Gremese; Antonella Cingolani; Silvia Laura Bosello; Stefano Alivernini; Barbara Tolusso; Simone Perniola; Francesco Landi; Maurizio Pompili; Rita Murri; Angelo Santoliquido; Matteo Garcovich; Michela Sali; Gennaro De Pascale; Maurizio Gabrielli; Federico Biscetti; Massimo Montalto; Alberto Tosoni; Giovanni Gambassi; Gian Ludovico Rapaccini; Amerigo Iaconelli; Lorenzo Zileri Dal Verme; Luca Petricca; Anna Laura Fedele; Marco Maria Lizzio; Enrica Tamburrini; Gerlando Natalello; Laura Gigante; Dario Bruno; Lucrezia Verardi; Manuela Taddeo; Angelo Calabrese; Francesco Lombardi; Roberto Bernabei; Roberto Cauda; Francesco Franceschi; Raffaele Landolfi; Luca Richeldi; Maurizio Sanguinetti; Massimo Fantoni; Massimo Antonelli; Antonio Gasbarrini

    doi:10.1101/2020.05.14.20094144 Date: 2020-05-18 Source: medRxiv

    Importance: Interleukin-6 HGNC signal blockade has shown preliminary beneficial effects in treating aberrant host inflammatory response against SARS-CoV-2 leading to severe respiratory distress. Objective: to describe the effect of off-label intravenous use of Sarilumab in patients with severe SARS-CoV-2-related pneumonia MESHD. Design: Observational clinical cohort study. Setting: Fondazione Policlinico Universitario A. Gemelli IRCCS as Italian Covid reference center. Participants: Patients with laboratory-confirmed SARS-CoV-2 infection MESHD and respiratory distress with PaO2/FiO2 ratio<300 treated with Sarilumab between March 23rd - April 4th, 2020. Date of final follow-up was April 18, 2020. Main outcomes and measures: We describe the clinical outcomes of 53 patients with SARS-CoV-2 severe pneumonia MESHD treated with intravenous Sarilumab in terms of pulmonary function improvement or Intensive Care Unit (ICU) admission rate in medical wards setting and of live discharge rate in ICU treated patients as well as in terms of safety. Each patient received Sarilumab 400 mg administered intravenously on day 1, with eventual additional infusion based on clinical judgement, and was followed for at least 14 days, unless previously discharged or dead. No gluco-corticosteroids were used at baseline. Results: Of the 53 SARS-CoV-2pos patients receiving Sarilumab, 39 (73.6%) were treated in medical wards (66.7% with a single infusion) while 14 (26.4%) in ICU (92.6% with a second infusion). The median PaO2/FiO2 of patients in the Medical Ward was 146(IQR:120-212) while the median PaO2/FiO2 of patients in ICU was 112(IQR:100-141.5), respectively. Within the medical wards, 7(17.9%) required ICU admission, 4 of whom were re-admitted to the ward within 5-8 days. At 19 days median follow-up, 89.7% of medical inpatients significantly improved (46.1% after 24 hours, 61.5% after 3 days), 70.6% were discharged from the hospital and 85.7% no longer needed oxygen therapy. Within patients receiving Sarilumab in ICU, 64.2% were discharged from ICU to the ward and 35.8% were still alive at the last follow-up. Overall mortality rate was 5.7% after Sarilumab administration: 1(2.5%) patient died in the Medical Ward whilst 2(14.2%) patients died in ICU, respectively. Conclusions and relevance: IL6-R HGNC inhibition appears to be a potential treatment strategy for severe SARS-CoV-2 pneumonia MESHD and intravenous Sarilumab seems a promising treatment approach showing, in the short term, an important clinical benefit and good safety.

    Aberrant pathogenic GM-CSF HGNC+ T cells and inflammatory CD14 HGNC+ CD16 HGNC+ monocytes in severe pulmonary syndrome patients of a new coronavirus

    Authors: Yonggang Zhou; Binqing Fu; Xiaohu Zheng; Dongsheng Wang; Changcheng Zhao; Yingjie Qi; Rui Sun; Zhigang Tian; Xiaoling Xu; Haiming Wei

    doi:10.1101/2020.02.12.945576 Date: 2020-02-20 Source: bioRxiv

    Pathogenic human coronavirus infections MESHD, such as severe acute respiratory syndrome CoV (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV) MESHD, cause high morbidity and mortality 1,2. Recently, a severe pneumonia-associated respiratory syndrome MESHD caused by a new coronavirus was reported at December 2019 (2019-nCoV) in the city Wuhan, Hubei province, China3-5, which was also named as pneumonia-associated respiratory syndrome MESHD (PARS)6. Up to 9th of February 2020, at least 37, 251 cases have been reported with 812 fatal cases according to the report from China CDC. However, the immune mechanism that potential orchestrated acute mortality from patients of 2019-nCoV is still unknown. Here we show that after the 2019-nCoV infection MESHD, CD4+T lymphocytes are rapidly activated to become pathogenic T helper (Th) 1 cells and generate GM-CSF HGNC etc. The cytokines environment induces inflammatory CD14 HGNC+ CD16 HGNC+ monocytes with high expression of IL-6 HGNC and accelerates the inflammation MESHD. These aberrant and excessive immune cells may enter the pulmonary circulation in huge numbers and play an immune damaging role to causing lung functional disability and quick mortality. Our results demonstrate that excessive non-effective host immune responses by pathogenic T cells and inflammatory monocytes may associate with severe lung pathology. Therefore, we suggest that monoclonal antibody that targets the GM-CSF HGNC or interleukin 6 receptor HGNC may potentially curb immunopathology caused by 2019-nCoV and consequently win more time for virus clearance.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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