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HGNC Genes

SARS-CoV-2 proteins

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    Clinical course and risk factors for in-hospital mortality of 205 patients with SARS-CoV-2 pneumonia MESHD in Como, Lombardy Region, Italy

    Authors: Mauro Turrini; Angelo Gardellini; Livia Beretta; Lucia Buzzi; Stefano Ferrario; Sabrina Vasile; Raffaella Clerici; Andrea Colzani; Luigi Liparulo; Giovanni Scognamiglio; Gianni Imperiali; Giovanni Corrado; Antonella Strada; Marco Galletti; Nunzio Castiglione; Claudio Zanon

    doi:10.1101/2021.02.25.20134866 Date: 2021-03-05 Source: medRxiv

    Importance: With randomized clinical trials ongoing and vaccine still a long distance away, efforts to repurpose old medications used for other diseases provide hope for treatment of COVID-19 MESHD. Objectives: To examine the risk factors for in-hospital mortality and describe the effectiveness of different treatment strategies in a real-life setting of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia MESHD. Design: Real-life single-center study during the Lombardy COVID-19 MESHD outbreak. Setting: Valduce Hospital in Como, Lombardy Region, Italy. Participants: 205 laboratory-confirmed patients presenting with SARS-Cov-2 pneumonia MESHD requiring hospitalization. Interventions: All patients received best supportive care and, based on their clinical needs and comorbidities, specific interventions that included the main drugs being tested for repurposing to treat COVID-19 MESHD, such as hydroxychloroquine, anticoagulation, antiviral drugs, steroids or interleukin-6 HGNC pathway inhibitors. Main outcomes and measures: Clinical, laboratory and treatment characteristics were analyzed with univariate and multivariate logistic regression methods to explore their impact on in-hospital mortality and compared with current literature data. Results: Univariate analyses for clinical variables showed prognostic significance for age equal or greater than 70 years (estimated 28-days survival: 21.4 vs 67.4%; p<0.0001), presence of 2 or more relevant comorbidities (35.3 vs 61.8%; p=0.0008), ratio of arterial oxygen partial pressure to fractional inspired oxygen (P/F) less than 200 at presentation (21-days survival: 14.7 vs 52.4%;p<0.0001), high levels of lactate dehydrogenase (LDH) (26.4 vs 65.3%; p=0.0001), and elevated C-reactive protein HGNC (CRP) values (25.4 vs 74.9%; p=0.0001), while no statistical significance was found for all the other clinical variables tested. At univariate analysis for the different treatment scheduled, prognostic significance for survival was showed for intermediate or therapeutic-dose anticoagulation (estimated 28-days survival: 37.1 vs 23.4%; p=0.0001), hydroxychloroquine (35.7 vs 27.3%; p=0.0029), early antiviral therapy with lopinavir/ritonavir (60.1 vs 22.4%; p<0.0001), late short-course of steroids (47.9 vs 18.2%; p<0.0001) or tocilizumab therapy (69.4 vs 29.4%; p=0.0059). Multivariable regression confirmed increasing odds of in-hospital death associated with age older than 70 years (odds ratio 3.26, 95% CI 1.81 - 5.86; p<0.0001) and showed a reduction in mortality for patients treated with anticoagulant (-0.37, 0.49 - 0.95; p=0.0273), antiviral (-1.22, 0.16 - 0.54; p<0.0001), or steroids (-0.59, 0.35 - 0.87; p=0.0117) therapy.

    Prognostic value of thrombin HGNC generation parameters in hospitalized COVID-19 MESHD patients 

    Authors: María Eugenia de la Morena-Barrio; Carlos Bravo-Pérez; Antonia Miñano; Belén de la Morena-Barrio; María Piedad Fernandez-Perez; Enrique Bernal; José Miguel Gómez-Verdu; María Teresa Herranz; Vicente Vicente; Javier Corral; María Luisa Lozano

    doi:10.21203/rs.3.rs-115220/v1 Date: 2020-11-24 Source: ResearchSquare

    Background. SARS-CoV-2 infection MESHD ARS-CoV-2 infection increases MESHDthe risk of t hrombosis MESHDby different mechanisms not fully characterized. Although still debated, an increase in D-dimer has been proposed as a first-line hemostasis test associated with t hromboembolic MESHDrisk and unfavorable prognosis. Objective. We aim to systematically and comprehensively evaluate the association between t hrombin HGNCgeneration parameters and the inflammatory and hypercoagulable state, as well as their prognostic value in COVID-19 MESHD patientsMethods. A total of 127 hospitalized patients with confirmed COVID-19 MESHD, 24 hospitalized patients with SARS-CoV-2-negative p neumonia MESHDand 12 healthy subjects were included. Clinical characteristics, t hrombin HGNCgeneration triggered by tissue factor with and without soluble thrombomodulin, and also by silica, as well as other biochemical parameters were assessed.Results. Despite the frequent use of heparin, COVID-19 MESHD patients had similar t hrombin HGNCgeneration than healthy controls. In COVID-19 MESHD patients, the t hrombin HGNCgeneration lag-time positively correlated with markers of cell lysis (LDH), i nflammation MESHD(CRP, I L-6) HGNC and coagulation (D-dimer), while the endogenous t hrombin HGNCpotential (ETP) inversely correlated with D-dimer and LDH, and positively correlated with f ibrinogen HGNClevels. Patients with more prolonged lag-time and decreased ETP presented with increased ISTH-DIC scores, and had more severe disease (vascular events and d eath) MESHD. The ROC curve and Kaplan Meier estimate indicated that the D-dimer/ETP ratio was associated with in-hospital mortality (HR 2.5; p=0.006), and with the occurrence of major adverse events (composite end-point of vascular events and d eath) MESHD (HR 2.38; p=0.004).Conclusions. The t hrombin HGNCgeneration ETP and lag-time variables correlate with thromboinflammatory markers, and the D-dimer/ETP ratio can predict major adverse events in COVID-19 MESHD.

    Anakinra To Prevent Respiratory Failure In COVID-19 MESHD

    Authors: Evdoxia Kyriazopoulou; Periklis Panagopoulos; Simeon Metallidis; George Dalekos; Garyfallia Poulakou; Nikolaos Gatselis; Eleni Karakike; Maria Saridaki; Georgia Loli; Aggelos Stefos; Danai Prasianaki; Sarah Georgiadou; Olga Tsachouridou; Vasileios Petrakis; Konstantinos Tsiakos; Maria Kosmidou; Vassiliki Lygoura; Maria Dareioti; Haralampos Milionis; Ilias C Papanikolaou; Karolina Akinosoglou; Dimitra-Melia Myrodia; Areti Gravani; Aliki Stamou; Theologia Gkavogianni; Konstantina Katrini; Theodoros Marantos; Ioannis P Trontzas; Konstantinos Syrigos; Lukas Chatzis; Stamatios Chatzis; Nikolaos Vechlidis; Christina Avgoustou; Stamatios Chalvatzis; Miltiades Kyprianou; Jos WM van der Meer; jesper eugen-olsen; Mihai Netea; Evangelos Giamarellos-Bourboulis

    doi:10.1101/2020.10.28.20217455 Date: 2020-10-29 Source: medRxiv

    Introduction The management of pneumonia MESHD caused by SARS-CoV-2 should rely on early recognition of the risk for progression to severe respiratory failure MESHD ( SRF HGNC SRF MESHD) and its prevention. We investigated if early suPAR (soluble urokinase plasminogen activator receptor HGNC)-guided anakinra treatment could prevent COVID-19 MESHD-assocated SRF HGNC. Methods In this open-label prospective trial, 130 patients admitted with SARS-CoV-2 pneumonia SARS-CoV-2 MESHD and suPAR levels [≥]6 g/l were assigned to subcutaneous anakinra 100mg once daily for 10 days. The primary outcome was the incidence of SRF MESHD SRF HGNC at day 14. Secondary outcomes were 30-day mortality, changes in sequential organ failure assessment (SOFA) score, of cytokine-stimulation pattern and of circulating inflammatory mediators. Equal number of propensity score-matched comparators for comorbidities, severity on admission and standard-of care (SOC) were studied. Results The incidence of SRF MESHD SRF HGNC was 22.3% (95% CI, 16.0-30.2%) among anakinra-treated patients and 59.2% (95% CI, 50.6-67.3%; P: 4.6 x 10-8) among SOC comparators (hazard ratio, 0.30; 95%CI, 0.20-0.46). 30-day mortality was 11.5% (95% CI, 7.1-18.2%) and 22.3% (95% CI, 16.0-30.2%) respectively (hazard ratio 0.49; 95% CI 0.25-0.97%; P: 0.041). Anakinra treatment was associated with decrease in SOFA score and in circulating interleukin (IL)-6 HGNC, sCD163 and sIL2-R; the serum IL-10 HGNC/ IL-6 HGNC ratio on day 7 was inversely associated with the change in SOFA score. Duration of stay at the intensive care unit and at hospital was shortened compared to the SOC group; the cost of hospitalization was decreased. Conclusions Early suPAR-guided anakinra treatment is associated with decrease of the risk for SRF MESHD SRF HGNC and restoration of the pro- /anti-inflammatory balance.

    Transcriptional Profiling of Leukocytes in Critically Ill COVID19 MESHD Patients: Implications for Interferon Response and Coagulation

    Authors: Sean E. Gill; Claudia C. dos Santos; David B. O’Gorman; David E. Carter; Eric K. Patterson; Marat Slessarev; Claudio Martin; Mark Daley; Michael R. Miller; Gediminas Cepinskas; Douglas D. Fraser

    doi:10.21203/rs.3.rs-63632/v2 Date: 2020-08-21 Source: ResearchSquare

    Background: COVID19 MESHD is caused by the SARS-CoV-2 virus MESHD and has been associated with severe inflammation MESHD leading to organ dysfunction and mortality. Our aim was to profile the transcriptome in leukocytes from critically ill patients positive for COVID19 MESHD compared to those negative for COVID19 MESHD to better understand the COVID19 MESHD associated host response. For these studies, all patients admitted to our tertiary care intensive care unit (ICU) suspected of being infected with SARS-CoV-2, using standardized hospital screening methodologies, had blood samples collected at the time of admission to the ICU. Transcriptome profiling of leukocytes via ribonucleic acid sequencing (RNAseq) was then performed and differentially expressed genes as well as significantly enriched gene sets were identified.Results: We enrolled seven COVID19 MESHD+ (PCR positive, 2 SARS-CoV-2 genes) and seven age- and sex-matched COVID19 MESHD- (PCR negative) control ICU patients. Cohorts were well-balanced with the exception that COVID19 MESHD- patients had significantly higher total white blood cell counts and circulating neutrophils and COVID19 MESHD+ patients were more likely to suffer bilateral pneumonia MESHD. The mortality rate for this cohort of COVID19 MESHD+ ICU patients was 29%. As indicated by both single-gene based and gene set (GSEA) approaches, the major disease-specific transcriptional responses of leukocytes in critically ill COVID19 MESHD+ ICU patients were: (i) a robust overrepresentation of interferon related gene expression; (ii) a marked decrease in the transcriptional level of genes contributing to general protein synthesis and bioenergy metabolism; and (iii) the dysregulated expression of genes associated with coagulation, platelet function, complement activation, and tumour necrosis factor MESHD/ interleukin 6 HGNC signalling.  Conclusions: Our findings demonstrate that critically ill COVID19 MESHD+ patients on day 1 of admission to the ICU display a unique leukocyte transcriptional profile that distinguishes them from COVID19 MESHD- patients, providing guidance for future targeted studies exploring novel prognostic and therapeutic aspects of COVID19 MESHD.

    Point mutation bias in SARS-CoV-2 variants results in increased ability to stimulate inflammatory responses

    Authors: Masato Kosuge; Emi Furusawa-Nishii; Koyu Ito; Yoshiro Saito; Kouetsu Ogasawara

    doi:10.21203/rs.3.rs-48745/v1 Date: 2020-07-25 Source: ResearchSquare

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection MESHD induces severe pneumonia MESHD and is the cause of a worldwide pandemic. Coronaviruses, including SARS-CoV-2, have RNA proofreading enzymes in their genomes, resulting in fewer gene mutations than other RNA viruses. Nevertheless, variants of SARS-CoV-2 exist and may induce different symptoms; however, the factors and the impacts of these mutations are not well understood. We found that there is a bias to the mutations occurring in SARS-CoV-2 variants, with disproportionate mutation to uracil (U). These point mutations to U are mainly derived from cytosine (C), which is consistent with the substrate specificity of host RNA editing enzymes, APOBECs. We also found the point mutations which are consistent with other RNA editing enzymes, ADARs. For the C-to-U mutations, the context of the upstream uracil and downstream guanine from mutated position was found to be most prevalent. Further, the degree of increase of U in SARS-CoV-2 variants correlates with enhanced production of cytokines, such as TNF-a HGNC and IL-6 HGNC, in cell lines when compared with stimulation by the ssRNA sequence of the isolated virus in Wuhan. Therefore, RNA editing is a factor for mutation bias in SARS-CoV-2 variants, which affects host inflammatory cytokines production.

    Clinical characteristics, outcomes and follow-up of COVID-19 MESHD infection in cancer patients

    Authors: Minghao Fang; Jianmin Ling; Yanqing Wu; Zhaohua Wang; Le Yang

    doi:10.21203/rs.3.rs-33276/v1 Date: 2020-06-04 Source: ResearchSquare

    Purpose: The study is to describe the clinical characteristics, outcomes and follow-up  of cancer MESHD patients with COVID-19 MESHD. Methods: Clinical records, demographic data, signs and symptoms, laboratory results, cytokine profiles, chest CT scans, comorbidities, treatments, clinical outcomes, and RT-PCR of SARS-CoV-2 after discharge were retrospectively collected for fifty-six cancer MESHD patients with laboratory-confirmed COVID-19 MESHD pneumonia MESHD who were admitted to Tongji Hospital of Huazhong University of Science and Technology, Wuhan, China, from Feb 1 to Apr 1 HGNC, 2020. Evidence of cytokine profiles were assessed by testing for the IL1β HGNC, IL2R HGNC, IL6 HGNC, IL8 HGNC, IL10 HGNC, and TNF - α HGNC in the peripheral blood of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infected cancer MESHD patients. Results: Of 2143 patients with COVID-19 MESHD, 56 cancer MESHD patients were included. The patients were divided into two groups, as cancer MESHD survivors, and cancer MESHD non-survivors. 12 (21%) patients with lymphopenia MESHD (0.5 [0.3-0.7]) had died during hospital stay. In non-survivors, IL2R HGNC, IL6 HGNC, and IL10 HGNC were higher. 3(6.8%) cancer MESHD survivors with COVID-19 MESHD had positive RT-PCR test results again shortly after discharge. Conclusion: The mortality rate of COVID-19 MESHD among cancer MESHD patients are considerable. Cancer non-survivors are characterized by more severe lymphopenia MESHD and a higher levels of cytokines. Recovered cancer MESHD survivors still may be virus carriers.

    A blood-based comprehensive and systems-level analysis of disease stages, immune regulation and symptoms in COVID-19 MESHD patients

    Authors: Anguraj Sadanandam; Tobias Bopp; Santosh Dixit; David JHF Knapp; Chitra Priya Emperumal; Krishnaraj Rajalingam; Alan Melcher; Nagarajan Kannan

    doi:10.21203/rs.3.rs-30473/v1 Date: 2020-05-20 Source: ResearchSquare

    COVID-19 MESHD patients show significant clinical heterogeneity in presentation and outcomes that makes pandemic control and strategy difficult; optimising management requires a systems biology approach of understanding the disease. Here we sought to understand and infer complex system-wide changes in patients infected with coronaviruses ( SARS-CoV and SARS-CoV-2 MESHD; n=38 and 57 samples) at two different disease stages compared with healthy individuals (n=16) and patients with other infections (n=144). We applied inferential statistics/machine-learning approaches (the COVID-engine platform) to RNA profiles derived from peripheral blood mononuclear cells (PBMCs). Compared to healthy individuals, an integrated blood-based gene signatures distinguished acute-like (mimicking coronavirus-infected MESHD patients with prolonged hospitalisation) from recovering-like patients. These signatures also hierarchically represented systems-level parameters associated with PBMC including dysregulated cytokines, genes, pathways, networks of pathways/concepts, immune status, and cell types. Proof-of-principle confirmatory observations included PBMC-associated increases in ACE2 HGNC, cytokine storm-associated IL6 HGNC, enhanced innate immunity (macrophages and neutrophils), and lower adaptive T and B cell immunity in patients with acute-like disease compared to those with recovery-like disease. Patients in the recovery-like stage had significantly enhanced TNF HGNC, IFN-g HGNC, anti-viral, HLA-DQA1 HGNC, and HLA-F HGNC gene expression and cytolytic activity, and reduced pro-viral gene expression compared to those in the acute-like stage in PBMC. Besides, PBMC-derived surrogate-based approach revealed overlapping genes associated with comorbidities (associated diabetes MESHD), and disease-like symptoms (associated with thromboembolism MESHD, pneumonia MESHD, lung disease MESHD and septicaemia MESHD). Overall, our study involving PBMC-based RNA profiling may further help understand complex and variable systems-wide responses displayed by coronavirus-infected MESHD patients.

    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.

    Epidemiological,clinical and radiological findings in medical staff with COVID-19 MESHD in Wuhan, China: a single-centered, retrospective cohort study

    Authors: Jie Liu; Liu Ouyang; Pi Guo; Haisheng Wu; Peng Fu; Yuliang Chen; Dan Yang; Xiaoyu Han; Yukun Cao; Osamah Alwalid; Hanping Wu; Heshui Shi; Fan Yang; Yu Hu; Chuansheng Zheng

    doi:10.21203/rs.3.rs-28753/v1 Date: 2020-05-14 Source: ResearchSquare

    Backgrounds In December 2019, a pneumonia MESHD associated with the severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) emerged in Wuhan city, China. As of 20 Feb 2020, a total of 2,055 medical staff infected with SARS-Cov-2 in China had been reported. The predominant cause of the infection and the failure of protection among medical staff remains unclear. We sought to explore the epidemiological, clinical characteristics and prognosis of novel coronavirus-infected MESHD medical staff.Methods Medical staff who infected with SARS-Cov-2 and admitted to Union Hospital, Wuhan between 16 Jan, 2020 to 25 Feb, 2020 were included retrospectively. Epidemiological, clinical and radiological data were compared by occupation and analyzed with the Kaplan-Meier and Cox regression methods.Results A total of 101 medical staff (32 males and 69 females; median age: 33 years old) were included in this study and 74% were nurses. None had an exposure to Huanan seafood wholesale market or wildlife. A small proportion of the cohort had contact with specimens (3%) as well as patients infected with SARS-Cov-2 in fever clinics (15%) and isolation wards (3%). 80% of medical staff showed abnormal IL-6 HGNC levels and 33% had lymphocytopenia MESHD. Chest CT mainly manifested as bilateral (62%), septal/subpleural (77%) and ground­glass opacities (48%). The major differences between doctors and nurses manifested in laboratory indicators. As of the last observed date, no patient was transferred to intensive care unit or died, and 98 (97%) had been discharged. Fever MESHD (HR=0.57; 95% CI 0.36-0.90) and IL-6 HGNC levels greater than >2.9 pg/ml (HR=0.50; 95% CI 0.30-0.86) on admission were unfavorable factors for discharge.Conclusions Our findings suggested that the infection of medical staff mainly occurred at the early stages of SARS-CoV-2 epidemic MESHD in Wuhan, and only a small proportion of infection had an exact mode. Meanwhile, medical staff infected with COVID-19 MESHD have relatively milder symptoms and favorable clinical course than other ordinary patients, which may be partly due to their medical expertise, younger age and less underlying diseases. The potential risk factors of presence of fever MESHD and IL-6 HGNC levels greater than >2.9 pg/ml could help to identify medical staff with poor prognosis at an early stage.

    Disruption of the CCL5 HGNC/ RANTES HGNC- CCR5 HGNC Pathway Restores Immune Homeostasis and Reduces Plasma Viral Load in Critical COVID-19 MESHD

    Authors: Bruce K Patterson; Harish Seethamraju; Kush Dhody; Michael J Corley; Kazemm Kazempour; Jay P Lalezari; Alina PS Pang; Christopher Sugai; Edgar B Francisco; Amruta Pise; Hallison Rodrigues; Matthew Ryou; Helen L Wu; Gabriela M Webb; Byung S Park; Scott Kelly; Nadar Pourhassan; Alena Lelic; Lama Kdouh; Monica Herrera; Eric Hall; Enver Aklin; Lishomwa Ndhlovu; Jonah B Sacha

    doi:10.1101/2020.05.02.20084673 Date: 2020-05-05 Source: medRxiv

    Severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), the causative agent of coronavirus disease 2019 MESHD ( COVID-19 MESHD), is now pandemic with nearly three million cases reported to date. Although the majority of COVID-19 MESHD patients experience only mild or moderate symptoms, a subset will progress to severe disease with pneumonia MESHD and acute respiratory distress syndrome MESHD ( ARDS MESHD) requiring mechanical ventilation. Emerging results indicate a dysregulated MESHD immune response characterized by runaway inflammation MESHD, including cytokine release syndrome (CRS), as the major driver of pathology in severe COVID-19 MESHD. With no treatments currently approved for COVID-19 MESHD, therapeutics to prevent or treat the excessive inflammation MESHD in severe disease caused by SARS-CoV-2 infection MESHD are urgently needed. Here, in 10 terminally-ill, critical COVID-19 MESHD patients we report profound elevation of plasma IL-6 HGNC and CCL5 HGNC ( RANTES HGNC), decreased CD8 HGNC+ T cell levels, and SARS-CoV-2 plasma viremia MESHD. Following compassionate care treatment with the CCR5 HGNC blocking antibody leronlimab, we observed complete CCR5 HGNC receptor occupancy on macrophage and T cells, rapid reduction of plasma IL-6 HGNC, restoration of the CD4 HGNC/ CD8 HGNC ratio, and a significant decrease in SARS-CoV-2 plasma viremia MESHD. Consistent with reduction of plasma IL-6 HGNC, single-cell RNA-sequencing revealed declines MESHD in transcriptomic myeloid cell clusters expressing IL-6 HGNC and interferon-related genes. These results demonstrate a novel approach to resolving unchecked inflammation MESHD, restoring immunologic deficiencies MESHD, and reducing SARS-CoV-2 plasma viral load via disruption of the CCL5 HGNC- CCR5 HGNC axis, and support randomized clinical trials to assess clinical efficacy of leronlimab-mediated inhibition of CCR5 HGNC for COVID-19 MESHD.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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