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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    Authors: Zelalem Temesgen; Charles D. Burger; Jason Baker; Christopher Polk; Claudia Libertin; Colleen Kelley; Vincent C Marconi; Robert Orenstein; Cameron Durrant; Dale Chappell; Omar Ahmed; Gabrielle Chappell; Andrew Badley

    doi:10.1101/2021.05.01.21256470 Date: 2021-05-05 Source: medRxiv

    BACKGROUND: Severe COVID19 MESHD pneumonia MESHD results from a hyperinflammatory immune response (cytokine storm, CS), characterized by GM CSF HGNC mediated activation and trafficking of myeloid cells, leading to elevation of downstream inflammatory chemokines ( MCP1 HGNC, IL8 HGNC, IP10 HGNC), cytokines ( IL6 HGNC, IL1 HGNC), and other markers of systemic inflammation MESHD ( CRP HGNC, D dimer, ferritin). CS leads to fever MESHD, hypotension MESHD, coagulopathy MESHD, respiratory failure MESHD, ARDS, and death MESHD. Lenzilumab is a novel Humaneered anti-human GM CSF HGNC monoclonal antibody that directly binds GM CSF HGNC and prevents signaling through its receptor. The LIVE AIR Phase 3 randomized, double blind, placebo controlled trial investigated the efficacy and safety of lenzilumab to assess the potential for lenzilumab to improve the likelihood of ventilator free survival (referred to herein as survival without ventilation, SWOV), beyond standard supportive care, in hospitalized subjects with severe COVID-19 MESHD. METHODS: Subjects with COVID-19 MESHD (n=520), >18 years <94% oxygen saturation on room air and/or requiring supplemental oxygen, but not invasive mechanical ventilation, were randomized to receive lenzilumab (600 mg, n=261) or placebo (n=259) via three intravenous infusions administered 8 hours apart. Subjects were followed through Day 28 following treatment. RESULTS: Baseline demographics were comparable between the two treatment groups: male, 64.7%; mean age, 60.5 years; mean BMI, 32.5 kg/m2; mean CRP HGNC, 98.36 mg/L; CRP HGNC was <150 mg/L in 77.9% of subjects. The most common comorbidities were obesity MESHD (55.1%), diabetes MESHD (53.4%), chronic kidney disease MESHD (14.0%), and coronary artery disease MESHD (13.6%). Subjects received steroids (93.7%), remdesivir (72.4%), or both (69.1%). Lenzilumab improved the likelihood of SWOV by 54% in the mITT population (HR: 1.54; 95% CI: 1.02 to 2.31, p=0.041) and by 90% in the ITT population (HR: 1.90; 1.02 to 3.52, nominal p=0.043) compared to placebo. SWOV also relatively improved by 92% in subjects who received both corticosteroids and remdesivir (1.92; 1.20 to 3.07, nominal p=0.0067); by 2.96-fold in subjects with CRP HGNC<150 mg/L and age <85 years (2.96; 1.63 to 5.37, nominal p=0.0003); and by 88% in subjects hospitalized <2 days prior to randomization (1.88; 1.13 to 3.12, nominal p=0.015). Survival was improved by 2.17-fold in subjects with CRP HGNC<150 mg/L and age <85 years (2.17; 1.04 to 4.54, nominal p=0.040). CONCLUSION: Lenzilumab significantly improved SWOV in hospitalized, hypoxic subjects with COVID-19 MESHD pneumonia MESHD over and above treatment with remdesivir and/or corticosteroids. Subjects with CRP HGNC<150 mg/L and age <85 years demonstrated an improvement in survival and had the greatest benefit from lenzilumab. NCT04351152

    Comparative Survival Analysis of Immunomodulatory Therapy for COVID-19 MESHD 'Cytokine Storm': A Retrospective Observational Cohort Study

    Authors: Sonali Narain; Dimitre Stefanov; Alice S Chau; Andrew G Weber; Galina S Marder; Blanka Kaplan; Prashant Malhotra; Ona Bloom; Audrey Liu; Martin Lesser; Negin Hajizadeh

    doi:10.1101/2020.06.16.20126714 Date: 2020-06-19 Source: medRxiv

    BackgroundCytokine storm is a marker of COVID-19 MESHD illness severity and increased mortality. Immunomodulatory treatments have been repurposed to improve mortality outcomes. MethodsWe conducted a retrospective analysis of electronic health records across the Northwell Health system. COVID-19 MESHD patients hospitalized between March 1, 2020 and April 15, 2020, were included. Cytokine storm was defined by inflammatory markers: ferritin >700ng/mL, C-reactive protein HGNC >30mg/dL, or lactate dehydrogenase >300U/L. Patients were subdivided into six groups -no immunomodulatory treatment (standard of care) and five groups that received either corticosteroids, anti- interleukin 6 HGNC ( IL-6 HGNC) antibody (tocilizumab) or anti- IL-1 HGNC therapy (anakinra) alone or in combination with corticosteroids. The primary outcome was hospital mortality. ResultsThere were 3,098 patients who met inclusion criteria. The most common comorbidities were hypertension MESHD (40-56%), diabetes MESHD (32-43%) and cardiovascular disease MESHD (2-15%). Patients most frequently met criteria with high lactate dehydrogenase (74.8%) alone, or in combination, followed by ferritin (71.4%) and C-reactive protein HGNC (9.4%). More than 80% of patients had an elevated D-dimer. Patients treated with a combination of tocilizumab and corticosteroids (Hazard Ratio [HR]: 0.459, 95% Confidence Interval [CI]: 0.295-0.714; p<0.0001) or corticosteroids alone (HR: 0.696, 95% CI: 0.512-0.946; p=0.01) had improved hospital survival compared to standard of care. Corticosteroids and tocilizumab was associated with increased survival when compared to corticosteroids and anakinra (HR: 0.612, 95% CI: 0.391-0.958; p-value=0.02). ConclusionsWhen compared to standard of care, corticosteroid and tocilizumab used in combination, or corticosteroids alone, was associated with reduced hospital mortality for patients with COVID-19 MESHD cytokine storm.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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