Dataset Information

The Activin/FLRG Pathway Associates with Poor COVID-19 Outcomes in Hospitalized Patients.

ABSTRACT: A subset of hospitalized COVID-19 patients, particularly the aged and those with comorbidities, develop the most severe form of the disease, characterized by acute respiratory disease syndrome (ARDS), coincident with experiencing a "cytokine storm." Here, we demonstrate that cytokines which activate the NF-κB pathway can induce activin A. Patients with elevated activin A, activin B, and FLRG at hospital admission were associated with the most severe outcomes of COVID-19, including the requirement for mechanical ventilation, and all-cause mortality. A prior study showed that activin A could decrease viral load, which indicated there might be a risk to giving COVID-19 patients an inhibitor of activin. To evaluate this, the role for activin A was examined in a hamster model of SARS-CoV-2 infection, via blockade of activin A signaling. The hamster model demonstrated that use of an anti-activin A antibody did not worsen the disease and there was no evidence for increase in lung viral load and pathology. The study indicates blockade of activin signaling may be beneficial in treating COVID-19 patients experiencing ARDS.

SUBMITTER: McAleavy M

PROVIDER: S-EPMC8773081 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Activin/FLRG Pathway Associates with Poor COVID-19 Outcomes in Hospitalized Patients.

McAleavy Megan M Zhang Qian Q Ehmann Peter J PJ Xu Jianing J Wipperman Matthew F MF Ajithdoss Dharani D Pan Li L Wakai Matthew M Simonson Raphael R Gadi Abhilash A Oyejide Adelekan A Hamon Sara C SC Boyapati Anita A Morton Lori G LG Shavlakadze Tea T Kyratsous Christos A CA Glass David J DJ

Molecular and cellular biology 20211101 1

A subset of hospitalized COVID-19 patients, particularly the aged and those with comorbidities, develop the most severe form of the disease, characterized by acute respiratory disease syndrome (ARDS), coincident with experiencing a "cytokine storm." Here, we demonstrate that cytokines which activate the NF-κB pathway can induce activin A. Patients with elevated activin A, activin B, and FLRG at hospital admission were associated with the most severe outcomes of COVID-19, including the requiremen ...[more]

PMID: 34723652

Similar Datasets

Project description:BackgroundDue to pro-inflammatory and hypercoagulation states, COVID-19 infection is believed to increase the risk of stroke and worsen the outcomes of the patients having pre-existing cerebrovascular diseases (CeVD). There is limited literature on prevalence of pre-existing CeVD in COVID-19 patients, and outcomes are unknown. The objective of this meta-analysis is to evaluate the outcomes of COVID-19 patients with pre-existing CeVD.MethodsEnglish full-text-observational studies having data on epidemiological characteristics of COVID-19 patients were identified searching PubMed, Web of Science, and Scopus using MeSH-terms COVID-19 OR coronavirus OR SARS-CoV-2 OR 2019-nCoV from December 1, 2019 to April 30, 2020. Studies having CeVD or stroke as one of the pre-existing comorbidities and described outcomes including intensive care unit (ICU) admission, mechanical ventilation utilization, and mortality were selected with consensus of three reviewers. Following MOOSE protocol, 11 studies were included. The pooled prevalence of CeVD and outcomes were calculated. Meta-regression was performed, and correlation coefficient (r) and odds ratio (OR) were estimated to evaluate the effects of pre-existing CeVD on outcomes of COVID-19 patients. Meta-analysis with random-effects model was used to calculate OR along with its 95% CI from the studies containing data on composite poor outcome.ResultsOut of 8/11 studies showing data on mortality and mechanical ventilation, and 7/11 on ICU admission, pooled prevalence of pre-existing CeVD was 4.4% (244/4987). In age-adjusted meta-regression analysis, pre-existing CeVD was associated with ICU admission [r: 0.60; OR: 1.82 (1.25-2.69)], mechanical ventilation [r: 0.29; OR: 1.33 (1.09-1.63)], and mortality [r: 0.35; OR: 1.42 (1.14-1.77)] amongst COVID-19 hospitalizations. 9/11 studies reported data on binary composite outcomes, the pooled prevalence of pre-existing CeVD was 4.3% (155/3603) and 7.46% (83/1113) amongst COVID-19 hospitalizations and COVID-19 hospitalization-related poor outcomes, respectively. In meta-analysis, COVID-19 patient with pre-existing CeVD had 2.67-fold (1.75-4.06) higher odds of poor outcomes.ConclusionCOVID-19 patients with pre-existing cerebrovascular disease have poor outcomes and extra precautions should be taken in managing such patients during the ongoing pandemic.

Project description:The lack of available biomarkers for diagnosing and predicting different stages of coronavirus disease 2019 (COVID-19) is currently one of the main challenges that clinicians are facing. Recent evidence indicates that the plasma levels of specific miRNAs may be significantly modified in COVID-19 patients. Large-scale deep sequencing analysis of small RNA expression was performed on plasma samples from 40 patients hospitalized for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (between March and May 2020) (median 13.50 [IQR 9–24] days since symptoms initiation) and 21 healthy noninfected individuals. Patients were categorized as hospitalized not requiring oxygen therapy (n = 6), hospitalized requiring low-flow oxygen (n = 23), and hospitalized requiring high-flow oxygen support (n = 11). A total of 1218 different micro(mi)RNAs were identified. When compared with healthy noninfected donors, SARS-CoV-2 infected patients showed significantly (fold change [FC] >1.2 and adjusted p [padj] <0.05) altered expression of 190 miRNAs. The top 10 differentially expressed (DE) miRNAs were miR-122-5p, let-7b-5p, miR-146a-5p, miR-342-3p, miR-146b-5p, miR-629-5p, miR-24-3p, miR-12136, let-7a-5p, and miR-191-5p, which displayed FC and padj values ranging from 153 to 5 and 2.51 × 10-32 to 2.21 × 10-21, respectively, which unequivocally diagnosed SARS-CoV-2 infection. No differences in blood cell counts and biochemical plasma parameters, including interleukin 6, ferritin and D-dimer, were observed between COVID-19 patients on high-flow oxygen therapy, low-flow oxygen therapy, or not requiring oxygen therapy. Notably, 31 significantly deregulated miRNAs were found when patients on high- and low-flow oxygen therapy were compared. Similarly, 6 DE miRNAs were identified between patients on high flow and those not requiring oxygen therapy. SARS-CoV-2 infection generates a specific miRNA signature in hospitalized patients. Furthermore, specific miRNA profiles are associated with COVID-19 prognosis in severe patients.

Dataset Information

The Activin/FLRG Pathway Associates with Poor COVID-19 Outcomes in Hospitalized Patients.

Publications

The Activin/FLRG Pathway Associates with Poor COVID-19 Outcomes in Hospitalized Patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets