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Interferon-?2b Treatment for COVID-19 Is Associated with Improvements in Lung Abnormalities.

ABSTRACT: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes coronavirus disease 2019 (COVID-19), a lung disease that may progress to systemic organ involvement and in some cases, death. The identification of the earliest predictors of progressive lung disease would allow for therapeutic intervention in those cases. In an earlier clinical study, individuals with moderate COVID-19 were treated with either arbidol (ARB) or inhaled interferon (IFN)-?2b +/-ARB. IFN treatment resulted in accelerated viral clearance from the upper airways and in a reduction in the circulating levels of the inflammatory biomarkers IL-6 and C-reactive protein (CRP). We have extended the analysis of this study cohort to determine whether IFN treatment had a direct effect on virus-induced lung abnormalities and also to ascertain whether any clinical or immune parameters are associated with worsening of lung abnormalities. Evidence is provided that IFN-?2b treatment limits the development of lung abnormalities associated with COVID-19, as assessed by CT images. Clinical predictors associated with worsening of lung abnormalities include low CD8+ T cell numbers, low levels of circulating albumin, high numbers of platelets, and higher levels of circulating interleukin (IL)-10, IL-6, and C-reactive protein (CRP). Notably, in this study cohort, IFN treatment resulted in a higher percentage of CD8+ T cells, lower tumor necrosis factor (TNF)-? levels and, as reported earlier, lower IL-6 levels. Independent of treatment, age and circulating levels of albumin and CRP emerged as the strongest predictors of the severity of lung abnormalities.

SUBMITTER: Zhou Q

PROVIDER: S-EPMC7824252 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Interferon-α2b Treatment for COVID-19 Is Associated with Improvements in Lung Abnormalities.

Zhou Qiong Q MacArthur Michael R MR He Xinliang X Wei Xiaoshan X Zarin Payam P Hanna Bola S BS Wang Zi-Hao ZH Xiang Xuan X Fish Eleanor N EN

Viruses 20201230 1

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes coronavirus disease 2019 (COVID-19), a lung disease that may progress to systemic organ involvement and in some cases, death. The identification of the earliest predictors of progressive lung disease would allow for therapeutic intervention in those cases. In an earlier clinical study, individuals with moderate COVID-19 were treated with either arbidol (ARB) or inhaled interferon (IFN)-α2b +/-ARB. IFN treatment resulte ...[more]

PMID: 33396578

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Project description:BackgroundThe efficacy of a single dose of pegylated interferon lambda in preventing clinical events among outpatients with acute symptomatic coronavirus disease 2019 (Covid-19) is unclear.MethodsWe conducted a randomized, controlled, adaptive platform trial involving predominantly vaccinated adults with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Brazil and Canada. Outpatients who presented with an acute clinical condition consistent with Covid-19 within 7 days after the onset of symptoms received either pegylated interferon lambda (single subcutaneous injection, 180 μg) or placebo (single injection or oral). The primary composite outcome was hospitalization (or transfer to a tertiary hospital) or an emergency department visit (observation for >6 hours) due to Covid-19 within 28 days after randomization.ResultsA total of 933 patients were assigned to receive pegylated interferon lambda (2 were subsequently excluded owing to protocol deviations) and 1018 were assigned to receive placebo. Overall, 83% of the patients had been vaccinated, and during the trial, multiple SARS-CoV-2 variants had emerged. A total of 25 of 931 patients (2.7%) in the interferon group had a primary-outcome event, as compared with 57 of 1018 (5.6%) in the placebo group, a difference of 51% (relative risk, 0.49; 95% Bayesian credible interval, 0.30 to 0.76; posterior probability of superiority to placebo, >99.9%). Results were generally consistent in analyses of secondary outcomes, including time to hospitalization for Covid-19 (hazard ratio, 0.57; 95% Bayesian credible interval, 0.33 to 0.95) and Covid-19-related hospitalization or death (hazard ratio, 0.59; 95% Bayesian credible interval, 0.35 to 0.97). The effects were consistent across dominant variants and independent of vaccination status. Among patients with a high viral load at baseline, those who received pegylated interferon lambda had lower viral loads by day 7 than those who received placebo. The incidence of adverse events was similar in the two groups.ConclusionsAmong predominantly vaccinated outpatients with Covid-19, the incidence of hospitalization or an emergency department visit (observation for >6 hours) was significantly lower among those who received a single dose of pegylated interferon lambda than among those who received placebo. (Funded by FastGrants and others; TOGETHER ClinicalTrials.gov number, NCT04727424.).

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Interferon-?2b Treatment for COVID-19 Is Associated with Improvements in Lung Abnormalities.

Publications

Interferon-α2b Treatment for COVID-19 Is Associated with Improvements in Lung Abnormalities.

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