Effect of Early Treatment with Pegylated Interferon Lambda for Covid-19

ABSTRACT

Background: We assessed the efficacy of a single dose of peginterferon lambda in preventing clinical events among acutely symptomatic COVID-19 outpatients. Method(s) We conducted a placebo-controlled, randomized, adaptive platform trial among predominantly vaccinated SARS-CoV-2-positive adults in Brazil and Canada receiving either one subcutaneous injection of peginterferon lambda or placebo. The primary composite endpoint was medical admission to hospital, defined as either observation in a COVID-19 emergency setting for > 6 hours, or transfer to a tertiary hospital due to symptomatic COVID-19 within 28 days post-randomization. Result(s) For this evaluation, 931 patients received peginterferon lambda and 1018 received placebo. 84% of the population were vaccinated and the trial occurred across multiple COVID-19 variants. In the primary analysis of patients, the primary outcome was reduced by 51% in the peginterferon lambda vs. placebo groups (relative risk 0.49 [25/916 vs 57/1003], 95% Bayesian credible interval 0.30-0.76, posterior probability >99.9%). This effect was maintained in subgroup analyses including COVID-19-related hospitalization alone (relative risk 0.57, 95% Bayesian credible intervals 0.33-0.95, ) and COVID-19-related hospitalization or death (Hazard ratio 0.59, 95% Bayesian credible interval 0.35- 0.97). The effects were consistent across dominant variants and vaccination status. Among individuals with a high viral level at baseline, peginterferon lambda resulted in lower viral loads by Day 7, compared to placebo. The incidence of adverse events was similar in the two groups. Conclusion(s) Among predominantly vaccinated outpatients with COVID-19, single-dose of peginterferon lambda resulted in significantly decreased clinical events.