Peginterferon Lambda-1a for treatment of outpatients with uncomplicated COVID-19: a randomized placebo-controlled trial

Abstract

Type III interferons have been touted as promising therapeutics in outpatients with coronavirus disease 2019 (COVID-19). We conducted a randomized, single-blind, placebo-controlled trial (NCT04331899) in 120 outpatients with mild to moderate COVID-19 to determine whether a single, 180 mcg subcutaneous dose of Peginterferon Lambda-1a (Lambda) within 72 hours of diagnosis could shorten the duration of viral shedding (primary endpoint) or symptoms (secondary endpoint). In both the 60 patients receiving Lambda and 60 receiving placebo, the median time to cessation of viral shedding was 7 days (hazard ratio [HR] = 0.81; 95% confidence interval [CI] 0.56 to 1.19). Symptoms resolved in 8 and 9 days in Lambda and placebo, respectively, and symptom duration did not differ significantly between groups (HR 0.94; 95% CI 0.64 to 1.39). Both Lambda and placebo were well-tolerated, though liver transaminase elevations were more common in the Lambda vs. placebo arm (15/60 vs 5/60; p = 0.027). In this study, a single dose of subcutaneous Peginterferon Lambda-1a neither shortened the duration of SARS-CoV-2 viral shedding nor improved symptoms in outpatients with uncomplicated COVID-19.

Structurally and functionally distinct early antibody responses predict COVID-19 disease trajectory and mRNA vaccine response

“…Mice were intratracheally administered immune complexes composed of purified, polyclonal anti-SARS- bronchoalveolar lavage (BAL) was performed and the collected fluid was promptly analyzed for immune cell and cytokine content. This time point was chosen based on established mouse models of immune complex mediated activities in the lung 12,13 .…”

“…Longitudinal samples from 109 SARS-CoV-2-infected outpatients were obtained from a phase 2 randomized controlled trial of Peginterferon Lambda-1a (Lambda, NCT04331899). Inclusion/exclusion criteria and the study protocol for the trial have been published 12 . Plasma samples were collected up to 24 hours before first vaccine dose, up to 24 hours before second dose, and 4-8 weeks after second vaccine dose.…”

“…Overall, this cohort enabled a granular prospective study of the evolution of the different antibody types early after infection in patients with distinct clinical outcomes. Of note, the original purpose of this prospective study was to assess whether interferon lambda could modulate the course of mild COVID-19; thus, study subjects were randomized to receive pegylated interferon lambda (lambda) or placebo after enrollment 12 . Administration of lambda had no effect on the clinical course of disease 12 and there was no correlation between the generation of neutralizing antibodies after infection and receipt of lambda (Extended Data Fig.…”

Harnessing Type I IFN Immunity Against SARS-CoV-2 with Early Administration of IFN-β

“…Although the study was not powered to look at clinical evolution, 5 (16.7%) in the placebo group and 1 (3.3%) in the peg-IFN-λ group required visit to the emergency room by day 14. On the other hand, another study with a similar design showed that peg-IFN-λ did not shorten the duration of viral shedding [ 152 ]. Differences in results between these two studies may be due to differences in baseline viral loads (58% of subjects with >6.0 log copies/ml in the former vs. 75% with <5.5 log copies/ml in the latter) as well as differences in SARS-CoV-2 antibody positivity at baseline (0% in the treatment group and 10% in the placebo group in the former vs. 25% in the treatment group and 46.7% in the placebo group in the latter).…”

The Fight against COVID-19 on the Multi-Protease Front and Surroundings: Could an Early Therapeutic Approach with Repositioning Drugs Prevent the Disease Severity?

“…Some immunotherapies targeted directly to the cytokine storm have been evaluated in COVID-19 patients [129,130]. However, it has been evident that an optimal benefit of anti-cytokine therapies may be plausible if administered during a restricted window of time, at the onset of "cytokine storm" but before sudden disease causes irreparable tissue injury [131,132].…”