Early Treatment with Pegylated Interferon Lambda for Covid-19

Abstract

Background: The 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.

Methods: We 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.

Results: A 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.

Conclusions: Among 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.).

Figure 1. Randomization and Follow-up of the Patients.

Only the results in the interferon group as compared with the placebo group are reported in this article.

Figure 2. Subgroup Analyses.

Panel A shows the absolute reduction (with the 95% Bayesian credible interval) in the risk of hospitalization (or transfer from an emergency department to a tertiary hospital) owing to symptomatic coronavirus disease 2019 (Covid-19) or an emergency department visit due to Covid-19 (defined as observation for >6 hours) within 28 days after randomization (the primary composite outcome) among patients receiving peginterferon lambda and those receiving placebo (intention-to-treat population). SARS-CoV-2 denotes severe acute respiratory syndrome coronavirus 2. 𝙸 bars indicate the 95% credible interval. Panel B shows treatment effects according to subgroup. Panel C shows treatment effects according to SARS-CoV-2 dominant variant of concern. Arrows indicate that the 95% Bayesian credible interval extends outside the graphed range. In Panels A, B, and C, horizontal bars indicate the 95% credible interval. Panel D shows an alluvial plot of the change in viral load at day 7, as compared with baseline. The log₁₀ viral loads are denoted by the numbers in the gray columns. Values are rounded to the nearest integer for plotting. Most patients had a reduction in viral load, and a small percentage had an increase by day 7. Panel E shows the change in viral load in patients with a high viral load at baseline. All data are presented in box-and-whisker plots. The whiskers indicate the range, the top and bottom of the boxes indicate the interquartile range, and the horizontal line within each box indicates the median. N2 denotes the N2 gene of SARS-CoV-2.