COVID-19 Evidence Alerts
from McMaster PLUSTM

Current best evidence for clinical care (more info)

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Treatment Jagannathan P, Andrews JR, Bonilla H, et al. Peginterferon Lambda-1a for treatment of outpatients with uncomplicated COVID-19: a randomized placebo-controlled trial. Nat Commun. 2021 Mar 30;12(1):1967. doi: 10.1038/s41467-021-22177-1.

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.

Discipline / Specialty Area Score
Infectious Disease
Family Medicine (FM)/General Practice (GP)
General Internal Medicine-Primary Care(US)
Hospital Doctor/Hospitalists
Internal Medicine
Comments from MORE raters

Family Medicine (FM)/General Practice (GP) rater

There is no benefit from use of a treatment that is not all that practical for use in standard primary care settings.

General Internal Medicine-Primary Care(US) rater

Because the study population was primarily young, latinx, not obese, and had few health problems, we cannot apply the results of this study to other populations, where it might have been more effective. As the authors noted, the dose and timing of the study medication also may have affected the results.

Hospital Doctor/Hospitalists rater

Compared to the amazing progress that our vaccination colleagues have made, the efforts on therapeutics continue to disappoint. In this article, an RCT of interferon for mild-mod Covid-19 had no demonstrable effects on 100 patients with mild Covid-19. A larger sample size could have theoretically found the mild differences to be statistically significant, but would be unlikely to be clinically meaningful. This looks to be a dead end.

Infectious Disease rater

Peginterferon Lambda-1a has activity against a number of viruses so it seemed reasonable to test it against SARS CoV-2. In mild to moderate infection, a single subcutaneous dose had no effect but only mild toxicity. This is a well done negative study that needed to be published. Nature Communications is to be commended for going against the trend to avoid negative studies.