In a randomized trial, a single outpatient dose was associated with decreased hospitalization and emergency department visits.

Interferon lambda induces antiviral immunity and has fewer side effects than other interferons, perhaps because its receptor has a relatively limited tissue distribution. Now, investigators report results of a phase 3 clinical trial of pegylated interferon lambda involving approximately 2000 outpatients with COVID-19 (mostly in Brazil) who presented within 7 days of symptom onset and had at least one risk factor for progression. Participants were enrolled between June 2021 and February 2022; the most common variants were Delta and Omicron. All participants were randomly assigned to receive a single subcutaneous injection of interferon lambda or placebo; 83% had previously received at least one dose of a COVID-19 vaccine.

Common risk factors for progression included age ≥50 (39%) and obesity (37%); almost 58% of participants had multiple comorbidities. Rates of hospitalization or emergency department visits were 2.7% (interferon) and 5.6% (placebo; relative risk, 0.49; decrease, 51%). To allow comparison with studies of other treatments, the investigators also reported rates of hospitalization or death due to COVID-19 (2.4% [interferon] and 3.9% [placebo]; relative risk, 0.61). The benefit of interferon lambda was greater when analyses were limited to those participants who received it within 3 days of symptom onset.

Comment

Current COVID-19 treatments — nirmatrelvir/ritonavir, remdesivir, and molnupiravir — were authorized or approved (remdesivir) based on randomized trials in unvaccinated, high-risk individuals. The strength of this study of interferon lambda is that it shows a benefit (albeit smaller than that seen in the trials of nirmatrelvir/ritonavir and remdesivir in high-risk patients) in a mostly vaccinated population. The company developing interferon lambda is in talks with the FDA. opens in new tab; as of now, the drug is not yet available.