Type III interferons (also termed IFNλ) are the first line of defence against upper respiratory tract infections. Administered interferons can be used as a prophylactic or therapeutic agent against viral infections. It was previously shown that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces the expression of type III interferons following infection, and previous studies were undertaken to establish the efficacy of exogenous pegylated IFNλ in the treatment of patients with COVID-19. Now, Reis et al. have conducted a randomized, controlled, adaptive platform trial mostly involving vaccinated adults with SARS-CoV-2 infection in Brazil and Canada to further evaluate the efficacy of a single dose of pegylated IFNλ administered within 7 days following the onset of symptoms. The authors reported that the incidence of hospitalization or an emergency department visit due to COVID-19 was significantly lower among patients who received a single dose of pegylated IFNλ than among those who received placebo. This effect was consistent across SARS-CoV-2 variants and was independent of the vaccination status of the participants. The results support the notion that a single-dose regimen of pegylated IFNλ could be introduced as an early outpatient treatment option.