ABSTRACT
Background Evidence suggests that early, robust type 1 interferon responses to SARS-CoV-2 are critical determinants for COVID-19 disease outcomes, accelerating viral clearance and limiting viral shedding. Accordingly, we undertook a ring prophylaxis study to determine whether pegylated IFN{beta}-1 could reduce SARS-CoV-2 household transmission. Methods A household cluster randomized controlled study of IFN{beta}-1 administered to non-hospitalized, symptomatic COVID-19 index cases and treatment-eligible household contacts aged 18-70 years compared to standard care, was conducted. Following randomization participants received IFN{beta}-1 on days 1, 6, and 11 or standard care. Viral shedding was determined by sequential salivary polymerase chain reaction measurements until day 29 in both study arms. A post-hoc at risk population was defined as households where the index case was positive at the start of the study and there was at least one treatment eligible contact in a household who tested negative for SARS-CoV-2. Frequentist and Bayesian analyses were undertaken to determine the effects of treatment on (i) reducing viral shedding in index cases and (ii) reducing viral transmission to post-exposure household contacts. Results In total, 1172 participants in 341 households underwent randomization, with 607 assigned to receive IFN{beta}-1 and 565 to standard care. Based on intention to treat and per protocol analyses, IFN{beta}-1 treatment was ineffective. However, in the at risk population, the relative risk of infection was reduced by 23% in treated individuals and that there was a 95% probability that IFN{beta}-1 reduced household transmission. Conclusion Ring prophylaxis with IFN{beta}-1 reduces the probability of SARS-CoV-2 transmission within a household.