Interferon Beta-1α ring prophylaxis to reduce household transmission of SARS-CoV-2: the Containing Coronavirus Disease-19 randomized clinical trial

Abstract

AbstractImportanceEvidence 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.ObjectiveWe undertook a ring prophylaxis study to determine whether pegylated IFNβ-1α could reduce SARS-CoV-2 household transmission.DesignA cluster randomized clinical trial of pegylated IFNβ-1α conducted in Santiago, Chile. Recruitment was conducted between December 4th2020, and 31stMay 2021, with the last follow-up completed June 29th2021.SettingThe study was conducted across 341 households in the metropolitan area of Santiago, Chile.ParticipantsIndex cases were identified from databases of those with confirmed SARS-CoV-2 from COVID-19 clinics and emergency room visits in Santiago, Chile. 5,154 index cases were assessed for eligibility, 1,372 index cases were invited to participate, and 341 index cases and their household contacts (n = 831) were enrolled in the study.InterventionHouseholds were cluster randomized to receive 125µg subcutaneous pegylated IFNβ-1α (n = 172 households, 607 participants), or standard care (n = 169 households, 565 participants).Main Outcome(s) and Measure(s)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 treatment-eligible household contacts. Four secondary outcomes were assessed including duration of viral shedding, effects on viral transmission and seroconversion, incidence of hospitalization, and incidence and severity of reported adverse events. 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.ResultsIn total, 1172 participants in 341 households underwent randomization, with 607 assigned to receive IFNβ-1α and 565 to standard care. Based on intention to treat and per protocol analyses, IFNβ-1α 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 IFNβ-1α reduced household transmissionConclusions and RelevanceRing prophylaxis with IFNβ-1α reduces the probability of SARS-CoV-2 transmission within a household.Trial RegistrationClinicaltrials.govidentifier:NCT04552379