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

Importance 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. Objective We undertook a ring prophylaxis study to determine whether pegylated IFNβ-1α could reduce SARS-CoV-2 household transmission. Design A cluster randomized clinical trial of pegylated IFNβ-1α conducted in Santiago, Chile. Recruitment was conducted between December 4th 2020, and 31st May 2021, with the last follow-up completed June 29th 2021. Setting The study was conducted across 341 households in the metropolitan area of Santiago, Chile. Participants Index 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. Intervention Households 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. Results In 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 transmission Conclusions and Relevance Ring prophylaxis with IFNβ-1α reduces the probability of SARS-CoV-2 transmission within a household. Trial Registration [Clinicaltrials.gov][1] identifier: [NCT04552379][2] ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT04552379 ### Clinical Protocols ### Funding Statement This study was funded by: BHP Holdings Pty Ltd Biogen ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Pontifical Catholic University of Chile. Ethics approval granted I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors [1]: http://Clinicaltrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04552379&atom=%2Fmedrxiv%2Fearly%2F2022%2F06%2F24%2F2022.06.13.22276369.atom