Paper

Interferon Beta-1α ring prophylaxis to reduce household transmission of SARS-CoV-2

Chen, Virginia, Montgomery, Samuel, Gidi-Yunge, Francisca, Stick, Stephen M, Balshaw, Robert, Hartnell, Lucy, Tebbutt, Scott, Rym Ben Othman, Borzutzky, Arturo, García-Huidobro, Diego, Ho, Joseph, Urzúa, Marcela, Iturriaga, Carolina, Karpievitch, Yuliya, Casey, Shannon, Pérez-Mateluna, Guillermo, Perret, Cecilia, Castro-Rodriguez, José A, Kollmann, Tobi, Fish, Eleanor N, Aniba, Radhouana

2022

Overview

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 IFNβ-1α could reduce SARS-CoV-2 household transmission. Methods A household cluster randomized controlled study of IFNβ-1α 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 IFNβ-1α 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 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. Conclusion Ring prophylaxis with IFNβ-1α reduces the probability of SARS-CoV-2 transmission within a household. Competing Interest Statement The authors have declared no competing interest. Clinical Trial NCT04552379 Clinical Protocols https://pubmed.ncbi.nlm.nih.gov/34388972/ 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 Data Availability All data produced in the present study are available upon reasonable request to the authors

• Publisher: Cold Spring Harbor Laboratory Press
• Subject: Bayesian analysis / Clinical trials / Coronaviruses / COVID-19 / Disease prevention / Disease transmission / Households / Patients / Severe acute respiratory syndrome coronavirus 2 / β-Interferon