Proportion of Hospitalizations Preventable with Increased Oral SARS-CoV-2 Antiviral Treatment

We estimated the proportion of hospitalizations that could have been averted had all eligible high-risk adults with SARS-CoV-2 infection in a clinical cohort been treated with an oral SARS-CoV-2 antiviral agent early in infection. Among 3,037 patients with risk factors for progressing to severe COVID-19, 946 (31.1%) received an oral antiviral prescription (834 nirmatrelvir and 112 molnupiravir). Only 3.0% of treated patients vs 9.1% of untreated patients were hospitalized (adjusted risk ratio [RR]=0.27; 95% confidence interval [CI]: 0.18-0.41). If all patients had been treated, an estimated 63.3% (95% CI: 50.4-75.1) of hospitalizations within 30 days could have been prevented. This finding is attributed to large gaps in treatment and a strong protective association of antiviral treatment with subsequent hospitalization. ### Competing Interest Statement Drs. Levy, Chilunda, and Luo are employees of Helix, Inc. Drs. Levy and Luo report contracted research from Pfizer and the Centers for Disease Control and Prevention (CDC). Dr. Levy reports contracted research and travel support from Novavax. Dr. Heaton reports contracted research from Seegene USA and Helix, Inc. Dr. Grzymski is employed by the University of Nevada, Reno and Renown Health, and reports a professional relationship with the Desert Research Institute and research funding from Gilead Sciences and the National Institute of Environmental Health Sciences (NIEHS). Dr. Goldman reports contracted research from Helix, Gilead, Eli Lilly, and Regeneron, grants from Merck (BARDA) and Gilead, and collaborative services agreements with Adaptive Biotechnologies, Monogram Biosciences and LabCorp; and serving as a speaker or advisory board member for Gilead and Eli Lilly. Dr. Luo reports patents pending or issued to Helix, Inc. No other disclosures are reported. ### Funding Statement This study was funded by Helix, HealthPartners, the Nevada Governor's Office of Economic Development, Renown Health, and the Renown Health Foundation. ### 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: Protocols were reviewed by Salus IRB (Reliance on Salus for all sites) and approved (approval number 21143), the WIRB CG IRB (Western Institutional Review Board, WIRB-Copernicus Group) and approved (approval number 20224919), and the University of Nevada, Reno Institutional Review Board and approved (approval number 7701703417). 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, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data produced in the present study are not available due to data sharing agreements with partner institutions.