Characteristics and outcomes of US Veterans with immunocompromised conditions at high risk of severe SARS-CoV-2 infection with or without receipt of oral antiviral agents

Molnupiravir and nirmatrelvir-ritonavir were the first oral antiviral agents to demonstrate reduced hospitalization or death in patients with SARS-CoV-2, but patients with immunocompromised conditions were not well-represented. The objective of this study was to characterize and compare the clinical outcomes of US Veterans with immunocompromised conditions prescribed oral antivirals to those who did not receive oral antivirals for mild-to-moderate SARS-CoV-2 active infection.This was a retrospective, observational, nationwide propensity-matched analysis of US Veterans with immunocompromised conditions who developed documented SARS-CoV-2 infection. The primary outcome was the composite of any hospitalization or death within 30 days of diagnosis. Secondary outcomes included 30-day comparative rates of 1) any hospitalization, 2) death, 3) intensive care requirement, and subset analyses of outcomes by oral antiviral utilized and vaccination status.The composite primary outcome was significantly lower in patients receiving oral antiviral therapy compared to those who did not (23/390 [5.9%] vs 57/390 [14.6%]; odds ratio 0.37, 95% confidence interval 0.22-0.61). This difference was driven largely by fewer deaths in the oral antiviral group (1/390 [0.3%] vs 19/390 [4.9%]; odds ratio 0.05, 95% confidence interval 0.007-0.38). There was no significant difference in rate of intensive care requirement. The composite outcome was improved in vaccinated patients (completing the first series or first booster dose) who received oral antiviral agents compared to those who did not receive oral antiviral agents. Compared to those prescribed nirmatrelvir-ritonavir, patients given molnupiravir were older, had a higher incidence of cautions/contraindications, greater prevalence of tobacco use, and more cardiovascular complications.Use of molnupiravir or nirmatrelvir-ritonavir was associated with lower incidences of hospitalization or death within 30 days of diagnosis in US Veterans with immunocompromised conditions, regardless of vaccination status. These findings support the use of either oral antiviral in this patient population.