Non-randomized evaluation of hospitalization after a prescription for nirmatrelvir/ritonavir versus molnupiravir in high-risk COVID-19 outpatients

Objectives: To assess and compare subsequent hospital admissions within 30 days for patients after receiving a prescription for either oral nirmatrelvir/ritonavir or oral molnupiravir. Methods: We conducted a retrospective review of 3207 high-risk, non-hospitalized adult COVID-19 patients who received a prescription for molnupiravir (n=209) or nirmatrelvir/ritonavir (n=2998) at an academic medical centre in New York City from April to December 2022. Variables including age, vaccination status, high-risk conditions and demographic factors were pulled from the electronic medical record. We used multivariable logistic regression to adjust for potential confounding variables. Results: All-cause 30 day hospitalization was not significantly different between patients who received nirmatrelvir/ritonavir compared with molnupiravir (1.4% versus 1.9%, P value=0.55). The association between COVID-related hospitalization and medication was also not significant (0.7%versus 0.5%, P value=0.99). Patients who received molnupiravir were more likely to have more underlying high-risk conditions. After adjusting for potential confounders, the odds of all-cause hospitalizations were not significantly different between patients who received nirmatrelvir/ritonavir compared with molnupiravir (OR=1.16, 95% CI: 0.4-3.3, P value=0.79). Conclusions: These data provide additional evidence to support molnupiravir as a suitable alternative when other COVID-19 antivirals cannot be given.