Effectiveness of the Approved Nirmatrelvir/Ritonavir and Molnupiravir Regimens for Treatment of Mild/Moderate Laboratory-Confirmed SARS-CoV-2 Infection in Patients Aged 18–64 Years in Hong Kong: A Population-Based Cohort Study

BACKGROUND AND OBJECTIVES: To better inform clinical and public health decision-making on the use of antiviral drugs for mild/moderate SARS-CoV-2 infection in Hong Kong, we sought to assess effectiveness of the approved nirmatrelvir/ritonavir and molnupiravir treatment regimens. METHODS: We conducted a cohort study of patients aged 18-64 years with laboratory-confirmed SARS-CoV-2 infection in Hong Kong between April 2022 and January 2023. We utilised a conditional logistic regression model with a 5-strata propensity score-matched analysis adjusted for potential confounders such as age, sex, SARS-CoV-2 vaccination status, and chronic conditions. The outcomes were disease progression (development/worsening of clinical symptoms/conditions), intensive care unit (ICU) admission among hospitalised persons, and mortality at 28 days (infection-related) and 90 days (all-cause) following the recommended 5-day treatment course commencing within 5 days of symptom onset or laboratory confirmation and excluding persons who had a contraindication for the drugs. Results were expressed as adjusted odds ratios with associated 95% confidence intervals. RESULTS: We included 206,418 individuals, of which 53% were symptomatic at infection confirmation. About 33.3% of the individuals were treated with nirmatrelvir/ritonavir whereas only about 6.1% were treated with molnupiravir. Compared with no treatment, treatment with either nirmatrelvir/ritonavir or molnupiravir was associated with significantly reduced odds of disease progression in patients aged 18-44 years [0.20 (0.09-0.42) and 0.10 (0.04-0.26), respectively] and patients aged 45-64 years [0.14 (0.10-0.20) and 0.19 (0.14-0.25), respectively]. Whereas mostly no significant associations were observed with these drugs for the other outcomes in patients aged 18-44 years, they were associated with significantly reduced odds of the outcomes in patients aged 45-64 years. There was no significant difference in the head-to-head comparison between nirmatrelvir/ritonavir and molnupiravir against all the outcomes in patients aged 18-44 years, and against ICU admission in patients aged 45-64 years, but compared with molnupiravir in those aged 45-64 years, nirmatrelvir/ritonavir was associated with significantly reduced odds of disease progression, SARS-CoV-2 infection-related mortality, and all-cause mortality [0.39 (0.22-0.70), 0.20 (0.10-0.38), and 0.33 (0.21-0.53), respectively]. We made these observations mostly irrespective of symptom status. CONCLUSIONS: Nirmatrelvir/ritonavir and molnupiravir treatment regimens seemed effective against clinically relevant outcomes in patients aged 18-64 years with laboratory-confirmed SARS-CoV-2 infection in Hong Kong, particularly in those aged 45-64 years for whom nirmatrelvir/ritonavir seemed better than molnupiravir.