Real-world effectiveness of molnupiravir and nirmatrelvir plus ritonavir against mortality, hospitalisation, and in-hospital outcomes among community-dwelling, ambulatory patients with confirmed SARS-CoV-2 infection during the omicron wave in Hong Kong: an observational study.

backgroundLittle is known about the real-world effectiveness of oral antivirals against the SARS-CoV-2 omicron (B.1.1.529) variant. We aimed to assess the clinical effectiveness of two oral antiviral drugs among community-dwelling COVID-19 outpatients in Hong Kong.

methodsIn this observational study, we used data from the Hong Kong Hospital Authority to identify an unselected, territory-wide cohort of non-hospitalised patients with an officially registered diagnosis of SARS-CoV-2 infection between Feb 26 and June 26, 2022, during the period in which the omicron subvariant BA.2.2 was dominant in Hong Kong. We used a retrospective cohort design as primary analysis, and a case-control design as sensitivity analysis. We identified patients with COVID-19 who received either molnupiravir (800 mg twice daily for 5 days) or nirmatrelvir plus ritonavir (nirmatrelvir 300 mg and ritonavir 100 mg twice daily for 5 days, or nirmatrelvir 150 mg and ritonavir 100 mg if estimated glomerular filtration rate was 30-59 mL/min per 1·73 m

findingsAmong 1 074 856 non-hospitalised patients with COVID-19, 5383 received molnupiravir and 6464 received nirmatrelvir plus ritonavir in the community setting. Patients were followed up for a median of 103 days in the molnupiravir group and 99 days in the nirmatrelvir plus ritonavir group. Compared with nirmatrelvir plus ritonavir users, those on molnupiravir were older (4758 [85·9%] vs 4418 [88.7%] aged >60 years) and less likely to have been fully vaccinated (1850 [33·4%] vs 800 [16·1%]). Molnupiravir use was associated with lower risks of death (HR 0·76 [95% CI 0·61-0·95]) and in-hospital disease progression (0·57 [0·43-0·76]) than non-use was, whereas risk of hospitalisation was similar in both groups (0·98 [0·89-1·06]). Nirmatrelvir plus ritonavir use was associated with lower risks of death (0·34 [0·22-0·52]), hospitalisation (0·76 [0·67-0·86]), and in-hospital disease progression (0·57 [0·38-0·87]) than non-use was. We consistently found reduced risks of mortality and hospitalisation associated with early oral antiviral use among older patients. The findings from the case-control analysis broadly supported those from the primary analysis.

interpretationDuring Hong Kong's wave of SARS-CoV-2 omicron subvariant BA.2.2, among non-hospitalised patients with COVID-19, early initiation of novel oral antivirals was associated with reduced risks of mortality and in-hospital disease progression. Nirmatrelvir plus ritonavir use was additionally associated with a reduced risk of hospitalisation.

fundingHealth and Medical Research Fund, Health Bureau, Government of Hong Kong Special Administrative Region, China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.