Publication date: Nov 04, 2024

The real-world effectiveness of the oral antivirals nirmatrelvir-ritonavir and molnupiravir against the SARS-CoV-2 Omicron variant remains uncertain. We aimed to estimate their effectiveness in non-hospitalised adults with Covid-19. This retrospective cohort study used data from the Municipal Department for Public Health Services of Vienna, Austria, to identify non-hospitalised adults with confirmed SARS-CoV-2 infection between Jan-2022-May-2023. Nirmatrelvir-ritonavir users were compared with untreated controls and molnupiravir users with untreated controls by calculating adjusted risk differences (aRDs) using a covariate-adjusted logistic regression model with inverse probability weighting. Outcomes were hospitalisation and all-cause death within 28 days. We identified 113,399 eligible cases (90,481 untreated controls, 12,166 nirmatrelvir-ritonavir users, and 10,752 molnupiravir users). Over 96% of the patients were immunised by previous infection or vaccination. In the nirmatrelvir-ritonavir analysis, the estimated risk of hospitalisation was 0. 57% (95%CI, 0. 35-0. 78) in nirmatrelvir-ritonavir users and 1. 09% (95%CI, 0. 86-1. 32) in untreated controls (aRD -0. 53%; 95%CI, -0. 77–0. 28). The estimated risk of death was 0. 0% (95%CI, 0. 0-0. 0) in nirmatrelvir-ritonavir users and 0. 13% (95%CI, 0. 08-0. 18) in untreated controls (aRD -0. 13%, 95%CI, -0. 18–0. 08). The number needed to treat to prevent hospitalisation and death was 190 (95%CI, 130-356) and 792 (95%CI, 571-1289), respectively. These statistically significant aRDs were restricted to the subgroup of patients ≥60 years. In the molnupiravir analysis, the estimated risk of hospitalisation was 1. 36% (95%CI, 0. 95-1. 77) in molnupiravir users and 1. 16% (95%CI, 0. 93-1. 39) in untreated controls (aRD 0. 2%; 95%CI, -0. 08-0. 49). The estimated risk of death was 0. 12% (95%CI, 0. 01-0. 23) in molnupiravir users and 0. 14% (95%CI, 0. 06-0. 21) in untreated controls (aRD, -0. 01%; 95%CI, -0. 08–0. 06). Among outpatients aged ≥60 years with Covid-19 in an Omicron-dominated era, treatment with nirmatrelvir-ritonavir was associated with a lower risk of hospitalisation and all-cause death within 28 days, albeit with wide confidence intervals and high numbers needed to treat. This finding was not observed in molnupiravir users and younger nirmatrelvir-ritonavir users.

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