SARS-CoV-2 viral shedding and vaccination‑modified effects of oral antivirals in older COVID-19 patients: A retrospective cohort study in Hong Kong.

OBJECTIVES

To evaluate how oral antivirals (molnupiravir and nirmatrelvir-ritonavir) and COVID-19 vaccination affect SARS-CoV-2 viral kinetics in adults aged ≥60 years with symptomatic COVID-19 hospitalized in Hong Kong.

METHODS

We analyzed viral burden using cycle threshold (Ct) values from patients admitted between May 23, 2022 and Jan 23, 2023 when Omicron subvariants predominated. Viral trajectories were modelled with log-polynomial random-effects framework to estimate daily Ct values and duration of potentially infectious shedding (time to Ct ≥30). We then examined how antiviral timing and vaccination history modified these virological outcomes.

RESULTS

Among 3759 symptomatic COVID-19 patients included, 1318 received molnupiravir, 1613 received nirmatrelvir-ritonavir. Compared with no treatment, nirmatrelvir-ritonavir was associated with shorter shedding (mean difference -2.4 days, 95% CIs: -2.7, -2.2), especially with earlier initiation, whereas molnupiravir had a smaller effect (-0.6 days, 95% CIs: -0.9, -0.3). The virologic effect of nirmatrelvir-ritonavir was greater in unvaccinated than vaccinated patients, while the effect of molnupiravir did not differ notably by vaccination status.

CONCLUSION

Early nirmatrelvir-ritonavir substantially shortens SARS-CoV-2 shedding in older adults, especially if unvaccinated. These findings support timely antiviral use and consideration of vaccination history when optimizing treatment for high-risk populations.