Comparative effectiveness of antiviral treatment on household transmission of SARS-CoV-2: a retrospective cohort study using administrative data

Abstract Background Antiviral treatment reduces influenza transmission and differs in effectiveness among agents. Although SARS-CoV-2 antivirals lower viral shedding, their role in preventing secondary household transmission and the differences between agents remain unclear. Methods We conducted a retrospective cohort study using the JMDC administrative claims database in Japan. The study included married-couple households between 1 April and 31 August 2023, when the Omicron XBB variant was predominant. Households in which at least one person had been diagnosed with Coronavirus Disease 2019 (COVID-19) were included. We excluded households if the index patient did not receive antiviral treatment on day 0, or the spouse was diagnosed on day 0 or 1. The primary outcome was subsequent infection in the spouse by day 7. Cox proportional hazards models were used to estimate hazard ratios (HRs), after adjusting for potential confounders. Results Of the 326,827 married-couple households, 5,398 met the inclusion criteria. Among them, 1,143 households (21.2%) experienced presumed secondary transmission by day 7. The cumulative transmission rate, estimated using the Kaplan–Meier method, was lower among hospitalized patients (n = 73, 11.0%, 95% confidence interval [CI]: 5.7–20.8%) than among outpatients (n = 5,325, 21.5%, 95% CI: 20.4–22.6%, p = 0.035). Transmission rates did not significantly differ among the outpatient antiviral groups: molnupiravir (n = 3,093, 21.3%, 95% CI: 19.9–22.8%), ensitrelvir (n = 1,907, 21.6%, 95% CI: 19.8–23.6%), and nirmatrelvir/ritonavir (n = 323, 22.8%, 95% CI: 18.6–27.8%, p = 0.74). In multivariable Cox analysis, male sex (adjusted HR 1.43, 95% CI: 1.26–1.63; p < 0.001), history of COVID-19 in the index patient (adjusted HR 0.50, 95% CI: 0.33–0.76; p = 0.001), and history of COVID-19 in the partner (adjusted HR 0.31, 95% CI: 0.21–0.45; p < 0.001) were significantly associated with transmission risk. Hospitalization tended to be associated with a lower risk of transmission (adjusted HR, 0.51; 95% CI, 0.25–1.03; p = 0.062). Conclusions Household transmission rates were not statistically different among three different outpatient oral antiviral agents. Hospitalization was associated with a trend toward lower transmission rates, possibly due to physical isolation.