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

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.