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

Ikeuchi et al., BMC Infectious Diseases, doi:10.1186/s12879-025-11651-6, Sep 2025

https://c19early.org/ikeuchim.html

Retrospective 5,398 married couples in Japan showing no significant difference in household transmission rates between molnupiravir, ensitrelvir, and paxlovid. Hospitalized patients receiving antivirals showed a trend toward lower transmission rates compared to outpatients, likely due to physical isolation. Prior COVID-19 infection in either spouse reduced transmission risk by 50-69%. The study used administrative claims data which may underestimate true transmission rates since asymptomatic or mild cases might not seek medical care.

No adjusted results are provided for antiviral use vs. non-use, however authors note transmission for 30.4% of treated households vs. 24.0% for untreated households (for day 0-7, different to subsequent analysis).

Potential risks of molnupiravir include the creation of dangerous variants, and mutagenicity, carcinogenicity, teratogenicity, and embryotoxicity1-15. Multiple analyses have identified variants potentially created by molnupiravir16-20.

Important missing comments or errors? Let us know.

Study covers ensitrelvir, paxlovid, and molnupiravir.

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Ikeuchi et al., 29 Sep 2025, retrospective, Japan, peer-reviewed, 9 authors, study period 1 April, 2023 - 31 August, 2023. Contact: kikeuchi@g.ecc.u-tokyo.ac.jp.

This Paper Molnupiravir All

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

Kazuhiko Ikeuchi, Makoto Saito, Kazuya Okushin, Yuki Arisato, Toshiyuki Kishida, Shinya Matsumoto, Akira Kado, Hiroshi Yotsuyanagi, Takeya Tsutsumi

BMC Infectious Diseases, doi:10.1186/s12879-025-11651-6

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).

Abbreviations Supplementary Information The online version contains supplementary material available at h t t p s : / / d o i . o r g / 1 0 . 1 1 8 6 / s 1 2 8 7 9 -0 2 5 -1 1 6 5 1 -6. Supplementary Material 1 Authors' contributions KI, MS, and TT conceived the study. KI performed the data analysis and drafted the manuscript. KI and MS conducted the statistical analyses. KO, AK, SM, TK, YA, and HY contributed to the data interpretation and critically revised the manuscript. All the authors (KI, MS, TT, KO, AK, SM, TK, YA, and HY) reviewed the manuscript for important intellectual content and approved its final version. Declarations Ethics approval and consent to participate This study was approved by the Research Ethics Committee of the University of Tokyo (approval number 2024216NIe). The Ethics committee of University of Tokyo waived the requirement for informed consent because the study used fully anonymized administrative data that were not individually identifiable. Data confidentiality was strictly maintained in accordance with the Declaration of Helsinki. Consent for publication Not applicable. Competing interests The authors declare no competing interests. Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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DOI record: { "DOI": "10.1186/s12879-025-11651-6", "ISSN": [ "1471-2334" ], "URL": "http://dx.doi.org/10.1186/s12879-025-11651-6", "abstract": "Abstract\n \n Background\n 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.\n \n \n Methods\n 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.\n \n \n Results\n 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).\n \n \n Conclusions\n Household transmission rates were not statistically different among three different outpatient oral antiviral agents. 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Clin Infect Dis. 2021;72(11):e859–67.", "volume": "72", "year": "2021" }, { "DOI": "10.1038/s41467-023-40556-8", "author": "RM Cox", "doi-asserted-by": "publisher", "first-page": "4731", "issue": "1", "journal-title": "Nat Commun", "key": "11651_CR16", "unstructured": "Cox RM, Lieber CM, Wolf JD, Karimi A, Lieberman NAP, Sticher ZM, Roychoudhury P, Andrews MK, Krueger RE, Natchus MG, et al. Comparing molnupiravir and nirmatrelvir/ritonavir efficacy and the effects on SARS-CoV-2 transmission in animal models. Nat Commun. 2023;14(1):4731.", "volume": "14", "year": "2023" }, { "DOI": "10.3201/eid2704.204576", "author": "JK Bender", "doi-asserted-by": "publisher", "first-page": "1159", "issue": "4", "journal-title": "Emerg Infect Dis", "key": "11651_CR17", "unstructured": "Bender JK, Brandl M, Höhle M, Buchholz U, Zeitlmann N. Analysis of asymptomatic and presymptomatic transmission in SARS-CoV-2 outbreak, Germany, 2020. 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