SARS-CoV-2 infectious shedding and rebound among adults with and without oral antiviral use: two case-ascertained prospective household studies
et al., The Lancet Microbe, doi:10.1016/j.lanmic.2025.101227, Jan 2026
Prospective study of 160 non-hospitalized adults at high risk for severe COVID-19 showing paxlovid or molnupiravir associated with increased risk of viral rebound with infectious virus. Among treated participants, 25% experienced culture rebound (indicating potential infectiousness) compared to 8% of untreated participants. However, among participants without viral RNA rebound, treated individuals had shorter duration of infectious viral shedding (4 vs 6 days) and antigen positivity (5 vs 8 days) compared to untreated participants.
Adjusted results are only provided for the combined group including both paxlovid and molnupiravir.
Standard of Care (SOC) for COVID-19 in the study country,
the USA, is very poor with very low average efficacy for approved treatments1.
Only expensive, high-profit treatments were approved for early treatment. Low-cost treatments were excluded, reducing the probability of early treatment due to access and cost barriers, and eliminating complementary and synergistic benefits seen with many low-cost treatments.
Study covers molnupiravir and paxlovid.
|
culture rebound, 218.0% higher, RR 3.18, p = 0.01, treatment 54, control 106, adjusted per study, combined treatments.
|
|
culture rebound, 657.1% higher, RR 7.57, p = 0.002, treatment 4 of 7 (57.1%), control 8 of 106 (7.5%).
|
| Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates |
Shah et al., 9 Jan 2026, prospective, USA, peer-reviewed, median age 50.0, 42 authors, study period 1 January, 2022 - 10 June, 2023.
SARS-CoV-2 infectious shedding and rebound among adults with and without oral antiviral use: two case-ascertained prospective household studies
The Lancet Microbe, doi:10.1016/j.lanmic.2025.101227
Background The effect of COVID-19 oral antivirals on the duration of SARS-CoV-2 infectious viral shedding and viral rebound remains uncertain. This study aimed to examine the association of oral antivirals with viral dynamics, shedding of infectious virus, and SARS-CoV-2 rebound. Methods A prospective case-ascertained household study design was used. Participants were non-hospitalised adults older than 18 years with symptomatic SARS-CoV-2 enrolled in one of two prospective household transmission studies (University of California, San Francisco, FindCOVID and Respiratory Virus Transmission Network-Sentinel [RVTN-S]) conducted in the USA across six states at academic institutions from Jan 1, 2022 to June 10, 2023. We excluded those reporting receipt of multiple COVID-19 outpatient medications, treatment with remdesivir, a treatment duration of more than 6 days, and those from whom fewer than five daily anterior nasal swabs were collected during their illness. Participants were considered to be at high risk of severe COVID-19 (and, therefore, eligible for SARS-CoV-2 oral antiviral treatment) if they were aged 50 years or older or were aged 18 years or older and reporting at least one underlying condition. Study procedures included frequent selfcollected nasal swabs (daily for 14 days after symptom onset and then every 3 days until day 28 after symptom onset in FindCOVID and two nasal swabs daily for 10 days from enrolment in RVTN-S) and viral testing by quantitative reverse transcriptase PCR (qRT-PCR), at-home antigen testing, and viral culture. Treatment was defined as self-reported receipt of an oral antiviral (nirmatrelvir-ritonavir or molnupiravir). The primary analysis compared viral detection by qRT-PCR, antigen test positivity, and culture positivity and assessed SARS-CoV-2 viral rebound (viral RNA, antigen, culture, and symptom rebound) in untreated and treated participants at high risk of severe outcomes. We used multivariable Poisson regression to assess associations between treatment, duration of test positivity, and the presence of viral culture rebound, adjusting for age, underlying conditions, and recent immunological events. Findings Between Jan 1, 2022, and June 10, 2023, 160 individuals with symptomatic COVID-19 and at high risk of severe outcomes were included in FindCOVID and RVTN-S. There was no significant difference in the duration of viral detection between treated and untreated participants at high risk of severe COVID-19 by antigen test positivity (6 days [IQR 5-11] vs 8 days [5-10]; adjusted relative risk [RR] 1⋅07, 95% CI 0⋅24-4⋅81) or viral culture (7 days [4-11] vs 6 days [5-9]; 2⋅21, 0⋅45-10⋅79). Among 122 participants without viral RNA rebound, the last day of antigen test positivity and detection of culturable virus post-symptom onset was earlier in treated participants than in untreated participants (5 days [4-8] vs 8 days [5-10] for antigen test positivity; 0⋅19, 0⋅04-0⋅79; 4 days [3-6] vs 6 days [4-9]; 0⋅18,..
Respiratory Virus Transmission Network-Sentinel Study Group Jessica E Biddle, Meredith Davis-Gardner, Son McLaren, Joshua Petrie, Kathleen Pryor, Yuwei Zhu.
UCSF FindCOVID Study Group Khamal Anglin, Jessica Y Chen, Elizabeth Jump, Ana Martinez, Karen Pfister, Carolina Torres, Badri Viswanathan, Amethyst Zhang.
Contributors MMS, GRA, SL, MBH, CMM, AMM, JDK, and SES-J contributed to the conceptualisation of the study. SL, SAG, JP-R, SGD, JNM, MJP, RA, and MG-K, and members of the University of California, San Francisco FindCOVID Study Group AZ, AM, JYC, BV, KA, CT, KP, and EJ contributed to data curation for FindCOVID. SES-J, CGG, HKT, JS, KL, KDE, MelSSt, ES, HQN, SR, EJA, MehSS, JEB, MD-G, SM, JP, KP, and YZ contributed to data curation for the Respiratory Virus Transmission Network─Sentinel (RVTN─Sentinel) study. GRA, MMS, CMM, JDK, SES-J, and AMM contributed to formal data analysis. Overall study supervision and oversight was provided by JDK, MBH, MMS, CMM, HLK, and SES-J. MMS, GRA, and SES-J wrote the initial draft, with substantial review and editing provided by all coauthors. MMS and GRA accessed and verified the data from both RVTN and FindCOVID and accept responsibility for the decision to submit for publication. All authors reviewed the and approved the final version for publication. MMS and GRA had full access to all data for the analysis. All authors reviewed the data analysed, provided critical input the manuscript, and approved of submission for publication.
..
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