Incidence and Severity of Postacute Sequelae of SARS-CoV-2 Infection in the Omicron Era: A Prospective Cohort Study
et al., The Journal of Infectious Diseases, doi:10.1093/infdis/jiag026, Jan 2026
Prospective study of 2,960 nonhospitalized adults in the USA showing no significant difference in long-COVID with antiviral therapy using paxlovid or molnupiravir, aHR 1.02, 95% CI 0.87-1.21.
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. Studies show significantly increased risk of acute kidney injury21, cardiovascular toxocity22, and neurological symptoms21. Treatment may increase viral rebound23,24.
Study covers paxlovid and molnupiravir.
1.
Swanstrom et al., Lethal mutagenesis as an antiviral strategy, Science, doi:10.1126/science.abn0048.
2.
Hadj Hassine et al., Lethal Mutagenesis of RNA Viruses and Approved Drugs with Antiviral Mutagenic Activity, Viruses, doi:10.3390/v14040841.
3.
Shum, C., An investigational study into the drug-associated mutational signature in SARS-CoV-2 viruses, The University of Hong Kong, PhD Thesis, hub.hku.hk/handle/10722/344396.
4.
Waters et al., Human genetic risk of treatment with antiviral nucleoside analog drugs that induce lethal mutagenesis: the special case of molnupiravir, Environmental and Molecular Mutagenesis, doi:10.1002/em.22471.
5.
Huntsman, M., An assessment of the reproductive toxicity of the anti-COVID-19 drug molnupiravir using stem cell-based embryo models, Master's Thesis, scholarspace.manoa.hawaii.edu/items/cd11342c-b4dc-44c0-8b44-ce6e3369c40b.
6.
Huntsman (B) et al., Detection of developmental toxicity of the anti-COVID-19 drug molnupiravir using gastruloid-based in vitro assays, Toxicological Sciences, doi:10.1093/toxsci/kfaf093.
7.
Zibat et al., N4-hydroxycytidine, the active compound of Molnupiravir, promotes SARS-CoV-2 mutagenesis and escape from a neutralizing nanobody, iScience, doi:10.1016/j.isci.2023.107786.
8.
Shiraki et al., Convenient screening of the reproductive toxicity of favipiravir and antiviral drugs in Caenorhabditis elegans, Heliyon, doi:10.1016/j.heliyon.2024.e35331.
9.
Gruber et al., Molnupiravir increases SARS‐CoV‐2 genome diversity and complexity: A case‐control cohort study, Journal of Medical Virology, doi:10.1002/jmv.29642.
10.
Marikawa et al., An active metabolite of the anti-COVID-19 drug molnupiravir impairs mouse preimplantation embryos at clinically relevant concentrations, Reproductive Toxicology, doi:10.1016/j.reprotox.2023.108475.
11.
Rahman, M., Elucidation of the DNA repair mechanisms involved in the repair of DNA damage caused by the Arabinosides and Anti-COVID-19 drugs, tokyo-metro-u.repo.nii.ac.jp/records/2000972.
12.
Zhou et al., β-D-N4-hydroxycytidine Inhibits SARS-CoV-2 Through Lethal Mutagenesis But Is Also Mutagenic To Mammalian Cells, The Journal of Infectious Diseases, doi:10.1093/infdis/jiab247.
13.
Chamod et al., Molnupiravir Metabolite--N4-hydroxycytidine Causes Cytotoxicity and DNA Damage in Mammalian Cells in vitro: N4-hydroxycytidine Induced Cytotoxicity DNA Damage, Asian Medical Journal and Alternative Medicine, 23:3, asianmedjam.com/index.php/amjam/article/view/1448.
14.
Standing et al., Randomized controlled trial of molnupiravir SARS-CoV-2 viral and antibody response in at-risk adult outpatients, Nature Communications, doi:10.1038/s41467-024-45641-0.
15.
Mori et al., Reactive oxygen species-mediated cytotoxic and DNA-damaging mechanism of N4-hydroxycytidine, a metabolite of the COVID-19 therapeutic drug molnupiravir, Free Radical Research, doi:10.1080/10715762.2025.2469738.
16.
Focosi et al., The fitness of molnupiravir-signed SARS-CoV-2 variants: imputation analysis based on prescription counts and GISAID analyses by country, Intervirology, doi:10.1159/000540282.
17.
Sanderson et al., A molnupiravir-associated mutational signature in global SARS-CoV-2 genomes, Nature, doi:10.1038/s41586-023-06649-6.
18.
Fountain-Jones et al., Effect of molnupiravir on SARS-CoV-2 evolution in immunocompromised patients: a retrospective observational study, The Lancet Microbe, doi:10.1016/S2666-5247(23)00393-2.
19.
Kosakovsky Pond et al., Anti-COVID drug accelerates viral evolution, Nature, doi:10.1038/d41586-023-03248-3.
21.
Siby et al., Temporal Trends in Serious Adverse Events Associated with Oral Antivirals During the COVID-19 Pandemic: Insights from the FAERS Database (2020–2023), Open Forum Infectious Diseases, doi:10.1093/ofid/ofaf695.1825.
22.
Ozhan et al., Evaluation of the cardiopulmonary effects of repurposed COVID-19 therapeutics in healthy rats, Scientific Reports, doi:10.1038/s41598-025-31048-4.
Lin et al., 8 Jan 2026, prospective, peer-reviewed, 10 authors.
DOI record:
{
"DOI": "10.1093/infdis/jiag026",
"ISSN": [
"0022-1899",
"1537-6613"
],
"URL": "http://dx.doi.org/10.1093/infdis/jiag026",
"abstract": "<jats:title>Abstract</jats:title>\n <jats:p>In a prospective cohort study of 2960 nonhospitalized adults with acute SARS-CoV-2 infection, older age, female sex, rural residence, high body mass index, greater acute infection severity, chronic lung disease, and poorer general health at baseline were associated with higher risk and severity of postacute sequelae. Recent vaccination was associated with lower postacute sequelae risk and severity, while antiviral therapy was not.</jats:p>",
"author": [
{
"affiliation": [
{
"name": "Department of Biostatistics, University of North Carolina Gillings School of Global Public Health , Chapel Hill, North Carolina ,",
"place": [
"USA"
]
}
],
"family": "Lin",
"given": "Dan-Yu",
"role": [
{
"role": "author",
"vocabulary": "crossref"
}
],
"sequence": "first"
},
{
"ORCID": "https://orcid.org/0009-0008-2291-9209",
"affiliation": [
{
"name": "Department of Biostatistics, University of North Carolina Gillings School of Global Public Health , Chapel Hill, North Carolina ,",
"place": [
"USA"
]
}
],
"authenticated-orcid": false,
"family": "Mischell",
"given": "Melissa A",
"role": [
{
"role": "author",
"vocabulary": "crossref"
}
],
"sequence": "additional"
},
{
"ORCID": "https://orcid.org/0009-0004-1263-485X",
"affiliation": [
{
"name": "Department of Biostatistics, University of North Carolina Gillings School of Global Public Health , Chapel Hill, North Carolina ,",
"place": [
"USA"
]
}
],
"authenticated-orcid": false,
"family": "Zhang",
"given": "Xinyu",
"role": [
{
"role": "author",
"vocabulary": "crossref"
}
],
"sequence": "additional"
},
{
"affiliation": [
{
"name": "Department of Biostatistics, University of North Carolina Gillings School of Global Public Health , Chapel Hill, North Carolina ,",
"place": [
"USA"
]
},
{
"name": "Institute of Global Health and Infectious Diseases, University of North Carolina School of Medicine , Chapel Hill, North Carolina ,",
"place": [
"USA"
]
}
],
"family": "Mollan",
"given": "Katie R",
"role": [
{
"role": "author",
"vocabulary": "crossref"
}
],
"sequence": "additional"
},
{
"ORCID": "https://orcid.org/0000-0001-6590-2484",
"affiliation": [
{
"name": "Department of Epidemiology, University of North Carolina Gillings School of Global Public Health , Chapel Hill, North Carolina ,",
"place": [
"USA"
]
}
],
"authenticated-orcid": false,
"family": "Zhang",
"given": "Ning",
"role": [
{
"role": "author",
"vocabulary": "crossref"
}
],
"sequence": "additional"
},
{
"ORCID": "https://orcid.org/0009-0009-1945-3927",
"affiliation": [
{
"name": "Department of Biostatistics, University of North Carolina Gillings School of Global Public Health , Chapel Hill, North Carolina ,",
"place": [
"USA"
]
}
],
"authenticated-orcid": false,
"family": "Nanyakkara",
"given": "Dinelka",
"role": [
{
"role": "author",
"vocabulary": "crossref"
}
],
"sequence": "additional"
},
{
"ORCID": "https://orcid.org/0000-0001-5093-378X",
"affiliation": [
{
"name": "Institute of Global Health and Infectious Diseases, University of North Carolina School of Medicine , Chapel Hill, North Carolina ,",
"place": [
"USA"
]
}
],
"authenticated-orcid": false,
"family": "Keys",
"given": "Jessica R",
"role": [
{
"role": "author",
"vocabulary": "crossref"
}
],
"sequence": "additional"
},
{
"ORCID": "https://orcid.org/0009-0005-0170-5787",
"affiliation": [
{
"name": "Institute of Global Health and Infectious Diseases, University of North Carolina School of Medicine , Chapel Hill, North Carolina ,",
"place": [
"USA"
]
}
],
"authenticated-orcid": false,
"family": "Straub",
"given": "Becky",
"role": [
{
"role": "author",
"vocabulary": "crossref"
}
],
"sequence": "additional"
},
{
"affiliation": [
{
"name": "Institute of Global Health and Infectious Diseases, University of North Carolina School of Medicine , Chapel Hill, North Carolina ,",
"place": [
"USA"
]
}
],
"family": "Wohl",
"given": "David",
"role": [
{
"role": "author",
"vocabulary": "crossref"
}
],
"sequence": "additional"
},
{
"affiliation": [
{
"name": "Institute of Global Health and Infectious Diseases, University of North Carolina School of Medicine , Chapel Hill, North Carolina ,",
"place": [
"USA"
]
}
],
"family": "Fischer",
"given": "William",
"role": [
{
"role": "author",
"vocabulary": "crossref"
}
],
"sequence": "additional"
}
],
"container-title": "The Journal of Infectious Diseases",
"content-domain": {
"crossmark-restriction": false,
"domain": []
},
"created": {
"date-parts": [
[
2026,
1,
7
]
],
"date-time": "2026-01-07T12:39:24Z",
"timestamp": 1767789564000
},
"deposited": {
"date-parts": [
[
2026,
6,
16
]
],
"date-time": "2026-06-16T19:20:35Z",
"timestamp": 1781637635000
},
"indexed": {
"date-parts": [
[
2026,
7,
12
]
],
"date-time": "2026-07-12T00:39:00Z",
"timestamp": 1783816740705,
"version": "3.55.0"
},
"is-referenced-by-count": 1,
"issue": "6",
"issued": {
"date-parts": [
[
2026,
1,
8
]
]
},
"journal-issue": {
"issue": "6",
"published-online": {
"date-parts": [
[
2026,
1,
8
]
]
},
"published-print": {
"date-parts": [
[
2026,
6,
16
]
]
}
},
"language": "en",
"license": [
{
"URL": "https://academic.oup.com/pages/standard-publication-reuse-rights",
"content-version": "vor",
"delay-in-days": 0,
"start": {
"date-parts": [
[
2026,
1,
8
]
],
"date-time": "2026-01-08T00:00:00Z",
"timestamp": 1767830400000
}
}
],
"link": [
{
"URL": "https://academic.oup.com/jid/advance-article-pdf/doi/10.1093/infdis/jiag026/66312747/jiag026.pdf",
"content-type": "application/pdf",
"content-version": "am",
"intended-application": "syndication"
},
{
"URL": "https://academic.oup.com/jid/article-pdf/233/6/1063/66312747/jiag026.pdf",
"content-type": "application/pdf",
"content-version": "vor",
"intended-application": "syndication"
},
{
"URL": "https://academic.oup.com/jid/article-pdf/233/6/1063/66312747/jiag026.pdf",
"content-type": "unspecified",
"content-version": "vor",
"intended-application": "similarity-checking"
}
],
"member": "286",
"original-title": [],
"page": "1063-1068",
"prefix": "10.1093",
"published": {
"date-parts": [
[
2026,
1,
8
]
]
},
"published-online": {
"date-parts": [
[
2026,
1,
8
]
]
},
"published-other": {
"date-parts": [
[
2026,
6,
15
]
]
},
"published-print": {
"date-parts": [
[
2026,
6,
16
]
]
},
"publisher": "Oxford University Press (OUP)",
"reference": [
{
"DOI": "10.1001/jama.2022.11691",
"article-title": "Association between BNT162b2 vaccination and long COVID after infections not requiring hospitalization in health care workers",
"author": "Azzolini",
"doi-asserted-by": "crossref",
"first-page": "676",
"journal-title": "JAMA",
"key": "2026061615202679400_jiag026-B1",
"volume": "328",
"year": "2022"
},
{
"DOI": "10.1038/s41746-022-00623-8",
"article-title": "International electronic health record-derived post-acute sequelae profiles of COVID-19 patients",
"author": "Zhang",
"doi-asserted-by": "crossref",
"first-page": "81",
"journal-title": "NPJ Digit Med",
"key": "2026061615202679400_jiag026-B2",
"volume": "5",
"year": "2022"
},
{
"DOI": "10.1001/jamainternmed.2023.0743",
"article-title": "Association of treatment with nirmatrelvir and the risk of post-COVID-19 condition",
"author": "Xie",
"doi-asserted-by": "crossref",
"first-page": "554",
"journal-title": "JAMA Int Med",
"key": "2026061615202679400_jiag026-B3",
"volume": "183",
"year": "2023"
},
{
"DOI": "10.1056/NEJMoa2403211",
"article-title": "Postacute sequelae of SARS-CoV-2 infection in the pre-delta, delta, and omicron eras",
"author": "Xie",
"doi-asserted-by": "crossref",
"first-page": "515",
"journal-title": "N Engl J Med",
"key": "2026061615202679400_jiag026-B4",
"volume": "391",
"year": "2024"
},
{
"DOI": "10.1016/j.eclinm.2024.102654",
"article-title": "Association between acquiring SARS-CoV-2 during pregnancy and post-acute sequelae of SARS-CoV-2 infection: RECOVER electronic health record cohort analysis",
"author": "Bruno",
"doi-asserted-by": "crossref",
"first-page": "102654",
"journal-title": "EClinicalMedicine",
"key": "2026061615202679400_jiag026-B5",
"volume": "73",
"year": "2024"
},
{
"DOI": "10.1001/jamanetworkopen.2024.41970",
"article-title": "Body mass index and postacute sequelae of SARS-CoV-2 infection in children and young adults",
"author": "Zhou",
"doi-asserted-by": "crossref",
"first-page": "e2441970",
"journal-title": "JAMA Netw Open",
"key": "2026061615202679400_jiag026-B6",
"volume": "7",
"year": "2024"
},
{
"DOI": "10.1038/s41591-023-02274-y",
"article-title": "Potential pitfalls in the use of real-world data for studying long COVID",
"author": "Zhang",
"doi-asserted-by": "crossref",
"first-page": "1040",
"journal-title": "Nat Med",
"key": "2026061615202679400_jiag026-B7",
"volume": "29",
"year": "2023"
},
{
"DOI": "10.1136/bmjph-2025-002796",
"article-title": "Research protocol design and implementation of a hybrid no-touch and low-touch prospective observational study during the COVID-19 public health emergency: the VISION study",
"author": "Straub",
"doi-asserted-by": "crossref",
"first-page": "e002796",
"journal-title": "BMJ Public Health",
"key": "2026061615202679400_jiag026-B8",
"volume": "3",
"year": "2025"
},
{
"DOI": "10.1093/biomet/asw013",
"article-title": "Maximum likelihood estimation for semiparametric transformation models with interval-censored data",
"author": "Zeng",
"doi-asserted-by": "crossref",
"first-page": "253",
"journal-title": "Biometrika",
"key": "2026061615202679400_jiag026-B9",
"volume": "103",
"year": "2016"
},
{
"DOI": "10.1093/biomet/73.1.13",
"article-title": "Longitudinal data analysis using generalized linear models",
"author": "Liang",
"doi-asserted-by": "crossref",
"first-page": "13",
"journal-title": "Biometrika",
"key": "2026061615202679400_jiag026-B10",
"volume": "73",
"year": "1986"
},
{
"DOI": "10.1038/s41467-025-57849-9",
"article-title": "Long COVID after SARS-CoV-2 during pregnancy in the United States",
"author": "Zang",
"doi-asserted-by": "crossref",
"first-page": "3005",
"journal-title": "Nat Commun",
"key": "2026061615202679400_jiag026-B11",
"volume": "16",
"year": "2025"
}
],
"reference-count": 11,
"references-count": 11,
"relation": {},
"resource": {
"primary": {
"URL": "https://academic.oup.com/jid/article/233/6/1063/8417526"
}
},
"score": 1,
"short-title": [],
"source": "Crossref",
"subject": [],
"subtitle": [],
"title": "Incidence and Severity of Postacute Sequelae of SARS-CoV-2 Infection in the Omicron Era: A Prospective Cohort Study",
"type": "journal-article",
"volume": "233"
}
lin11