{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T19:07:45Z","timestamp":1774292865705,"version":"3.50.1"},"reference-count":64,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":48,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of General Medical Sciences of the National Institutes of Health","award":["R35GM138233"],"award-info":[{"award-number":["R35GM138233"]}]},{"name":"National Institute of General Medical Sciences of the National Institutes of Health","award":["R35GM136381"],"award-info":[{"award-number":["R35GM136381"]}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Physics Frontier Center for Living Systems","award":["PHY-2317138"],"award-info":[{"award-number":["PHY-2317138"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Multiple SARS-CoV-2 variants have arisen during the first years of the pandemic, often bearing many new mutations. Several explanations have been offered for the surprisingly sudden emergence of multiple mutations that enhance viral fitness, including cryptic transmission, spillover from animal reservoirs, epistasis between mutations, and chronic infections. Here, we simulated pathogen evolution combining within-host replication and between-host transmission. We found that, under certain conditions, chronic infections can lead to SARS-CoV-2-like bursts of mutations even without epistasis. Chronic infections can also increase the global evolutionary rate of a pathogen even in the absence of clear mutational bursts. Overall, our study supports chronic infections as a plausible origin for highly mutated SARS-CoV-2 variants. More generally, we also describe how chronic infections can influence pathogen evolution under different scenarios.<\/jats:p>","DOI":"10.1093\/ve\/veag008","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T09:47:18Z","timestamp":1771408038000},"source":"Crossref","is-referenced-by-count":0,"title":["Chronic infections can generate SARS-CoV-2-like bursts of viral evolution without epistasis"],"prefix":"10.1093","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6690-629X","authenticated-orcid":false,"given":"Edwin","family":"Rodr\u00edguez-Horta","sequence":"first","affiliation":[{"name":"Department of Computational and Systems Biology, University of Pittsburgh School of Medicine , 4200 Fifth Ave, Pittsburgh, PA 15260 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Strahan","sequence":"additional","affiliation":[{"name":"Department of Chemistry and James Franck Institute, 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