{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T06:36:08Z","timestamp":1777358168464,"version":"3.51.4"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The intra-host evolution represents the mechanism causing the continued emergence of new, highly divergent SARS-CoV-2 variants. The aim of this work was to investigate the intra-host evolution to ass the conditions associated with the acquisition of new viral mutations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Whole genome sequences of 58 cases of COVID-19 with 2 or more consecutive positive swabs were analyzed. Variant calling and minority mutations analysis were performed using Nextclade and Stanford Coronavirus Antiviral &amp;amp; Resistance Database.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Fifty-seven subjects were hospitalized for a median of 23\u202fdays, and 12 died (20.7%) after a median of 25\u202fdays. 78.9% (45\/58) were vaccinated and 22.4% (13\/58) received more than one treatment for SARS-CoV-2 infection. None reported previous SARS-CoV-2 infection. Negativization period showed longer intervals in BQ.1 infections (38.5\u202fdays) and shorter in BA.1 infections (16.5\u202fdays). Comparing the first positive swab to the second swab (T1 and T2), 36.7 and 38.8% decreased\/increased number of mutations while 24.5% maintained the same number. Subjects with constant numbers of mutations maintained the same pattern while 57% of the acquisitions and losses were confirmed compared to the previous timepoint. Comparing the second to the third swab (T2 and T3), 66.7 and 33.3% of strains increased or maintained the same number of mutations, respectively. 75% of subjects with constant number of mutations maintained the same pattern. 63% of the acquisitions were confirmed. In T1 vs. T2 the acquisitions were prevalent in the S gene and the losses in ORF1a, in T2 vs. T3 the opposite was observed. Subjects with cardiovascular disease showed a significantly higher acquisition of mutations over time.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Our data suggested a mechanism with different steps of fitness selection of SARS-CoV-2 mutations and highlighted the presence of highly divergent intra-patient variants within 3\u202fweeks of infection, regardless of treatment, confirming data from other studies showing that new viral variants can also emerge during acute infections.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1794039","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T05:39:14Z","timestamp":1777354754000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["SARS-CoV-2 intra-host evolution during acute infection in COVID-19 patients"],"prefix":"10.3389","volume":"17","author":[{"given":"Carla","family":"della Ventura","sequence":"first","affiliation":[{"name":"Department of Biomedical and Clinical Sciences, University of Milan","place":["Milan, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annalisa","family":"Bergna","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences, University of Milan","place":["Milan, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cosmin Lucian","family":"Ciubotariu","sequence":"additional","affiliation":[{"name":"III Division of Infectious Diseases, ASST Fatebenefratelli Sacco, Luigi Sacco Hospital","place":["Milan, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mirko","family":"Liturri","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences, University of Milan","place":["Milan, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Conflitti","sequence":"additional","affiliation":[{"name":"National PhD Programme in One Health Approaches to Infectious Diseases and Life Science Research, Department of Public Health, Experimental and Forensic Medicine, University of Pavia","place":["Pavia, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Corbellino","sequence":"additional","affiliation":[{"name":"III Division of Infectious Diseases, ASST Fatebenefratelli Sacco, Luigi Sacco Hospital","place":["Milan, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Spinello","family":"Antinori","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences, University of Milan","place":["Milan, Italy"]},{"name":"III Division of Infectious Diseases, ASST Fatebenefratelli Sacco, Luigi Sacco Hospital","place":["Milan, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agostino","family":"Riva","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences, University of Milan","place":["Milan, Italy"]},{"name":"III Division of Infectious Diseases, ASST Fatebenefratelli Sacco, Luigi Sacco Hospital","place":["Milan, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianguglielmo","family":"Zehender","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences, University of Milan","place":["Milan, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessia","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Clinical Sciences, University of Milan","place":["Milan, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,28]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"3773","DOI":"10.21105\/joss.03773","article-title":"Nextclade: clade assignment, mutation calling and quality control for viral genomes","volume":"6","author":"Aksamentov","year":"2021","journal-title":"J. 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