{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T01:43:51Z","timestamp":1767836631343,"version":"3.49.0"},"reference-count":59,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T00:00:00Z","timestamp":1759017600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Quantitative Biosciences Institute Coronavirus Research Group (QCRG) Antiviral Drug Discovery (AViDD) center","award":["NIH U19AI171110"],"award-info":[{"award-number":["NIH U19AI171110"]}]},{"name":"Successful Clinical Response to Pneumonia Therapy (SCRIPT) Center","award":["NIH U19AI135964"],"award-info":[{"award-number":["NIH U19AI135964"]}]},{"name":"NIH","award":["R01AI177498"],"award-info":[{"award-number":["R01AI177498"]}]},{"name":"NIH","award":["S10OD032243"],"award-info":[{"award-number":["S10OD032243"]}]},{"name":"Center for Pathogen Genomics and Microbial Evolution"},{"name":"Immunology and Molecular Sciences Training Grant at Northwestern University","award":["NIH T32AI007476"],"award-info":[{"award-number":["NIH T32AI007476"]}]},{"DOI":"10.13039\/100017930","name":"Academic Pediatric Association","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100017930","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Viruses"],"abstract":"<jats:p>The Coronavirus disease 2019 (COVID-19) pandemic had a profound global impact, yet children exhibited distinct clinical and epidemiological patterns compared to adults. Pediatric cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were generally characterized by milder disease, lower hospitalization rates, and few long-term sequelae. However, a subset of children developed severe complications such as multisystem inflammatory syndrome in children (MIS-C), highlighting the heterogeneity in disease presentation. Differences in immune system maturity and comorbidities likely contribute to the age-dependent manifestation of SARS-CoV-2 and other respiratory viruses. Persistent SARS-CoV-2 infection, particularly in immunocompromised individuals, has been implicated in the emergence of new viral variants with immune escape characteristics due to ongoing viral replication in the presence of selective pressure. While SARS-CoV-2 evolution in persistently infected adults has been well-documented, it is less clear how the virus evolves during persistent infection in the pediatric population. To address this question, we performed viral whole genome sequencing of longitudinal specimens collected from immunocompetent and immunocompromised pediatric COVID-19 patients. Similarly to what has been observed in adult cohorts, mutations associated with enhanced viral fitness and immune escape arose intra-host over time. Intra-host diversity accumulated at similar rates in immunocompetent and immunocompromised children, though more mutations overall were observed in the immunocompromised cohort due to the longer infection time courses. Overall, we identified similar viral evolutionary trends over the course of infection despite clinical differences in pediatric COVID-19 manifestation and severity. This similarity suggests that persistent infection in children may be an additional, but not unique, source of ongoing viral diversification.<\/jats:p>","DOI":"10.3390\/v17101313","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T08:00:32Z","timestamp":1759132832000},"page":"1313","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Intra-Host Evolution of SARS-CoV-2 During Persistent Infection of Pediatric COVID-19 Patients"],"prefix":"10.3390","volume":"17","author":[{"given":"Charlie R.","family":"Boyle","sequence":"first","affiliation":[{"name":"Division of Pediatric Infectious Diseases, Anne and Robert H. Lurie Children\u2019s Hospital, Chicago, IL 60611, USA"},{"name":"Center for Pathogen Genomics and Microbial Evolution, Northwestern University Havey Institute for Global Health, Chicago, IL 60611, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4049-6465","authenticated-orcid":false,"given":"Tien","family":"Doan","sequence":"additional","affiliation":[{"name":"Center for Pathogen Genomics and Microbial Evolution, Northwestern University Havey Institute for Global Health, Chicago, IL 60611, USA"},{"name":"Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1399-7546","authenticated-orcid":false,"given":"Estefany","family":"Rios-Guzman","sequence":"additional","affiliation":[{"name":"Center for Pathogen Genomics and Microbial Evolution, Northwestern University Havey Institute for Global Health, Chicago, IL 60611, USA"},{"name":"Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5556-3281","authenticated-orcid":false,"given":"Jessica","family":"Maciuch","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4041-6775","authenticated-orcid":false,"given":"Lacy M.","family":"Simons","sequence":"additional","affiliation":[{"name":"Center for Pathogen Genomics and Microbial Evolution, Northwestern University Havey Institute for Global Health, Chicago, IL 60611, USA"},{"name":"Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3951-4621","authenticated-orcid":false,"given":"Dulce S.","family":"Garcia","sequence":"additional","affiliation":[{"name":"Center for Pathogen Genomics and Microbial Evolution, Northwestern University Havey Institute for Global Health, Chicago, IL 60611, USA"},{"name":"Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David B.","family":"Williams","sequence":"additional","affiliation":[{"name":"Stanley Manne Children\u2019s Research Institute, Ann & Robert H. Lurie Children\u2019s Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3638-2218","authenticated-orcid":false,"given":"Arghavan","family":"Alisoltani","sequence":"additional","affiliation":[{"name":"Center for Pathogen Genomics and Microbial Evolution, Northwestern University Havey Institute for Global Health, Chicago, IL 60611, USA"},{"name":"Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7131-3691","authenticated-orcid":false,"given":"Egon A.","family":"Ozer","sequence":"additional","affiliation":[{"name":"Center for Pathogen Genomics and Microbial Evolution, Northwestern University Havey Institute for Global Health, Chicago, IL 60611, USA"},{"name":"Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramon","family":"Lorenzo-Redondo","sequence":"additional","affiliation":[{"name":"Center for Pathogen Genomics and Microbial Evolution, Northwestern University Havey Institute for Global Health, Chicago, IL 60611, USA"},{"name":"Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6424-4280","authenticated-orcid":false,"given":"Judd F.","family":"Hultquist","sequence":"additional","affiliation":[{"name":"Center for Pathogen Genomics and Microbial Evolution, Northwestern University Havey Institute for Global Health, Chicago, IL 60611, USA"},{"name":"Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1542\/pir.2022-005686","article-title":"COVID-19: A Pediatric Update in Epidemiology, Management, Prevention, and Long-term Effects","volume":"44","author":"Inagaki","year":"2023","journal-title":"Pediatr. 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