{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T01:57:28Z","timestamp":1774317448361,"version":"3.50.1"},"reference-count":32,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T00:00:00Z","timestamp":1763337600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2023YFC3041500"],"award-info":[{"award-number":["2023YFC3041500"]}]},{"name":"Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences","award":["2023-PT320-01"],"award-info":[{"award-number":["2023-PT320-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>SARS-CoV-2 evolution in persistent infection, which may induce long COVID-19, is predominantly manifested in immunocompromised hosts, who act as the viral reservoirs for future outbreaks. Therefore, understanding the evolutionary mechanisms of novel variants that can evade preexisting immune responses is critical to guide public health measures and develop vaccines tailored for vulnerable populations. We used next-generation sequencing and phylogenetic methods to delineate the evolutionary and mutational profiles of SARS-CoV-2 variants using serial oropharyngeal swab samples from 5 individuals with persistent infections. Our results revealed that the intra-host evolutionary patterns of different variants varied significantly, and the evolutionary rate in 3 immunocompromised hosts was 20 times higher than in 2 other patients. These variations likely stem from differences in immune suppression status, the strength of preexisting immune responses, and the extent of error-generating mutations. There were 15 intra-host single-nucleotide variants (iSNVs) in the spike gene among at least two variants, suggesting convergent evolution. Although most new iSNVs do not reach fixation, some of them belong to lineage-defined mutations in variants of concern (VOCs) and recent variants of interest (VOIs). The observations indicate that persistent infections serve as sources for novel, potentially harmful variants, whereas the viral evolutionary dynamics are impacted by virological, immunological, and genetic factors. Thus, there is an urgent need for individualized monitoring and management of immunocompromised hosts to prevent outbreaks caused by the viral seeds generated from them and to study viral factors associated with post-acute COVID-19 sequelae.<\/jats:p>","DOI":"10.3390\/microorganisms13112613","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T09:58:42Z","timestamp":1763459922000},"page":"2613","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Immune Suppression, Preexisting Immunity, and Mutation Tendency Shaped SARS-CoV-2 Evolution in Persistent Infection"],"prefix":"10.3390","volume":"13","author":[{"given":"Minghui","family":"An","sequence":"first","affiliation":[{"name":"State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, NHC Key Laboratory of AIDS Prevention and Treatment, National Clinical Research Center for Laboratory Medicine, The First Hospital of China Medical University, China Medical University, Shenyang 110001, China"},{"name":"Key Laboratory of AIDS Immunology, Chinese Academy of Medical Sciences, Shenyang 110001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1449-7535","authenticated-orcid":false,"given":"Xiaolong","family":"Dong","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Laboratory Medicine, Department of Laboratory Medicine, The First Hospital of China Medical University, Shenyang 110001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Gao","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Laboratory Medicine, Department of Laboratory Medicine, The First Hospital of China Medical University, Shenyang 110001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinming","family":"Ouyang","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Laboratory Medicine, Department of Laboratory Medicine, The First Hospital of China Medical University, Shenyang 110001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haibo","family":"Ding","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, NHC Key Laboratory of AIDS Prevention and Treatment, National Clinical Research Center for Laboratory Medicine, The First Hospital of China Medical University, China Medical University, Shenyang 110001, China"},{"name":"Key Laboratory of AIDS Immunology, Chinese Academy of Medical Sciences, Shenyang 110001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zheming","family":"Zhu","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Laboratory Medicine, Department of Laboratory Medicine, The First Hospital of China Medical University, Shenyang 110001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linan","family":"Bao","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Laboratory Medicine, Department of Laboratory Medicine, The First Hospital of China Medical University, Shenyang 110001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yonghui","family":"Feng","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Laboratory Medicine, Department of Laboratory Medicine, The First Hospital of China Medical University, Shenyang 110001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen","family":"Tian","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, NHC Key Laboratory of AIDS Prevention and Treatment, National Clinical Research Center for Laboratory Medicine, The First Hospital of China Medical University, China Medical University, Shenyang 110001, China"},{"name":"Key Laboratory of AIDS Immunology, Chinese Academy of Medical Sciences, Shenyang 110001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pan","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, NHC Key Laboratory of AIDS Prevention and Treatment, National Clinical Research Center for Laboratory Medicine, The First Hospital of China Medical University, China Medical University, Shenyang 110001, China"},{"name":"Key Laboratory of AIDS Immunology, Chinese Academy of Medical Sciences, Shenyang 110001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoxu","family":"Han","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Laboratory Medicine, Department of Laboratory Medicine, The First Hospital of China Medical University, Shenyang 110001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Shang","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, NHC Key Laboratory of AIDS Prevention and Treatment, National Clinical Research Center for Laboratory Medicine, The First Hospital of China Medical University, China Medical University, Shenyang 110001, China"},{"name":"Key Laboratory of AIDS Immunology, Chinese Academy of Medical Sciences, Shenyang 110001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,17]]},"reference":[{"key":"ref_1","first-page":"162","article-title":"SARS-CoV-2 variant biology: Immune escape, transmission and fitness","volume":"21","author":"Carabelli","year":"2023","journal-title":"Nat. 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