{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T03:03:39Z","timestamp":1793675019267,"version":"4.5.1"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T00:00:00Z","timestamp":1705968000000},"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. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Post-acute sequelae of COVID-19 affects the quality of life of many COVID-19 survivors, yet the etiology of post-acute sequelae of COVID-19 remains unknown. We aimed to determine if persistent inflammation and ongoing T-cell activation during convalescence were a contributing factor to the pathogenesis of post-acute sequelae of COVID-19.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We evaluated 67 individuals diagnosed with COVID-19 by nasopharyngeal polymerase chain reaction for persistent symptoms during convalescence at separate time points occurring up to 180 days post-diagnosis. Fifty-two of these individuals were evaluated longitudinally. We obtained whole blood samples at each study visit, isolated peripheral blood mononuclear cells, and stained for multiple T cell activation markers for flow cytometry analysis. The activation states of participants\u2019 CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T-cells were next analyzed for each of the persistent symptoms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Overall, we found that participants with persistent symptoms had significantly higher levels of inflammation at multiple time points during convalescence when compared to those who fully recovered from COVID-19. Participants with persistent dyspnea, forgetfulness, confusion, and chest pain had significantly higher levels of proliferating effector T-cells (CD8<jats:sup>+<\/jats:sup>Ki67<jats:sup>+<\/jats:sup>), and those with chest pain, joint pain, difficulty concentrating, and forgetfulness had higher levels of regulatory T-cells (CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup>). Additionally, those with dyspnea had significantly higher levels of CD8<jats:sup>+<\/jats:sup>CD38<jats:sup>+<\/jats:sup>, CD8<jats:sup>+<\/jats:sup> Granzyme B<jats:sup>+<\/jats:sup>, and CD8<jats:sup>+<\/jats:sup>IL10<jats:sup>+<\/jats:sup> cells. A retrospective comparison of acute phase inflammatory markers in adults with and without post-acute sequelae of COVID-19 showed that CD8<jats:sup>+<\/jats:sup>Ki67<jats:sup>+<\/jats:sup> cells were significantly higher at the time of acute illness (up to 14 days post-diagnosis) in those who developed persistent dyspnea.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These findings suggest continued CD8+ T-cell activation following SARS-CoV-2 infection in adults experiencing post-acute sequelae of COVID-19 and that the increase in T regulatory cells for a subset of these patients represents the ongoing attempt by the host to reduce inflammation.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1303971","type":"journal-article","created":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T04:22:26Z","timestamp":1705983746000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Persistent CD8+ T cell proliferation and activation in COVID-19 adult survivors with post-acute sequelae: a longitudinal, observational cohort study of persistent symptoms and T cell markers"],"prefix":"10.3389","volume":"14","author":[{"given":"Stephanie M.","family":"LaVergne","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taru S.","family":"Dutt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"McFann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bridget A.","family":"Baxter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy L.","family":"Webb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kailey","family":"Berry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maddy","family":"Tipton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia","family":"Stromberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian M.","family":"Sullivan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Dunn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcela","family":"Henao-Tamayo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth P.","family":"Ryan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,1,23]]},"reference":[{"key":"B1","unstructured":"Johns Hopkins Coronavirus Resource Center"},{"key":"B2","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1186\/s12879-022-07153-4","article-title":"Post-COVID-19 syndrome. 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