{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:28:27Z","timestamp":1785432507018,"version":"3.56.0"},"posted":{"date-parts":[[2026,4,29]]},"group-title":"Immunology","reference-count":102,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"award":["R03AI175977"],"award-info":[{"award-number":["R03AI175977"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["5R35GM142795"],"award-info":[{"award-number":["5R35GM142795"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"U.S. National Science Foundation","doi-asserted-by":"crossref","award":["2045054"],"award-info":[{"award-number":["2045054"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,29]]},"abstract":"<jats:p>\n                  T-cells are central to SARS-CoV-2 clearance and immunological memory, yet their contribution to the persistence of post-acute sequelae of COVID-19 (PASC) remains poorly understood. The immunological features that distinguish individuals who develop PASC from those who recover fully are unresolved, in part due to the phenotypic heterogeneity of the condition and the likely multiplicity of its underlying mechanisms. Here, we profiled longitudinal bulk TCR\n                  <jats:italic>\u03b2<\/jats:italic>\n                  repertoires from 120 individuals in the INCOV cohort\u201371 with PASC and 49 without\u2013sampled at two to three time points spanning the acute and post-acute phases of infection. Using robust statistical modeling of repertoire composition and clonal dynamics, we found that global statistics such as V, J gene usage and CDR3 length do not differ between groups, but that locally enriched sequence motifs and differentially dynamic clones reveal distinct T-cell signatures associated with PASC status. Clones contracting following the peak of the acute response were significantly enriched for SARS-CoV-2 specificity in both groups. Interestingly, Influenza A-specific TCRs were disproportionately enriched among contracting clones in PASC\n                  <jats:sup>+<\/jats:sup>\n                  repertoires, implicating viral co-infection as a potential contributor to early disease severity and, possibly, PASC pathogenesis. Rare public TCR clones were markedly enriched for SARS-CoV-2 specificity, with PASC\n                  <jats:sup>+<\/jats:sup>\n                  individuals harboring a modestly but significantly higher proportion than PASC\n                  <jats:sup>\u2212<\/jats:sup>\n                  individuals. Together, we identified over 1,000 candidate TCR\n                  <jats:italic>\u03b2<\/jats:italic>\n                  receptors potentially discriminating PASC\n                  <jats:sup>+<\/jats:sup>\n                  from PASC\n                  <jats:sup>\u2212<\/jats:sup>\n                  immune responses, opening a path toward the identification of disease-relevant T-cell specificities and the development of T-cell-based immunological biomarkers for long COVID.\n                <\/jats:p>","DOI":"10.64898\/2026.04.27.721205","type":"posted-content","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T01:15:33Z","timestamp":1777511733000},"source":"Crossref","is-referenced-by-count":0,"title":["T-cell repertoire response in individuals with post-acute sequelae of COVID-19"],"prefix":"10.64898","author":[{"given":"Zachary","family":"Montague","sequence":"first","affiliation":[{"name":"Department of Physics, University of Washington, 3910 15th Avenue Northeast, Seattle, WA 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhea M","family":"Grover","sequence":"additional","affiliation":[{"name":"Department of Physics, University of Washington, 3910 15th Avenue Northeast, Seattle, WA 98195, USA"},{"name":"Department of Mathematics, University of California, Berkeley, Berkeley, CA, USA"},{"name":"Department of Applied Mathematics, University of Washington, 4182 W Stevens Way NE, Seattle, WA 98105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Baumgartner","sequence":"additional","affiliation":[{"name":"Institute for Systems Biology, Seattle, WA, USA"},{"name":"Phenome Health, 2101 4th Ave, Seattle, WA 98121, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Assya","family":"Trofimov","sequence":"additional","affiliation":[{"name":"Department of Physics, University of Washington, 3910 15th Avenue Northeast, Seattle, WA 98195, USA"},{"name":"Fred Hutchinson Cancer Center, 1241 Eastlake Ave E, Seattle, WA 98102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6103-7606","authenticated-orcid":false,"given":"Jennifer","family":"Hadlock","sequence":"additional","affiliation":[{"name":"Institute for Systems Biology, Seattle, WA, USA"},{"name":"Department of Biomedical Informatics and Medical Education, University of Washington, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armita","family":"Nourmohammad","sequence":"additional","affiliation":[{"name":"Department of Physics, University of Washington, 3910 15th Avenue Northeast, Seattle, WA 98195, USA"},{"name":"Department of Applied Mathematics, University of Washington, 4182 W Stevens Way NE, Seattle, WA 98105, USA"},{"name":"Fred Hutchinson Cancer Center, 1241 Eastlake Ave E, Seattle, WA 98102, USA"},{"name":"Paul G. Allen School of Computer Science and Engineering, University of Washington, 85 E Stevens Way NE, Seattle, WA 98195, USA"},{"name":"Center for Systems and Engineering Immunology, and the Departments of Immunobiology, Biomedical Engineering, and Physics, Yale University, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026050400501569000_2026.04.27.721205v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-022-00846-2"},{"key":"2026050400501569000_2026.04.27.721205v1.2","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/S0140-6736(24)01136-X","article-title":"Long covid: a clinical update","volume":"404","year":"2024","journal-title":"The Lancet"},{"key":"2026050400501569000_2026.04.27.721205v1.3","doi-asserted-by":"publisher","DOI":"10.1136\/bmjgh-2021-005427"},{"key":"2026050400501569000_2026.04.27.721205v1.4","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/S2213-2600(23)00239-4","article-title":"Post-acute sequelae of covid-19: understanding and addressing the burden of multisystem manifestations","volume":"11","year":"2023","journal-title":"The Lancet Respiratory Medicine"},{"key":"2026050400501569000_2026.04.27.721205v1.5","first-page":"796","article-title":"Postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection","volume":"6","year":"2021","journal-title":"JACC: Basic to Translational Science"},{"key":"2026050400501569000_2026.04.27.721205v1.6","first-page":"e230010","volume-title":"in JAMA Health Forum","volume":"4","year":"2023"},{"key":"2026050400501569000_2026.04.27.721205v1.7","first-page":"927","article-title":"Use of cardiopulmonary stress testing for patients with unexplained dyspnea post\u2013coronavirus disease","volume":"9","year":"2021","journal-title":"JACC: Heart Failure"},{"key":"2026050400501569000_2026.04.27.721205v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32507-6"},{"key":"2026050400501569000_2026.04.27.721205v1.9","doi-asserted-by":"crossref","first-page":"6664","DOI":"10.1038\/s41467-024-50339-4","article-title":"Non-human primate model of long-covid identifies immune associates of hyperglycemia","volume":"15","year":"2024","journal-title":"Nature communications"},{"key":"2026050400501569000_2026.04.27.721205v1.10","doi-asserted-by":"crossref","unstructured":"V. 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