{
  "abstract": "Long COVID (LC) affects millions of people worldwide, yet its driving mechanisms remain incompletely defined and no treatment has been approved. Persistence of SARS-CoV-2 and reactivation of herpesviruses have been implicated in LC, but direct detection of these viral antigens in blood and tissues has been challenging. T cells are exquisitely sensitive to viral antigens, survey organs throughout the body, and can be readily sampled in peripheral blood. Using high-dimensional spectral flow cytometry and single-cell sequencing approaches with multiplexed peptide/HLA tetramers, we profiled virus-specific T cells from hundreds of people with LC and recovered controls. We identified a subset of people with LC that maintained elevated activation of CD8 T cells targeting SARS-CoV-2 spike and/or lytic antigens from Epstein-Barr virus, but not other viral specificities. Spike-specific cells in LC expressed genes linked to TCR stimulation, terminal effector differentiation, and exhaustion and demonstrated reduced functionality upon cognate peptide stimulation ex vivo. Thus, T cells from a subset of people with LC are likely chronically stimulated by persistent SARS-CoV-2 antigens. These findings establish the use of T cells as biosensors of persisting antigen in LC and other disease settings and may help develop new therapeutic strategies for LC.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 30,
  "authors": [
    {
      "name": "Mark M. Painter",
      "orcid": "0000-0002-0180-2748"
    },
    {
      "name": "David B. Reeg"
    },
    {
      "name": "Naomi R. Douek"
    },
    {
      "name": "Sophie L. Gray-Gaillard"
    },
    {
      "name": "Sasikanth Manne"
    },
    {
      "name": "Josephine R. Giles"
    },
    {
      "name": "Thomas Dalhuisen"
    },
    {
      "name": "Melissa Buitrago"
    },
    {
      "name": "Emily A. Fehrman"
    },
    {
      "name": "Dylan Ryder"
    },
    {
      "name": "Meghann C. Williams"
    },
    {
      "name": "Ava-Kathleen Rybicki"
    },
    {
      "name": "Gwen Baraniecki-Zwil"
    },
    {
      "name": "Zina Ahn"
    },
    {
      "name": "John P. Reilly"
    },
    {
      "name": "Danielle K. Sandsmark"
    },
    {
      "name": "Michael O. Harhay"
    },
    {
      "name": "Sasha Tabachnikova"
    },
    {
      "name": "Bornali Bhattacharjee",
      "orcid": "0000-0002-0801-1543"
    },
    {
      "name": "David Putrino"
    },
    {
      "name": "Amy D. Proal"
    },
    {
      "name": "J. Daniel Kelly"
    },
    {
      "name": "Jeffrey N. Martin",
      "orcid": "0000-0002-9773-3256"
    },
    {
      "name": "Benjamin A. Abramoff"
    },
    {
      "name": "Nuala J. Meyer"
    },
    {
      "name": "Akiko Iwasaki",
      "orcid": "0000-0002-7824-9856"
    },
    {
      "name": "Timothy J. Henrich"
    },
    {
      "name": "Steven G. Deeks",
      "orcid": "0000-0001-6371-747X"
    },
    {
      "name": "Michael J. Peluso"
    },
    {
      "name": "E. John Wherry"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5gzbgtsym3xg6.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.14.759221",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.14.759221v1.full",
  "id": "5gzbgtsym3xg6",
  "issns": [
    "2692-8205"
  ],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.14.759221v1",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "immunology"
    ],
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2728|Long-Term Effects of COVID-19"
    ]
  ],
  "openalex": "W7222830723",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.14.759221v1.full.pdf",
  "pmcid": "PMC13738412",
  "pmid": "42995851",
  "published": "2026-10-14",
  "publisher": "Cold Spring Harbor Laboratory Preprints",
  "ris": "https://research.draconitic.com/paper/5gzbgtsym3xg6.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:28:18Z",
      "native_id": "10.64898/2026.10.14.759221",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.14.759221v2"
    },
    {
      "first_seen": "2026-11-09T12:23:24Z",
      "native_id": "PMC13738412",
      "source": "pmc",
      "url": "https://doi.org/10.64898/2026.10.14.759221"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Persistently activated virus-specific CD8 T cells indicate antigen-driven immune aberrations in long COVID",
  "title_text": "Persistently activated virus-specific CD8 T cells indicate antigen-driven immune aberrations in long COVID",
  "type": "preprint",
  "updated_at": "2026-11-09T12:23:24Z",
  "url": "https://research.draconitic.com/paper/5gzbgtsym3xg6",
  "venue": "bioRxiv",
  "versions": []
}