Cell Reports Medicine · Published 2026-07-01 · DOI 10.1016/j.xcrm.2026.102946
Tongcui Ma, Heeju Ryu, Kailin Yin, Thomas Dalhuisen, Douglas Robbins, Tyrine T. Bailey, Sean A. Thomas, Emily A. Fehrman, J. Daniel Kelly, Jeffrey N. Martin, Kara L. Lynch, Sulggi A. Lee, Steven G. Deeks, Timothy J. Henrich, Michael J. Peluso, Evan W. Newell, Nadia R. Roan
Summary: Viral-specific CD8+ T cells play roles in protective immunity and immunopathology including during COVID-19. Leveraging combinatorial tetramers, we profiled CD8+ T cells specific for SARS-CoV-2, as well as those for cytomegalovirus (CMV) and Epstein-Barr virus (EBV)—herpesviruses implicated in COVID-19 pathogenesis. During severe COVID-19, EBV-specific CD8+ T cells exhibit a stem-like state, whereas CMV-specific ones are terminally differentiated and cytolytic. Comparing post-acute samples from long COVID (LC) individuals to those recovered revealed that LC-associated CMV-specific CD8+ T cells are T central memory cell (Tcm)- instead of terminally differentiated memory T cell (Temra)-biased. In LC individuals, CD8+ T cells specific for SARS-CoV-2, CMV, and EBV are preferentially terminally differentiated, exhausted, and cytolytic. Cytolytic granzyme-B-expressing CD8+ T cells are particularly prominent among LC women. As granzyme B is upregulated on viral-specific CD8+ T cells during acute viremia, an inability to shut down COVID-19-induced cytolytic effector expression may drive preferential persistence of cytolytic CD8+ T cells in people with LC, which may contribute to LC pathogenesis.
Abstract from DOAJ. Public domain (CC0 1.0).
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Ma, T., Ryu, H., Yin, K., et al. (2026). Persistent cytolytic CD8+ T cells recognize SARS-CoV-2 and herpesvirus epitopes in long COVID. Cell Reports Medicine. https://doi.org/10.1016/j.xcrm.2026.102946