Long COVID manifests with T cell dysregulation, inflammation and an uncoordinated adaptive immune response to SARS-CoV-2

Kailin Yin(Gladstone Institutes), Michael J. Peluso(University of California, San Francisco), Xiaoyu Luo(Gladstone Institutes), Reuben Thomas(Gladstone Institutes), Min‐Gyoung Shin(Gladstone Institutes), Jason Neidleman(Gladstone Institutes), Alicer K. Andrew(Gladstone Institutes), Kyrlia C. Young(Gladstone Institutes), Tongcui Ma(Gladstone Institutes), Rebecca Hoh(University of California, San Francisco), Khamal Anglin(University of California, San Francisco), Beatrice Huang(University of California, San Francisco), Urania Argueta(University of California, San Francisco), Mónica López‐Peña(University of California, San Francisco), Daisy Valdivieso(University of California, San Francisco), Kofi Asare(University of California, San Francisco), Tyler‐Marie Deveau(University of California, San Francisco), Sadie E. Munter(University of California, San Francisco), Rania Ibrahim(University of California, San Francisco), Ludger Ständker(Universität Ulm), Scott Lu(University of California, San Francisco), Sarah A. Goldberg(University of California, San Francisco), Sulggi A. Lee(San Francisco General Hospital), Kara L. Lynch(University of California, San Francisco), J. Daniel Kelly(University of California, San Francisco), Jeffrey N. Martin(University of California, San Francisco), Jan Münch(Universität Ulm), Steven G. Deeks(University of California, San Francisco), Timothy J. Henrich(University of California, San Francisco), Nadia R. Roan(Gladstone Institutes)
Nature Immunology
January 11, 2024
10.1038/s41590-023-01724-6
Cited by 330Open Access
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Abstract

Abstract Long COVID (LC) occurs after at least 10% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, yet its etiology remains poorly understood. We used ‘omic” assays and serology to deeply characterize the global and SARS-CoV-2-specific immunity in the blood of individuals with clear LC and non-LC clinical trajectories, 8 months postinfection. We found that LC individuals exhibited systemic inflammation and immune dysregulation. This was evidenced by global differences in T cell subset distribution implying ongoing immune responses, as well as by sex-specific perturbations in cytolytic subsets. LC individuals displayed increased frequencies of CD4 + T cells poised to migrate to inflamed tissues and exhausted SARS-CoV-2-specific CD8 + T cells, higher levels of SARS-CoV-2 antibodies and a mis-coordination between their SARS-CoV-2-specific T and B cell responses. Our analysis suggested an improper crosstalk between the cellular and humoral adaptive immunity in LC, which can lead to immune dysregulation, inflammation and clinical symptoms associated with this debilitating condition.

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