CellFeb 26, 2022

Several early signs may predict long-term symptoms after COVID-19

Updated Jan 13, 2026

Abstract

Four quantifiable risk factors for post-acute sequelae of COVID-19 (PASC) were identified in 309 patients at diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific auto-antibodies.

Patients with gastrointestinal PASC exhibited unique dynamics in SARS-CoV-2-specific and CMV-specific CD8T cells during recovery.
Immunological signatures associated with symptoms indicated a polarization of immunity into four distinct endotypes.
The relationship between PASC-associated immunological factors and patient condition appeared to decrease over time.
Early measurement of PASC risk factors at diagnosis may enhance understanding of chronic conditions following COVID-19.

Simplified

Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data and patient-reported symptoms. We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific auto-antibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes, exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time, leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies. +

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Competing interests

Declaration of interests J.R.H. and A.R. are founders and board members of PACT Pharma. J.R.H. is a board member of Isoplexis, and A.R. is the scientific advisor to Isoplexis. M.M.D. is a member of the Scientific Advisory Board of PACT Pharma. J.A.B. is a member of the Scientific Advisory Boards of Arcus, Solid, and VIR. J.A.B. is a member of the Board of Directors of Gilead and Provention. J.A.B. is the CEO of Sonoma Biotherapeutics. L.L.L. is on the scientific advisory boards of Alector, Atreca, Dragonfly, DrenBio, Nkarta, Obsidian Therapeutics, and SBI Biotech. R.G. has received consulting income from Juno Therapeutics, Takeda, Infotech Soft, Celgene, and Merck, has received research support from Janssen Pharmaceuticals and Juno Therapeutics, and declares ownership in CellSpace Biosciences. P.D.G. is on the Scientific Advisory Board of Celsius, Earli, Elpiscience, Immunoscape, Rapt, and Nextech, was a scientific founder of Juno Therapeutics, and receives research support from Lonza. J.D.G. declared contracted research with Gilead, Lilly, and Regeneron. J.A.H. received consulting fees or honoraria from Gilead Sciences, Amplyx, Allovir, Allogene therapeutics, CRISPR therapeutics, CSL Behring, OptumHealth, Octapharma, and Takeda and research funding from Takeda, Allovir, Karius, and Gilead Sciences. Q.D., D.H.M., R.T., R.M.G., M.K., and T.M.S. have employment and equity ownership with Adaptive Biotechnologies. The remaining authors declare no competing interests.

PubMed

Several early signs may predict long-term symptoms after COVID-19

Abstract

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Funding

Competing interests

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Abstract

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Funding

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