Multiple Early Factors Anticipate Post-Acute COVID-19 Sequelae

Highlights

  • Longitudinal multiomics associate PASC with autoantibodies, viremia and comorbidities
  • Reactivation of latent viruses during initial infection may contribute to PASC
  • Subclinical autoantibodies negatively correlate with anti-SARS-CoV-2 antibodies
  • Gastrointestinal PASC uniquely present with post-acute expansion of cytotoxic T cells

SUMMARY

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 autoantibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8+ T 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.

Article Info

Publication History

Accepted: January 19, 2022Received in revised form: December 14, 2021Received: September 29, 2021

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https://www.cell.com/cell/pdf/S0092-8674(22)00072-1.pdf?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867422000721%3Fshowall%3Dtrue

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