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Multiple early factors anticipate post-acute COVID-19 sequelae

Yapeng Su1, Dan Yuan2, Daniel G Chen3

  • 1Institute for Systems Biology, Seattle, WA 98109, USA; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Clinical Research Division, Program in Immunology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

Cell
|February 26, 2022
PubMed

Insights

Four key factors predict post-acute sequelae of COVID-19 (PASC). Early detection of type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus, and auto-antibodies aids in understanding and managing PASC.

Area of Science:

  • Immunology
  • Virology
  • Endocrinology
  • Genomics

Background:

  • Post-acute sequelae of COVID-19 (PASC) is a growing global health concern.
  • Quantifiable risk factors and biological underpinnings of PASC remain incompletely understood.

Purpose of the Study:

  • To identify quantifiable risk factors for PASC.
  • To explore the biological associations and immunological signatures of PASC.
  • To investigate the longitudinal changes in immune states during COVID-19 convalescence.

Main Methods:

  • A deep multi-omic, longitudinal study of 309 COVID-19 patients from diagnosis to 2-3 months post-recovery.
  • Integration of clinical data and patient-reported symptoms with multi-omic data.
  • Analysis of immunological signatures, including SARS-CoV-2 and CMV-specific CD8+ T cells, and auto-antibodies.

Main Results:

  • Four PASC-predicting risk factors identified at initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific auto-antibodies.
  • Distinct dynamics of SARS-CoV-2 and CMV-specific CD8+ T cells observed in patients with gastrointestinal PASC.
  • Four immunological endotypes identified, correlating with acute severity and PASC development.
  • Immunological associations between PASC factors diminish over time, leading to distinct convalescent immune states.

Conclusions:

  • Early identification of specific risk factors at the time of COVID-19 diagnosis is crucial for predicting and understanding PASC.
  • Immunological signatures and T cell dynamics offer insights into PASC pathogenesis.
  • Understanding longitudinal immune changes is key to developing effective PASC treatment strategies.

Keywords:
COVID-19PASCRNAemiaantibodiesauto-antibodiescomputational biologyimmune systemimmunologylong COVIDmetabolomicsmulti-omicsproteomicssingle cellsingle-cell CITE-seqsingle-cell RNA-seqsingle-cell TCR-seqsingle-cell secretomesymptomstranscriptomeviremia

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