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Persistent serum protein signatures define an inflammatory subcategory of long COVID

Author

Listed:
  • Aarthi Talla

    (Allen Institute for Immunology)

  • Suhas V. Vasaikar

    (Allen Institute for Immunology
    Seagen)

  • Gregory Lee Szeto

    (Allen Institute for Immunology
    Seagen)

  • Maria P. Lemos

    (Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center)

  • Julie L. Czartoski

    (Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center)

  • Hugh MacMillan

    (Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center)

  • Zoe Moodie

    (Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center)

  • Kristen W. Cohen

    (Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
    Moderna)

  • Lamar B. Fleming

    (Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center)

  • Zachary Thomson

    (Allen Institute for Immunology)

  • Lauren Okada

    (Allen Institute for Immunology)

  • Lynne A. Becker

    (Allen Institute for Immunology)

  • Ernest M. Coffey

    (Allen Institute for Immunology)

  • Stephen C. Rosa

    (Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center)

  • Evan W. Newell

    (Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center)

  • Peter J. Skene

    (Allen Institute for Immunology)

  • Xiaojun Li

    (Allen Institute for Immunology)

  • Thomas F. Bumol

    (Allen Institute for Immunology)

  • M. Juliana McElrath

    (Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center)

  • Troy R. Torgerson

    (Allen Institute for Immunology)

Abstract

Long COVID or post-acute sequelae of SARS-CoV-2 (PASC) is a clinical syndrome featuring diverse symptoms that can persist for months following acute SARS-CoV-2 infection. The aetiologies may include persistent inflammation, unresolved tissue damage or delayed clearance of viral protein or RNA, but the biological differences they represent are not fully understood. Here we evaluate the serum proteome in samples, longitudinally collected from 55 PASC individuals with symptoms lasting ≥60 days after onset of acute infection, in comparison to samples from symptomatically recovered SARS-CoV-2 infected and uninfected individuals. Our analysis indicates heterogeneity in PASC and identified subsets with distinct signatures of persistent inflammation. Type II interferon signaling and canonical NF-κB signaling (particularly associated with TNF), appear to be the most differentially enriched signaling pathways, distinguishing a group of patients characterized also by a persistent neutrophil activation signature. These findings help to clarify biological diversity within PASC, identify participants with molecular evidence of persistent inflammation, and highlight dominant pathways that may have diagnostic or therapeutic relevance, including a protein panel that we propose as having diagnostic utility for differentiating inflammatory and non-inflammatory PASC.

Suggested Citation

  • Aarthi Talla & Suhas V. Vasaikar & Gregory Lee Szeto & Maria P. Lemos & Julie L. Czartoski & Hugh MacMillan & Zoe Moodie & Kristen W. Cohen & Lamar B. Fleming & Zachary Thomson & Lauren Okada & Lynne , 2023. "Persistent serum protein signatures define an inflammatory subcategory of long COVID," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38682-4
    DOI: 10.1038/s41467-023-38682-4
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    References listed on IDEAS

    as
    1. Yan Xie & Benjamin Bowe & Ziyad Al-Aly, 2021. "Burdens of post-acute sequelae of COVID-19 by severity of acute infection, demographics and health status," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
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