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Chronic inflammation, neutrophil activity, and autoreactivity splits long COVID

Author

Listed:
  • Matthew C. Woodruff

    (Emory University
    Emory University)

  • Kevin S. Bonham

    (Department of Biological Sciences, Wellesley College)

  • Fabliha A. Anam

    (Emory University
    Emory University)

  • Tiffany A. Walker

    (Emory University)

  • Caterina E. Faliti

    (Emory University
    Emory University)

  • Yusho Ishii

    (Emory University
    Emory University)

  • Candice Y. Kaminski

    (Emory University)

  • Martin C. Ruunstrom

    (Emory University)

  • Kelly Rose Cooper

    (Emory University
    Emory University)

  • Alexander D. Truong

    (Emory University)

  • Adviteeya N. Dixit

    (Emory University)

  • Jenny E. Han

    (Emory University)

  • Richard P. Ramonell

    (University of Pittsburgh)

  • Natalie S. Haddad

    (MicroB-plex)

  • Mark E. Rudolph

    (Exagen Inc.)

  • Srilakshmi Yalavarthi

    (University of Michigan)

  • Viktoria Betin

    (ImmuneID Inc.)

  • Ted Natoli

    (ImmuneID Inc.)

  • Sherwin Navaz

    (University of Michigan)

  • Scott A. Jenks

    (Emory University
    Emory University)

  • Yu Zuo

    (University of Michigan)

  • Jason S. Knight

    (University of Michigan)

  • Arezou Khosroshahi

    (Emory University
    Emory University)

  • F. Eun-Hyung Lee

    (Emory University)

  • Ignacio Sanz

    (Emory University
    Emory University)

Abstract

While immunologic correlates of COVID-19 have been widely reported, their associations with post-acute sequelae of COVID-19 (PASC) remain less clear. Due to the wide array of PASC presentations, understanding if specific disease features associate with discrete immune processes and therapeutic opportunities is important. Here we profile patients in the recovery phase of COVID-19 via proteomics screening and machine learning to find signatures of ongoing antiviral B cell development, immune-mediated fibrosis, and markers of cell death in PASC patients but not in controls with uncomplicated recovery. Plasma and immune cell profiling further allow the stratification of PASC into inflammatory and non-inflammatory types. Inflammatory PASC, identifiable through a refined set of 12 blood markers, displays evidence of ongoing neutrophil activity, B cell memory alterations, and building autoreactivity more than a year post COVID-19. Our work thus helps refine PASC categorization to aid in both therapeutic targeting and epidemiological investigation of PASC.

Suggested Citation

  • Matthew C. Woodruff & Kevin S. Bonham & Fabliha A. Anam & Tiffany A. Walker & Caterina E. Faliti & Yusho Ishii & Candice Y. Kaminski & Martin C. Ruunstrom & Kelly Rose Cooper & Alexander D. Truong & A, 2023. "Chronic inflammation, neutrophil activity, and autoreactivity splits long COVID," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40012-7
    DOI: 10.1038/s41467-023-40012-7
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    as
    1. Matthew C. Woodruff & Richard P. Ramonell & Natalie S. Haddad & Fabliha A. Anam & Mark E. Rudolph & Tiffany A. Walker & Alexander D. Truong & Adviteeya N. Dixit & Jenny E. Han & Monica Cabrera-Mora & , 2022. "Dysregulated naive B cells and de novo autoreactivity in severe COVID-19," Nature, Nature, vol. 611(7934), pages 139-147, November.
    2. Qian Zhang & Paul Bastard & Aurélie Cobat & Jean-Laurent Casanova, 2022. "Human genetic and immunological determinants of critical COVID-19 pneumonia," Nature, Nature, vol. 603(7902), pages 587-598, March.
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