Chronic inflammation, neutrophil activity, and autoreactivity splits long COVID

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, Adviteeya N. Dixit, Jenny E. Han, Richard P. Ramonell, Natalie S. Haddad, Mark E. Rudolph, Srilakshmi Yalavarthi, Viktoria Betin, Ted Natoli, Sherwin Navaz, Scott A. Jenks, Yu Zuo, Jason S. Knight, Arezou Khosroshahi, F. Eun-Hyung Lee () and Ignacio Sanz ()
Additional contact information
Matthew C. Woodruff: Emory University
Kevin S. Bonham: Department of Biological Sciences, Wellesley College
Fabliha A. Anam: Emory University
Tiffany A. Walker: Emory University
Caterina E. Faliti: Emory University
Yusho Ishii: Emory University
Candice Y. Kaminski: Emory University
Martin C. Ruunstrom: Emory University
Kelly Rose Cooper: 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
Yu Zuo: University of Michigan
Jason S. Knight: University of Michigan
Arezou Khosroshahi: Emory University
F. Eun-Hyung Lee: Emory University
Ignacio Sanz: Emory University

Nature Communications, 2023, vol. 14, issue 1, 1-13

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-40012-7

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