Chronic inflammation, neutrophil activity, and autoreactivity splits long COVID

While immunologic correlates of COVID-19 have been highly 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 disease immunologic process and therapeutic opportunities is important. Here we provide a path to highlight disease features associated with a unique immunologic line of signatures of ongoing antiviral B cell activity in PASC patients but not in controls with uncomplicated recovery. Plasma and immune profiling further show 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.

Matthew C. Woodruff, Kevin S. Bonham, Fabliah A. Anam, Tiffany A. Walker, Caterina E. Faliti, Yusho Ishii, Candice Y. Kaminski, Martin C. Runstrom, Kelly Rose Cooper, Alexander D. Truong, Adviteeya N. Dixit, Jenny E. Han, Richard P. Ramoniello, 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, Ignacio Sanz