Characterizing Host Inflammatory Bioprofiles in People With Postacute Sequelae SARS-CoV-2 Infection (PASC)

Postacute sequelae of COVID-19 or "PASC" is a common but heterogeneous condition associated with significant morbidity. Although its pathogenesis remains poorly understood, proposed underlying mechanisms include altered host immune and inflammatory responses and altered coagulation. We measured 57 circulating plasma biomarkers mapping eight biological pathways (axonal injury, inflammation, antiviral immune responses, immune regulation/innate immune activation, tissue damage and repair, endothelial dysfunction, coagulation, and microbial translocation) in a cohort of 356 participants attending with PASC. Using principal component analysis (PCA) and unsupervised clustering, we identified six distinct inflammatory clusters within this PASC cohort, three of which were characterized by elevated biomarkers related to tissue damage and repair, coagulation, axonal injury, and antiviral immune responses. These three "highly inflamed" clusters were associated with reported cardiovascular and respiratory symptoms in fully adjusted analysis. These data suggest a link between distinct host immune responses and different clinical PASC phenotypes.