Seroconversion stages COVID19 into distinct pathophysiological states.

COVID19 is a heterogeneous medical condition involving diverse underlying pathophysiological processes including hyperinflammation, endothelial damage, thrombotic microangiopathy, and end-organ damage. Limited knowledge about the molecular mechanisms driving these processes and lack of staging biomarkers hamper the ability to stratify patients for targeted therapeutics. We report here the results of a cross-sectional multi-omics analysis of hospitalized COVID19 patients revealing that seroconversion status associates with distinct underlying pathophysiological states. Low antibody titers associate with hyperactive T cells and NK cells, high levels of IFN alpha, gamma and lambda ligands, markers of systemic complement activation, and depletion of lymphocytes, neutrophils, and platelets. Upon seroconversion, all of these processes are attenuated, observing instead increases in B cell subsets, emergency hematopoiesis, increased D-dimer, and hypoalbuminemia. We propose that seroconversion status could potentially be used as a biosignature to stratify patients for therapeutic intervention and to inform analysis of clinical trial results in heterogenous patient populations.
Competing Interests: MG, KK, RB, PA, KJ, SR, KS, RG, JS, MD, TG, AM, AD, KH, TB, EH No competing interests declared, KS is a co-inventor on two patents related to JAK inhibition in COVID19: U.S. Provisional Patent Application Serial No. 62/992,855 entitled 'JAK1 Inhibition For Modulation Of Overdrive Anti-Viral Response To COVID-19'; U.S. Provisional Patent Application Serial No. 62/993,749 entitled 'Compounds and Methods for Inhibition or Modulation of Viral Hypercytokinemia'. JE Reviewing editor, eLife, is a co-inventor on two patents related to JAK inhibition in COVID19: U.S. Provisional Patent Application Serial No. 62/992,855 entitled 'JAK1 Inhibition For Modulation Of Overdrive Anti-Viral Response To COVID-19'; U.S. Provisional Patent Application Serial No. 62/993,749 entitled 'Compounds and Methods for Inhibition or Modulation of Viral Hypercytokinemia'.
(© 2021, Galbraith et al.)