Abstract
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.
Highlights
COVID19, the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused more than 2.33 million deaths worldwide since late2019
COVID19 patients tested positive for SARS-CoV-2 infection by PCR and/or antibody testing and were hospitalized due to COVID19 symptoms, but none of them had developed severe pathology requiring ICU
Research blood draws were obtained from consented participants and analyzed by matched SARS-CoV-2 seroconversion assays, plasma proteomics using two alternative platforms [mass-spectrometry (MS) and SOMAscan assays], 82-plex cytokine profiling using multiplex immunoassays with Meso Scale Discovery (MSD) technology, and immune cell profiling via mass cytometry (MC) (Figure 1a)
Summary
COVID19 (coronavirus disease of 2019), the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused more than 2.33 million deaths worldwide since late. Several pathophysiological processes have been implicated in the etiology of severe COVID19 symptoms, including but not restricted to a hyperinflammation-driven pathology (Tay et al, 2020), disruption of lung barrier function by Type I and III interferons (IFN) (Broggi et al, 2020; Major et al, 2020), organ damage by systemic activation of the complement cascade (Holter et al., 2020), vascular pathology caused by a bradykinin storm (Garvin et al, 2020), and a dysregulated fibrinolytic system (D’Alessandro et al, 2020) The interplay between these non-mutually exclusive processes is yet to be fully elucidated, and each of them offers opportunities for therapeutic interventions currently being tested in clinical trials. These results indicate that a quantitative assessment of seroconversion status could be employed to map the trajectory of underlying pathophysiological processes, with potential utility in stratification of patients in the clinic and enhanced interpretation of clinical trial data
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