Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, United States; Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, United States
Kohl T Kinning
Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, United States
Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, United States; Department of Pediatrics, Division of Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, United States
Ryan Baxter
Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, United States
Paula Araya
Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, United States
Kimberly R Jordan
Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, United States
Data Science to Patient Value, University of Colorado Anschutz Medical Campus, Aurora, United States
Keith P Smith
Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, United States
Ross E Granrath
Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, United States
Jessica R Shaw
Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, United States
Monika Dzieciatkowska
Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, United States
Tusharkanti Ghosh
Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, United States
Andrew A Monte
Department of Emergency Medicine, University of Colorado Anschutz Medical Campus, Aurora, United States
Angelo D'Alessandro
Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, United States
Kirk C Hansen
Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, United States
Tellen D Benett
Department of Pediatrics, Sections of Informatics and Data Science and Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, United States
Elena WY Hsieh
Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, United States; Department of Pediatrics, Division of Allergy/Immunology, University of Colorado Anschutz Medical Campus, Aurora, United States
Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, United States; Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, United 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.
