CYTO Virtual Interactive 2021 Oral Presentation - Integrated Plasma Proteomic and Single-Cell Immune Signaling Network Signatures Demarcate Mild, Moderate, and Severe COVID-19
The biological determinants that differentiate patients across the wide spectrum of COVID-19 clinical manifestations are not fully understood. Here, over 1,400 plasma proteins and 2,600 single-cell immune features comprising cell phenotype, basal signaling activity, and signaling responses to inflammatory ligands were assessed in peripheral blood from patients with mild, moderate, and severe COVID-19. Using an integrated computational approach to analyze the combined plasma and single-cell proteomic data, we identified and independently validated a multivariate model classifying COVID-19 severity (multi-class AUCtraining = 0.799, p-value = 4.2e-6; multi-class AUCvalidation = 0.773, p-value = 7.7e-6). Features of this high-dimensional model recapitulated recent COVID-19 related observations of immune perturbations and revealed novel biological signatures of severity, including the mobilization of elements of the renin-angiotensin system and primary hemostasis, as well as dysregulation of JAK/STAT, MAPK/mTOR, and NF-κB immune signaling networks. These results provide a set of early determinants of COVID-19 severity that may point to therapeutic targets for the prevention of COVID-19 progression.
Dorien Feyaerts, PhD
Department of Anesthesiology
Perioperative and Pain Medicine
Dr. Dorien Feyaerts joined the laboratory of Dr. Brice Gaudillière at Stanford University as a postdoctoral fellow at the beginning of 2020 after completing her PhD in reproductive immunology at the Radboud University Medical Center (Nijmegen, the Netherlands). Her research interest lies in enhancing our understanding of the maternal immune dynamics of healthy and complicated pregnancies both from a systemic and local tissue-specific viewpoint, as well as determining biological signatures of COVID-19 severity and post-COVID complications using high-dimensional translational studies (i.e., suspension and imaging mass cytometry).
CMLE Credit: 1.0