RT Journal Article
SR Electronic
T1 Integrated plasma proteomic and single-cell immune signaling network signatures demarcate mild, moderate, and severe COVID-19
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.02.09.430269
DO 10.1101/2021.02.09.430269
A1 Dorien Feyaerts
A1 Julien Hédou
A1 Joshua Gillard
A1 Han Chen
A1 Eileen S. Tsai
A1 Laura S. Peterson
A1 Kazuo Ando
A1 Monali Manohar
A1 Evan Do
A1 Gopal K.R. Dhondalay
A1 Jessica Fitzpatrick
A1 Maja Artandi
A1 Iris Chang
A1 Theo T. Snow
A1 R. Sharon Chinthrajah
A1 Christopher M. Warren
A1 Rich Wittman
A1 Justin G. Meyerowitz
A1 Edward A. Ganio
A1 Ina A. Stelzer
A1 Xiaoyuan Han
A1 Franck Verdonk
A1 Dyani K. Gaudillière
A1 Nilanjan Mukherjee
A1 Amy S. Tsai
A1 Kristen K. Rumer
A1 Sizun Jiang
A1 Sergio Iván Valdés Ferrer
A1 J. Daniel Kelly
A1 David Furman
A1 Nima Aghaeepour
A1 Martin S. Angst
A1 Scott D. Boyd
A1 Benjamin A. Pinsky
A1 Garry P. Nolan
A1 Kari C. Nadeau
A1 Brice Gaudillière
A1 David R. McIlwain
YR 2021
UL http://biorxiv.org/content/early/2021/02/12/2021.02.09.430269.abstract
AB The biological determinants of the wide spectrum of COVID-19 clinical manifestations are not fully understood. Here, over 1400 plasma proteins and 2600 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, at the time of diagnosis. 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.Summary Feyaerts et al. demonstrate that an integrated analysis of plasma and single-cell proteomics differentiates COVID-19 severity and reveals severity-specific biological signatures associated with the dysregulation of the JAK/STAT, MAPK/mTOR, and NF-κB immune signaling networks and the mobilization of the renin-angiotensin and hemostasis systems.Competing Interest StatementThe authors have declared no competing interest.