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In Cell reports. Medicine

The biological determinants underlying the range of coronavirus 2019 (COVID-19) clinical manifestations are not fully understood. Here, over 1,400 plasma proteins and 2,600 single-cell immune features comprising cell phenotype, endogenous signaling activity, and signaling responses to inflammatory ligands are cross-sectionally assessed in peripheral blood from 97 patients with mild, moderate, and severe COVID-19 and 40 uninfected patients. Using an integrated computational approach to analyze the combined plasma and single-cell proteomic data, we identify and independently validate a multi-variate model classifying COVID-19 severity (multi-class area under the curve [AUC]training = 0.799, p = 4.2e-6; multi-class AUCvalidation = 0.773, p = 7.7e-6). Examination of informative model features reveals biological signatures of COVID-19 severity, including the dysregulation of JAK/STAT, MAPK/mTOR, and nuclear factor κB (NF-κB) immune signaling networks in addition to recapitulating known hallmarks of COVID-19. These results provide a set of early determinants of COVID-19 severity that may point to therapeutic targets for prevention and/or treatment of COVID-19 progression.

Feyaerts Dorien, Hédou Julien, Gillard Joshua, Chen Han, Tsai Eileen S, Peterson Laura S, Ando Kazuo, Manohar Monali, Do Evan, Dhondalay Gopal K R, Fitzpatrick Jessica, Artandi Maja, Chang Iris, Snow Theo T, Chinthrajah R Sharon, Warren Christopher M, Wittman Richard, Meyerowitz Justin G, Ganio Edward A, Stelzer Ina A, Han Xiaoyuan, Verdonk Franck, Gaudillière Dyani K, Mukherjee Nilanjan, Tsai Amy S, Rumer Kristen K, Jacobsen Danielle R, Bjornson-Hooper Zachary B, Jiang Sizun, Saavedra Sergio Fragoso, Valdés Ferrer Sergio Iván, Kelly J Daniel, Furman David, Aghaeepour Nima, Angst Martin S, Boyd Scott D, Pinsky Benjamin A, Nolan Garry P, Nadeau Kari C, Gaudillière Brice, McIlwain David R

2022-Jun-28

COVID-19, CyTOF, Olink, PBMC, SARS-CoV-2, immunophenotyping, mass cytometry, phosphosignaling response, proteomics, stacked generalization