Author: 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, Rich; Meyerowitz, Justin G.; Ganio, Edward A.; Stelzer, Ina A.; Han, Xiaoyuan; Verdonk, Franck; Gaudillière, Dyani K.; Mukherjee, Nilanjan; Tsai, Amy S.; Rumer, Kristen K.; Jiang, Sizun; 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.
Title: Integrated plasma proteomic and single-cell immune signaling network signatures demarcate mild, moderate, and severe COVID-19 Cord-id: 0ik929ny Document date: 2021_2_10
ID: 0ik929ny
Snippet: 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 dat
Document: 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 AUC(training) = 0.799, p-value = 4.2e–6; multi-class AUC(validation) = 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.
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