Department
Biomedical Sciences
Document Type
Article
Publication Title
bioRxiv
DOI
10.1101/2021.02.09.430269
Publication Date
2-12-2021
Abstract
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.
Recommended Citation
Feyaerts, D.,
Hedou, J.,
Gillard, J.,
Chen, H.,
Tsai, E. S.,
Peterson, L. S.,
Ando, K.,
Manohar, M.,
Do, E.,
Chinthrajah, G. K.,
Warren, C. M.,
Wittman, R.,
Meyeroqitz, J. G.,
Ganio, E. A.,
Stelzer, I. A.,
Han, X.,
Verdonk, F.,
Gaudilliere, D. K.,
Mukherjee, N.,
Tsai, A. S.,
Rumer, K. K.,
Jiang, S.,
Ferrer, S. I.,
Kelly, J. D.,
Furman, D.,
Aghaeepour, N.,
Angst, M. S.,
Boyd, S. D.,
Pinsky, B. A.,
Nolan, G. P.,
Nadeau, K. C.,
Gaudilliere, B.,
&
McIlwain, D. R.
(2021).
Integrated plasma proteomic and single-cell immune signaling network signatures demarcate mild, moderate, and severe COVID-19.
bioRxiv, ,
DOI: 10.1101/2021.02.09.430269
https://scholarlycommons.pacific.edu/dugoni-facarticles/730
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Comments
This is an unpublished pre-print that has not undergone peer review. It should not be considered conclusive, used to inform clinical practice, or referenced by the media as validated information.