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Integrated plasma proteomic and single-cell immune signaling network signatures demarcate mild, moderate, and severe COVID-19.

Dorien FeyaertsJulien HedouJoshua GillardHan ChenEileen S TsaiLaura S PetersonKazuo AndoMonali ManoharEvan DoGopal K R DhondalayJessica FitzpatrickMaja ArtandiIris ChangTheo T SnowR Sharon ChinthrajahChristopher M WarrenRich WittmanJustin G MeyerowitzEdward A GanioIna A StelzerXiaoyuan HanFranck VerdonkDyani K GaudilliereNilanjan MukherjeeAmy S TsaiKristen K RumerSizun J JiangSergio Iván Valdés-FerrerJ Daniel KellyDavid FurmanNima AghaeepourMartin S AngstScott D BoydBenjamin A PinskyGarry P NolanKari C NadeauBrice GaudilliereDavid R McIlwain
Published in: bioRxiv : the preprint server for biology (2021)
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.
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