Abstract
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 AUC validation = 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.
Keywords: COVID-19; CyTOF; Olink; PBMC; SARS-CoV-2; immunophenotyping; mass cytometry; phosphosignaling response; proteomics; stacked generalization.
【저자키워드】 COVID-19, SARS-CoV-2, proteomics, Immunophenotyping, PBMC, CyTOF, mass cytometry, Olink, phosphosignaling response, stacked generalization., 【초록키워드】 Treatment, proteomics, coronavirus, severe COVID-19, COVID-19 severity, immune, Peripheral blood, clinical manifestations, Immunophenotyping, response, Patient, phenotype, Mild, PBMC, plasma, Coronavirus 2019, moderate, patients, single-cell, proteomic, therapeutic targets, NF-κB, Olink, plasma proteins, JAK/STAT, Signaling, Ligand, STAT, mTOR, Inflammatory, MAPK, AUC, therapeutic target, dysregulation, clinical manifestation, plasma protein, determinant, COVID-19 progression, examination, hallmark, nuclear, uninfected, approach, feature, Cell, identify, addition, reveal, 【제목키워드】 severe COVID-19, immune, Mild, plasma, moderate, single-cell, proteomic, Signaling,