Longitudinal plasma proteomic analysis of 1117 hospitalized patients with COVID-19 identifies features associated with severity and outcomes

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is characterized by highly heterogeneous manifestations ranging from asymptomatic cases to death for still incompletely understood reasons. As part of the IMmunoPhenotyping Assessment in a COVID-19 Cohort study, we mapped the plasma proteomes of 1117 hospitalized patients with COVID-19 from 15 hospitals across the United States. Up to six samples were collected within ~28 days of hospitalization resulting in one of the largest COVID-19 plasma proteomics cohorts with 2934 samples. Using perchloric acid to deplete the most abundant plasma proteins allowed for detecting 2910 proteins. Our findings show that increased levels of neutrophil extracellular trap and heart damage markers are associated with fatal outcomes. Our analysis also identified prognostic biomarkers for worsening severity and death. Our comprehensive longitudinal plasma proteomics study, involving 1117 participants and 2934 samples, allowed for testing the generalizability of the findings of many previous COVID-19 plasma proteomics studies using much smaller cohorts.

Biomarkers of tissue remodelling are elevated in serum of COVID-19 patients who develop interstitial lung disease - an exploratory biomarker study

“…Previous studies have shown that severe COVID-19 patients have an increased blood neutrophil count, neutrophil-to-lymphocyte ratio, and elevated serum levels of neutrophil related cytokines, proposing an increased neutrophil activity [ 22 – 24 , 27 ]. Thus, in this study, two neutrophil activity biomarkers, CPa9-HNE and ELP-3, were measured to investigate this biological process.…”

“…Neutrophils have shown to play a prominent role in COVID-19 and increased blood neutrophil count, neutrophil-to-lymphocyte ratio, and elevated serum levels of neutrophil related cytokines have been observed in patients with severe disease [ 21 – 24 ]. Additionally, increased concentration of neutrophil extracellular traps (NETs) has been observed in tracheal aspirate, plasma, airways, and in the alveoli of SARS-CoV-2 infected patients [ 25 – 27 ]. In excess, NETs can contribute to a cytokine storm which may further exacerbate disease severity, progress into acute respiratory distress syndrome (ARDS), and lead to multiorgan failure and death [ 28 , 29 ].…”