Protein Posttranslational Signatures Identified in COVID-19 Patient Plasma

Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a highly contagious virus of the coronavirus family that causes coronavirus disease-19 (COVID-19) in humans and a number of animal species. COVID-19 has rapidly propagated in the world in the past 2 years, causing a global pandemic. Here, we performed proteomic analysis of plasma samples from COVID-19 patients compared to healthy control donors in an exploratory study to gain insights into protein-level changes in the patients caused by SARS-CoV-2 infection and to identify potential proteomic and posttranslational signatures of this disease. Our results suggest a global change in protein processing and regulation that occurs in response to SARS-CoV-2, and the existence of a posttranslational COVID-19 signature that includes an elevation in threonine phosphorylation, a change in glycosylation, and a decrease in arginylation, an emerging posttranslational modification not previously implicated in infectious disease. This study provides a resource for COVID-19 researchers and, longer term, will inform our understanding of this disease and its treatment.Key PointsPlasma from COVID-19 patients exhibits prominent protein- and peptide-level changesProteins from COVID-19 patient plasma exhibit prominent changes in several key posttranslational modifications

Plasma proteomic signature predicts who will get persistent symptoms following SARS-CoV-2 infection

“…A number of studies have previously undertaken a discovery proteomics approach to study the perturbation of the plasma proteome during acute infection, 23 including serial proteomics in mild or low symptom individuals, 24 and in hospitalized patients. 25 , 26 In line with previous works and using our assay that was enriched for neuroinflammatory biomarkers, we found that drivers of proteomic perturbation include oxidative stress markers 27 (e.g., QSOX1), metabolic reprogramming factors 28 (e.g., FGF21) and cell adhesion molecules 29 (e.g., NCAM2). However, plasma proteome signatures of severe hospitalized patients are expectedly different from ours as a result of acute inflammatory changes that would occur not just from initial infection but from the subsequent cascade of events that are not COVID-specific, such as mechanical ventilation or prolonged immobilisation.…”

COVID‐19 plasma proteome reveals novel temporal and cell‐specific signatures for disease severity and high‐precision disease management

“…[4][5][6][7] The uncertainty in disease severity and progression makes uniform COVID-19 management difficult, indicating that patients could benefit from a precision medicine approach. 8-12 Among the next generation technologies used to investigate COVID-19, 10,[13][14][15][16][17][18][19][20][21][22][23][24][25]…”

Detection of unusual high molecular form of albumin in blood serum of COVID-19 patients

“…We consider PTMs as most probable way of generating of fig. 1 In a recent study, proteomes of Covid-19 patients and healthy donors were compared [7]. Global analysis of PTMs demonstrated a marked up-and down-regulation in such PTMs as phosphorylation, glycosylation, citrullination, and arginylation in Covid-19 patients compared to healthy donors.…”