TY - JOUR

T1 - High-resolution serum proteome trajectories in COVID-19 reveal patient-specific seroconversion

AU - Geyer, Philipp E.

AU - Arend, Florian M

AU - Doll, Sophia

AU - Louiset, Marie-Luise

AU - Virreira Winter, Sebastian

AU - Müller-Reif, Johannes B

AU - Torun, Furkan M

AU - Weigand, Michael

AU - Eichhorn, Peter

AU - Bruegel, Mathias

AU - Strauss, Maximilian T

AU - Holdt, Lesca M

AU - Mann, Matthias

AU - Teupser, Daniel

N1 - © 2021 The Authors. Published under the terms of the CC BY 4.0 license.

PY - 2021

Y1 - 2021

N2 - A deeper understanding of COVID-19 on human molecular pathophysiology is urgently needed as a foundation for the discovery of new biomarkers and therapeutic targets. Here we applied mass spectrometry (MS)-based proteomics to measure serum proteomes of COVID-19 patients and symptomatic, but PCR-negative controls, in a time-resolved manner. In 262 controls and 458 longitudinal samples of 31 patients, hospitalized for COVID-19, a remarkable 26% of proteins changed significantly. Bioinformatics analyses revealed co-regulated groups and shared biological functions. Proteins of the innate immune system such as CRP, SAA1, CD14, LBP, and LGALS3BP decreased early in the time course. Regulators of coagulation (APOH, FN1, HRG, KNG1, PLG) and lipid homeostasis (APOA1, APOC1, APOC2, APOC3, PON1) increased over the course of the disease. A global correlation map provides a system-wide functional association between proteins, biological processes, and clinical chemistry parameters. Importantly, five SARS-CoV-2 immunoassays against antibodies revealed excellent correlations with an extensive range of immunoglobulin regions, which were quantified by MS-based proteomics. The high-resolution profile of all immunoglobulin regions showed individual-specific differences and commonalities of potential pathophysiological relevance.

AB - A deeper understanding of COVID-19 on human molecular pathophysiology is urgently needed as a foundation for the discovery of new biomarkers and therapeutic targets. Here we applied mass spectrometry (MS)-based proteomics to measure serum proteomes of COVID-19 patients and symptomatic, but PCR-negative controls, in a time-resolved manner. In 262 controls and 458 longitudinal samples of 31 patients, hospitalized for COVID-19, a remarkable 26% of proteins changed significantly. Bioinformatics analyses revealed co-regulated groups and shared biological functions. Proteins of the innate immune system such as CRP, SAA1, CD14, LBP, and LGALS3BP decreased early in the time course. Regulators of coagulation (APOH, FN1, HRG, KNG1, PLG) and lipid homeostasis (APOA1, APOC1, APOC2, APOC3, PON1) increased over the course of the disease. A global correlation map provides a system-wide functional association between proteins, biological processes, and clinical chemistry parameters. Importantly, five SARS-CoV-2 immunoassays against antibodies revealed excellent correlations with an extensive range of immunoglobulin regions, which were quantified by MS-based proteomics. The high-resolution profile of all immunoglobulin regions showed individual-specific differences and commonalities of potential pathophysiological relevance.

U2 - 10.15252/emmm.202114167

DO - 10.15252/emmm.202114167

M3 - Journal article

C2 - 34232570

VL - 13

JO - EMBO Molecular Medicine

JF - EMBO Molecular Medicine

SN - 1757-4676

IS - 8

M1 - e14167

ER -