High-resolution longitudinal serum proteome trajectories in COVID-19 reveal patients-specific seroconversion

Abstract

AbstractBiomarkers for COVID-19 are urgently needed. Here we bring the powerful technology of mass spectrometry (MS)-based proteomics to bear on this challenge. We measured serum proteomes of COVID-19 patients and symptomatic, but PCR-negative controls, in a time-resolved manner. In 262 controls and 458 longitudinal samples (average of 31 days) 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. In contrast, 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 systems-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.Graphical AbstractHighlightsA total of 720 proteomes of 262 symptomatic controls and 458 longitudinal samples (average 31 days) of hospitalized COVID-19 cases were analyzed26% of the 502 quantified proteins significantly changed in COVID-19 patientsThe innate immune and the coagulation system were strongly regulatedMS-based profiles of immunoglobulin regions allow the detection of seroconversion in a highly detailed fashion on the patient levelITIH4 may be a prospective marker of COVID-19 mortality