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

ABSTRACT

Biomarkers 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 Abstract O_FIG O_LINKSMALLFIG WIDTH=198 HEIGHT=200 SRC="FIGDIR/small/21252236v1_ufig1.gif" ALT="Figure 1"> View larger version (86K) org.highwire.dtl.DTLVardef@4f1770org.highwire.dtl.DTLVardef@8bdc12org.highwire.dtl.DTLVardef@1d4e21org.highwire.dtl.DTLVardef@1f49622_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIA total of 720 proteomes of 262 symptomatic controls and 458 longitudinal samples (average 31 days) of hospitalized COVID-19 cases were analyzed C_LIO_LI26% of the 502 quantified proteins significantly changed in COVID-19 patients C_LIO_LIThe innate immune and the coagulation system were strongly regulated C_LIO_LIMS-based profiles of immunoglobulin regions allow the detection of seroconversion in a highly detailed fashion on the patient level C_LIO_LIITIH4 may be a prospective marker of COVID-19 mortality C_LI