Journal Article

Identification of Robust Protein Associations With COVID-19 Disease Based on Five Clinical Studies

Krumsiek, Jan, Choi, Augustine M. K., Sarwath, Hina, Sohail, Muhammad Umar, Schmidt, Frank, Whalen, William, Suhre, Karsten, Cho, Soo Jung, Alvarez-Mulett, Sergio, Engelke, Rudolf

2022

Overview

Multiple studies have investigated the role of blood circulating proteins in COVID-19 disease using the Olink affinity proteomics platform. However, study inclusion criteria and sample collection conditions varied between studies, leading to sometimes incongruent associations. To identify the most robust protein markers of the disease and the underlying pathways that are relevant under all conditions, it is essential to identify proteins that replicate most widely. Here we combined the Olink proteomics profiles of two newly recruited COVID-19 studies (N=68 and N=98) with those of three previously published COVID-19 studies (N=383, N=83, N=57). For these studies, three Olink panels (Inflammation and Cardiovascular II & III) with 253 unique proteins were compared. Case/control analysis revealed thirteen proteins (CCL16, CCL7, CXCL10, CCL8, LGALS9, CXCL11, IL1RN, CCL2, CD274, IL6, IL18, MERTK, IFNγ, and IL18R1) that were differentially expressed in COVID-19 patients in all five studies. Except CCL16, which was higher in controls, all proteins were overexpressed in COVID-19 patients. Pathway analysis revealed concordant trends across all studies with pathways related to cytokine-cytokine interaction, IL18 signaling, fluid shear stress and rheumatoid arthritis. Our results reaffirm previous findings related to a COVID-19 cytokine storm syndrome. Cross-study robustness of COVID-19 specific protein expression profiles support the utility of affinity proteomics as a tool and for the identification of potential therapeutic targets.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Aged / Biomarkers - blood / Blood Proteins - metabolism / Cardiovascular disease / CCL16 / COVID-19 / COVID-19 - blood / COVID-19 - immunology / CXCL10 / CXCL10 protein / CXCL11 protein / Cytokine Release Syndrome - blood / Cytokine Release Syndrome - pathology / Cytokine storm / cytokine storm syndrome / Cytokines - blood / Cytokines - metabolism / Demographics / Diabetes / Epidemics / Ethnicity / Female / Fluid flow / Gene Expression Profiling / Hospitals / Humans / Immune response / Immunology / Inflammation / Inflammation - blood / inflammation and cardiovascular markers / Interleukin 18 / Kidney diseases / Male / Mechanical stimuli / Medical research / Middle Aged / Middle East respiratory syndrome / Monocyte chemoattractant protein 1 / Mortality / Olink proteomics / Pandemics / Pathogenesis / Patients / Plasma / Proteins / Proteomics / Respiratory diseases / Rheumatoid arthritis / SARS-CoV-2 - immunology / Severe acute respiratory syndrome coronavirus 2 / Signal Transduction / Therapeutic targets / Transcriptome - genetics / γ-Interferon