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

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

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


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.

Original languageEnglish (US)
Article number781100
Pages (from-to)781100
JournalFrontiers in immunology
StatePublished - Jan 25 2022


  • CCL16
  • COVID-19
  • CXCL10
  • IL18
  • IL6
  • Olink proteomics
  • cytokine storm syndrome
  • inflammation and cardiovascular markers
  • Signal Transduction
  • Humans
  • Middle Aged
  • Male
  • COVID-19/blood
  • Gene Expression Profiling
  • Cytokines/blood
  • Transcriptome/genetics
  • Inflammation/blood
  • SARS-CoV-2/immunology
  • Proteomics
  • Biomarkers/blood
  • Female
  • Aged
  • Cytokine Release Syndrome/blood
  • Blood Proteins/metabolism

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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