Frontiers in Immunology (Mar 2022)

Immunogenic SARS-CoV-2 S and N Protein Peptide and Cytokine Combinations as Biomarkers for Early Prediction of Fatal COVID-19

  • Ekaterina Martynova,
  • Shaimaa Hamza,
  • Maria Markelova,
  • Ekaterina Garanina,
  • Yuriy Davidyuk,
  • Venera Shakirova,
  • Neha Kaushal,
  • Manoj Baranwal,
  • Robert J. Stott-Marshall,
  • Toshana L. Foster,
  • Albert Rizvanov,
  • Svetlana Khaiboullina

DOI
https://doi.org/10.3389/fimmu.2022.830715
Journal volume & issue
Vol. 13

Abstract

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Early indications of the likelihood of severe coronavirus disease 2019 COVID-19 can influence treatments and could improve clinical outcomes. However, knowledge on the prediction markers of COVID-19 fatality risks remains limited. Here, we analyzed and quantified the reactivity of serum samples from acute (non-fatal and fatal) and convalescent COVID-19 patients with the spike surface glycoprotein (S protein) and nucleocapsid phosphoprotein (N protein) SARS-CoV-2 peptide libraries. Cytokine activation was also analyzed. We demonstrated that IgM from fatal COVID-19 serum reacted with several N protein peptides. In contrast, IgM from non-fatal serum reacted more with S protein peptides. Further, higher levels of pro-inflammatory cytokines were found in fatal COVID-19 serum compared to non-fatal. Many of these cytokines were pro-inflammatory and chemokines. Differences in IgG reactivity from fatal and non-fatal COVID-19 sera were also demonstrated. Additionally, the longitudinal analysis of IgG reactivity with SARS-CoV-2 S and N protein identified peptides with the highest longevity in humoral immune response. Finally, using IgM antibody reactivity with S and N SARS-CoV-2 peptides and selected cytokines, we have identified a panel of biomarkers specific to patients with a higher risk of fatal COVID-19 compared with that of patients who survive. This panel could be used for the early prediction of COVID-19 fatality risk.

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