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Immunopathogenesis and Immunogenetic Variants in COVID-19

Pakorn Sagulkoo1,2, Kitiporn Plaimas3,4, Apichat Suratanee5,6

  • 1Program in Bioinformatics and Computational Biology, Graduate School, Chulalongkorn University, Bangkok 10330, Thailand.

Current Pharmaceutical Design
|May 22, 2022
PubMed

Insights

This study investigates immunogenetic variants, specifically NLRP3 and IL-18, in severe COVID-19 and cytokine storm development. Protein-protein interaction network analysis identified potential drug targets and predictive markers for severe disease outcomes.

Area of Science:

  • Immunology
  • Genetics
  • Virology

Background:

  • Despite vaccine availability, Coronavirus disease 2019 (COVID-19) continues to spread globally, leading to severe complications like acute respiratory distress syndrome and cytokine storms.
  • Immunopathology and immunogenetics are crucial for understanding, diagnosing, and treating severe COVID-19 and its associated cytokine storm.
  • While many immune-related genetic variants have been studied, the roles of NOD-like receptor protein 3 (NLRP3) and interleukin 18 (IL-18) in COVID-19 clinical outcomes remain underexplored.

Purpose of the Study:

  • To review the current understanding of COVID-19 immunopathogenesis and immunogenetic factors contributing to severe disease and cytokine storms.
  • To construct and analyze protein-protein interaction (PPI) networks focusing on NLRP3 and IL-18 variants in severe COVID-19.
  • To identify potential drug targets and predictive biomarkers for severe COVID-19 and associated cytokine storms.

Main Methods:

  • Literature review on COVID-19 immunopathogenesis and immunogenetics.
  • Construction and analysis of protein-protein interaction (PPI) networks using enrichment and annotation analysis.
  • Focus on NLRP3 and IL-18 variants and their association with severe COVID-19.

Main Results:

  • PPI network and enrichment analyses identified key antiviral pathways, including Toll-Like-Receptor cascades, NOD-like receptor signaling, and interferon signaling.
  • Significant involvement of interleukins (IL-1, IL-6, IL-12, IL-18) and tumor necrosis factor signaling in severe COVID-19 pathophysiology was predicted.
  • Innate immune evasion by SARS-CoV-2 and the roles of MYD88 and MAVS in severe COVID-19 were highlighted.

Conclusions:

  • The study predicts potential drug targets for preventing severe COVID-19 by modulating identified antiviral and inflammatory pathways.
  • Genetic variants within the constructed PPI network may serve as predictors for severe COVID-19 outcomes.
  • Targeted preventive treatments can be developed based on these predictive markers and identified therapeutic targets.

Keywords:
COVID-19IL-18NLRP3SARS-CoV-2cytokine storminflammationvariant genotypes

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