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COVID-19: A Possible Contribution of the MAPK Pathway

Jessica Cusato1, Alessandra Manca1, Alice Palermiti1

  • 1Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, 10149 Turin, Italy.

Biomedicines
|May 27, 2023
PubMed
Abstract

Insights

This study investigated the mitogen-activated protein kinase (MAPK) pathway in COVID-19, finding elevated MAPK biomarkers in infected individuals. These biomarkers may help identify patients at risk for severe COVID-19 complications.

Area of Science:

  • Immunology
  • Molecular Biology
  • Virology

Background:

  • COVID-19 involves uncontrolled inflammation and cytokine production, often via intracellular pathways like mitogen-activated protein kinase (MAPK).
  • The specific role of the MAPK pathway in severe COVID-19 pathogenesis remains unclear.
  • Viruses can manipulate host cell pathways, including MAPK, for their replication and spread.

Purpose of the Study:

  • To quantify biomarkers associated with the MAPK pathway in individuals with and without SARS-CoV-2 infection.
  • To explore the potential association between MAPK pathway biomarkers and clinical manifestations of COVID-19.

Main Methods:

  • Quantification of H-RAS, C-RAF, MAPK1, MAPK2, and ERK proteins using Enzyme-Linked Immunosorbent Assay (ELISA).
  • Evaluation of genetic polymorphisms in MAPK pathway-related genes via real-time Polymerase Chain Reaction (PCR).
  • Prospective recruitment of 201 participants (158 SARS-CoV-2 positive, 43 negative).

Main Results:

  • MAPK pathway biomarker levels were significantly higher in SARS-CoV-2 positive individuals compared to negative controls.
  • Shortness of breath (dyspnea) in positive participants correlated with peripheral blood mononuclear cell (PBMC) C-RAF levels and ventilation type.
  • A significant portion of positive participants required respiratory support, including invasive ventilation and continuous positive airway pressure (CPAP).

Conclusions:

  • This research provides the first evidence linking MAPK pathway biomarkers to specific clinical features of COVID-19.
  • Elevated MAPK biomarkers may serve as indicators for identifying COVID-19 patients at higher risk of developing severe complications.
  • Further investigation into the MAPK pathway could lead to improved diagnostic and prognostic tools for COVID-19.
Keywords:
PBMCsSARS-CoV-2inflammation mechanismmolecular pathwayoxygenation

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