Evaluation of hypoxia pathway genes and serum parameters in new coronavirus pneumonia (COVID-19)

Gene. 2025 Jul 5:955:149395. doi: 10.1016/j.gene.2025.149395. Epub 2025 Mar 12.

Abstract

Background: Coronavirus disease-2019 (COVID-19) causes severe hypoxemia. Unlike normal pneumonia, pneumonia due to COVID-19 causes oxygen deprivation without breathing difficulties (i.e., silent hypoxia). We evaluated the relationship between COVID-19 and hypoxemia and examined possible mechanisms of pneumonia from the perspective of gene expression (HIF1A, vascular endothelial growth factor [VEGF], NF-kB, MEKK1, and EGFR) using real-time PCR and ELISA for serum parameters.

Methods: We evaluated 100 individuals (50 patients and 50 controls). The patients were individuals with respiratory symptoms and pneumonia who were COVİD-19 positive. The relative quantification of standardized samples wa s calculated according to the formula 2 -ΔΔCT. Receiver operating curve (ROC) analysis was made to define the diagnostic power of the genes. The expression changes of four genes in the hypoxia pathway were significant (excluding VEGF) and upregulated in the patients' serums.

Results: The fold change values of the HIF1A, VEGF, NF-kB, MEKK1, and EGFR genes were 0.048, 0.688, 0.168, 0.207, and 0.171, respectively, in the cases checked against to the controls. The areas under the ROC values indicating the diagnostic power of the genes were 0.727, 0.538, 0.815, 0.734, and 0.936, respectively. Some serum parameters were significant (age, PCR, urea, LDH, WBC, ferritin, and pO2).

Conclusions: The upregulation of some genes in the hypoxia pathway in COVID-19 pneumonia shows that these genes and protein products are candidates for treatment targets. At the same time, the high discriminative power of two genes (NF-κB and EGFR) in patients compared to controls indicates their diagnostic potential in serum samples.

Keywords: Covid-19; Gene expression; Hypoxemia; Pneumonia; SARS-CoV-2; Serum biochemistry.

MeSH terms

  • Adult
  • Aged
  • COVID-19* / blood
  • COVID-19* / genetics
  • Case-Control Studies
  • ErbB Receptors / blood
  • ErbB Receptors / genetics
  • Female
  • Humans
  • Hypoxia* / blood
  • Hypoxia* / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / blood
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Male
  • Middle Aged
  • NF-kappa B / blood
  • NF-kappa B / genetics
  • ROC Curve
  • SARS-CoV-2
  • Vascular Endothelial Growth Factor A / blood
  • Vascular Endothelial Growth Factor A / genetics

Substances

  • Vascular Endothelial Growth Factor A
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • HIF1A protein, human
  • NF-kappa B
  • ErbB Receptors
  • VEGFA protein, human
  • EGFR protein, human