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Extracellular DNA, hyaluronic acid, HIF pathways, and LncRNAs as predictive biomarkers of severe COVID-19

Evgen Dubrovskyi1, Tetiana Drevytska1, Alla Portnychenko1

  • 1Bogomoletz Institute of Physiology, National Academy of Science, Kyiv, Ukraine.

Virology Journal
|July 23, 2025
PubMed

Insights

New biomarkers like cell-free DNA and hyaluronic acid show promise in predicting severe COVID-19 complications. These markers, including hypoxia-inducible factors, may aid early risk assessment for better patient outcomes.

Area of Science:

  • Biochemistry
  • Immunology
  • Molecular Biology

Background:

  • COVID-19 severity varies widely, with standard markers like IL-6 and CRP often failing to predict patient outcomes.
  • Accurate prediction of severe COVID-19 is crucial for timely clinical intervention.

Purpose of the Study:

  • To evaluate emerging biomarkers for early identification of high-risk COVID-19 patients.
  • To assess the utility of cell-free DNA (cfDNA), hyaluronic acid (HA), and hypoxia-inducible factor (HIF) pathways in predicting severe disease.

Main Methods:

  • Literature review and analysis of existing data on novel biomarkers.
  • Investigated cfDNA related to neutrophil extracellular trap formation (NETosis), HA, HIF isoforms, and long non-coding RNAs (lncRNAs) like HAS2-AS1 and HIF1-AS1.

Main Results:

  • Elevated cfDNA/NETs, HA, and HIF pathway components (isoforms and lncRNAs) correlate with severe COVID-19 features.
  • These features include immune-mediated blood clotting, hypoxia, vascular damage, and persistent inflammation.

Conclusions:

  • Emerging biomarkers including cfDNA, HA, and HIF-related molecules show significant potential for early COVID-19 risk stratification.
  • These markers could enhance clinical decision-making and improve patient management strategies for severe COVID-19.

Keywords:
BiomarkersCOVID-19Extracellular DNA (cfDNA)Hyaluronic acid (HA)Hypoxia-inducible factors (HIF-1α, HIF-2α, HIF-3α)ImmunothrombosisInflammationLong non-coding RNAs (HAS2-AS1, HIF1-AS1)NETosisSARS-CoV-2

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