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Genes Encoding Heat Shock Proteins Are Associated with Risk and Clinical Course of Severe COVID-19: A Pilot Study
Andrey R Karpenko1,2, Ksenia A Kobzeva1, Yuriy L Orlov3,4
1Laboratory of Genomic Research, Research Institute for Genetic and Molecular Epidemiology, Kursk State Medical University, 305041 Kursk, Russia.
International Journal of Molecular Sciences
|September 27, 2025
Summary
Genetic variants in human heat shock proteins (HSPs) are linked to severe COVID-19 risk. Specific HSPs gene variants influence disease severity, impacting outcomes in males, females, and smokers.
Area of Science:
- Immunology
- Genetics
- Virology
Background:
- Human heat shock proteins (HSPs) exhibit dual roles in viral infections, potentially protecting or aiding viruses.
- While HSPs roles are studied in various diseases, their specific involvement in COVID-19 progression is not well understood.
- Genetic variations in HSPs may influence individual susceptibility and severity of COVID-19.
Purpose of the Study:
- To investigate the association between genetic variants of HSPs and their regulators and the risk of severe COVID-19.
- To identify specific single nucleotide polymorphisms (SNPs) in HSP genes that correlate with COVID-19 severity.
- To explore the impact of these SNPs on clinical parameters and disease manifestations.
Main Methods:
- Genotyping of 20 single nucleotide polymorphisms (SNPs) in HSP genes and their regulators among 1228 subjects (199 COVID-19 patients, 962 controls).
- Statistical analysis to determine the association between specific SNPs and severe COVID-19 risk across different demographic and lifestyle groups.
- Evaluation of SNP influence on clinical indicators like ground-glass opacity, blood coagulation, and inflammation markers.
Main Results:
- SNP rs7189628 in DNAJA2 (T allele) was associated with increased severe COVID-19 risk in the general cohort, males, and smokers.
- SNP rs910652 in HSPA12B (C allele) was linked to decreased severe COVID-19 risk in the general cohort, females, and individuals with normal physical activity.
- SNP rs1136141 in HSPA8 (A allele) correlated with increased severe COVID-19 risk in patients with low fruit/vegetable intake. Significant associations were also found between various HSP SNPs and clinical parameters.
Conclusions:
- Preliminary evidence suggests that specific genetic variants (SNPs) in human heat shock protein (HSP) genes can significantly modulate the risk and severity of COVID-19.
- These findings highlight the potential role of HSPs genetics in determining individual COVID-19 outcomes.
- Further research into the molecular mechanisms is warranted to elucidate the precise pathways involved.
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