Genes Encoding Heat Shock Proteins Are Associated with Risk and Clinical Course of Severe COVID-19: A Pilot Study

DOI record: { "DOI": "10.3390/ijms26188967", "ISSN": [ "1422-0067" ], "URL": "http://dx.doi.org/10.3390/ijms26188967", "abstract": "<jats:p>In viral infections human heat shock proteins (HSPs) play a dual role by either protecting host cells or acting on viruses’ needs. The roles of HSPs have been extensively studied in various human pathologies, but their involvement in the progression of COVID-19 remains unexplored. It makes HSPs genetic variants particularly interesting in the context of severe COVID-19 risk. In this study, 1228 subjects (199 hospitalized COVID-19 patients and 962 controls) were genotyped for 20 SNPs in genes encoding HSPs and their regulators. SNP rs7189628 DNAJA2 (effect allele [EA] T) increased the risk of severe COVID-19 in the entire group (p = 0.002), males (p = 0.00008), and smokers (p = 0.0003). SNP rs910652 HSPA12B (EA C) decreased the risk of severe COVID-19 in the entire group (p = 0.01), females (p = 0.04), and patients with normal physical activity levels (p = 0.01). SNP rs1136141 HSPA8 (EA A) increased the risk of severe COVID-19 in patients with low fruit/vegetable intake (p = 0.004). Moreover, we observed significant changes in ground-glass opacity and alterations in blood coagulation and inflammation parameters, influenced by the SNPs of BAG3, HSF2, HSPA6, HSPA8, HSPA9, and DNAJA2. The molecular mechanisms underlying these associations are discussed. Together, our study provides preliminary evidence that SNPs of HSPs can significantly modulate the risk of severe COVID-19.</jats:p>", "alternative-id": [ "ijms26188967" ], "author": [ { "affiliation": [ { "name": "Laboratory of Genomic Research, Research Institute for Genetic and Molecular Epidemiology, Kursk State Medical University, 305041 Kursk, Russia" }, { "name": "Department of Anesthesia and Critical Care, Institute of Continuing Education, Kursk State Medical University, 305004 Kursk, Russia" } ], "family": "Karpenko", "given": "Andrey R.", "sequence": "first" }, { "ORCID": "https://orcid.org/0000-0002-0652-2219", "affiliation": [ { "name": "Laboratory of Genomic Research, Research Institute for Genetic and Molecular Epidemiology, Kursk State Medical University, 305041 Kursk, Russia" } ], "authenticated-orcid": false, "family": "Kobzeva", "given": "Ksenia A.", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0003-0587-1609", "affiliation": [ { "name": "Institute of Biodesign and Complex Systems Modeling, Sechenov First Moscow State Medical University of the Russian Ministry of Health (Sechenov University), 119991 Moscow, Russia" }, { "name": "Agrarian and Technological Institute, Patrice Lumumba Peoples’ Friendship University of Russia, 117198 Moscow, Russia" } ], "authenticated-orcid": false, "family": "Orlov", "given": "Yuriy L.", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0003-3333-0623", "affiliation": [ { "name": "Laboratory of Genomic Research, Research Institute for Genetic and Molecular Epidemiology, Kursk State Medical University, 305041 Kursk, Russia" }, { "name": "Department of Biology, Medical Genetics and Ecology, Kursk State Medical University, 305041 Kursk, Russia" } ], "authenticated-orcid": false, "family": "Bushueva", "given": "Olga Yu.", "sequence": "additional" } ], "container-title": "International Journal of Molecular Sciences", "container-title-short": "IJMS", "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2025, 9, 16 ] ], "date-time": "2025-09-16T08:56:46Z", "timestamp": 1758013006000 }, "deposited": { "date-parts": [ [ 2025, 9, 16 ] ], "date-time": "2025-09-16T09:00:24Z", "timestamp": 1758013224000 }, "funder": [ { "name": "Kursk State Medical University" } ], "indexed": { "date-parts": [ [ 2025, 9, 17 ] ], "date-time": "2025-09-17T03:13:03Z", "timestamp": 1758078783672, "version": "3.44.0" }, "is-referenced-by-count": 0, "issue": "18", "issued": { "date-parts": [ [ 2025, 9, 15 ] ] }, "journal-issue": { "issue": "18", "published-online": { "date-parts": [ [ 2025, 9 ] ] } }, "language": "en", "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0/", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2025, 9, 15 ] ], "date-time": "2025-09-15T00:00:00Z", "timestamp": 1757894400000 } } ], "link": [ { "URL": "https://www.mdpi.com/1422-0067/26/18/8967/pdf", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "1968", "original-title": [], "page": "8967", "prefix": "10.3390", "published": { "date-parts": [ [ 2025, 9, 15 ] ] }, "published-online": { "date-parts": [ [ 2025, 9, 15 ] ] }, "publisher": "MDPI AG", "reference": [ { "DOI": "10.1007/s00508-020-01760-4", "article-title": "Clinical Manifestations of COVID-19 in the General Population: Systematic Review", "doi-asserted-by": "crossref", "first-page": "377", "journal-title": "Wien. 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