{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T15:43:25Z","timestamp":1790091805008,"version":"4.0.1"},"reference-count":93,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The epigenetics of COVID-19 is a rapidly expanding field that reveals how the SARS-CoV-2 virus initiates alterations in the host\u2019s genome, influencing the susceptibility to infection, the disease severity, and long-term consequences, known as \u201clong COVID.\u201d In this review, we describe the mechanisms utilized by the virus to manipulate the host epigenome, suppressing antiviral responses and creating a favorable environment for viral replication. We also highlight virus-induced epigenetic changes across diverse cell populations that contribute to COVID-19 pathogenesis. Notably, the virus reprograms hematopoietic stem and progenitor cells, leading to long-lasting alterations in innate immunity, a phenomenon known as \u201ctrained immunity.\u201d These epigenetic modifications are maintained in differentiated daughter cells and may explain the persistent inflammation and other symptoms of long COVID. Furthermore, we discuss emerging epigenetic biomarkers of disease severity, including methylation signatures in genes such as AIM2, HLA-C, and PARP9, as well as dysregulated miRNA profiles. Understanding this complex interplay between the virus and the host\u2019s epigenetic landscape is crucial for developing new therapeutic approaches that target specific epigenetic modifications to suppress pathological processes and improve clinical outcomes for COVID-19 patients.<\/jats:p>","DOI":"10.3390\/ijms262110372","type":"journal-article","created":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T00:51:42Z","timestamp":1761526302000},"page":"10372","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["COVID-19 Hijacking of the Host Epigenome: Mechanisms, Biomarkers and Long-Term Consequences"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6983-8387","authenticated-orcid":false,"given":"Alena D.","family":"Zolotarenko","sequence":"first","affiliation":[{"name":"Laboratory of Functional Genomics, Vavilov Institute of General Genetics, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hakob M.","family":"Poghosyan","sequence":"additional","affiliation":[{"name":"Laboratory of Functional Genomics, Vavilov Institute of General Genetics, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria V.","family":"Sheptiy","sequence":"additional","affiliation":[{"name":"Laboratory of Functional Genomics, Vavilov Institute of General Genetics, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0653-7418","authenticated-orcid":false,"given":"Sergey A.","family":"Bruskin","sequence":"additional","affiliation":[{"name":"Laboratory of Functional Genomics, Vavilov Institute of General Genetics, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,24]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2025, September 05). 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