Kgatle, MankgopoLawal, Ismaheel OpeyemiMashabela, GabrielBoshomane, Tebatso M.G.Koatale, Palesa CarolineMahasha, Phetole WalterNdlovu, HonestVorster, MarizaRodrigues, Hosana GomesZeevaart, Jan RijnGordon, SiamonMoura-Alves, PedroSathekge, Mike Machaba2022-03-102022-03-102021-10-08Kgatle, M.M., Lawal, I.O., Mashabela, G., Boshomane, T.M.G., Koatale, P.C., Mahasha, P.W., Ndlovu, H., Vorster, M., Rodrigues, H.G., Zeevaart, J.R., Gordon, S., Moura-Alves, P. & Sathekge, M.M. (2021) COVID-19 Is a Multi-Organ Aggressor: Epigenetic and Clinical Marks. Frontiers in Immunology 12:752380. DOI: 10.3389/fimmu.2021.7523801664-3224 (online)10.3389/fimmu.2021.752380http://hdl.handle.net/2263/84424The progression of coronavirus disease 2019 (COVID-19), resulting from a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, may be influenced by both genetic and environmental factors. Several viruses hijack the host genome machinery for their own advantage and survival, and similar phenomena might occur upon SARS-CoV-2 infection. Severe cases of COVID-19 may be driven by metabolic and epigenetic driven mechanisms, including DNA methylation and histone/chromatin alterations. These epigenetic phenomena may respond to enhanced viral replication and mediate persistent long-term infection and clinical phenotypes associated with severe COVID-19 cases and fatalities. Understanding the epigenetic events involved, and their clinical significance, may provide novel insights valuable for the therapeutic control and management of the COVID- 19 pandemic. This review highlights different epigenetic marks potentially associated with COVID-19 development, clinical manifestation, and progression.en© 2021 Kgatle, Lawal,Mashabela, Boshomane, Koatale,Mahasha, Ndlovu, Vorster, Rodrigues, Zeevaart, Gordon, Moura-Alves and Sathekge. This is an openaccess article distributed under the terms of the Creative Commons Attribution License (CC BY).Cytokine stormEpigeneticsMulti-organPro-inflammatory cytokinesCoronavirus disease 2019 (COVID-19)COVID-19 pandemicSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)Angiotensin-converting enzyme 2 (ACE2)Transmembrane serine protease 2 (TMPRSS2)Article