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This infection is caused by the SARS\u2010CoV\u20102 virus, and depending on age, sex and health status of the patient, it can present with variety of clinical symptoms such as mild infection, a very severe form or even asymptomatic course of the disease. Similarly to other viruses, innate immune response plays a vital role in protection against COVID\u201019. However, dysregulation of innate immunity could have a significant influence on the severity of the disease. Despite various efforts, there is no effective vaccine against the disease so far. Recent data have demonstrated that the Bacillus Calmette\u2013Gu\u00e9rin (BCG) vaccine could reduce disease severity and the burden of several infectious diseases in addition to targeting its primary focus tuberculosis. There is growing evidence for the concept of beneficial non\u2010specific boosting of immune responses by BCG or other microbial compounds termed trained immunity, which may protect against COVID\u201019. In this manuscript, we review data on how the development of innate immune memory due to microbial compounds specifically BCG can result in protection against SARS\u2010CoV\u20102 infection. We also discuss possible mechanisms, challenges and perspectives of using innate immunity as an approach to reduce COVID\u201019 severity.<\/jats:p>","DOI":"10.1002\/cti2.1228","type":"journal-article","created":{"date-parts":[[2020,12,23]],"date-time":"2020-12-23T21:00:35Z","timestamp":1608757235000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Trained immunity as a novel approach against COVID\u201019 with a focus on Bacillus Calmette\u2013Gu\u00e9rin vaccine: mechanisms, challenges and perspectives"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5268-238X","authenticated-orcid":false,"given":"Yahya","family":"Sohrabi","sequence":"first","affiliation":[{"name":"Department of Cardiology I \u2013 Coronary and Peripheral Vascular Disease, Heart Failure University Hospital M\u00fcnster M\u00fcnster Germany"},{"name":"Institute of Molecular Genetics of the Czech Academy of 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