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Despite a large population and limited health infrastructure, the incidence and mortality of Coronavirus Disease 2019 (COVID-19) has been lower in South Asia than many regions. The underlying reasons and mechanisms for this relative protection are not established. However both genetic and environmental factors might play a role. Polymorphisms in ACE2 gene, ACE gene and in genes for some of the host cell proteases could affect the viral entry and replication. There is some evidence that HLA polymorphisms and several pathways involved in immune and inflammatory response could contribute to ethnic variation. Cross immunity because of past exposure to viral infections as well as malaria is likely to protect from the severe manifestations of disease. Role of BCG vaccination in trained innate immunity is recognised and could be a protective factor against COVID-19. There is limited evidence of the possibility of a less virulent viral strain circulating in South Asia. There is evidence from different parts of the world that temperature and humidity can influence viral survival as well as the host immune response. Finally implementation of early containment measures by some South Asian countries has also contributed to a less disease burden. [ABSTRACT FROM AUTHOR]