LAUSR

While this article was being written, the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had infected over 4.48 million people in the United States, and killed over 152 000 of them (CDC COVID Data Tracker, 2020). The numbers for the rest of the world were not any better, with over 12.3 million people infected and nearly 510 000 killed by coronavirus disease 2019 (COVID-19) (COVID-19 Dashboard, 2020). Due to inconsistently applied public health practices and quarantines, an inadequate national response, and widely varying access to health care, the pandemic continues to spread in the US, raising serious concerns about SARSCoV-2 possibly killing several hundreds of thousands of people by the time it runs its course. Phylogenetically related to both SARS-CoV (SARS) and Middle East Respiratory Syndrome Coronavirus (MERS) (Boni et al., 2020; Fani et al., 2020; Lu, Wang, & Gao, 2015; Sironi et al., 2020; Zhou, Chen, et al., 2020; Zhou, Yu, et al., 2020), SARS-CoV-2 is fairly new to humans. Considerable effort has been made to trace its genetic origins in nonhuman species (eg, bats, pangolins, civets) that serve as reservoirs for this and related viruses, and track its path of transmission to humans (Lan et al., 2020; Sironi et al., 2020; Zhou, Chen, et al., 2020; Zhou, Yu, et al., 2020). Regardless of the source of the zoonotic transmission, it is clear that SARS-CoV-2 evolved and adapted in another host before being transferred to humans (Andersen, Rambaut, Ian Lipkin, Holmes, & Garry, 2020). There is further speculation that, before being identified in late 2019, SARS-CoV-2 had been infecting humans for some time, possibly causing mild illness (Andersen et al., 2020; Sironi et al., 2020). Through the process of human transmission, this coronavirus (CoV) may have acquired some key mutations that ultimate led to the emergence of the current pandemic strain (Boni et al., 2020; Sironi et al., 2020). In fact, recent data suggest that, since emerging and spreading globally, SARS-CoV-2 has evolved into two major forms in Europe and Asia, with both appearing in US populations at frequencies associated with their geographic proximity to these source areas (Forster, Forster, Renfrew, & Forster, 2020). Building on insights from studies of SARS and MERS, ongoing research has enlarged our understanding of the origin of SARS-CoV-2 and its greater virulence compared to other CoVs. At the same time, the global health crisis caused by its spread from populations based in Asia has led to questions about how to mitigate its impact from clinical and public health standpoints, particularly for individuals and communities who have disproportionately suffered from coronavirus infection. This short commentary explores the epidemiology and biology of SARS-CoV-2 before examining the host genetic factors that may lead to differential susceptibility to COVID-19 and varying immunological responses to viral infection. It concludes by reflecting on the way that knowledge about these genetic risk factors and the mechanism of SARS-CoV-2 infection is now being used for vaccine development.