The emergence of COVID-19 infection (caused by the SARS-CoV-2 virus) in Wuhan, China in the latter part of 2019 has, within a relatively short time, led to a global pandemic . Amidst the initial spread of SARS-CoV-2 across Asia, an epidemiologic trend emerged in relation to high altitude (HA) populations . Compared with the rest of Asia, SARS-CoV-2 exhibited attenuated rates of expansion with limited COVID-19 infection severity along the Tibetan plateau . These characteristics were soon evident in additional HA regions across Bolivia, central Ecuador, Nepal, Bhutan, and the Sichuan province of mainland China . This mini-review presents a discussion surrounding attributes of the HA environment, aspects of HA physiology, as well as, genetic variations among HA populations which may provide clues for this pattern of SARS-CoV-2 expansion and COVID-19 infection severity . Explanations are provided in the hypothetical, albeit relevant historical evidence is provided to create a foundation for future research.