ACE2 and COVID-19: Thus, a tempting hypothesis that remains to be experimentally validated is that external or biological factors leading to enhanced ACE2 expression may exacerbate SARS-CoV-2 replication and/or expand its cellular tropism (14), thereby increasing the severity of COVID-19 in individuals of certain risk groups, including the elderly, smokers, and those with coinfections or comorbidities (15).