Can ACE2 expression explain SARS‐CoV‐2 infection of the respiratory epithelia in COVID‐19?

Infection with severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) leads to coronavirus disease 2019 (COVID‐19), which poses an unprecedented worldwide health crisis, and has been declared a pandemic by the World Health Organization (WHO) on March 11, 2020. The angiotensin converting enzyme 2 (ACE2) has been suggested to be the key protein used by SARS‐CoV‐2 for host cell entry. In their recent work, Lindskog and colleagues (Hikmet et al, 2020) report that ACE2 is expressed at very low protein levels—if at all—in respiratory epithelial cells. Severe COVID‐19, however, is characterized by acute respiratory distress syndrome and extensive damage to the alveoli in the lung parenchyma. Then, what is the role of the airway epithelium in the early stages of COVID‐19, and which cells need to be studied to characterize the biological mechanisms responsible for the progression to severe disease after initial infection by the novel coronavirus?