ACE2 role in SARS-CoV-2 infectivity and Covid-19 severity

In 2003, it was discovered that the entry receptor for the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) is a protein called the angiotensin-converting enzyme 2 (ACE2). This protein is present in a number of cell types, including those from the respiratory tract. Soon after the emergence of SARS-CoV-2 that is responsible for the disease Covid-19, scientists found that ACE2 was also used by the new coronavirus to infect cells. This opened some interesting possibilities to explain the striking variation in risks of catching and dying from Covid-19. The best recognised of these are the much higher risk of serious illness in older than younger people, in men than women, and in those with pre-existing comorbidities such as hypertension and cardiovascular diseases. There are several ways in which the ACE2 protein might contribute to this variation. The most obvious would be if there is more ACE2, there would be more entry points for the virus to infect the cell, e.g. in older people or in men. However, the evidence for this is rather small, partly because it is not that easy to obtain representative healthy tissues. Alternatively, it could be related to ACE2 membership of a family of proteins that has one end of the protein anchored inside the cell while most of the protein protrudes from the outside of the cell which therefore can be shed when cleaved by proteases at the cell membrane. Herein we review current evidence and theories of ACE2 role on SARS-CoV-2 infectivity and Covid-19 severity.