SARS-CoV and SARS-CoV-2 both use the same keyhole to enter cells, the ACE2 receptor. There’s an abundance of this receptor in cells in the lower lung, which may explain the high incidence of pneumonia and bronchitis in those with severe COVID-19 infection. A recent study showed that ACE2 is also highly expressed in the mouth and tongue, granting the virus easy access to a new host. ACE2 receptor abundance goes down in the elderly in all these tissues, but, counterintuitively, this might place them at a greater risk of severe illness.
This is because the ACE2 enzyme is an important regulator of the immune response, especially inflammation. It protects mice against acute lung injury triggered by sepsis. And a 2014 study found that the ACE2 enzyme offers protection against lethal avian influenza. Some patients with better outcomes had higher levels of the protein in their sera, and turning off the gene for ACE2 led to severe lung damage in mice infected with H5N1, while treating mice with human ACE2 dampened lung injury.
A fall in ACE2 activity in the elderly is partly to blame for humans’ poorer ability to put the brakes on our inflammatory response as we age, according to emailed comments from Hongpeng Jia of Johns Hopkins Medicine. Reduced abundance of ACE2 receptors in older adults could leave them less able to cope with SARS-CoV-2, says Baric, though the hypothesis still needs more research.
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