As COVID-19 vaccine rollouts begin, a large focus has been on vaccinating target groups, including the elderly. Choosing target groups has been informed by studies revealing that SARS-CoV-2, the virus that causes COVID-19, affects different people in different ways.
Global data has found those aged over 70 are at the greatest risk of dying if infected with the virus. Researchers have also found a clear association between the male sex and SARS-CoV-2 susceptibility, complications and outcomes.
Now, Australian researchers from a range of institutions have a possible explanation.
They suggest that males and the elderly may have greater numbers of a receptor, called angiotensin-converting enzyme 2 (ACE2), on cells in their lower lungs.
The ACE2 receptor is the protein that provides an entry point for SARS-CoV-2 to bind to and infect a wide range of human cells – like a key unlocking a door.
“It is likely that the level of ACE2 expression in lower airway cells may be an important factor in determining more severe infection,” the researchers explain in their paper, published in Respirology.
They also found that the ACE2 gene and protein levels were lower in study subjects with asthma.
“People with chronic respiratory disease, especially asthma and chronic obstructive pulmonary disease (COPD), are usually at heightened risk of complications from acute respiratory viral infections,” the authors write.
“However, this is not clearly the case with COVID-19… those with asthma do not appear to be over-represented. Age and male sex appear to be associated with worse outcomes, and children generally experience only mild illness.”
The team analysed lower airway epithelial – surface layer – cells from 145 people aged 2–89 years. They found that increased gene expression of ACE2 was associated with older age and males.
“One factor that may predispose to more severe disease and pneumonia is the level of expression of the ACE2 receptor in airway epithelial cells (AEC) of the lower respiratory tract allowing infection to spread more easily from the upper airway, resulting in a more intense lower airway immune response and more severe clinical disease,” the authors write.
They suggest the reduced ACE2 expression could be a potential mechanism that should be further investigated as a therapeutic target to reduce SARS-Cov-2 infection of the airway epithelium.