In the spring of 2020, ACE2—angiotensin-converting enzyme 2—became a major focus of attention as the entryway of the coronavirus SARS-CoV-2, which is the virus that causes COVID-19.

As of early November 2020, over 47 million cases of COVID-19 were confirmed worldwide, with more than 9 million cases in the U.S. Since the beginning of the pandemic, doctors and scientists have made the important observation that children are less likely to develop COVID-19 symptoms that require hospitalization, including cough, fever and shortness of breath. Older adults, however, especially those with diabetes and obesity, have a higher risk of getting severely ill. The recovery time is often longer for older adults, too.

To understand why the coronavirus attacks older adults more aggressively, scientists looked at the number of ACE2 receptors—the protein that the coronavirus binds to—in different age groups. ACE2 receptors are found in different organs, including the lungs, arteries and heart. When the virus affects the receptors in the lungs, acute respiratory distress syndrome can develop. Studies, including one published in the American Journal of Physiology-Lung Cellular and Molecular Physiology, have shown that infants and very young children have only a few ACE2 receptors in their lungs. The expression of ACE2 receptors increases in older children, but it is still lower than in adults, which makes it harder for SARS-CoV-2 to enter the body.

One of ACE2’s normal jobs is to lower high blood pressure and reduce inflammation. But when the coronavirus enters the body of older people, it prevents ACE2 from performing its job by blocking its receptors. This can weaken the heart and blood vessels of adults who are infected.  

In addition to the role of ACE2, the immune system response in children versus older adults also makes a difference in how COVID-19 affects the body. Babies are born with an immature immune system and benefit from antibodies found in breast milk. At first glance, this should make infants and young children more susceptible to any infection, including SARS-CoV-2. However, the immune system is very complex and contains many types of white blood cells, antibodies and other chemicals that fight off viruses and bacteria. T cells, a type of white blood cell, help our body fight respiratory viruses. Researchers have found that adults with moderate or severe COVID-19 have fewer T cells, which has helped us realize that these cells not only offer protection from the coronavirus, they also protect healthy cells from increased inflammation.

Understanding how age, ACE2 and the immune system are linked will help doctors and scientists develop and refine age-based treatment for COVID-19.