Does a cell protein explain covid-19 severity?

DOES a protein on the surface of some of our cells explain why certain people are more at risk from covid-19?

Studies of confirmed cases so far show that people with coronary heart disease or diabetes are more likely to die than other people if they catch the coronavirus. Individuals with lung disorders, such as chronic obstructive pulmonary disease (COPD), and smokers are also at greater risk, says Janice Leung at the University of British Columbia in Canada.

As we begin to understand the virus better, focus is turning to a protein called ACE2. The coronavirus attaches to this receptor protein on the surface of our cells to gain entry to them. The protein is carried by cells in the nose, lungs and gut.

It is possible that variation in how much of this protein people have may help explain why some are more likely to die from covid-19. When Leung and her colleagues looked at lung tissue samples from volunteers, they found that the cells of smokers and those with COPD make much more ACE2 (medRxiv, doi.org/dqx2).

This may explain why these people are more likely to have severe covid-19 infections, says Leung. “If you ever needed another reason to stop smoking, this would be it,” she says.

People with diabetes also seem to produce more ACE2. But we don't know yet if ACE2 levels really do have an effect on coronavirus infections.

People with coronary heart disease or diabetes are more likely to die of the coronavirus

The link between covid-19 deaths and diabetes and cardiovascular and heart conditions has led to some concern over ACE inhibitor drugs. These drugs, which are used to treat high blood pressure, coronary artery disease, heart failure and diabetes, work by targeting the ACE enzyme – a different protein, but one that works alongside ACE2 to regulate blood pressure.

A study of 106 people with covid-19 by Yong Xiong at Zhongnan Hospital of Wuhan University, China, and his colleagues found that having hypertension, diabetes or cardiovascular disease was linked to patients clearing the virus from their bodies more slowly.

The team suggests that ACE inhibitor drugs taken by some of these patients may have increased their levels of ACE2, providing the virus with more opportunities to dock onto their cells, although the study didn't show whether this was the case (medRxiv, doi.org/dqx3).

Just as we don't yet know if ACE2 levels contribute to symptom severity, we also don't know if taking ACE inhibitors has a negative effect. All we can really say so far is that people with certain conditions are at higher risk of death from covid-19, and that these people are likely to have higher ACE2 levels and also be taking ACE inhibitors.

Because no clinical studies have so far shown that ACE inhibitors raise the risk of covid-19, many organisations, including the American Heart Association and the European Medicines Agency, recommend that those prescribed these drugs continue to take them.

Ultimately, ACE2 might be a good target for drugs to block infection by the virus, but we don't yet know if interfering with the protein would be safe. Several studies in mice suggest that ACE2 plays an important role in responding to injury in the lungs, so blocking its function might prevent such injuries from healing.

“We know a little bit about ACE2, but we clearly don't know enough to actually say anything intelligent yet,” says Jose Ordovas-Montanes at Boston Children's Hospital in Massachusetts.