Why do more men than women die from the coronavirus?

29 Apr 2020 | Back to News, Publications and Annual Reports



This is one of the many enigmas surrounding the coronavirus. It is definitely striking: worldwide two to three times more men than women die of the coronavirus. BPRC scientists also racked their brains about this remarkable fact and published a hypothesis.

At the genetic level, they studied differences between men and women that may be involved. We already know that the virus needs a certain protein (the ACE2 receptor) to enter our body. In case this protein differs between men and women, this could be a possible explanation. However ... previous research has shown that this is probably not the case.

Recognizing pathogens

Another possibility is that the immune system of women reacts differently than that of men. Pathogens can be recognized in different ways before triggering the immune system. In the primary recognition of pathogens, a specific family of proteins, the so-called "Toll-like receptors" (TLR), plays an essential role. Different TLR can recognize different parts of pathogens and then trigger the immune system to react. This raises the question: which TLR can recognize the coronavirus?

Recognition of the coronavirus

We know from four TLR proteins that they can recognize parts of viruses. Two of the four TLR proteins, TLR7 and 8, are genetically encoded in the X chromosome. Women have two of these X chromosomes and men only one. While one of the two X chromosomes normally is inactive, the TLR7 and probably also the TLR8 genes avoid this inactivity. As a result, women have more of these TLR proteins than men.

Inside the lungs

Furthermore, we know that many immune cells with TLR7 and TLR8 are present inside the lungs -the site where the damage takes place due to the coronavirus. In women, increased amounts of TLR7 and TLR8 may result in improved on site recognition of the virus in the lungs. Unfortunately, high expression of TLR7 and TLR8 may also induce unwanted effects. If this is the case, the immune system attacks the body and an autoimmune disease develops. Therefore, it is essential that there is a good balance in the expression of TLR7 and TLR8.

It is even more complicated

To complicate matters further: on the X chromosomes TLR7 and -8 are also present in different numbers of copies per individual. This may also result in differences in immune responses to the coronavirus. The researchers therefore recommend genetically mapping the TLR7 and -8 genes in corona patients. More knowledge about this is important, because it allows us to determine how a vaccine against the coronavirus can best be implemented in the future.