Sex hormones, chromosomes behind better Covid-19 outcomes in women than men, study says

Women face less severe complications and a lower risk of dying from Covid-19 than men due to the presence of hormones and chromosomes that contribute to a stronger immune response in female patients, according to a study.

The research, published in the American Journal of Physiology-Heart and Circulatory Physiology, highlights how the sex differences in Covid-19 are linked to ACE2, an enzyme that acts as the receptor allowing SARS-CoV-2 virus to enter the body.

ACE2 is also key in protecting against cardiovascular, lung and kidney diseases, the researchers said.

"Because of their chromosomes, women have two copies of the ACE2 gene and men have only one copy," said senior study author Gavin Oudit, professor at the University of Alberta in Canada.

"This does not seem to make women more susceptible to Covid-19 infection, but it does protect them from the complications associated with the virus," Oudit said.

ACE2 is an X chromosome-linked gene, Oudit explained.

To avoid duplication, one X chromosome tends to be inactivated, however, due to its location ACE2 escapes inactivation.

This means women have twice as many active genetic instructions to make ACE2, he said. Another gene that is twice as strong in women due to this X-inactivation escape is called Toll-like receptor seven, a key part of the innate immune system.

"The stronger presence of Toll-like receptor seven in women explains why women's immune systems are stronger than men's and can tolerate virus infection better, including the common cold," said Oudit, adding "the man-cold phenomenon is real."

The study found that men face more severe illness and poorer outcomes around the world, even when women likely face more exposure to SARS-CoV-2 than men.

"Due to gender issues, women face more risk, so it's reassuring to know that their outcomes are not any worse; in fact they are clearly better than men's," Oudit said.

The researchers said they are trying to understand how manipulating ACE2 levels might help Covid-19 patients, to prevent infection by blocking the enzyme or to protect the cardiovascular system, lungs and kidneys by enhancing it.

"We need to look at the factors that are responsible for better outcomes for everyone, taking sex differences into consideration when we test new therapies and provide Covid-19 care," Oudit said.