The science behind why COVID-19 is killing more men than women

Although women contract COVID-19 at a comparable rate as men, the latter is more likely to develop critical manifestations of the disease--irrespective of age or region. In fact, on balance, men are 60% more likely to succumb to COVID-19 than women.

This is in part due to the disproportionate number of men who have pr-existing conditions known to compound coronavirus symptoms.

In addition, women tend to have a more effective auto-immune response, thanks to the production of white blood cells important to off antigens.

These biological advantages were recently explored in a paper published in the journal Nature.

“A growing body of evidence indicates sex differences in the clinical outcomes of coronavirus disease 2019 (COVID-19)1–5. However, whether immune responses against SARS-CoV-2 differ between sexes, and whether such differences explain male susceptibility to COVID-19, is currently unknown,” the authors wrote in the new study. “In this study, we examined sex differences in viral loads, SARS-CoV-2-specific antibody titers, plasma cytokines, as well as blood cell phenotyping in COVID-19 patients.”

After the researchers recruited a study pool, they collected nasal, saliva, and blood samples from non-infected control individuals and patients who previously tested positive for COVID-19. They then monitored patients to look at their immune responses.

The data revealed that women have a higher reserve of T lymphocytes, which influences one’s immune response to foreign substances in the body.

For men, T-cell activity decreases with age while women’s t-cell activity continues to be active in old age.

Adding to this, men typically produce more inflammatory proteins called cytokines.

“By focusing our analysis on patients with moderate disease who had not received immunomodulatory medications, our results revealed that male patients had higher plasma levels of innate immune cytokines such as IL-8 and IL-18 along with more robust induction of non-classical monocytes. In contrast, female patients mounted significantly more robust T cell activation than male patients during SARS-CoV-2 infection, which was sustained in old age,” the authors added.

When fighting off a virus, cytokines bind to receptors on neighboring cells. When a surplus of cytokines are produced they enter the bloodstream and begin to target healthy cells.

This is what’s known as a cytokine storm. Individuals who experience cytokine storm increase risk for developing a fever, vascular leakage, tissue damage to multiple organs, and death. In women, cytokine storms are much deadlier than they are in men.

The strength of these finds regards the development of targeted therapeutics. With a better understanding of the biological features that define an ideal auto-immune response to COVID-19, researchers can hone in on a shortlist of clinical substitutes.

“Importantly, we found that a poor T cell response negatively correlated with patients’ age and was associated with worse disease outcome in male patients, but not in female patients. Conversely, higher innate immune cytokines in female patients associated with worse disease progression, but not in male patients,” the authors concluded. “These findings reveal a possible explanation underlying observed sex biases in COVID-19, and provide an important basis for the development of a sex-based approach to the treatment and care of men and women with COVID-19.”