It is a disparity that raises questions. According to initial statistics, men die more from Covid-19 than women. In Switzerland, figures from the Federal Office of Public Health on April 3 indicate that men account for 63.5% of illness-related deaths and 61% of hospitalized cases. This over-representation can be seen at almost all ages, with more or less significant differences. But at the same time, women are more affected by the disease since they constitute 52.4% of laboratory confirmed cases.
This trend in deaths was first observed in China, where the pandemic broke out. According to a count by the Chinese Center for Disease Control and Prevention between December and February, the case fatality rate for men was 2.8% compared to 1.7% for women. Of the 44,672 cases observed, men represented 51.4% of the patients and 63.8% of the deaths. A proportion which is also observed elsewhere in Europe. In Italy, men represent around 71% of the deaths recorded. For the moment, these statistics are questionable since they are only provisional.
A genetic hypothesis
The explanations for this phenomenon remain difficult to determine. These gender differences have already been observed in epidemics linked to similar viruses such as SARS-CoV-1 in 2003 and MERS-CoV in 2013. “We cannot rule out a biological effect on immunity linked to sex, which could involve either steroid hormones such as estrogens or androgens, or genetic factors linked to sex chromosomes “, details Jean-Charles Guéry, head of the research team” Gender-related differences in immunity : mechanisms and pathophysiology ”at the French National Institute for Health and Medical Research (Inserm).
The X chromosome, found in a single copy in humans, contains many genes involved in immunity. “Women have two X chromosomes, data shows that they can therefore express certain important genes in two copies under certain conditions, which is not possible in men,” he said.
The role of estrogen under the microscope
Regarding the role of hormones, a study conducted on mice, published in 2017 in the Journal of Immunology, shows that there may be a link between estrogen production and death. The mice studied, of different ages, were infected with SARS-CoV-1. As a result, males experienced more deaths than females. But removal of the ovaries or treatment to suppress the action of estrogen in female mice has resulted in increased mortality.
“This study suggests an effect on the immune system, it does not demonstrate it,” says Jean-Charles Guéry. This track alone is not enough to explain the difference in mortality since it persists in older patients, including age groups after menopause, when the body no longer produces these hormones. “The immune system of young women responds stronger and earlier than in men,” says Maria Teresa Ferretti, scientific manager of the Women’s Brain Project (WBP), an organization dedicated to highlighting gender differences in the field of mental health.
“But after 65, pro-inflammatory responses are stronger in men,” she continues. An over-reaction of the immune system is also an explanation being studied for severe cases of the disease.
In addition to the biological aspects, gender differences are also studied. Comorbidities such as hypertension, diabetes or cardiorespiratory diseases affect men more. They are also more likely to smoke. In China, 50% of men are smokers against 2% of women. This difference is less significant in Europe, especially among the younger generations, but remains marked.
Some researchers also highlight a tendency among men to less respect the hygiene measures put in place. An explanation that does not convince Antonella Santuccione Chadha, co-founder of the WBP and doctor: “If this was the case, children should be more affected. There is not really any data on the question of compliance with hygiene measures. “
Distinguish women and men facing the disease
Women are also the majority in occupations very exposed to contamination, particularly in the health sector. However, they do not constitute the majority of deaths, only cases. Beyond SARS-CoV-2, medical research has long underestimated the biological differences linked to sex in the face of diseases. “For the first time, we have ample evidence that we must take into account the differences between women and men in the diagnosis, prevention and treatment of diseases,” insists Antonella Santuccione Chadha.
These differences must also be taken into account in the design of a treatment, even if the crisis situation does not necessarily lend itself to it. “There is a lot of data showing that the response to vaccines differs between the two sexes,” says Jean-Charles Guéry. For example, for a half the dose of the flu virus, women develop a similar immune response to men receiving a full dose. ” Side effects, on the other hand, can also be more pronounced for women.
The gender-related effects of this pandemic don’t stop at Covid-19. “In the long run, women are more likely to suffer from anxiety or depression,” said Annemarie Schumacher Dimech, WBP president and doctor of psychology. This crisis may therefore be an opportunity to also review the way in which medicine and research tackle gender differences.