Why are women more resistant to coronavirus, at any age?

At the height of the first waves of SARS-Cov2, intensive care unit beds were more often occupied by men than by women. The pandemic has shown that they resist Covid-19 better than their male counterparts thanks to a more effective immune response to this infection. This is also the case with other viruses such as influenza or HIV.

According to a recent study carried out by a joint team from Inserm, CNRS, Toulouse III – Paul-Sabatier University and Toulouse University Hospital, published in the journal eBioMedicinehormonal and genetic factors may explain this difference, and continue to play a role even in older women.

We already knew that when an RNA-type virus attacks, cells called pDC manage to detect its presence thanks to their TLR7 receptor. They also react to defend themselves and release cytokines into the blood, in particular those known as type 1 interferons, an army of powerful antiviral molecules, quick to inhibit the replication of the virus.

“When you activate this TRL7 receptor, women generally produce more interferons than men. The TRL7 gene is on the X chromosome, in two copies in women,” recalls Jean-Charles Guery, Inserm research director, co-author of the study. If this mechanism in the immunity was known, the studies until now had leaned on rather young subjects, of less than 60 years. However, if age is an aggravating risk factor, older patients always resisted better than men of their generation.

After closely scrutinizing a cohort of 310 women and men aged 19 to 97 in apparent good health, the researchers took a closer look at the production of interferons when the TRL7 receptor is tickled by the presence of viruses. “We observed that this immune response was maintained with age. Even in people over 80, there were more interferons in women than in men. At an advanced age, the sex bias persists, women will better control the virus during the early phase, when they will produce more interferons. This time it involves a mechanism that is no longer linked to estrogens, since their production decreases with age, but probably to genetic effects”, continues Jean-Charles Guéry.

A clinical study to test an interferon booster

Now that we have deciphered how the immune response is set up, scientists will try to use it to successfully activate it and thus give better weapons to infected people. A clinical trial could thus be set up in Toulouse in the coming weeks on a molecule developed by an American company.

This should boost the production of interferons in the elderly. “We are trying to see if, on people who take this molecule, there is a response, and to boost the immune defenses. It could be against the Covid, but also the seasonal flu, ”concludes Jean-Charles Guéry.

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