As researchers strive to understand the new coronavirus causing the pandemic Covid-19, this Thursday a study was released that points to a possible cause why SARS-CoV-2 affects men and those over 65 more seriously.

Magazine Science has published an investigation, in which Spanish scientists have participated, which reveals why the individual response to infection by the SARS-CoV-2 virus varies so much from one person to another. According to these new findings, 10% of people who develop Covid-19 have antibodies that attack the immune system itself and prevent an adequate response against the virus.

Another of the conclusions of this research, led by the Rockefeller University in New York and the Necker Hospital for Sick Children in Paris, and which has had the participation of the Vall d’Hebron Research Institute (VHIR) of the Vall d ‘University Hospital. Hebron de Barcelona, ​​is that in 15% of cases there are genetic and immunological factors that can explain the appearance of severe forms of the Covid-19.

The identified patients have in common a “decreased or defective function” of type I interferon activity, molecules of the immune system that play a key role in fighting virus infections. These proteins can be blocked by the patient’s own antibodies or, if certain mutations exist, they may not be produced in adequate quantities. This can cause a inadequate immune response against the virus and, therefore, a greater severity of the disease.

Image of doctor Andrea Martin and doctors Pere Soler (center) and Roger Colobran, from Hospital Vall d’Hebron in Barcelona.
VHIR

In a first study, researchers analyzed genetic variations from blood samples of more than 650 patients who had been hospitalized for severe pneumonia by Covid-19, 14% of whom died. Samples from another group of more than 530 patients asymptomatic or with infection Light. The researchers looked for differences between the two groups, analyzing 13 genes known to be important in defense against the flu virus by type I interferons.

Alterations in interferons

As explained in a press release, the results obtained showed that a significant number of people with severe Covid had some alteration in these 13 genes and, specifically, the 3.5% had mutations than prevented an adequate response against SARS-CoV-2 due to lack of activity of type I interferons, which are molecules generated by the immune system “that interfere – hence their name – in viral replication and are especially important in the early stages of infection,” he explains to 20minutos Dr. Roger Colobran, from the VHIR Diagnostic Immunology Research Group.

“Type I interferons are one of the main mechanisms that innate immunity has to fight against viral infections. In fact, during the last 15 years, mutations in these 13 genes have already been described in specific and exceptionally severe cases of other viral infections such as gripe or herpesvirus encephalitis. What is very striking in this study is the high frequency with which we have found these alterations in patients with severe Covid-19 “, Colobran has abounded.

“Although 3.5% seems a small percentage, the truth is that it is high considering the number of people who have developed Covid in a serious way around the world and that so far the alteration in interferons was observed very rarely“Exposes the biologist and doctor of immunology, who emphasizes that this point of the research is the most clinically relevant.

Genetic factors

On the other hand, a second work describes a autoimmune response against type I interferons. In this case, the researchers examined 987 patients with severe Covid-19 pneumonia and found that more than 10% had their own antibodies against interferons at the beginning of the infection. Of the 101 patients with these antibodies against type I interferons, 95 were men.

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“It is gender bias suggests the presence of some genetic factor (which could be located in the X chromosome) that somehow favors the appearance of this autoimmune phenomenon more prevalent in men. This is one of the hypotheses that is being worked on within the consortium COVID Human Genetic Effort“Colobran added.

Also, near half of the patients who had these antibodies were over 65 years old, while they were only found in 38% of those under 65 years of age, so it seems that the frequency of these antibodies increases with age. Thus, the autoimmune response against interferons could explain the greater vulnerability of men and people over 65 years of age to suffer severe COVID-19, continues the note released by the VHIR.

It should be mentioned at this point that in the starting sample there were 75% men and 25% women, since this has been the usual percentage in severe Covid patients in ICUs, the researchers explained.

Cause and not consequence

The presence of autoantibodies was also analyzed in the healthy general population. In these cases, only 4 of the 1,227 people analyzed they had these kinds of antibodies. “These findings reinforce the idea that these autoantibodies have a role as cause of these serious ways and that they are not a consequence “, has added Dr. Andrea Martín, from the Investigation Group on Infection in the Immunosuppressed Pediatric Patient.

Finally, the researchers have highlighted that these results demonstrate the clinical utility of performing test Elisa (a laboratory technique used to detect antibodies) to patients in the first days of SARS-Cov-2 infection, in order to “try to predict if they will get worse, and intervene so that they do not develop seriously the disease. Covid “, has pointed out Colobran.

“Doors are opened to the treatment of severe forms of Covid-19 such as plasmapheresis, uuse of other types of interferons or drug elimination of plasma cells“, has added in the pediatrician and Colobran’s partner, Pere Soler-Palacín, head of the Investigation Group of Infection in the Immunosuppressed Pediatric Patient of the VHIR.