Defects in the TLR7 gene in people under 60 years of age and the presence of autoantibodies against type I interferons in the elderly they increase the severity of Covid-19, according to two international studies in which the Vall d’Hebron Hospital in Barcelona has participated.
In reality, this gene is not the first time it has made the news. As early as July last year, researchers from Radboud University Medical Center they pointed out that genetic factors played a key role in compromising your immune system. And they were not wrong, because the results of their research, published in the journal JAMA, showed that the TLR7 gene was an essential actor in the immune response against Sars-Cov-2.
Now, the studies, led by the Rockefeller University of New York and the Necker-Enfants Malades Hospital in Paris, are published today in the journal Science Immunology. The first of them establishes that patients with mutations or deficiencies in the TLR7 gene are more likely to contract a severe or critical Covid-19 diagnosis, especially in men under the age of 60.
TLR7 is an immune system gene that contributes to the production of type I interferons (IFN-I), keys to giving an immune response against SARS-CoV-2, so if it suffers a defect, it increases the chances of presenting a serious diagnosis.
“We have seen that these genetic errors appear especially in younger patients, less than 60 years old,” stated Pere Soler-Palacín, head of the Pediatric Infectious Pathology and Immunodeficiencies Unit at Hospital Vall d’Hebron.
In addition, TLR7 is a gene that is on the X chromosome and therefore has a role in men and only occasionally in women, which could explain the worse prognosis of Covid-19 in men regarding females. The study analyzed 1,202 patients, 20 of whom, aged 7 to 71, had TLR7 deficiencies and had no prior diagnosis or serious illness.
The second work started from the experience that age is the main risk factor for suffering from Covid-19 and from the data that show that the risk of hospitalization and death from pneumonia doubles every 5 years. Well, it has been confirmed that this increase in risk is explained, at least in part, by the presence of autoantibodies against type I IFN, that is, the development of an autoimmune response against own type I interferons.
The results show that, globally, 13.6% of patients with Covid-19 have this type of autoantibodies, a percentage that increases up to 20% in patients older than 80 years with this condition.
“These autoantibodies may explain the increased risk for severe Covid-19 and we show that they do so especially in the case of older people,” according to Roger Colobran, head of the Research Group in Diagnostic Immunology at the Vall d’Hebron Research Institute ( VHIR).
According to Colobran, these autoantibodies are a cause and not a consequence of SARS-CoV-2 infection, and in people under 70 years of age, between 0.17 and 1.1% of people have autoantibodies and, in those over the age of 70 70, are between 1.4 and 4.4%, while between 80 and 85 years there is an increase of between 4.2 and 7.1%.
“With age, the immune system ages: is what is known as immunosenescence. This makes it more likely that autoimmunity phenomena like this appear “, pointed out Soler-Palacín.
For this analysis, the researchers studied blood samples from 3,595 patients hospitalized for critical Covid-19, 623 seriously ill patients, 1,639 patients with mild or asymptomatic infection, and 34,159 healthy individuals to study whether they had this type of autoantibody.
The authors of the two papers have insisted on the importance of knowing the factors that influence the response to SARS-CoV-2 and hope that it will open the door to targeted therapies depending on the profile of each patient.