Are Italians really more exposed to Covid-19 for genetic reasons? And is it true that men are more vulnerable than women? And how can the analysis of genetic differences help in treatment and prevention? To answer these questions, we directly asked the Professor Stefano Duga, Full Professor of Molecular Biology of Humanitas University, who is conducting a study together with other researchers aimed at understanding the genetic factors that influence the susceptibility to infection, the severity of the clinical course of the disease and also the greater severity of symptoms observed in men compared to women: "A first analysis, carried out on the sample of the entire population and focusing on two membrane proteins, called ACE2 and TMPRSS2, which act as receptors for the entry of the virus into cells, has actually highlighted genetic variants between the Italian and Chinese populations, and also the European one. Now, however, we are studying the entire genome, analyzing the data of patients hospitalized in our hospital in recent months, in collaboration with the Milan Polyclinic and the Milano Bicocca University. The results will come in a few weeks."
Professor, so we still can't say that Italians have a genome that puts them at greater risk than Covid-19?
"No. For now we have always known that genetic differences between individuals influence the susceptibility to a disease or the severity of symptoms depending on the person. This was also the case for Sars and Mers, the two previous coronavirus epidemics. Certainly, however, the results of our research will be important for two aspects".
Which?
“In the meantime, to identify, through DNA, the patients most at risk. So far the virus has taken us by surprise and we have not been able to predict its severity and those most at risk, except generally those of an advanced age and with previous pathologies. By deepening the genetic link we will be able to stratify patients and better organize health care. And then as regards treatments, while waiting for the vaccine, it will be decisive to identify targets in order to be able to exploit the characteristics of already existing drugs and used for other pathologies ".
Will your studies also be useful in the vaccine race?
“The vaccine consists in inducing an immune response, in particular against the surface proteins of the virus, the so-called spikes. We already have information about the proteins found on the surface of the virus, the genome sequence of the virus has been known for months, now the problem is to find an effective vaccine. However, it will take time, I think a year and a half at least, also because the surface proteins of the virus, the ones needed to penetrate our cells, are rich in sugars and this makes it more difficult to obtain antibodies capable of binding them specifically ".
Returning to genetics, is it therefore true that men are more at risk than women? At first it seemed like this, then the data on infections showed an overtaking of women.
“It is true, now there are slightly more infected women, but male individuals continue to record more serious symptoms and an average mortality double compared to females. This is true in almost every country in the world except India, Iran and Pakistan, for reasons that may have more to do with the social habits of those countries. In general, women are less seriously ill because they have immune systems that are notoriously different and more resilient than men's. Also an important role could be played by androgen hormones. In fact, our very recent studies show that patients taking drugs against prostatic hyperplasia, a very common disease beyond a certain age, were less susceptible to the more serious forms of SARS-CoV-2 disease. This is likely because the drugs used to combat it reduce androgen stimulation."
Which then could also be considered to prevent the virus among men?
“In Switzerland they are also testing it preventively, for now these are preliminary trials, but I do not exclude that they could be useful on a therapeutic level. It should not be forgotten that another factor that exposes men more is comorbidity, i.e. the coexistence of several different pathologies in the same individual. The main comorbidity in the case of Covid-19, even more than tumors, is cardiovascular disease, which affects the male population more frequently".
Could the results of your studies also be useful in a hypothetical Phase 3, for the so-called "immunity licenses"?
“No, also because genetic differences seem to affect the probability of suffering a serious form of the disease rather than the probability of being infected. Our studies will therefore be useful for organizing assistance to the most fragile categories of patients in a more effective way and for finding new therapeutic targets, i.e. new drugs".
The virus has proven to be very persistent and to know how to "hide" in our cells: many patients are asymptomatic and there are also cases of recovered patients who first test negative and then test positive again. How are we to explain this?
“This mechanism also happens with other viruses: they are capable of remaining quiescent in our body for a certain time, and then reactivate. We have seen that there are many infected people who are not infected enough to test positive for the swab. They are the asymptomatic ones, the most dangerous with a view to containing the contagion, as they are very difficult to identify. For this reason, together with serological tests, it is important to continue swabs to search for the virus. In South Korea, the spot checks worked, but also the data from Vo' Euganeo, one of the first Italian outbreaks, told us that 40% of the patients had no symptoms".
Were the other coronaviruses like this too?
“No, Sars was more serious but there were no asymptomatic cases, and therefore it was enough to monitor individuals with symptoms. Mers was even more lethal but also not very contagious. Sars-CoV-2 compared to these two is less lethal but much more contagious ".
What is your idea of what will happen in the coming months?
“For the vaccine, as I said, it will take time. It is true that there is a hurry, but there are necessary steps to be respected. This is a virus that we still know little about, we are discovering it now. A small rise in infections in some time would not surprise me ”.
