Covid, how the three genes that clear all symptoms work

Why do some people, in contact with Covid, become infected and others not? A question of genes. And why do some patients have symptoms, even severe ones, and others don’t even notice? A question of genes. The confirmation, to the second statement, comes from a study on asymptomatic patients concluded by the team of the University of Naples Federico II and Ceinge researchers, who added a new piece to the complex picture of the genetic predisposition to the different clinical phenotypes of Covid.

The study was published in the international journal Genetics in Medicine. “The mutations in the human genome that attenuate this excessive immune reaction to Covid – explain the researchers – can predispose to an infection without serious symptoms”.


Risk factors such as age, gender and previous illnesses play a major role in determining the severity of Covid disease in SARS-CoV-2 infected patients. Less known, however, are the genetic factors of man that can contribute to determining the different forms of the disease, starting from asymptomatic ones up to clinically serious ones. Factors to which the Ceinge researchers, directed by Mario Capasso And Achille Iolasconprofessors of medical genetics, with whom they collaborated Pellegrino Cerinoof the Zooprophylactic Institute of Portici, e Massimo Zollocoordinator of the Covid task force of Ceinge and professor of Genetics at Federico II.

They analyzed the DNA samples of about 800 people infected with the virus, but who had not developed serious symptoms despite being at risk, for example due to old age. The data is now available online to all researchers around the world.

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Three genetic mutations behind the asymptomatic cases

It turned out that there are at least three rare genetic mutations at the origin of asymptomatic cases of Covid. They work by weakening the genes involved in the activation processes of the immune system, and their discovery could pave the way for new diagnostic techniques and new therapies.

“All the genes known so far have been analyzed using the latest generation sequencers and thus obtaining an enormous amount of genetic data – explains Capasso -. Advanced bioinformatics analysis strategies, developed thanks to the contribution of the young researcher Giuseppe D’Alterio and the team of bioinformatics experts from Ceinge, then made it possible to identify rare pathogenic mutations, significantly more frequent in infected and asymptomatic subjects than in a large series of about 57,000 healthy subjects “.

The three genes involved in asymptomatic infections are called Masp1, Colec10 and Colec11 and belong to the lectin family of proteins, the protein involved in the cell recognition process.

An excessive immune response

“Today it is widely demonstrated that the excessive immune response to Covid and the subsequent hyper-activation of pro-inflammatory and pro-coagulation processes are the main cause of damage to organs such as lungs, heart, kidney – continues Capasso -. Our research proves that mutations in the human genome that attenuate this excessive immune reaction can predispose to an infection without severe symptoms. ” A discovery that opens up new paths in the future of diagnostic and therapeutic approaches. For this reason, the team made available, in an online database, all the genetic data obtained.

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An open door to new discoveries

“So other scholars will be able to freely consult them to develop new research – underlines Iolascon -. We can use these mutations to identify subjects who are predisposed to developing less severe or asymptomatic Covid forms. In addition, the serum levels of the three identified genes could be used as markers. prognostics of severe disease. Finally, today we know more about the biological basis of this disease and therefore we have something to work on to develop new pharmacological treatments “.

Those that don’t get infected

And then there are those who don’t get infected, don’t get sick at all. Analysis already emerged in recent months. “In all infectious diseases there is always a share of people who are naturally resistant to infection – he confirmed Fausto Baldanti, which two and a half years analyzes the Covid variants in the Molecular Virology Laboratory of the San Matteo Polyclinic in Pavia -. Who I am? Many reports concern individuals who, having very close contact with infected people, do not become infected themselves. I’m talking about families in which one out of many is spared by the virus, in the sense that there is no evidence of it, not that they are asymptomatic. So for all infectious diseases there is a share of resistant. Even the most terrible ones do not kill 100% of the people involved: smallpox, for example, has a mortality of 80%, Ebola 90% “.

The natural factors that neutralize the contagion

But what are the mechanisms that provide natural protection against viruses, including Covid? “There are two – highlighted Baldanti – the first is the presence of a pre-existing immunity, crossed by similar infections. Some people, for example, have resisted Covid because they had contracted a previous infection due to other Coronavirus”.

“Let me explain – he continued -. There are four strains of Corona that cause Beta Coronavirus infection in humans: of these, two give a cross-response against Sars. In practice, having contracted something similar to Covid confers a protection because it generated a cross-response. I am an example, because from a blood sample that I had taken three years ago and then stored, I discovered that I had produced an immune response against Covid. In practice I had contracted a Beta Coronavirus human being called HKU1. It is estimated that 25-30% of people who do not get Covid have a residual T-Cell response caused by an infection with a virus related to Covid itself. So this can protect against new infection or cause it mild or asymptomatic “.

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The genetic variation underlying the study

And what is the second natural virus protection mechanism we know from 2020? “This is what a work coordinated by the University of Melbourne and the Foundation for Biomedical Research of the Academy of Athens speaks of – explained Baldanti -. It speaks of it precisely because it is due to some genetic trait which is then favorable towards the new infection. For example, individuals who have a lower density of Ace2 and Trmpss receptors (proteins) would be less prone to become infected. Or it may happen that some subjects have both a genetic variation that protects against Covid, but have also contracted a previous infection with a virus relative. And this makes them practically intangible. “

How do you realize you are resistant to Covid?

It is difficult, if not impossible, before direct contact with the disease, to realize that you are resistant to Covid. To confirm this, from direct experience, is Baldanti himself, who only three years later realized that he had already encountered a Coronavirus that made him practically impermeable to Covid. “One realizes one’s state of super-protected only in the evidence of not being infected – he concluded -. The interested parties do not know they are. I myself, only now have I discovered that in a sample of my blood stored in the freezer for three years there was a T-cell response against Covid. It will be a coincidence, but I have never had a positive swab “. How many are the super-protected, that is the people who have genetic variants that allow them to resist the virus more? According to the virologist almost 10%.

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