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lunedì, 27 Giugno 2022

Covid and genetics: what’s behind asymptomatic cases?

24.05.2022 – 09.00 – It has been almost two and a half years since the first cases of SarsCoV2 were documented in Europe. Since then, scientists in scientific laboratories here and around the world have patiently tried to tame this monster, unravel the unprecedented nature of this virus and slowly break the sea of uncertainty in which we were swimming. Through studies and experiments on the first patients, we began to learn about the behaviour of this virus. With larger and larger data sets, over the weeks and months we were able to narrow down, define and make less and less trivial distinctions about the dynamics of the contagion and the measures to contain it. Thanks to the collaborative work of hundreds of research teams, it was possible to make several vaccines available in an extraordinarily short time. But two years is not enough time to put all the pieces of such a complex puzzle together, and the path of research is still open on many fronts. On 5 May, the latest study examining asymptomatic cases of SarsCoV2 was published in the journal Genetics in Medicine. The study was conducted by the Ceinge-Biotecnology group in Naples in collaboration with Federico University II.

In the years we have been living with the virus, we have observed how the response to infection in terms of symptoms covers a very wide range of possibilities: there are obvious ‘risk factors‘ for the onset of severe forms of the disease (identified very early with advanced age and specific pathologies such as hypertension and cardiovascular disease); likewise, we have gradually discovered that most young people do not experience severe forms of the disease – with the exceptions of very young people who die or are admitted to intensive care. And even outside the critical group of at-risk people, it can happen seemingly by chance that one person is severely affected by the typical symptoms of Covid-19 and others only show a few symptoms in a mild form. Then there are the asymptomatic, those who show no reaction at all despite being infected with the virus. And what about those who contracted covid without showing any symptoms, even at an advanced age? The range of cases covered by the contagion probability is enormous, and without a more in-depth investigation into the causes of this diversity, our body’s response to the virus could appear to be a random event, another game of the virus for us to play. “So far I have no symptoms, I hope it stays that way!”, “Just a cold, my throat itches”.

In an attempt to get to the bottom of this chaos, Ceinge analysed the category of patient without any symptoms. The results support a picture that began to emerge as early as September 2020, when a study by the International Covid hge Genetics Consortium was published in Science. The study states succinctly: The severity of SarsCoV2 symptoms depends on genetic and immunological factors. In particular, research has shown that the onset of severe SarsCoV2 symptoms is due to an overreaction of our immune system, which hyperactivates self-defence processes in response to the virus, acting particularly aggressively on the lungs, heart and kidneys – the reason why severe patients require intensive medical treatment; in fighting the virus, their bodies damage vital organs.

Genetics and immunology are also the lenses of the latest Ceinge study. It looked at a dataset of 1121 people, divided into asymptomatic patients under 60 (587), asymptomatic patients over 60 (192), hospitalised patients (147) and negative cases (195). All individuals in the data set were infected in a small time window around March and April 2020, thus probably by the same viral strain. Examination of the genetic data from the sample identified three rare genetic mutations responsible for asymptomatic Covid 19 cases: Masp1, Colec10, Colec11; these are proteins related to cellular recognition. How can genetic mutations weaken our body’s response to an external virus and prevent the onset of typical disease symptoms? Our research shows that in the presence of certain genetic mutations, the genes involved in activating the immune response are less reactive and aggressive,” said Mario Capasso, professor of medical genetics at the University Federico II, who was directly involved in the research. This leads to an immune response to the virus that causes virtually no symptoms. Most of the asymptomatic individuals in the sample had one of the three genetic mutations responsible for this weakening of the immune response.

Ceinge’s research opens up new insights into the study of responses to the virus. Remarkable is the team’s decision to make the research data available online to all researchers worldwide as well as to civil society – an act of transparency of enormous value, all the more so as this is research of collective interest.

[Rossella Marvulli]

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