It is now known that risk factors such as older age, male sex and previous illnesses play an important role in determining the severity of Covid-19 disease. So why do some people who have contracted the SARS-CoV-2 infection develop an asymptomatic form, despite having one or more risk factors? The answer is in the DNA. According to what was discovered by a research team of the Ceinge Biotechnologies advanced in Naples, directed by Mario Capasso and Achille Iolascon, professors of medical genetics at the University of Naples Federico II, some genetic mutations predispose to asymptomatic forms of Covid-19 rare that weaken the genes involved in the activation processes of the body’s immune response.
“Today – Prof. Capasso explains to NapoliToday – it is widely demonstrated that the excessive immune response to SARS-CoV-2 infection and the subsequent hyper-activation of pro-inflammatory and pro-coagulative processes are the main cause of the damage to organs such as lungs, heart, kidney, etc. Our research shows that mutations in the human genome that attenuate this excessive immune reaction can predispose to an infection without severe symptoms. ” The Neapolitan study was published in the international scientific journal Genetics in Medicine.
Prof. Capasso, what are these genetic factors that predispose to asymptomaticity?
“The genetic factors we have identified are rare DNA mutations that can be inherited from generation to generation and which represent a part of the complex genetic picture associated with the less clinically severe development of Covid-19. Other international research groups are contributing, in parallel, to identify genetic variants linked to the predisposition of more or less aggressive phenotypes of Covid-19 to explain this complicated enigma that characterizes the human genome “.
What is the link between these genetic factors and the immune response triggered by SARS-CoV-2 infection?
“The identified mutations alter the function of three genes MASP1, COLEC10, COLEC11 belonging to the lectin family that are activated to fight viral and bacterial infections. However, SARS-CoV-2 infection causes an excessive response of these genes which results in severe inflammation and activation of blood clotting. Our research group has shown that there are rare mutations in these genes that can mitigate the excessive inflammatory response and protect against severe Covid-19 ”.
What intuition started the research?
“We had a first intuition of studying asymptomatic patients in May 2020 when we realized that among the infected in the Ariano Irpino population there were elderly subjects who, despite having clinical risk factors, did not develop severe forms of the disease. We therefore decided to study the DNA of this population, and thanks to the contribution of Dr. Cerino Pellegrino of the Zooprophylactic Institute of Portici and Prof. Massimo Zollo, coordinator of the COVID task force of Ceinge, we have started a massive collection of biological samples. to be sequenced. In addition to the enormous effort made to sequence around 800 samples in such a short time, we then had to perform bioinformatics analyzes of an enormous amount of genetic data to identify, among hundreds of thousands of mutations, those actually associated with the asymptomatic phenotype. This was made possible thanks to the team of bioinformatics of CEINGE, directed by me, and in particular to Dr. Giuseppe D’Alterio, a young researcher who is pursuing a doctorate in bioinformatics from the European School of Molecular Medicine ”.
How will this discovery affect future diagnostic and therapeutic approaches?
“In the future we could exploit these mutations in combination with others identified by other research groups, to generate a polygenic value capable of identifying in the general population who is predisposed to develop a severe Covid-19 or an asymptomatic Covid. Furthermore, thanks to this research we have increased our knowledge on the biological processes that underlie the immune response to SARS-CoV-2 infection. Therefore, we could think of developing drugs that inhibit severe inflammation by targeting the genes we have identified when their levels in the blood are excessively high. The measurement of the amount of expression of the same genes could also function as a potential prognostic factor in the aggravation of the disease “.
Next research goals?
“Our goal is to continue unraveling the genetic basis of the various clinical degrees of Covid-19 disease which, like all complex traits, are determined by a combination of multiple genetic factors. I imagine Covid-19 as a painting made up of many colors and a myriad of shades, our role is to understand what these colors are and how they integrate with each other in forming this complex design. So it is clear that we still need a lot of research to fully understand this disease and to have a practical-clinical implication of our discoveries “.