Who risks more with Covid? Who is predisposed to aggravate? How to cure these people? – time.news

by time news

Studies by the Italian Consortium of Genomic Analysis help to understand which genetic factors influence why some patients develop serious and life-threatening diseases, while others “get away with” mild symptoms or are even asymptomatic

Although effective vaccines against Covid-19 and the serious disease induced by the virus are now less scary, there are many unknowns to be discovered about SARS-CoV-2 and how it works in our body. In particular, it remains current to understand which people are most at risk and what characteristics make them such, to decide how to best protect them, perhaps studying for them “personalized” drugs.

Genetics play a prominent role in these studies because it helps pinpoint which genes may make people more vulnerable to the virus. There are several, which are added to the known risk factors that aggravate Sars-CoV-2 infection (such as advanced age and concomitant diseases such as diabetes, obesity, respiratory problems) and constitute what can be defined as a “Genetic predisposition” which drives the body’s “abnormal” (or insufficient) reaction to the coronavirus.

The GEN-COVID consortium is made up of doctors from 40 Italian hospitals, physicists, mathematicians, data scientists and artificial intelligence experts. Professor Alessandra Renieri, Professor of Medical Genetics at the University of Siena and director of the UOC of Medical Genetics of the Sienese University Hospital, which coordinates the work of the group, explains the objectives of the consortium.

“The GEN-COVID consortium was born in March 2020 with the aim of decoding the rules of the genetics of each one that govern the reaction to Covid-19. Knowledge of medicine, biology and mathematics are essential in this undertaking, because we must retrace the path that Mendel made 155 years ago, when he postulated the guidelines still used today to encode rare diseases. The difference is that, in this case, not a single gene is involved (as in rare diseases), but many geniuses which, when combined, determine different pathways of disease in different groups of patients. 18 months after its foundation, GEN-COVID has opened a negotiation with AIFA (the Italian Medicines Agency, ed) for a CLINGEN-COVID clinical trial platform for the treatment of Covid, based on the selection of patients based on genetic characteristics “.

What does this mean in practice?

«Knowing our genes is a valuable aid to therapy. Deciphering the genetic code is not easy and you need knowledge not only of genetics, medicine (most medical specialties are involved) and biology, but also of mathematics and artificial intelligence. For this reason, the GEN-COVID consortium is made up of an interdisciplinary team that is working on perfecting the DNA reading of each of us who help in disease prediction and in the analysis-discovery of more suitable therapies. The road has been opened and there are already practical repercussions, but there is still a lot to do ».

How does the consortium work?

«The enrollment of clinical centers is on a voluntary and continuous basis. The consortium is open to the inclusion of physics, mathematics and engineering professors and doctoral students. The activity report was recently presented (on 21 October 2021), with an invitation reading, at the international conference: “ASHG meeting 2021 American Society of Human Genetics”. The reading of the genetic code of the patients, during the hospitalization, gives us the information for the drugs that can determine their recovery. These drugs are not the same for all patients Covid. Clinical trials (trials) on caseloads of groups of patients enrolled without taking into account genetics and disease mechanisms have so far been unsuccessful, because the drug was effective only on a part of the patients, resulting in negative statistics ».

What “culprit” genes have been identified, for example, and how is this knowledge used in clinical practice?

“For instance, some males they have a defect in the RNA sensor of the virus. It is called TLR7. The organism does not immediately feel that the virus has arrived and does not activate the first defense barrier (innate immunity). The TLR7 gene is on the X chromosome and the females who have this defect have the second chromosome with the active compensating gene, so they are still fine, even when infected. The seriously ill are the males. Knowledge of this anomaly in patients allows treatment with interferon (the key molecule of innate immunity). Other subjects, always males, have a protein (Selectin P) that triggers blood clots too easily in the blood vessels. It is mainly about men over 60 or with less active testosterone receptors and a high laboratory value of (D-dimer) which is the signal for the presence of thrombosis. For these patients, negotiations have been initiated with Novartis to obtain Crizanlizumab, a monoclonal antibody against Selectin P, which would be of great help in the treatment of acute infection ».

Other implications of this knowledge in the immediate future?

“Knowing our genes sometimes also helps to understand which drug we should not take. A group of males who have another defective viral RNA sensor (TLR3) induces little autophagy (which is a defense mechanism). Treatment with Chloroquine reduces autophagy, so this drug is not recommended in this type of patients. Unfortunately, when the clinical trials with Chloroquine were done, the patients were not selected in the correct way, because this knowledge was not there and the drug was put into disuse ».

With the spread of vaccines, the presence of monoclonal antibodies and the hope of the first antiviral to come, what are the prospects for this type of study? How do they integrate into drug research against Covid?

“The vaccine decreases the likelihood of serious illness and infection. Monoclonal antibodies are an aid in a very early stage of the disease. Antivirals fire on the virus by reducing its charge inside the cells. Personalized adjuvant therapy based on genetic markers, on which the GEN-COVID consortium works, is useful in cases where all these barriers have been forced and the process of organ damage. It is therefore a concrete objective for the help of those who are still hospitalized and risk your life. We ask that the drug agency AIFA adopt a more modern yardstick for the approval judgment of clinical trials. Many of the drugs we are proposing are already on the market (except Crizanlizumab) and therefore validated for some time for safety. The novelty lies in proposing the right drug to the right patient on the basis of how his own organism was “built” ».

October 28, 2021 (change October 28, 2021 | 07:31)

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