Genetic susceptibility to COVID-19 discovered step by step

Genetic susceptibility to COVID-19 discovered step by step

2023-09-21 17:45:35

It all started at the beginning of March 2020 when patients with serious infections due to COVID-19, the disease caused by the SARS-CoV-2 coronavirus, began to be admitted. The number of cases and deaths did not stop increasing. These were uncertain times and many questions arose, among them, why did some people experience COVID-19 with mild symptoms and others with severe symptoms? What made us susceptible to that virus?

Luis Bujanda, professor of Medicine at the University of the Basque Country (UPV/EHU), head of the Liver and Gastrointestinal Diseases Area of ​​the IIS Biodonostia- OSI Donostialdea, and Head of the Research Group of the Network Biomedical Research Center in the thematic area of Liver and Digestive Diseases (CIBEREHD) in Spain, as well as Beatriz Nafría, Pedro M. Rodrigues, Laura Izquierdo-Sanchez, Koldo Garcia-Etxebarria and Jesús M. Bañales, researchers from the aforementioned Area, have participated in a new study that delves into in the genetic bases of COVID-19. This work is a new link in a fruitful chain of international research in which Bujanda and his collaborators have participated over the last three years.

Three years ago, a group of international researchers, who were united by a great friendship with these IIS Biodonostia researchers (Dr. Karlsen from Norway and Dr. Frauke from Germany), decided to contribute their knowledge and work to try to help solve these great problems. questions about COVID-19. In less than four weeks, the project was written, presented and approved by the Euskadi Drug Research Ethics Committee (CEIm-E, April 8, 2020). The great help of Iciar Alfonso from CEIm-E in all these procedures was essential.

To draw relevant conclusions and in parallel, this group of researchers involved other friends (highly prestigious hepatologist researchers) from other centers in Spain (Vall d’Hebron Hospital and Clinic of Barcelona, ​​Hospital Ramón y Cajal of Madrid, Hospital Virgen del Rocío de Sevilla) and centers in Italy. In less than six weeks from the beginning of the idea and in the midst of a wave of admissions, in the first weeks of April 338 patients were recruited from the Donostia University Hospital. The samples were sent to Germany (to Dr. Andre Franke’s laboratory) and genotyped there to obtain information on genetic variants. In addition, for the study this group contributed 987 healthy subjects from the Basque Country who were also analyzed in Germany. Thanks to the efforts of researchers, nurses, healthcare doctors, laboratory technicians and clinical analysis doctors (Dr. Adolfo Garrido), this number of patients was achieved. With the money provided by the Stein Erik Hagen Foundation (Norway) and the group’s own funds, genetic analyzes were able to be carried out on the patients and the group of healthy people (control group).

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The first fruit of that collaboration was published in June 2020 in the academic journal New England Journal of Medicine. In this work, more than eight million genetic variants were analyzed from more than 1,600 patients with severe COVID-19 and more than 2,200 healthy people. Among the information collected, there was data obtained by IIS Biodonostia researchers.

The results of this study showed that there were two genetic regions that affected the severity of COVID-19: one was located in a region of chromosome 3 where several genes are located and the other in the region that determines the AB0 blood system. . It was the first study to be published on the genetic bases of COVID-19 and today it has more than a thousand citations, underlining the quality and impact that this pioneering work had.

Image obtained using a scanning electron microscope and subsequently processed, showing a cell infected with SARS-CoV-2 viral particles (shown in green), isolated from a patient sample. (Image: NIAID/NIH)

In addition, this group of researchers continued to collaborate to incorporate more patients, 590 until the end of 2020. They also managed to incorporate samples deposited in the Basque Biobank of the Galdakao, Cruces and Basurto Hospitals (573 patients in total), thanks to the help of their director, Roberto Bilbao and the doctors who deposited the samples from their respective hospitals.

The next step was to jointly analyze these data with patients from other places. Thus, the genetic variants of almost 50,000 COVID-19 patients and two million people without the disease from 19 countries were analyzed to discover the genes involved in both the susceptibility to contracting COVID-19 and the severity of COVID-19. 19. In total, 13 genetic regions were detected involved in the susceptibility to contracting COVID-19 and/or developing a severe form of the disease. Among these genetic regions were the two previously detected and several regions involved in lung, autoimmune or inflammatory diseases. In addition, smoking and body mass index were found to affect the severity of COVID-19. These results were published in the academic journal Nature.

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A latest work has recently been published, also in Nature, in which the results of the previous one are updated. On this occasion, almost 220,000 cases of COVID-19 and almost 3 million healthy people from 35 countries were analyzed. Thus, 51 genetic regions involved in susceptibility to COVID-19 and/or severity were detected, of which 28 were new. By including these new genetic regions, genes involved in virus entry, defense of the airway mucosa, and one of the immune response mechanisms were identified.

In addition to these works, the data obtained by the IIS Biodonostia researchers were analyzed in other studies, together with samples from other countries, in which other aspects of COVID-19 were analyzed in more detail. Thus, it was determined that some of these genetic variants affected differently depending on age, more in-depth and specific analyzes were carried out to determine the role of certain genes, or interactions that occur between genes that increase the risk of severity were detected. of COVID-19.

This entire line of work has led to advances in the knowledge of risk groups and how the disease develops, opening lines for prevention and the search for new treatments.

The COVID-19 pandemic posed a great challenge for both science and society in general. Everything that advances in knowledge entails was experienced in real time, with its successes and errors, carrying out a great exercise in the dissemination of scientific culture. The researchers, and all those who helped to achieve it altruistically, contributed these grains of sand and hope that these international collaborations continue to bear fruit, being aware of the responsibility that biomedical research has and the impact it has on society. This commitment to quality, international and responsible science reflects the professional and human quality of the researchers involved in these studies. (Source: UPV/EHU)

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