They identify the genetic links behind the most serious covid-19

2023-05-17 17:00:15

Magazine Nature publishes this Wednesday an international study, led by the University of Edinburgh and with important Spanish participation, which has revealed multiple genetic mutations associated with an increased risk of severe covid-19, and which has identified possible new therapeutic targets to treat the infection. Numerous Spanish research centers, universities and hospitals have been part of this work.

The Carlos III Health Institute (ISCIII) has been involved in the study in various ways: it has financed part of its development through the covid-19 Fund, it has had the presence of various groups and areas of the Online Biomedical Research Consortium (CIBER) and has added the collaboration of researchers from its National Center for Microbiology. The results of the work point to 49 genetic alterations, 16 of which had not been discovered Until now.

The alterations affect a total of 149 genes. Some of the identified mutations could be used to develop new therapies i

These alterations affect a total of 149 genes, and the authors point out that some of the identified genetic mutations could facilitate the development of new immunomodulatory therapies against the infection.

Among these possible therapeutic targets, a total of 114, are the KAK1, PDE4A, SLC2A5, AK5, TMPRSS2 and RAB2A genes, related to functions such as inflammatory signalingthe activation of immune cells such as macrophages, the metabolism of the immune system and the viral replication.

The identification of these variants has been possible thanks to a genome-wide association study (GWAS) and the analysis of close to a million genetic variations known as single nucleotide polymorphisms (SNPs). The comparison of the data obtained in patients with severe covid, patients with mild disease and healthy people has allowed us to achieve new knowledge about susceptibility to different phenotypes, confirming the relevance that genetics has in the prognosis and severity of the infection and opening the door to the discovery of possible new therapies.

The results confirm that therapeutic strategies based on the drug repositioningthat is, in the use of drugs already applied to other diseases and that could be effective in treating covid, may represent a particularly promising line of study.

Spain provides data from almost 6,000 patients

The research has worked with data from the complete genome sequencing of more than 24,200 patients with severe covid-19, thanks to data obtained from various international initiatives, including the SCOURGE project, which has provided data from almost 6,000 Spanish patients.

SCOURGE, which emerged in Spain in 2020 thanks to financing from the ISCIII covid-19 Fund, and which has funds from the Amancio Ortega Foundation and Banco de Santander, has had the participation of more than 400 Spanish hospitals and research centers and Latin American countriesica.

The research has worked with data from the complete genome sequencing of more than 24,200 patients with severe covid-19

The genome-wide association study carried out by the SCOURGE consortium, which has included close to 20,000 million genotypes, was carried out at the Galician Public Foundation for Genomic Medicine node of the National Genotyping Center (CEGEN), and the analysis The statistical analysis was carried out at CIMUS (Universidad de Santiago) with the support of ITER of Tenerife. The consortium has been led by researchers Angel Carracedofrom CIBER-ISCIII and from the University of Santiago de Compostela, and paul lapunzinaalso from CIBER-ISCIII and the Health Research Institute of Hospital La Paz.

Both researchers state that the results published in the article by Nature They represent a new advance in the understanding of the involvement of genetics in the course of covid-19. Carracedo points out: “The statistical analysis of the data and the use of new models of association of complete transcriptomes (TWAS) and Mendelian randomization have been key to the results; In this sense, the role of Rachel Cruz y Silvia SaysCIBERER and CIMUS-USC, and other collaborators trained at USC and who now work in other leading research centers around the world”.

For her part, Lapunzina explains that this work “is further evidence that the collaborative work of a huge number of professionals, from many centers in the country and abroad, is necessary to reach conclusions of scientific relevance that result in a better health decision making”. As he adds, the SCOURGE consortium, funded by the ISCIII, “has made a great contribution to this work and will continue to provide scientific evidence in the multiple associated subprojects over the coming years.”

Reference:

K. Baillie et al. “GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19”. Nature (mayo, 2023).

Rights: Creative Commons.