The journal Nature publishes this Wednesday an international study, led by the University of Edinburgh and with significant Spanish participation, which revealed multiple genetic mutations associated with an increased risk of severe covid-19, and which identified possible new therapeutic targets to treat the disease. infection. Numerous research centers, universities and Spanish hospitals were part of this work.
The Instituto de Saúde Carlos III (ISCIII) has been involved in the study in several ways: it financed part of its development through the Covid-19 Fund, had the presence of several groups and areas of the Online Biomedical Research Consortium (CIBER) and had the collaboration of researchers from its National Microbiology Center. The results of the work point to 49 genetic alterations, 16 of which had not been discovered until now.
The changes 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 genetic mutations identified may 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 signaling, activation of immune cells such as macrophages, metabolism of the immune system and virus replication .
The identification of these variants was possible thanks to a genome-wide association study (GWAS) and the analysis of about one million genetic variations known as single nucleotide polymorphisms (SNPs). The comparison of data obtained from patients with severe covid, patients with mild disease and healthy people 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 doors to the discovery of possible new therapies.
The results confirm that therapeutic strategies based on drug repositioning, that is, on the use of drugs already applied in other diseases and that could be effective in the treatment of covid, may represent a particularly promising path of study.
Spain provides data on nearly 6,000 patients
The research worked with data from the complete genome sequencing of more than 24,200 patients with severe covid-19, thanks to data obtained from several international initiatives, including the SCOURGE project, which provided data from almost 6,000 Spanish patients.
SCOURGE, which emerged in Spain in 2020 thanks to funding from the ISCIII Covid-19 Fund, and which has funds from the Amancio Ortega Foundation and Banco de Santander, involved the participation of more than 400 hospitals and research centers in Spanish countries. and Latin Americans.
The research worked with data from the complete genome sequencing of more than 24,200 patients with severe covid-19
The genomic association study carried out by the SCOURGE consortium, which included approximately 20,000 million genotypes, was carried out at the Galician Public Foundation of Genomic Medicine node of the National Genotyping Center (CEGEN), and the statistical analysis was carried out at CIMUS (Universidade from Santiago) with the support of ITER from Tenerife. The consortium was led by researchers Ángel Carracedo, from CIBER-ISCIII and the University of Santiago de Compostela, and Pablo Lapunzina, also from CIBER-ISCIII and the Health Research Institute of Hospital La Paz.
Both researchers claim that the results published in the Nature article represent a new advance in understanding the involvement of genetics in the course of covid-19. Carracedo points out: “The statistical analysis of the data and the use of new association models of complete transcriptomes (TWAS) and Mendelian randomization were fundamental for the results; In this sense, the role of Raquel Cruz and Silvia Diz, from CIBERER and CIMUS-USC, and other collaborators trained at USC and who today work in other prominent research centers in the world, stands out”.
For her part, Lapunzina explains that this work “is yet another proof that the collaborative work of a large number of professionals, from various centers in the country and abroad, is necessary to reach conclusions of scientific relevance that result in a better decision making. of decision in health. As he adds, the SCOURGE consortium, financed by 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”.
K. Baillie et al. “GWAS and meta-analysis identify 49 genetic variants underlying critical COVID-19.” Nature (May 2023).