Since the SARS-CoV-2 coronavirus pandemic began, scientists have been investigating to discover why some people who contracted the infection were asymptomatic, while others developed a severe form of the disease or died from it. Now, a study carried out by an international team in which the La Paz University Hospitalfrom Madrid, has identified 49 genetic variations directly related to a increased risk of severe COVID-1916 of which have not been discovered until now.
Researchers have also found potential therapeutic targets that could favor the development of new treatments, since the results of the work confirm that using drugs that are already used to treat other diseases and that could be effective against COVID-19 can be a very promising strategy.
The research has been led by the University of Edinburgh and has been carried out thanks to the data provided by three international consortia, one of them SCOURGE, which is funded by the Carlos III Health Institute (ISCIII) and in which numerous hospitals participate. and Spanish research centers. The consortium has been coordinated from the ISCIII Network Biomedical Research Center (CIBER) by Angel Carracedo (University of Santiago de Compostela (CIMUS) and the Health Research Institute of Santiago I (DIS) and by paul lapunzina of the Health Research Institute of the La Paz University Hospital (IdiPAZ).
Genetics are key in coronavirus infection
The results of this international study have been published in Nature and show that 49 genetic alterations that affect a total of 149 genes predispose to developing severe COVID-19. In addition, according to the authors, some of the genetic mutations identified could help develop new immunomodulatory therapies against coronavirus infection.
The results of the study confirm the great importance of genetics in the prognosis and severity of COVID-19 and open up promising avenues for finding new therapeutic options.
Among these potential therapeutic targets – a total of 114 – the KAK1, PDE4A, SLC2A5, AK5, TMPRSS2 and RAB2A genes stand out, which are related to functions such as inflammatory signaling, activation of immune cells such as macrophages, metabolism of the immune system and viral replication.
The researchers have used data from the genome-wide association study of more than 24,200 patients with severe COVID-19, thanks to data 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 the financing of the ISCIII COVID-19 Fund, and which has COVID funds from the Amancio Ortega Foundation and Banco de Santander, has had the participation of more than 400 hospitals and Spanish research centers and Latin American countries.
Researchers have compared data from patients with severe COVID-19, patients with mild disease, and healthy people, allowing them to better understand the susceptibility to different phenotypes of COVID-19and has confirmed the great importance of genetics in the prognosis and severity of this disease and has opened up promising avenues for finding possible new therapies.
Ángel Carracedo and Pablo Lapunzina state that the results published in the article by Nature represent a new advance in the understanding of the implication of genetics in the course of COVID-19. “The statistical analysis of the data and the use of new whole transcriptome association (TWAS) models and Mendelian randomization have been key to 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 now work in other leading research centers around the world is noteworthy”, stated Carracedo.
Lapunzina, for her part, explains that this study “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 ISCIII-funded SCOURGE consortium “has made a great contribution to this work and will continue to provide scientific evidence in the many associated subprojects over the next few years.”
Source: Health Research Institute of the La Paz University Hospital (IdiPAZ)