An international study identifies new genetic variants related to severe covid-19
The investigation, participated by IDIAPJGol researchers, associates for the first time genetic variants previously related to heart disease, thrombosis and inflammation with the severity of covid-19
The CARGENCORS study (CARdiovascular GENetic risk score for Risk Stratification of patients positive for SARS-CoV-2 (COVID-19) virus) has made it possible to establish a direct relationship between some of the genetic factors that increase the risk of heart disease and severity of covid-19. The work, published by the Journal of Medical Virology, marks a further step towards understanding the mechanisms of severity of covid-19 through susceptibility to heart disease.
The mechanisms used by the virus that causes covid-19, SARS-CoV-2, to enter the host’s cells are well known, as well as its ability to cause cardiovascular, thrombotic complications and the hyperinflammatory syndrome. However, the mechanisms involved in the severity of the disease are not fully understood. As explained by Dr. Jaume Marrugat, coordinator of the REGICOR group (Registre Gironí del Cor) and main researcher of the study and of the Hospital del Mar Research Institute, “since the beginning of the pandemic we knew that patients with covid-19 with pre-existing cardiovascular risk factors, such as advanced age, male sex, hypertension, obesity, diabetes or an overt cardiovascular disease had a higher risk of suffering serious manifestations of covid-19. This led us to analyze what role the genetic variants that had previously been related to heart disease, thrombosis and inflammation played on the severity of the disease.”
The study was designed with the objective of analyzing whether genetic variants previously related to heart disease, thrombosis, inflammation, and viral infectivity were associated with the severity of covid-19. The results were verified in two external populations, with a meta-analysis that used data from the SCOURGE cohort in Spain and the UK Biobank in the United Kingdom. CARGENCORS has been led by researchers from the Hospital del Mar Research Institute, the University of Girona, the Girona Biomedical Research Institute Dr. Josep Trueta (IDIBGI), the Girona University Hospital Doctor Josep Trueta, the Institut d’Investigació en Atenció Primària Jordi Gol i Gurina (IDIAPJGol), and the University of Vic – Central University of Catalonia.
3,000 people analyzed
The study was designed during the first weeks of the pandemic and managed to recruit more than 3,000 covid-19 patients between 35 and 74 years old, before the start of vaccination, between the years 2020 and 2021. Some of these people had suffered severe covid-19, which had required hospitalization and oxygen therapy. These people were included in the study as an intervention group. The rest were asymptomatic infected persons or with mild or moderate symptoms treated at home, who constituted the control group.
In the first phase of the study, fourteen new genetic variants associated with the severity of covid-19 were identified. In addition, eight previously described variants related to the infectivity and severity of covid-19 were confirmed. In the meta-analysis of the three cohorts (CARGENCORS, SCORUGE, UK Biobank), the association of four variants related to two genes linked to infectivity (ACE2 and TMPRSS2) and the severity of the disease was confirmed. In addition, the importance of a variant previously related to heart disease, which is found in the genomic region between the VAMP5 and VAMP8 genes, was also established for the first time. These two genes are involved in several processes related to the trafficking of vesicles, including the release of cytokines (inflammatory factors) and phagocytosis (the mechanism by which some blood cells swallow germs and potentially harmful materials). Previous studies had already linked this variant with IL-6 levels and some heart diseases.
These results highlight the influence of genetic variation on the severity of covid-19. People who had a single risk allele of one of these variants presented an increase of between 10 and 60 % in the probability of developing a serious disease. As stated by Dra. Irene Román Dégano, co-principal investigator of the study, “this work highlights the need to continue exploring genetic factors in the severity of covid-19 and presents possible candidates for future genetic risk scores for risk stratification, which could guide screening, the reinforcement of the vaccine, or the prioritization of patients to receive new antiviral therapies.”
The Intensive Medicine, Infectious Diseases, Internal Medicine, and Cardiology services of the Hospital del Mar have also collaborated in the work, as well as the CIBER of Cardiovascular Diseases (CIBERCV), the CIBER of Fragility and Healthy Aging (CIBERFES), of CIBER for Rare Diseases (CIBERER), and CIBER for Infectious Diseases (CIBERINFEC).
Reference of the paper
Anna Camps-Vilaró, Mel·lina Pinsach-Abuin, Irene Roman Degano, Rafel Ramos, Ruth Martí-Lluch, Roberto Elosua, Isaac Subirana, Clàudia Solà-Richarte, Marta Puigmulé, Alexandra Pérez, Ingrid Vilaró, Raquel Cruz, Silvia Diz-de Almeida, Xavier Nogues, Joan Ramon Masclans, Roberto Güerri-Fernández, Judith Marin, Helena Tizon-Marcos, Beatriz Vaquerizo, Ramon Brugada, Jaume Marrugat. Genetic characteristics involved in COVID-19 severity. The CARGENCORS case-control study and metaanalysis. J Med Virol. 2024;96:e29404.
