Scientists based in Italy studying the exomes of patients with COVID-19 identified links between genetic and molecular markers and susceptibility to infection, as well as disease severity. Presenting at the European Society of Human Genetics on Saturday, June 6, the researchers with the GEN-COVID project identified a number of common susceptibility genes that were linked to a favorable or unfavorable course of disease.
The GEN-COVID team based at the University Hospital of Siena, Italy performed whole exome sequencing (WES) on 130 patients with COVID-19 to try to find any genetic causes for differences in clinical outcomes. The group’s larger plan is to collect and analyze 2,000 patient samples.
The group first looked for common genes in affected patients against a control group but that approach did not reveal many significant differences. Moving forward, they focused solely on COVID-19-affected patients, trying to identify genetic differences with clinical outcomes. Using that study form, for each patient the team identified an average of three disease-causing mutations involved in COVID-19 susceptibility.
“This result was not unexpected, since we already knew from studies of twins that Covid-19 has a strong genetic basis,” said GEN-COVID’s team leader Professor Alessandra Renieri, Director of the Medical Genetics Unit at the University Hospital of Siena.
Understanding the genetic profile of patients may allow the repurposing of existing medicines for specific therapeutic approaches against COVID-19 as well as speeding the development of new antiviral drugs. The team also hopes that by identifying any links between genetic information and patients at higher risk for severe disease and their likely response to specific drugs will help guide treatment strategies.
The group intends to compare these preliminary results with traditional genome-wide association studies (GWAS) in the context of the COVID-19 Host Genetics Initiative. That project, which currently includes 187 registered studies, invites the human genetics community to generate, share, and analyze data to learn the genetic determinants of COVID-19 susceptibility, severity, and outcomes.
Launched in March 2020, GEN-COVID is a network of more than 20 Italian Hospitals led by Professor Renieri. The intent is to collect a detailed patient registry and biobank of 2,000 samples to develop a genetic-based approach to understand the clinical variability of COVID-19. This involves an understanding of the genetic and molecular basis of susceptibility to SARS-CoV-2 infection.
Their specific goals include perform genotyping (GWAS) at the Institute for Molecular Medicine in Finland and whole exome sequencing (at the University of Siena) on these 2,000 samples.
Additionally, they are sharing phenotypic data and samples across the GEN-COVID network platform as well as in cooperation research institutions and national platforms through the GEN-COVID Disease Registry and Biobank, which will be available to academic and industry partners.