Findings may help in vaccine design and therapeutics
People who become infected with the virus that causes COVID-19 experience a spectrum of outcomes, from no symptoms at all to severe disease leading to death.
The Frederick National Laboratory’s Basic Science Program is investigating whether variations in genes that control the immune system may influence the severity of COVID-19. This could help guide vaccine design and point to personalized treatment plans for patients.
FNL scientists are focusing on the human leukocyte antigen (HLA) molecules, which are central in developing immune responses to pathogens. HLA molecules present fragments of the virus to T cells, triggering either cellular killing or cytokine production.
Gene variations may influence disease severity
The genes encoding HLA molecules are extremely variable, with thousands of variants across humans. Several diseases and conditions, including cancer, transplantation outcome, and autoimmune and infectious diseases, have been associated with HLA variation. Given their central role in regulating the immune response, HLA genes are strong candidates for studying how a person’s genetics influence the outcome of COVID-19 infection.
The Basic Science team, led by Mary Carrington, Ph.D., is also studying other immune response genes, as well as genes encoding proteins interacting with SARS-CoV-2, such as ACE2 and TMPRSS2.
Worldwide collaboration adds power to research
The Basic Science laboratory is performing genetic analysis on DNA from individuals participating in a multidisciplinary study developed by the Massachusetts Consortium on Pathogen Readiness at Harvard University. They include hospitalized patients and home-care patients with active COVID-19, patients believed to be cured of COVID-19, healthcare staff with likely exposure to SARS-CoV-2, and individuals with likely community exposure to the virus.
The laboratory is also contributing data to the COVID-19 Host Genetics Initiative, an international collaboration among the human genetics community to share, generate, and analyze data. More than 190 studies are underway, with some participants conducting HLA genotyping. Carrington will combine her team’s data with those from other laboratories for meta-analysis, adding statistical power to results.