Project Title: Genetic Determinants of Susceptibility to Severe COVID-19 Infection
NIAID Principal Investigator: Helen Su, M.D., Ph.D
Chief, Human Immunological Diseases Section, LCIM
Why does COVID-19 cause only mild or no illness in some individuals, but severe or deadly disease in others?
The Human Immunological Diseases Section of the Laboratory of Clinical Immunology & Microbiology (LCIM) believes that the answer may lie in our genetic makeup. As a part of the COVID Human Genetic Effort Consortium, the lab will sequence and analyze the genomes of previously healthy patients who experienced severe or fatal COVID-19 infection. This genomic sequencing effort has two goals. First, we will look for rare or novel monogenic mutations that can leave an individual unable to fight off the virus. The Human Immunological Diseases Section will then use its expertise in functional validation to determine if these mutations compromise the cell’s ability to sense or control replication of SARS-CoV-2, the virus that causes COVID-19 disease. Sequencing priority will be given to patients who have a family history of consanguinity or have multiple severely affected family members. Where possible and potentially informative, sequencing will also be performed for family members. Second, for those patients in whom monogenic studies are unrevealing, the Human Immunological Diseases Section will undertake additional analyses across the entire cohort of severely ill COVID-19 patients as compared to the general population to look for multigenic variants that could contribute to susceptibility to severe disease.
Biocomputing support provided by NIAID Office of Cyber Infrastructure and Computational Biology, NIAID Collaborative Bioinformatics Resource, and NIH High Performing Computation (HPC) group / Biowulf cluster.
- Kyle Fahr, Illumina
This project will require one sample per patient. Whole blood (0.5 to 2 mL, the latter preferred if patient is leukopenic), frozen at -20˚C. Patients eligible for this study will 1) be less than 50 years old, 2) have been previously healthy, and 3) have experienced severe COVID-19 infection (characterized by an ICU admission for requirement of high-flow oxygen therapy, mechanical ventilation, or ECMO, or unusual complications). Younger patients, or patients with a history of consanguinity or multiple severely affected family members, will be prioritized. For monogenic cases in pediatric populations, samples from parents and/or affected family members, if available, may be requested for follow up genetic studies.