Racial Disparity in COVID-19 and the Role of Immunoglobulin Genes
Abstract
This project deals with COVID-19, which is caused by the virus named SARS-CoV-2, and thus it addresses the FY21 PRMRP Topic Area: Emerging Viral Diseases. There is tremendous variability from person to person and between different racial groups in the severity of the COVID-19 disease. Minorities are disproportionately affected by this disease. There are probably multiple factors that are responsible for this disparity. Several studies suggest that a patient’s genetic makeup may also, at least partially, contribute to the disparity in the severity of COVID-19 symptoms. People infected with SARS-CoV-2 make antibodies to protect themselves. These antibodies neutralize the virus and also mediate killing of the cells infected with the virus, thus preventing further spread. Some people generate highly potent antibodies while others do not. This ability is genetically/inherently controlled. This project will investigate certain genes of the immune system—called GM, KM, and FCGR—to assess whether they influence a patient’s ability to make antibodies to the virus and also kill the cells infected with the virus. These genes have many variants (alleles) and some are found in only a particular racial group. Thus, their evaluation may shed light on the racial disparity in COVID-19. An antibody molecule consists of two chains, heavy and light. Both chains have two regions, variable and constant. GM and KM genes are expressed on the constant region of heavy and light chains, respectively. SARS-CoV-2 is mutating/changing rapidly and generating variants. The currently available vaccines may need to be updated to protect from the variants, which are more infectious. Results from this project will be helpful in this endeavor. Evaluation of GM and KM genes is novel to this proposal, as they are not being investigated by any other research projects. This project will obtain patients’ blood and clinical data from a large COVID-19 biorepository. DNA from the blood will be isolated and typed for GM, KM, and FCGR genes, using DNA-based molecular methods. Serum from blood will be used to measure the antibodies against the virus’s spike protein, which latches the virus on human cells. Using appropriate statistical methods, this project will determine whether GM, KM, and FCGR genes—alone or in particular combinations—are associated with antibody responses to the virus, killing of the cells infected with the virus, and with the severity of the COVID-19 symptoms. Results of this investigation will aid in manufacturing therapeutic antibodies for personalized immunotherapy against COVID-19, by making different versions of the antibodies suited for people expressing different (FCGR) genes on their immune cells, called effector cells. An antibody expressing a particular GM gene could preferentially bind to a particular FCGR expressed by the patient’s effector cells, and thus be more efficient in killing the virally infected cells. This project will identify the most efficacious, racially associated combinations of GM and FCGR genes. A deeper understanding of the factors that influence immunity to the virus is imperative for updating active (vaccine) and passive (antibody) immunotherapy against the emerging variants of SARS-CoV-2.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210072
Entities
People
- Janardan P Pandey
Organizations
- Medical University of South Carolina
- United States Army