Thanks to the remarkable generosity of our Board of Overseers and many other donors, WCM is able to provide one-year grants of $100,000 to support innovative research on COVID-19. Congratulations to the following faculty members for receiving the first two COVID-19 Research Grants.
Patients of Black African ancestry across several countries are disproportionately affected by the COVID-19 pandemic. Despite being underrepresented among patients, individuals of Black African ancestry hospitalized with COVID-19 are more likely to fare worse in terms of symptom severity and mortality. Our study investigates the contribution of both genetic variation and obesity as key biological factors influencing these outcomes. We propose that a naturally occurring mutation in the ACKR1 gene impacts a wide range of inflammatory factors strongly influencing COVID-19 disease course. Specifically, the mutation (known as Duffy-null or Fy) causes a loss of DARC expression on red blood cells, the presence of which would otherwise serve to bind free-floating molecules that guide accumulation of inflammatory white blood cells. Thus, the Fy- mutation removes a buffering effect important to reducing systemic levels of tissue inflammation. Duffy-null is essentially ubiquitous among individuals of Sub Saharan African ancestry. Obesity, as a strong correlate of lower socioeconomic status, is also prevalent among the American- and European- residing Black African diaspora. Our study will reconcile COVID-19 clinical outcomes with inflammatory molecules, and white blood cell types found in the lungs, blood, bone and marrow. We will then analyze these data in light of demographic features such as race/ethnicity, and body mass index (a measure of obesity). Finally, we will also generate a mouse model that recapitulates the pathobiology associated both with the Fy mutation and obesity. Our study will improve our understanding of COVID-19 disparity, optimize our treatment strategies and may lead to improve therapies.
COVID-19 is a deadly global pandemic. Pregnant women make up a highly vulnerable patient population and data pertaining to the effects of COVID-19 infection throughout pregnancy and post-birth is limited. During pregnancy, the immune system is very unique and functions in a heightened state to defend the mother against severe illness, while maintaining a protected and tolerant environment for baby to grow and develop. Early COVID-19 studies indicate a low risk of transmission from mother to baby; however, it is not clear how pregnancy influences immune response to offer additional protective benefits in the presence of infection. To date, pregnant women remain as the only population undergoing universal COVID-19 testing with longitudinal care, therefore, presenting as a unique opportunity to identify a complete cohort to better study the infection and immune response. Here we propose to study the 1) prevalence, 2) how differences in the virus affect differences in infection, 3) and how the immune response and the placenta contribute to the wide range in clinical presentation in the infected patients. This comprehensive approach to study the many variables of the infection and response, on a vulnerable patient population with universal testing, will allow us to get a clearer understanding of the COVID-19 pandemic. The insights gained here will have universal impact on all patients, as these studies will impact clinical testing, elucidate potential drug targets, and guide clinical management of COVID-19 and many other infections.
As COVID-19 hospitalizations decline and US states prepare to return to work, many people are asking, “Am I protected from coronavirus infection?” The antibody test will identify those who recovered, but the WHO warned “there is currently no evidence that people who have recovered from COVID-19 and have antibodies are protected from a second infection”. Low antibody levels in some individuals suggest that cellular immunity, protective against viral infection, may also be important for recovery. An urgent need therefore emerges to find biomarkers of protection. Analyzing blood from WCM Healthcare workers in the NYP-WELCOME study who recovered from infection, we will isolate unique CD8 T cells that are highly protective and see pieces of virus proteins, called peptides, processed without the usual help of a protein called TAP. We know a large percentage of TAP-independent CD8 T cells use one dominant T cell receptor (TCR) to see virus peptides and kill infected cells. We will identify the dominant TCR for SARS-CoV-2 on TAP-independent CD8 T cells, and then use a specific antibody to look for it in the blood of other study participants. We will correlate the presence of this TCR with protection or disease. Because TAP-independent peptides are shared among different members of a single family of viruses, we will know whether having the TAP-independent CD8 TCR from a previous infection with common cold coronaviruses, confers pre-existing immunity to COVID-19. Identification of the TAP-independent coronavirus TCR will be a reliable biomarker for both pre-existing and post-infection immunity to COVID-19.