This Rapid Response Research (RAPID) award supports research to understand virus-host interactions that may lead to increased morbidity in COVID19 patients with pre-existing inflammatory conditions. Current data suggests that of all US patients with COVID-19, 74% had pre-existing hypertension, and 30% had diabetes. A key feature COVID-19 is acute respiratory distress syndrome (ARDS), which is caused by the infiltration of monocyte/macrophages (MOs). Monocyte/macrophages are key members of the innate immune system that maintain tissue homeostasis. This is because they phagocytose foreign pathogens and dying cells, and this stimulates with the adaptive immune system to make antibodies. However, it is not well-understood how monocyte/macrophages are affected by SARS-CoV-2 infection, the causative agent of COVID-19. The goal of this study is to understand how SARS-CoV-2 exacerbates monocyte function in monocytes from healthy individuals as compared to individuals with diabetes. Results from this research may identify therapeutics to minimize COVID-19 disease. This research involves several disciplines including immunology, virology, and biomedical engineering. This multi-disciplinary approach will help broaden participation of under-represented groups in research, as well as contribute to the immunological study of COVID-19 health disparity populations. This proposal also supports the training of a post-doctoral fellow, a graduate and undergraduate student.
There are clinical observations of high monocyte/macrophage activation observed in COVID19 patients. However, the intracellular events that lead to this activation are unknown. This project will build on existing measurements of SARS-CoV-2 infection from other cell types, and now provides vital missing information about monocyte/macrophage functions and responses to infection. The objective of the research is to determine (1) the contributions of healthy and diabetic monocytes to SARS-CoV-2 infection-induced cytokine release storms, and (2) the global role of virus-host interactions with key receptors on monocytes that are dysregulated (upregulated or downregulated expression compared to normal physiological function). The study will increase the knowledge of how impaired macrophage functions from diabetic people may affect outcomes of COVID-19 disease. Results from this study can help aid the development of desperately needed therapies for COVID-19. This RAPID award is made by the Physiological and Structural Systems Cluster in the BIO Division of Integrative Organismal Systems, using funds from the Coronavirus Aid, Relief, and Economic Security (CARES) Act.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
