Immune mediated lung injury in COVID-19

SARS-CoV-2 and the disease it causes (COVID-19) has emerged as a major global public health threat in the span of a few months. In particular, SARS-CoV-2 adds to the present number of acute respiratory infections, including influenza and bacterial pneumonia, which are endangering the health of our veterans and aging population. In particular, severe COVID-19 disease is characterized by severe lung injury, which results in severely impaired oxygen delivery and ultimately multiple organ failure and death. Our ongoing research has focused on a population of white blood cells called neutrophils, which are the most abundant white blood cell in our body and which have been shown to be a pivotal immune cell that contributes greatly to lung injury. However, our current medical knowledge is inadequate for understanding what neutrophils do in the context of viral infection. Although neutrophils are critical for eliminating many types of infections, they are believed to be a major contributor to the development of lung injury, and how to balance their beneficial activities with their harmful functions is poorly understood. Therefore, a better understanding of how neutrophils behavior and phenotype are altered during severe SARS-CoV-2 and other viral infections would aid in developing novel therapies to improve their antimicrobial functions, while limiting their injurious effects. The research we propose in this grant will examine how well neutrophils eliminate SARS-CoV-2 viruses, or if they are an excessively activated population of immune cells recruited to the lung whose harmful activities outweighs their benefits. We also will test an exciting new treatment approach developed by our collaborator at UCLA to see if this can block the damaging effects of neutrophils on lung cells, while blocking viral replication. The results of this 2-year project will provide insights into the beneficial versus harmful contributions of neutrophils in the development of severe COVID-19 disease, and potentially identify new therapies to benefit veterans and other vulnerable patients.