Understanding the pathogenesis of COVID-19

Pulmonary infections by viruses such virulent Severe Acute Respiratory Syndrome (SARS) coronavirus (CoV) and Middle East Respiratory Syndrome (MeRS) CoV associated with significant morbidity and mortality. Clinically, infections by these viruses are associated with a pronounced lung inflammation, causing respiratory problems that often develop in secondary pneumonia. Inflammation is the result of immune activation in response to infection. When activation is too pronounced or sustained for extended periods of time, complications occur. Two main mediators of inflammation are known: Cytokines and lipid mediators of inflammation (LMI). In the current proposal we will study the inflammatory response during infection/exposure of lung and blood cells to the newly described COVID-19 and compare this response to that of SARS-CoV-2 and MeRS-CoV to obtain correlates of pathogenicity between these viruses. We will use primary lung cells and white blood cells from donors to conduct our studies. The mediators of inflammation will be identified and quantitated using state of the art methodology available in our laboratories. More than 200 LMI and 150 cytokine/cytokine receptors will be examined. Upon completion of this proposal, a detailed analysis of the response of primary epithelial cells and leukocytes to COVID-19 will be obtained, enabling the rational design of therapeutic strategies to help combat COVID-19.