Research Project: Uncovering Clues to COVID Associated Pulmonary Aspergillosis Mold Infection
COVID-19 Respiratory Virus Research Award
basic biologic mechanisms
Unlike most invasive mold infections, COVID Associated Pulmonary Aspergillosis (CAPA) occurs in individuals with otherwise intact immune systems. This suggests novel biological mechanisms make people susceptible to fungal infection. We seek to evaluate whether immune responses targeting intracellular viruses (viruses that live inside host cells) compromise the ability of the immune system to simultaneously control mold infection. First, we will determine how SARS-CoV-2 (the virus that causes COVID-19) renders people with normal immune systems susceptible to mold infection. Second, we will use a novel mouse model of CAPA to study how SARS-CoV-2 infection kills lung cells, recruits less immune cells, and promotes mold growth. We will also evaluate the utility of novel drugs to prevent the establishment of secondary mold infection. Our overall goal is to better understand why these infections occur in order to prevent their development in patients with an emerging viral respiratory infection.
We have found statistically significant increases in total airway iron, heme (a precursor to hemoglobin) and hemoglobin in samples from patients with severe COVID-19 versus bacterial pneumonia. We have also found evidence for a role for iron in promoting mold growth and are working to identify the lung source of excess airway iron during severe COVID-19 using lung epithelial cells and a novel CAPA mouse model. Experiments are also ongoing to determine if excess iron, heme and hemoglobin directly impair the ability of human neutrophils to kill mold spores.