PROJECT SUMMARY Recently, individuals with COVID-19 were found to harbor replicating SARS-CoV-2 inside salivary epithelial cells resulting in inflammation, architectural distortion, and atrophy of minor and major salivary glands. We have previously demonstrated the importance of histatin-5, a secreted salivary antimicrobial peptide exclusively produced in the salivary glands, in protecting the oral cavity against the opportunistic pathogen Candida albicans. In light of the findings indicating that COVID-19 patients likely suffer from salivary gland dysfunction, we hypothesize that histatin-5 salivary levels are compromised in COVID-19 patients potentially predisposing these individuals to long term opportunistic infections and other oral mucosal conditions. In this proposed clinical study, we will utilize our developed immunoassay to demonstrate the impact of COVID-19 on histatin-5 production, Candida colonization, and induction of local immune activation. We expect the findings generated from these studies to provide lacking mechanistic insights into the pathophysiology of salivary gland dysfunction in COVID-19 patients, and its implications on the health of the oral cavity.