SARS-CoV-2 infection of salivary glands compromises the production of a secreted antifungal peptide with potential implications for development of oral candidiasis

• DOI: 10.1371/journal.ppat.1012375
• Publication Date: 2024-12-12T18:48:50Z
• Authors: Areej A. Alfaifi; Tristan W. Wang; Paola Perez; Ahmed S. Sultan; Timothy F. Meiller; Peter Rock; David E. Kleiner; Daniel S. Chertow; Stephen M. Hewitt; Billel Gasmi; Sydney Stein; Sabrina Ramelli; Daniel Martin; Blake M. Warner; Mary Ann Jabra-Rizk
• Keywords: 0303 health sciences; 03 medical and health sciences; Short Reports; QH301-705.5; Immunologic diseases. Allergy; RC581-607; Biology (General)

Saliva contains antimicrobial peptides considered integral components of host innate immunity, and crucial for protection against colonizing microbial species. Most notable is histatin-5 which exclusively produced in salivary glands with uniquely potent antifungal activity the opportunistic pathogen Candida albicans . Recently, SARS-CoV-2 was shown to replicate gland acinar cells eliciting local immune cell activation. In this study, we performed studies investigate implications infection on production colonization. Bulk RNA-sequencing parotid from COVID-19 autopsies demonstrated statistically significant decreased expression histatin amylase genes. situ hybridization, coupled immunofluorescence co-localization spike cells, showed that absent or minimally present replicating viruses. To clinical these findings, levels oral burden saliva samples three independent cohorts mild severe patients matched healthy controls were evaluated. Results revealed significantly reduced infected subjects, concomitant enhanced prevalence C. Analysis prospectively recovered indicated decrease likely reversible mild-moderate disease as concentrations tended increase during post-acute phase. Importantly, cytokine profiling correlations between activation Th17 inflammatory pathway, changes concentrations, subsequent clearance a heavily colonized subject. The importance controlling proliferation using an ex vivo assay where able proliferate low histatin-5, but not high histatin-5. Taken together, findings study potentially implicate compromised potential predisposition candidiasis.