Impact of SARS-CoV-2 mediated salivary gland dysfunction on secreted salivary antimicrobial peptides and the risk for oral opportunistic infections

SARS-CoV-2介导的唾液腺功能障碍对分泌的唾液抗菌肽的影响以及口腔机会性感染的风险

• 批准号: 10594559
• 负责人: MARY ANN Y JABRA-RIZK
• 金额: $ 19.31万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10594559
• 关键词: 2019-nCoV; ACE2; Acinar Cell; Acinus organ component; Acute; Architecture; Atrophic; Biological; COVID-19; COVID-19 impact; COVID-19 patient; Candida; Candida albicans; Candidiasis; Cells; Chronic; Clinical Research; Data Set; Disease; Duct (organ) structure; Ductal Epithelial Cell; Epithelial Cells; Etiology; Exocytosis; Functional disorder; Goals; HIV; HIV Infections; Human; Immunoassay; Immunologic Factors; In Vitro; Individual; Infection; Inflammation; Inflammatory; Innate Immune System; Intercalated Duct; Light; Lymphocyte; Major salivary gland structure; Mediating; Minor salivary gland structure; Mucous Membrane; Mucous body substance; Opportunistic Infections; Oral; Oral Manifestations; Oral Ulcer; Oral candidiasis; Oral cavity; Oral health; Oral mucous membrane structure; Patients; Physiological; Process; Production; Reporting; Risk; Risk Assessment; Role; Rupture; SARS-CoV-2 infection; Saliva; Salivary; Salivary Glands; Secretory Vesicles; Serous; Serous Salivary Gland; Sialadenitis; Site; Symptoms; Tissues; Viral; Viral Load result; Xerostomia; antimicrobial peptide; cohort; histatin 5; histidine-rich proteins; immune activation; in vivo; inflammatory marker; insight; microbial colonization; novel; opportunistic pathogen; pathogenic fungus; patient population; post-COVID-19; receptor; saliva secretion; salivary cell; single-cell RNA sequencing; wound healing

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.

项目摘要 最近，发现COVID-19患者体内携带复制的SARS-CoV-2 唾液腺上皮细胞导致炎症、结构变形和小细胞萎缩， 和大唾液腺。我们以前已经证明了组胺素-5的重要性， 分泌型唾液抗菌肽专门产生于唾液腺，在保护 口腔对机会致病菌白色念珠菌。根据调查结果 表明COVID-19患者可能患有唾液腺功能障碍，我们假设 在COVID-19患者中，组胺素-5唾液水平受损， 这些个体长期机会性感染和其他口腔粘膜病症。在这 在拟议的临床研究中，我们将利用我们开发的免疫测定来证明 COVID-19对组胺素-5产生、念珠菌定植和诱导局部免疫的影响 activation.我们希望这些研究的结果能够提供缺乏机制的 深入了解COVID-19患者唾液腺功能障碍的病理生理学， 对口腔健康的影响。

项目成果

Long-Term Post-COVID-19 Associated Oral Inflammatory Sequelae.

• DOI: 10.3389/fcimb.2022.831744
• 发表时间: 2022
• 期刊: Frontiers in cellular and infection microbiology
• 影响因子: 5.7
• 作者: Alfaifi A;Sultan AS;Montelongo-Jauregui D;Meiller TF;Jabra-Rizk MA
• 通讯作者: Jabra-Rizk MA