Spliid Charlotte B, Mehta Sanjay, Fuster Mark M, Martino Cameron, Morris Claire L, Lee Nharae, Florentino Ivan, Tong Khang, Liu Lin, Ackermann Gail, Knight Rob, Esko Jeffrey D, Hurtado de Mendoza Tatiana
Department of Cellular and Molecular Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0687, United States.
Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-9111, United States.
Glycobiology. 2024 Dec 10;34(12). doi: 10.1093/glycob/cwae084.
The human oral cavity and upper airway serves as an early barrier and reservoir in the transmission of SARS-CoV-2. Saliva in this microenvironment may serve as a key host factor that can modulate susceptibility to infection and eventual infection of the lower respiratory tract. We sought to analyze the content and composition of heparan sulfate, a glycosaminoglycan identified as an important co-receptor for viral entry, and whether there is any correlation with SARS-CoV-2 infection. We enlisted 98 participants stratified by age, gender, race, and COVID-19 history. Notably, the concentration of heparan sulfate in saliva increased with age, and its composition showed a wide range of variability within each age group independently of age. Heparan sulfate concentration and composition did not differ significantly with gender, ethnicity or race. Compared to patients with no COVID-19 history, patients with previous infection had a similar salivary heparan sulfate concentration, but significant increases in overall sulfation were noted. Moreover, in a subset of participants, for which data was available pre- and post- infection, significant elevation in N-sulfoglucosamine in heparan sulfate was observed post- COVID-19. Examination of salivary bacterial 16S rRNA, showed a significant reduction in species predicted to possess heparan sulfate-modifying capacity among participants >60 years old, which correlates with the increase in heparan sulfate content in older individuals. These findings demonstrate a surprisingly wide variation in heparan sulfate content and composition in saliva across the sampled population and confirm other findings showing variation in content and composition of glycosaminoglycans in blood and urine.
人类口腔和上呼吸道是严重急性呼吸综合征冠状病毒2（SARS-CoV-2）传播的早期屏障和储存库。这种微环境中的唾液可能是一个关键宿主因素，可调节对感染的易感性以及最终下呼吸道感染情况。我们试图分析硫酸乙酰肝素（一种被确定为病毒进入重要共受体的糖胺聚糖）的含量和组成，以及它与SARS-CoV-2感染是否存在任何关联。我们招募了98名按年龄、性别和种族以及新冠病毒疾病（COVID-19）病史分层的参与者。值得注意的是，唾液中硫酸乙酰肝素的浓度随年龄增长而增加，并且其组成在每个年龄组内都有很大的变异性，与年龄无关。硫酸乙酰肝素的浓度和组成在性别、民族或种族方面没有显著差异。与无COVID-19病史的患者相比，既往感染过的患者唾液中硫酸乙酰肝素浓度相似，但总硫酸化程度显著增加。此外，在一部分有感染前和感染后数据的参与者中，COVID-19感染后观察到硫酸乙酰肝素中N-磺基葡糖胺显著升高。对唾液细菌16S核糖体RNA（rRNA）的检测显示，在60岁以上的参与者中，预测具有硫酸乙酰肝素修饰能力的物种显著减少，这与老年人硫酸乙酰肝素含量的增加相关。这些发现表明，在整个抽样人群中，唾液中硫酸乙酰肝素的含量和组成存在惊人的广泛差异，并证实了其他显示血液和尿液中糖胺聚糖含量和组成存在差异的研究结果。
