Moreno Elena, Ciordia Sergio, Fátima Santos Milhano, Jiménez Daniel, Martínez-Sanz Javier, Vizcarra Pilar, Ron Raquel, Sánchez-Conde Matilde, Bargiela Rafael, Sanchez-Carrillo Sergio, Moreno Santiago, Corrales Fernando, Ferrer Manuel, Serrano-Villar Sergio
Department of Infectious Diseases, Facultad de Medicina, Hospital Universitario Ramón y Cajal, IRYCIS, Carretera de Colmenar Viejo, Km 9.100, 28034, Madrid, Spain.
CIBERINFEC, Instituto de Salud Carlos III, 28029, Madrid, Spain.
Clin Proteomics. 2024 May 22;21(1):37. doi: 10.1186/s12014-024-09482-9.
Information on the microbiome's human pathways and active members that can affect SARS-CoV-2 susceptibility and pathogenesis in the salivary proteome is very scarce. Here, we studied a unique collection of samples harvested from April to June 2020 from unvaccinated patients.
We compared 10 infected and hospitalized patients with severe (n = 5) and moderate (n = 5) coronavirus disease (COVID-19) with 10 uninfected individuals, including non-COVID-19 but susceptible individuals (n = 5) and non-COVID-19 and nonsusceptible healthcare workers with repeated high-risk exposures (n = 5).
By performing high-throughput proteomic profiling in saliva samples, we detected 226 unique differentially expressed (DE) human proteins between groups (q-value ≤ 0.05) out of 3376 unambiguously identified proteins (false discovery rate ≤ 1%). Major differences were observed between the non-COVID-19 and nonsusceptible groups. Bioinformatics analysis of DE proteins revealed human proteomic signatures related to inflammatory responses, central cellular processes, and antiviral activity associated with the saliva of SARS-CoV-2-infected patients (p-value ≤ 0.0004). Discriminatory biomarker signatures from human saliva include cystatins, protective molecules present in the oral cavity, calprotectins, involved in cell cycle progression, and histones, related to nucleosome functions. The expression levels of two human proteins related to protein transport in the cytoplasm, DYNC1 (p-value, 0.0021) and MAPRE1 (p-value, 0.047), correlated with angiotensin-converting enzyme 2 (ACE2) plasma activity. Finally, the proteomes of microorganisms present in the saliva samples showed 4 main microbial functional features related to ribosome functioning that were overrepresented in the infected group.
Our study explores potential candidates involved in pathways implicated in SARS-CoV-2 susceptibility, although further studies in larger cohorts will be necessary.
关于微生物组在人类体内的作用途径以及唾液蛋白质组中可能影响新冠病毒易感性和发病机制的活跃成分的信息非常匮乏。在此，我们研究了2020年4月至6月从未接种疫苗的患者中采集的一组独特样本。
我们将10例感染新冠病毒并住院的患者（其中5例为重症新冠病毒病（COVID-19），5例为中度COVID-19）与10例未感染个体进行比较，后者包括非COVID-19但易感个体（5例）和反复暴露于高风险环境的非COVID-19且不易感医护人员（5例）。
通过对唾液样本进行高通量蛋白质组分析，在3376种明确鉴定的蛋白质（错误发现率≤1%）中，我们检测到两组之间有226种独特的差异表达（DE）人类蛋白质（q值≤0.05）。在非COVID-19且不易感组之间观察到了主要差异。对DE蛋白质的生物信息学分析揭示了与炎症反应、核心细胞过程以及与SARS-CoV-2感染患者唾液相关的抗病毒活性有关的人类蛋白质组特征（p值≤0.0004）。来自人类唾液的鉴别生物标志物特征包括半胱氨酸蛋白酶抑制剂（口腔中的保护分子）、参与细胞周期进程的钙卫蛋白以及与核小体功能相关的组蛋白。两种与细胞质中蛋白质转运相关的人类蛋白质DYNC1（p值，0.0021）和MAPRE1（p值，0.047）的表达水平与血管紧张素转换酶2（ACE2）的血浆活性相关。最后，唾液样本中存在的微生物蛋白质组显示出与核糖体功能相关的4种主要微生物功能特征，这些特征在感染组中过度表达。
我们的研究探索了参与与SARS-CoV-2易感性相关途径的潜在候选物，不过有必要在更大的队列中进行进一步研究。
