PDF(Pubmed)
Abstract：
Outbreaks of influenza A viruses are generally seasonal and cause annual epidemics worldwide. Due to their frequent reassortment and evolution, annual surveillance is of paramount importance to guide vaccine strategies. The aim of this study was to explore the molecular epidemiology of influenza A virus and nasopharyngeal microbiota composition in infected patients in Saudi Arabia. A total of 103 nasopharyngeal samples from 2015 and 12 samples from 2022 were collected from patients positive for influenza A. Sequencing of influenza A as well as metatranscriptomic analysis of the nasopharyngeal microbiota was conducted using Oxford Nanopore sequencing. Phylogenetic analysis of hemagglutinin, neuraminidase segments, and concatenated influenza A genomes was performed using MEGA7. Whole-genome sequencing analysis revealed changing clades of influenza A virus: from 6B.1 in 2015 to 5a.2a in 2022. One sample containing the antiviral resistance-mediating mutation S247N toward oseltamivir and zanamivir was found. Phylogenetic analysis showed the clustering of influenza A strains with the corresponding vaccine strains in each period, thus suggesting vaccine effectiveness. Principal component analysis and alpha diversity revealed the absence of a relationship between hospital admission status, age, or gender of infected patients and the nasopharyngeal microbial composition, except for the infecting clade 5a.2a. The opportunistic pathogens Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis were the most common species detected. The molecular epidemiology appears to be changing in Saudi Arabia after the COVID-19 pandemic. Antiviral resistance should be carefully monitored in future studies. In addition, the disease severity of patients as well as the composition of the nasopharyngeal microbiota in patients infected with different clades should also be assessed.IMPORTANCEIn this work, we have found that the clade of influenza A virus circulating in Riyadh, KSA, has changed over the last few years from 6B.1 to 5a.2a. Influenza strains clustered with the corresponding vaccine strains in our population, thus emphasizing vaccine effectiveness. Metatranscriptomic analysis showed no correlation between the nasopharyngeal microbiome and the clinical and/or demographic characteristics of infected patients. This is except for the 5a.2a strains isolated post-COVID-19 pandemic. The influenza virus is among the continuously evolving viruses that can cause severe respiratory infections. Continuous surveillance of its molecular diversity and the monitoring of anti-viral-resistant strains are thus of vital importance. Furthermore, exploring potential microbial markers and/or dysbiosis of the nasopharyngeal microbiota during infection could assist in the better management of patients in severe cases.
摘要：
甲型流感病毒的爆发通常是季节性的，并在全球范围内引起年度流行。由于它们频繁的重组和进化，年度监测对于指导疫苗策略至关重要。这项研究的目的是探索沙特阿拉伯感染患者中甲型流感病毒和鼻咽微生物组成的分子流行病学。从甲型流感阳性患者中收集了2015年的103个鼻咽样本和2022年的12个样本。使用OxfordNanopore测序进行了甲型流感测序以及鼻咽微生物群的代谢组学分析。血凝素的系统发育分析，神经氨酸酶段，和串联的甲型流感基因组使用MEGA7进行。全基因组测序分析揭示了甲型流感病毒进化枝的变化：从2015年的6B.1到2022年的5a.2a。发现了一个包含针对奥司他韦和扎那米韦的抗病毒抗性介导突变S247N的样品。系统发育分析显示甲型流感毒株与相应疫苗毒株在各个时期的聚集,从而表明疫苗的有效性。主成分分析和α多样性揭示了住院状态之间没有关系，年龄,或感染患者的性别和鼻咽部微生物组成，除了感染进化枝5a.2a。机会致病菌金黄色葡萄球菌,肺炎链球菌,流感嗜血杆菌,和卡他莫拉菌是最常见的物种。COVID-19大流行后，沙特阿拉伯的分子流行病学似乎正在发生变化。在未来的研究中应仔细监测抗病毒耐药性。此外,还应评估患者的疾病严重程度以及感染不同进化枝的患者鼻咽部微生物群的组成。重要的是在这项工作中，我们发现利雅得的甲型流感病毒进化枝，KSA,在过去的几年中，从6B.1变为5a.2a。在我们的人群中，流感病毒株与相应的疫苗株聚集在一起，从而强调疫苗的有效性。代谢组学分析显示，鼻咽微生物组与感染患者的临床和/或人口统计学特征之间没有相关性。这是在COVID-19大流行后分离出的5a.2a菌株除外。流感病毒是可引起严重呼吸道感染的持续进化的病毒之一。因此，连续监测其分子多样性和监测抗病毒抗性菌株至关重要。此外，探索感染期间鼻咽部微生物群的潜在微生物标志物和/或菌群失调可能有助于在重症病例中更好地管理患者.
