Background

The risk factors determining short- and long-term morbidity following acute respiratory infection (ARI) due to respiratory syncytial virus (RSV) in infancy remain poorly understood.

Objectives

Our aim was to examine the associations of the upper respiratory tract (URT) microbiome during RSV ARI in infancy with the acute local immune response and short- and long-term clinical outcomes.

Methods

We characterized the URT microbiome by 16S ribosomal RNA sequencing and assessed the acute local immune response by measuring 53 immune mediators with high-throughput immunoassays in 357 RSV-infected infants. Our short- and long-term clinical outcomes included several markers of disease severity and the number of wheezing episodes in the fourth year of life, respectively.

Results

We found several specific URT bacterial-immune mediator associations. In addition, the Shannon ⍺-diversity index of the URT microbiome was associated with a higher respiratory severity score (β =.50 [95% CI = 0.13-0.86]), greater odds of a lower ARI (odds ratio = 1.63 [95% CI = 1.10-2.43]), and higher number of wheezing episodes in the fourth year of life (β = 0.89 [95% CI = 0.37-1.40]). The Jaccard β-diversity index of the URT microbiome differed by level of care required (P = .04). Furthermore, we found an interaction between the Shannon ⍺-diversity index of the URT microbiome and the first principal component of the acute local immune response on the respiratory severity score (P = .048).

Conclusions

The URT microbiome during RSV ARI in infancy is associated with the acute local immune response, disease severity, and number of wheezing episodes in the fourth year of life. Our results also suggest complex URT bacterial-immune interactions that can affect the severity of the RSV ARI.

中文翻译：

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婴儿呼吸道合胞病毒感染期间上呼吸道细菌免疫相互作用

背景

确定婴儿期呼吸道合胞病毒 (RSV) 引起的急性呼吸道感染 (ARI) 后短期和长期发病率的危险因素仍知之甚少。

目标

我们的目的是检查婴儿期 RSV ARI 期间上呼吸道 (URT) 微生物组与急性局部免疫反应以及短期和长期临床结果的关联。

方法

我们通过 16S 核糖体 RNA 测序来表征 URT 微生物组，并通过在 357 名 RSV 感染婴儿中使用高通量免疫测定法测量 53 种免疫介质来评估急性局部免疫反应。我们的短期和长期临床结果分别包括疾病严重程度的几个标志物和生命第四年的喘息发作次数。

结果

我们发现了几种特定的 URT 细菌免疫介质关联。此外，URT 微生物组的 Shannon ⍺ 多样性指数与较高的呼吸严重程度评分 (β =.50 [95% CI = 0.13-0.86])、较低 ARI 的几率较高 (优势比 = 1.63 [95] % CI = 1.10-2.43])，第四年喘息发作次数较多 (β = 0.89 [95% CI = 0.37-1.40])。URT 微生物组的 Jaccard β-多样性指数因所需护理水平而异 ( P  = .04)。此外，我们发现 URT 微生物组的 Shannon ⍺ 多样性指数与急性局部免疫反应的第一主要成分对呼吸严重程度评分之间存在相互作用 ( P  = .048)。

结论

婴儿期 RSV ARI 期间的 URT 微生物组与生命第四年的急性局部免疫反应、疾病严重程度和喘息发作次数相关。我们的结果还表明复杂的 URT 细菌免疫相互作用会影响 RSV ARI 的严重程度。