Christian Rosas-Salazar1, Zheng-Zheng Tang2, Meghan H Shilts3, Kedir N Turi4, Qilin Hong2, Derek A Wiggins4, Christian E Lynch4, Tebeb Gebretsadik5, James D Chappell6, R Stokes Peebles4, Larry J Anderson7, Suman R Das8, Tina V Hartert9. 1. Division of Allergy, Immunology, and Pulmonary Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn. 2. Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, Wis. 3. Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn. 4. Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn. 5. Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tenn. 6. Division of Infectious Diseases, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tenn. 7. Division of Infectious Diseases, Department of Pediatrics, Emory University and Children's Healthcare of Atlanta, Atlanta, Ga. 8. Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn; Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, Tenn. Electronic address: suman.r.das@vumc.org. 9. Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn. Electronic address: tina.hartert@vumc.org.
Abstract
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.
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.
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Authors: Christian Rosas-Salazar; Meghan H Shilts; Zheng-Zheng Tang; Qilin Hong; Kedir N Turi; Brittney M Snyder; Derek A Wiggins; Christian E Lynch; Tebeb Gebretsadik; R Stokes Peebles; Larry J Anderson; Suman R Das; Tina V Hartert Journal: J Allergy Clin Immunol Date: 2022-03-10 Impact factor: 14.290