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Author Notes:

Suman R. Das, PhD, Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, 1161 21st Avenue South, Medical Center North, Suite A2200, Nashville, TN 37232, Phone: (615) 322-0322, Fax: (615) 343-6160 Email: suman.r.das@vumc.org

Tina V. Hartert, MD, MPH, Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, 2525 West End Avenue, Suite 450, Nashville, TN 37232, Phone: (615) 936-3597, Fax: (615) 936-1269. Email: tina.hartert@vumv.org

CRS, ZT, MHS, RSP, SRD, LJA, and TVH contributed to the study design. CRS, CEL, and TVH contributed to the sample collection. CRS, MHS, KNT, DAW, TG, JDC, and SRD contributed to the sample and data processing. ZT and QH contributed to the statistical analysis. CRS, RSP, LJA, SRD, and TVH obtained the research funding supporting this study. CRS, ZT, and TVH wrote the initial version of the manuscript and all authors reviewed and approved the final version.

This work was supported by funds from the National Institute of Allergy and Infectious Diseases (under award numbers U19AI095227, K24AI77930, HHSN272200900007C, R21AI142321, U19AI110819, R21AI154016, R21AI149262, and UG3OD023282); the National Heart, Lung, and Blood Institute (under award numbers K23HL148638 and R01HL146401); the National Institute of General Medical Sciences (under award number R01GM140464); the Parker B. Francis Fellowship Program; the Vanderbilt Institute for Clinical and Translational Research (grant support from the National Center for Advancing Translational Sciences under award number UL1TR000445); the Department of Pediatrics at Vanderbilt University Medical Center (grant support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development under award number K12HD087023); the Vanderbilt Building Interdisciplinary Research Careers in Women’s Health K12 program (grant support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development under award number K12HD04348318); and the Vanderbilt Technologies for Advanced Genomics Core (grant support from the National Institutes of Health under award numbers UL1RR024975, P30CA68485, P30EY08126, and G20RR030956).

LJA has done paid consultancies on respiratory syncytial virus (RSV) vaccines for Bavarian Nordic, Novavax, Daiichi-Sankyo, ClearPath Development Company, and Pfizer. He receives funding from Pfizer through Emory University for laboratory surveillance studies of RSV infection in adults. He is a co-inventor on several Centers for Disease Control and Prevention patents on the RSV G protein and its CX3C chemokine motif relative to immune therapy and vaccine development. He is also co-inventor on a patent filing for the use of RSV platform virus-like particles with the F and G proteins for vaccines. The other authors do not have a commercial or other association that might pose a conflict of interest.

Subjects:

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Allergy
  • Immunology
  • Airway
  • bronchiolitis
  • chemokines
  • cytokines
  • growth factors
  • immune response
  • infancy
  • mediation
  • microbiome
  • nasopharynx
  • respiratory syncytial virus
  • severity
  • wheezing
  • NASOPHARYNGEAL MICROBIOME
  • SEVERITY
  • ASSOCIATION
  • CHILDREN
  • RHINOVIRUS
  • BURDEN
  • RISK

Upper respiratory tract bacterial-immune interactions during respiratory syncytial virus infection in infancy

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Journal Title:

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

Volume:

Volume 149, Number 3

Publisher:

, Pages 966-976

Type of Work:

Article | Post-print: After Peer Review

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.

Copyright information:

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/).
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