Does respiratory syncytial virus lower respiratory illness in early life cause recurrent wheeze of early childhood and asthma? Critical review of the evidence and guidance for future studies from a World Health Organization-sponsored meeting
- PMID: 31974017
- PMCID: PMC7049900
- DOI: 10.1016/j.vaccine.2020.01.020
Does respiratory syncytial virus lower respiratory illness in early life cause recurrent wheeze of early childhood and asthma? Critical review of the evidence and guidance for future studies from a World Health Organization-sponsored meeting
Abstract
Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection (LRTI) and hospitalization in infants and children globally. Many observational studies have found an association between RSV LRTI in early life and subsequent respiratory morbidity, including recurrent wheeze of early childhood (RWEC) and asthma. Conversely, two randomized placebo-controlled trials of efficacious anti-RSV monoclonal antibodies (mAbs) in heterogenous infant populations found no difference in physician-diagnosed RWEC or asthma by treatment group. If a causal association exists and RSV vaccines and mAbs can prevent a substantial fraction of RWEC/asthma, the full public health value of these interventions would markedly increase. The primary alternative interpretation of the observational data is that RSV LRTI in early life is a marker of an underlying predisposition for the development of RWEC and asthma. If this is the case, RSV vaccines and mAbs would not necessarily be expected to impact these outcomes. To evaluate whether the available evidence supports a causal association between RSV LRTI and RWEC/asthma and to provide guidance for future studies, the World Health Organization convened a meeting of subject matter experts on February 12-13, 2019 in Geneva, Switzerland. After discussing relevant background information and reviewing the current epidemiologic evidence, the group determined that: (i) the evidence is inconclusive in establishing a causal association between RSV LRTI and RWEC/asthma, (ii) the evidence does not establish that RSV mAbs (and, by extension, future vaccines) will have a substantial effect on these outcomes and (iii) regardless of the association with long-term childhood respiratory morbidity, severe acute RSV disease in young children poses a substantial public health burden and should continue to be the primary consideration for policy-setting bodies deliberating on RSV vaccine and mAb recommendations. Nonetheless, the group recognized the public health importance of resolving this question and suggested good practice guidelines for future studies.
Keywords: Asthma; Monoclonal antibody; Respiratory syncytial virus; Vaccine; Wheeze.
Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.
Conflict of interest statement
Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: LB has regular interaction with pharmaceutical and other industrial partners. He has not received personal fees or other personal benefits. He is the founding chairman of the ReSViNET Foundation. JAE has served as a consultant to Sanofi Pasteur and Meissa Vaccines and her institution receives support from Novavax, AstraZeneca, Merck, and GlaxoSmithKline. LLH reports research grants to her institution from Novavax, Merck, GSK, and Pfizer. TVH receives funding relevant to the submitted work from the National Institutes of Health and the WHO and served on the Pfizer RSV Infant/Maternal Health External Advisory Board in 2019. HN has received grant funding from Bill and Melinda Gates Foundation, Sanofi Pasteur, World Health Organization and Innovative Medicines Initiative. HN has received honoraria and speaker fees from Sanofi Pasteur, Abbvie and Janssen. EAFS reports grant support and personal fees in the last 36 months from Astra Zeneca Inc., Merck & Co., Regeneron Inc., and Pfizer Inc.; grant support from Novavax; and personal fees from Roche Inc. AbbVie Inc., and Alere Inc.
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