Assessing the strength of evidence for a causal effect of respiratory syncytial virus lower respiratory tract infections on subsequent wheezing illness: a systematic review and meta-analysis

Authors: Steven M. Brunwasser, Brittney M. Snyder, Amanda J. Driscoll, Deshayne B. Fell, David A. Savitz, Daniel R. Feikin, Becky Skidmore, Niranjan Bhat, Louis Bont, William D. Dupont, Pingsheng Wu, Tebeb Gebretsadik, Patrick G. Holt, Heather J. Zar, Justin R. Ortiz, Tina V. Hartert - The Lancet 2020 cited by 110

BACKGROUND: Although a positive association has been established, it is unclear whether lower respiratory tract infections (LRTIs) with respiratory syncytial virus (RSV) cause chronic wheezing illnesses. If RSV-LRTI were causal, we would expect RSV-LRTI prevention to reduce the incidence of chronic wheezing illnesses in addition to reducing acute disease. We aimed to evaluate the strength of evidence for a causal effect of RSV-LRTI on subsequent chronic wheezing illness to inform public health expectations for RSV vaccines. METHODS: OR) scale. FINDINGS: 1·21, 95% CI 0·73-1·99). There was generally a high threat of confounding bias in the observational studies. Additionally, in both the observational studies and immunoprophylaxis RCTs, there was high risk of bias due to missing outcome data. INTERPRETATION: Our findings, limited to exposure and immunoprophylaxis studies, do not support basing policy decisions on an assumption that prevention of RSV-LRTI will reduce recurrent chronic wheezing illnesses. FUNDING: Bill & Melinda Gates Foundation.