Respiratory Syncytial Virus-Associated Neurologic Complications in Children: A Systematic Review and Aggregated Case Series

Gemma L Saravanos; Catherine L King; Lucy Deng; Nicole Dinsmore; Isabelle Ramos; Mari Takashima; Nigel Crawford; Julia E Clark; Russell C Dale; Cheryl A Jones; Nicholas J Wood; Philip N Britton

doi:10.1016/j.jpeds.2021.06.045

Respiratory Syncytial Virus-Associated Neurologic Complications in Children: A Systematic Review and Aggregated Case Series

J Pediatr. 2021 Dec:239:39-49.e9. doi: 10.1016/j.jpeds.2021.06.045. Epub 2021 Jun 25.

Authors

Affiliations

¹ University of Sydney, Sydney, Australia; National Centre for Immunisation Research and Surveillance, Sydney, Australia. Electronic address: gemma.saravanos@health.nsw.gov.au.
² National Centre for Immunisation Research and Surveillance, Sydney, Australia.
³ The University of Notre Dame, Fremantle, Australia.
⁴ Griffith University, Brisbane, Australia.
⁵ Royal Children's Hospital, Melbourne, Australia.
⁶ Queensland Children's Hospital, Brisbane, Australia.
⁷ University of Sydney, Sydney, Australia; The Children's Hospital at Westmead, Sydney, Australia.
⁸ University of Sydney, Sydney, Australia; National Centre for Immunisation Research and Surveillance, Sydney, Australia; The Children's Hospital at Westmead, Sydney, Australia.

PMID: 34181989
DOI: 10.1016/j.jpeds.2021.06.045

Abstract

Objectives: To describe the features and frequency of respiratory syncytial virus (RSV)-associated severe acute neurologic disease in children.

Study design: We performed a systematic review of the literature to identify reports of severe acute neurologic complications associated with acute RSV infection in children aged <15 years (PROSPERO Registration CRD42019125722). Main outcomes included neurologic, clinical, and demographic features of cases and the frequency of disease. We aggregated available case data from the published literature and from the Australian Acute Childhood Encephalitis (ACE) study.

Results: We identified 87 unique studies from 26 countries describing a spectrum of RSV-associated severe acute neurologic syndromes including proven encephalitis, acute encephalopathy, complex seizures, hyponatremic seizures, and immune-mediated disorders. The frequency of RSV infection in acute childhood encephalitis/encephalopathy was 1.2%-6.5%. We aggregated data from 155 individual cases with RSV-associated severe acute neurologic complications; median age was 11.0 months (IQR 2.0-21.5), most were previously healthy (71/104, 68%). Seizure was the most frequently reported neurologic feature (127/150, 85%). RSV was detected in the central nervous system of 12 cases. Most children recovered (81/122, 66%); however, some reports described partial recovery (33/122, 27%) and death (8/122, 7%).

Conclusions: RSV-associated neurologic complications have been widely reported, but there is substantial heterogeneity in the design and quality of existing studies. The findings from our study have implications for the investigation, management, and prevention of RSV-associated neurologic complications. Further, this systematic review can inform the design of future studies aiming to quantify the burden of childhood RSV-associated neurologic disease.

Keywords: child; encephalitis; neurologic manifestations; respiratory syncytial viruses; seizures.

Publication types

Research Support, Non-U.S. Gov't
Systematic Review

MeSH terms

Adolescent
Child
Child, Preschool
Diagnostic Tests, Routine / statistics & numerical data
Female
Humans
Incidence
Infant
Male
Nervous System Diseases / epidemiology*
Respiratory Syncytial Virus Infections / epidemiology*
Respiratory Syncytial Virus, Human / isolation & purification