Global age-stratified seroprevalence of enterovirus D68: a systematic literature review

Abstract

Enterovirus D68 (EV-D68), first isolated in 1962, emerged in 2014, causing outbreaks of severe respiratory infections and acute flaccid myelitis. In this systematic review, we have compiled all available literature on age-stratified seroprevalence estimates of EV-D68. Ten studies from six countries were retained, all conducted using microneutralisation assays, despite wide variations in protocols and challenge viruses. The age profiles of seroprevalence were similar across time and regions; seroprevalence increased quickly with age, reaching roughly 100% by the age of 20 years and with no sign of decline throughout adulthood. This suggests continuous or frequent exposure of the populations to the virus, or possible cross-reactivity with other viruses. Studies with two or more cross-sectional surveys reported consistently higher seroprevalence at later timepoints, suggesting a global increase in transmission over time. This systematic review concludes that standardising serological protocols, understanding the contribution of cross-reactivity with other pathogens to the high reported seroprevalence, and quantifying individual exposure to EV-D68 over time are the main research priorities for the future.