Global prevalence and case fatality rate of Enterovirus D68 infections, a systematic review and meta-analysis

Abstract

A substantial amount of epidemiological data has been reported on Enterovirus D68 (EV-D68) infections after the 2014 outbreak. Our goal was to map the case fatality rate (CFR) and prevalence of current and past EV-D68 infections. We conducted a systematic review (PROSPERO, CRD42021229255) with published articles on EV-68 infections in PubMed, Embase, Web of Science and Global Index Medicus up to January 2021. We determined prevalences using a model random effect. Of the 4,329 articles retrieved from the databases, 89 studies that met the inclusion criteria were from 39 different countries with apparently healthy individuals and patients with acute respiratory infections, acute flaccid myelitis and asthma-related diseases. The CFR estimate revealed occasional deaths (7/1353) related to EV-D68 infections in patients with severe acute respiratory infections. Analyses showed that the combined prevalence of current and past EV-D68 infections was 4% (95% CI = 3.1–5.0) and 66.3% (95% CI = 40.0–88.2), respectively. The highest prevalences were in hospital outbreaks, developed countries, children under 5, after 2014, and in patients with acute flaccid myelitis and asthma-related diseases. The present study shows sporadic deaths linked to severe respiratory EV-D68 infections. The study also highlights a low prevalence of current EV-D68 infections as opposed to the existence of EV-D68 antibodies in almost all participants of the included studies. These findings therefore highlight the need to implement and/or strengthen continuous surveillance of EV-D68 infections in hospitals and in the community for the anticipation of the response to future epidemics.

Off-season circulation and characterization of enterovirus D68 with respiratory and neurological presentation using whole-genome sequencing

“…Using a modified WGS approach, we were able to obtain near-complete EV-D68 genomes from a wide range of Ct values, including Ct values >30 and sample material, including CSF. The summer/autumn seasonal circulation is well recognized for all enteroviruses in temperate climates, with a biennial recurrence of EV-D68 observed in North America and Europe ( Elrick et al, 2021 ; Fall et al, 2022 ). Interestingly, our data shows a general shift towards the later months, with the upsurge emerging in an odd year ( Figure 1 ).…”

Pan-Enterovirus Characterization Reveals Cryptic Circulation of Clinically Relevant Subtypes in Arizona Wastewater

“…Yet in just the past few years, there have been nationwide and global instances of morbidity and mortality due to non-reportable pathogens known to seasonally circulate (e.g. multiple adenoviruses and adeno-associated virus [58], EV-D68 [11,59,60]). Wastewater testing as an early warning system for viral outbreaks has been suggested by several teams, starting in the early 1940’s [61], but very purposefully implemented during the ongoing COVID-19 pandemic.…”

Seroprevalence of Enterovirus D68 Infection among Humans: A Systematic Review and Meta-Analysis

“…This study evaluated 13 published studies, showing that the positive rate of EV-D68 antibody was relatively high, with 74.4% (95% CI: 66.9–82.0%) in the general population and 72.6% (95% CI: 61.6–83.7%) in the Chinese population. In another systematic study, the researchers found that the prevalence of previous EV-D68 infection was 66.3% (95% CI: 40.0–88.2), while the overall prevalence of current EV-D68 infection was 4% in apparently healthy individuals and patients with acute respiratory infection, AFM, and asthma-related illness [ 21 ]. Both the prevalence rate and severe disease rates were much lower than the seropositivity rate of EV-D68 in this study, indicating that the virus may spread silently, and serological data may better reflect the regional epidemic situation of the virus.…”

“…Overall, there is a lack of systematic and comprehensive surveillance and documentation of EV-D68 prevalence globally, and latent infection of EV-D68 is not being taken seriously. Acute flaccid paralysis caused by EV-D68 infection is increasing, and there is currently a lack of effective drugs and vaccines against the virus [ 6 , 20 , 21 ]. Therefore, it is very important to further strengthen the understanding of virus serology for disease prevention.…”