Respiratory enterovirus D68: virology, clinical surveillance, host-pathogen interactions, and therapeutic prospects

Abstract

Enterovirus D68 (EV-D68), a unique enterovirus resembling human rhinoviruses, was long considered to cause only sporadic outbreaks of mild, self-limiting respiratory infections mainly in children. However, over the past decade, EV-D68 has exhibited a biennial outbreak pattern across multiple regions worldwide, coinciding with an increased incidence of severe respiratory illnesses and cases of acute flaccid myelitis (AFM) in children. The immune system plays a crucial role in providing rapid and effective defense. Nonetheless, our knowledge of the complex interactions between EV-D68 and the host immune responses is still very limited. Additionally, clinical detection of EV-D68 remains challenging, and there are no FDA-approved vaccines or antiviral treatments available. Therefore, ongoing research should focus on understanding the pathogenic mechanisms of EV-D68, as well as the development of reliable diagnostic methods and therapeutic options to control EV-D68 spread. This review intends to examine the initiatives undertaken for clinical surveillance of EV-D68 outbreaks, the immune responses elicited by EV-D68, and its strategies for immune evasion. Additionally, it explores recent advancements in antiviral drug development, thereby providing a comprehensive overview of current knowledge and identifying prospective directions for future research.

Key findings

• ▸EV-D68 exhibits a distinct biennial outbreak pattern worldwide over the past decade.
• ▸The virus is increasingly linked to severe respiratory illnesses and acute flaccid myelitis in pediatric populations.
• ▸Current clinical detection methods are challenging, and no FDA-approved vaccines or antiviral treatments exist.

Keywords

Identifiers

DOI

10.3389/fcimb.2026.1774711

Journal

Frontiers in Cellular and Infection Microbiology

Year

2026