Rare enterovirus strain in Spain raises alarms over potential outbreaks

By Dr. Chinta SidharthanReviewed by Susha Cheriyedath, M.Sc.Feb 17 2025

A newly detected virus in Spain has been linked to both respiratory illness and potential neurological complications in children, raising concerns about its evolving threat and the need for urgent surveillance.

Rapid communication: Detections of rare enterovirus C105 linked to an emerging novel clade, Spain, 2019 to 2024. Image Credit: Kateryna Kon / Shutterstock

In a recent study published in the journal Eurosurveillance, scientists from Spain reported the detection of Enterovirus C105 (EV-C105), a little-known virus recently linked to respiratory and potentially neurological illnesses in children. Their findings indicated an emerging viral strain that could pose unexpected health risks.

Background

Viruses within the enterovirus family are often etiological agents for various illnesses, ranging from mild colds to severe neurological diseases. While most enterovirus infections lead to brief respiratory issues, some can result in dangerous complications, particularly in children. Poliovirus, for instance, was once a major global threat, causing paralysis before widespread vaccination efforts brought it under control.

Non-polio enteroviruses have also occasionally caused severe outbreaks, such as Enterovirus D68, which has been linked to acute flaccid paralysis. Enterovirus C types, though less well-known, are increasingly drawing scientific attention due to their unpredictable behavior and genetic diversity. Rare variants such as EV-C105 have surfaced sporadically worldwide since their discovery in 2010, often tied to respiratory illness, but their confirmed role in causing severe neurological disease remains uncertain.

About the Study

The current study was part of Spain’s national non-polio enterovirus surveillance program, which collects samples from hospitals nationwide. From 2019 to 2024, close to 2,443 samples that were positive for enteroviruses were submitted for detailed genetic analysis. These samples were obtained from patients showing a variety of symptoms, including respiratory issues, meningitis, and other neurological conditions.

Samples from affected patients were analyzed using real-time polymerase chain reaction (RT-PCR) panels designed to detect respiratory viruses and enterovirus-specific tests. The viral genetic material was further studied through sequencing and metagenomic techniques, allowing researchers to map the virus's entire genome.

Once the virus was identified, the researchers compared its genetic characteristics to known strains worldwide. Special attention was given to the viral envelope protein VP1 region, a part of the virus that is key to its ability to infect cells and evade immune defenses. Advanced phylogenetic analyses revealed that EV-C105 had not undergone significant recombination events, indicating that the newly emerging strains evolved independently.

Furthermore, the team checked for genetic recombination events to understand how the virus spreads and evolves, which occurs when viruses exchange genetic material. They also compared the newly identified strains to past EV-C105 samples stored in public genetic databases.

Major Findings

The results showed that the rare EV-C105 virus had recently emerged in Spain and was linked to both respiratory and possible neurological illnesses in children. Genetic analysis revealed four of the five detected virus strains belonged to a newly identified subgroup, clade C1, which carried distinctive mutations in key regions that could alter the virus’s ability to spread and evade immunity.

Among the five infected patients, three presented with respiratory symptoms such as coughing and fever, while two developed serious neurological conditions. One child was diagnosed with meningitis, and another experienced acute flaccid paralysis, a rare but severe condition that can cause permanent muscle weakness. Both neurological cases required prolonged treatment in intensive care units.

The genetic comparison showed that the C1 strains detected in Spain closely matched those identified in Italy in 2023, suggesting a possible connection between cases in Spain and Italy rather than confirmed international transmission. The virus’s genetic differences from older strains, particularly changes in the VP1 protein, also raised concerns about increased transmissibility or immune evasion.

Importantly, the virus was only detected in respiratory samples, even in patients with neurological symptoms. This poses a diagnostic challenge, as EV-C105 may not always appear in cerebrospinal fluid, making traditional testing methods insufficient for severe cases. Similar detection challenges have been observed with other neurotropic enteroviruses, such as EV-D68 and poliovirus.

While the study provided critical insights, it also had limitations. The small number of detected cases prevented a complete understanding of the virus’s true prevalence. Additionally, the absence of cerebrospinal fluid samples means that a direct causal link between EV-C105 and neurological disease cannot be confirmed.

The study suggested that EV-C105, especially the emerging C1 clade, could represent an evolving health concern. The findings also indicate a shift in viral dominance, as clade C1 appears to be replacing older strains like C2, a pattern seen in other enteroviruses linked to outbreaks. Furthermore, enhanced surveillance and improved diagnostic practices are necessary to monitor the virus and prevent potential outbreaks of severe illness, particularly in children.

Conclusions

To summarize, the researchers reported on the discovery of the Enterovirus strain EV-C105 among children in Spain. Although cases remain rare, its association with both respiratory and possible neurological disease raises concerns. The emergence of a genetically distinct clade highlighted the virus’s potential threat. The detection of severe illness in children emphasized the need for heightened clinical vigilance and improved viral surveillance. Additionally, researchers caution that diagnostic tests relying on 5′ UTR targets may under-detect EV-C105 due to its genetic divergence, potentially leading to underreporting.

The team believes that further research is vital to understanding the virus’s behavior, assessing its true impact, and preventing wider outbreaks.