A new lineage of echovirus 11 detected in Spain not associated with an increase in cases of severe disease in neonates

The research, carried out by the Enterovirus and Viral Gastroenteritis Unit of the CNM-ISCIII in the framework of the outbreak that emerged in Europe last year and published in ‘Eurosurveillance’, has analyzed howwas the circulation of the virus in Spainwith the aim of defining its characteristics and its possible association with serious neonatal infections.

Increase in serious infections

In June 2023, France notified the Member States of the European Union and the European Economic Area (EU/EEA) of an increase in serious infections in neonates caused by a specific type of enterovirus, echovirus 11 (E11). In total, nine neonates infected with E11 were identified who presented sepsis and liver failure, of which seven died. All E11 sequences associated with these severe neonatal infections belonged to a new lineage, called lineage 1, which was first identified in April 2022.

Similarly, Italy reported two cases of premature twins with fulminant hepatitis due to E11 whose sequences were also grouped in lineage 1. Throughout 2023, four other countries (Croatia, Spain, the United Kingdom and Sweden) reported cases.

Thousands of samples

With the aim of verifying the situation in Spain, the research team studied 1,288 enterovirus-positive samples received and genotyped at the National Microbiology Center of the ISCIII through the Microbiological Surveillance Program between 2019 and 2023. Of this total of samples, 98 turned out to be positive for echovirus type 11 and 33.7 percent affected neonates.

As in the study carried out in France, phylogenetic analyzes indicated that E11 strains of lineage 1 appeared for the first time in Spain in 2022, and predominated during 2022 and 2023. Also in accordance with the French studynew lineage 1 included sequences from both severe and non-severe neonatal infections, as well as non-neonatal infections.

However, unlike France, the severe cases observed in 2022 and 2023 in Spain were not exclusively linked to the new lineage 1. That is, although the new lineage 1 has been circulating in Spain since 2022, has not been associated with an increase in severe disease in neonates. Another difference was that the E11 detection rate was similar before and after the detection of the new lineage 1 in Spain in 2022.

The authors of the study, including María Dolores Fernández García and María Cabrerizo as the first and last signatory, have explained that in enteroviruses, recombination events almost always occur outside the region that encodes the capsid used for genotyping, and that Therefore, it is essential to obtain the complete genome to analyze the incidence of cases and related events. Therefore, 10 E11-positive samples were sequenced with non-targeted metagenomics, obtaining the complete genome of these viruses.

Strengthen genomic surveillance of E11

Thanks to the analysis of these complete genomes, echovirus 11 was observed with three new recombinant genomic forms, none of which were within the new lineage 1. Two of these three new E11 recombinant viruses were associated with severe disease, requiring ICU admission. (one was associated with sepsis with liver failure, and the other with severe meningoencephalitis).

Finally, the study of the virome of these E11-positive samples using metagenomics allowed us to detect coinfecting viruses in four of the ten samples. This underlines the need to investigate possible (co)infections, since these could contribute to serious or fatal outcomes in E11 infections.

Specialists have pointed out that the results obtained underline the need to strengthen genomic surveillance of E11 to monitor whether these or other new recombinant forms are causing serious E11 infections. in Spain and other European countriesbeyond the strains of the new lineage 1.

Likewise, the authors have concluded that the data presented in this study highlight the value of conducting combined investigations at the molecular, genomic and clinical levels to fully describe the epidemiology and evolution of pediatric enterovirus infections in the context of a public health alert.