Enhanced echovirus 11 genomic surveillance in neonatal infections in Spain following a European alert reveals new recombinant forms linked to severe cases, 2019 to 2023

Abstract

Enteroviruses (EV) are common human viruses associated with diverse clinical syndromes ranging from minor febrile illness to rare but severe and potentially fatal conditions such as aseptic meningitis, paralysis, myocarditis and sepsis-like disease, particularly in newborns [1]. The incidence of EV infection among febrile infants admitted to hospital with systemic infection or infants with suspected sepsis has been reported by different authors to range from 3% to 50% [1,2]. Prematurity, maternal history of EV illness, onset of illness within the first days of life and infecting EV-type, especially B species such as coxsackievirus (CV) B or echovirus 11 (E11), are significant factors associated with severe or even fatal neonatal EV infections [1,3-5]. In 2023, France reported nine severe E11 neonatal infections with liver failure and high mortality rate, with pronounced prevalence in male twins [6]. All E11 sequences associated with severe cases clustered in a new lineage 1 that emerged in 2022 [6] leading to a public health international alert [7,8]. Two cases of severe hepatitis associated with the same lineage 1 were reported during the same period (2023) in Italy [9]. Analysis of the complete genomes demonstrated that all severe and fatal cases were associated with an E11 strain of recombinant origin [6,9]. In July 2023, the European Centre for Disease Prevention and Control appealed for enhancing surveillance regarding severe neonatal E11 infections to assess whether the new lineage 1 first detected in France was associated with more severe disease [7]. Similar to that observed in other European Union (EU) countries, E11 in Spain is among the most commonly notified EV genotypes, mostly affecting children under 3 months of age [10-13]. In this study, we describe the molecular epidemiology and clinical characteristics associated with E11 infections between 2019 and 2023 in Spain. The aim was to investigate whether the newly reported lineage 1 variant emerged and circulated in Spain after the COVID-19 pandemic, causing severe neonatal infections.