Eurosurveillance: Severe and fatal neonatal infections linked to a new variant of echovirus 11, France, July 2022 to April 2023

#17,479

Earlier today, in WHO: DON On Enterovirus (Echovirus-11 (E-11)) Uptick In France, we looked at report from the World Health Organization on an apparent new lineage of Echovirus-11 affecting neonates in France. 

In the past hour, the ECDC journal Eurosurveillance has published a detailed Rapid Communications on this emerging viral threat.  I've only reproduced the abstract, discussion, and conclusion below. 

Follow the link to read the full report. 

Severe and fatal neonatal infections linked to a new variant of echovirus 11, France, July 2022 to April 2023

Mathilde Grapin1,* , Audrey Mirand2,3,* , Didier Pinquier4 , Aurélie Basset5 , Matthieu Bendavid1 , Maxime Bisseux2,3 , Marion Jeannoël6 , Bérengère Kireche7 , Manoelle Kossorotoff8 , Anne-Sophie L’Honneur9 , Lila Robin7 , Yves Ville10 , Sylvain Renolleau1 , Véronique Lemee11 , Pierre-Henri Jarreau5 , Isabelle Desguerre8 , Florence Lacaille12 , Marianne Leruez-Ville13 , Clémence Guillaume14 , Cécile Henquell2,3 , Alexandre Lapillonne15 , Isabelle Schuffenecker6,** , Mélodie Aubart8,16,** 

Enteroviruses (EV) are a common cause of neonatal infections with clinical manifestations ranging from asymptomatic to severe and sometimes fatal disease [1–3]. Between July 2022 and April 2023, nine cases of severe neonatal infection with a liver failure were reported in France. Seven of these children died. All were associated with a new variant of echovirus 11 (E-11). We describe the clinical and virological characteristics of this upsurge of highly severe neonatal EV infections.

Discussion

We report a cluster of severe neonatal cases with liver failure and a high mortality rate associated with a new variant of E-11, leading to an alert in the European Union Early Warning and Response System on 4 May 2023, and inclusion in the ECDC Communicable Disease Threat Report [9]. Enterovirus infections in neonates may be associated with severe clinical illness and mortality depending on (i) the infecting EV type, of which the group B coxsackieviruses and E-11 are the most commonly EVs associated with neonatal sepsis [10] and (ii) the clinical infection phenotype, where the mortality rate is the highest for severe hepatitis or myocarditis manifestations [11].

Fulminant hepatitis associated with E-11 has already been described, but the high fatality rate within a nine-month period and the high proportion of twin cases were striking in this cluster. All patients presented with one or more well-known risk factors for severe neonatal EV infection, which are maternal evidence of a recent EV infection (four of the five mothers in this report), prematurity and onset of illness within the first few days of life [1,11].

The emergence of a new E-11 variant of recombinant origin in 2022, after a period of a low-level circulation of this type since 2008 may have led to a higher proportion of women susceptible to E-11 infection and subsequently to the higher proportion of E-11 associated neonatal infections observed in 2022–2023. Recombination, which frequently occurs in enteroviruses, is considered a factor driving viral emergence. Whether the genetic changes of the predominant circulating E-11 lineage have influenced the pathogenicity needs further investigation. Host genetic factors affecting immunity might also have influenced the clinical severity observed in the nine cases (by comparison with other patients infected with the same E-11 variant during their first week of life) as previously described in EV rhombencephalitis cases [12]. High prevalence of boys in severe neonatal EV infection might speak for a predisposition associated with X-chromosome.

Therapeutic options for neonatal EV infections are limited and include intravenous immunoglobulins or investigational/compassionated specific antiviral therapy consisting of pleconaril or pocapavir [13–15]. We used pocapavir for three patients, of whom two survived, but the efficacy of the treatment cannot be concluded from our data.

Conclusion

This report suggests that a new variant of E-11 is currently circulating and associated with a high risk of severe neonatal infection and death at least in France. Clinicians should be aware of potential involvement of EV in severe clinical presentations in neonates, as they are at the frontline to detect such cases. Enterovirus surveillance in France, as in most European country, is a voluntary system reporting EV-positive cases which could lead to an underestimation of the number of severe cases if EV genome detection is not considered. As a reminder, symptomatic neonatal EV disease initially presents as a neonatal sepsis, which is clinically indistinguishable from bacterial or herpes simplex virus infections.

Neonates with an unexplained sepsis who present with signs of myocarditis or liver failure with cytolysis should be rapidly evaluated for EV infection, especially if the mother has had acute symptoms of gastroenteritis in the days before birth. Blood, as well as respiratory, cerebrospinal fluid and stool samples should be collected for initial testing and further sequencing. Therapeutic options as IVIg or pocapavir should be considered.

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