Kimberley Samantha Meheriaha Benschop ^1* Caroline Klint Johannesen ² Sofie Midgley ³ Heli Harvala ⁴ Thea Kølsen Fischer ⁵

• ¹ National Institute for Public Health and the Environment (Netherlands), Bilthoven, Netherlands
• ² Nordsjællands Hospital, Hillerød, Zealand, Denmark
• ³ State Serum Institute (SSI), Copenhagen, Hovedstaden, Denmark
• ⁴ University College London, London, England, United Kingdom
• ⁵ University of Copenhagen, Copenhagen, Capital Region of Denmark, Denmark

The study by Johannsen et al (8) on EV infections linked to hospitalizations and outpatient visits in Denmark 2015-2022, shows that while the COVID-19 pandemic led to a drastic decrease in number of cases reported, it has not affected the seasonal patterns (also seen by Ursic et al, Landaas et al and Dudman et al (1,2,9)). Central nervous system (CNS) infections were commonly found among neonates in hospitalized settings, while skin infections were more common among outpatients. The age distribution of patients with CNS infection and skin infections remained similar before and after the pandemic, with neonates commonly affected with CNS infections and children aged 1-2 years with skin infections respectively. Of interest is that Dudman et al (9), who studied EV infections from 2016-2022 noted an increase in detection skin infections with coxsackievirus A6 (CVA6), a virus most often associated with skin infections and in particular atypical hand foot and mouth disease. The dominance of CVA6 continued also after the COVID-19 pandemic.In a similar study period, Ursic et al showed a similar seasonal pattern of EV circulation for 2014 and 2016. In addition, they demonstrated EV-D68 circulation in Slovenia during the biannual years pre COVID-19 pandemic, 2014-2016, and hardly any cases after that. Landaas et al (2)also showed also an upsurge of EV-D68 cases in these two years in Norway when studying a period from 2012-2022, with low numbers in 2018, 2019 and 2021.Of interest is that for 2021, a European wide upsurge of EV-D68 was observed following ease of the COVID-19 pandemic restriction (7) The studies in this research topic show the differences in the epidemiology of EV infections between countries/institutes. This may reflect the true circulation in these countries although its more likely to reflect the lack of standardized public health surveillance guidelines and/or systems, challenging the comparability among these and other studies (7,(10)(11)(12). These include the lack of a uniform case definition and sampling strategy, and differences in screening and typing methods across institutes. In addition, while the European region has set up uniform legal and ethical regulations concerning data sharing, the implementation and interpretation proves to be limiting uniform data sharing. The varied and in some cases incomplete reporting to larger ENPEN studies may lead to biases in the data. As such to understand and better determine the disease burden of EV infection, we need clear standardization of data collection with comprehensive reporting. Utilizing existing surveillance systems for poliovirus and non-polio enteroviruses, enables synergy between the different surveillance systems (clinical, sewage and AFP surveillance) which is needed for overall enterovirus surveillance as for poliovirus surveillance specifically (Fischer et al, manuscript submitted). The final study in this research topic reflects on the identification of a fatal case of EV-A71 in 2019. Despite their effort in enhanced communication, surveillance, and typing the overall number of clinical EV positive cases was low in 2019, yet environmental surveillance showed continued circulation of EVs and the EV-A71 strain.ENPEN is an interdisciplinary consortium which brings together specialists from clinical, diagnostic and research areas including clinical and molecular virology, epidemiology, public health, neurology, and pediatric infectious diseases across Europe and beyond. The main aim of ENPEN is to ensure harmonized, coordinated and standardized (real-time) data sharing and collaborative research.