Epidemiological and Clinical Insights into the Enterovirus D68 Upsurge in Europe 2021–2022 and Emergence of Novel B3-Derived Lineages, ENPEN Multicentre Study
Authors: Simoes Margarida Pires , Hodcroft Emma B , Simmonds Peter , Albert Jan , Alidjinou Enagnon K , Ambert-Balay Katia , Andrés Cristina , Antón Andrés , Auvray Christelle , Bailly Jean-Luc , Baldanti Fausto , Bastings Capser , Beard Stuart , Berengua Carla , Berginc Natasa , Bloemen Mandy , Blomqvist Soile , Bosma Froukje , Böttcher Sindy , Bubba Laura , Buderus Stafan , Cabrerizo Maria , Calvo Cristina , Celma Cristina , Ceriotti Ferruccio , Clark Gemma , Costa Inës , Coste-Burel Marianne , Couderé Karen , Cremer Jeroen , del Cuerpo Casas Margarita , Daehne Theo , de Beer Jessica , de Ceano-Vivas Maria , De Gascun Cillian , de Rougemont Alexis , Dean Jonathan , Dembinski Jennifer L , Diedrich Sabine , Diez-Domingo Javier , Dillner Lena , Dorenberg Dagny H , Ducancelle Alexandra , Dudman Susanne , Dyrdak Robert , Eis-Huebinger Anna-Maria , Falces-Romero Iker , Farkas Agnes , Feeney Susan , Fernandez-Garcia Maria D , Flipse Jacky , Franck Kristina T , Galli Cristina , Garrigue Isabelle , Geeraedts Felix , Georgieva Irina , Giardina Federica , Guiomar Raquel , Hauzenberger Elenor , Heikens Esther , Henquell Cécille , Hober Didier , Hönemann Mario , Howson-Wells Hannah , Hruškar Željka , Ikonen Niina , Imbert Berthemarie , Jansz Arjan R , Jeannoël Marion , Jiřincová Helena , Josset Laurence , Keeren Kathrin , Kramer-Lindhout Naomie , Krokstad Sidsel , Lazrek Mouna , Le Guillou-Guillemette Hélène , Lefeuvre Caroline , Lind Andreas , Lunar Maja M , Maier Melanie , Marque-Juillet Stéphanie , McClure C Patrick , McKenna James , Meijer Adam , Menasalvas Ruiz Ana , Mengual-Chuliá Beatriz , Midgley Sofie , Mirand Audrey , Molenkamp Richard , Montes Milagrosa , Moreno-Docón Antonio , Morley Ursula , Murk Jean-Luc , Navascués-Ortega Ana , Nijhuis Roel , Nikolaeva-Glomb Lubomira , Nordbø Svein A , Numanovic Sanela , Oggioni Massimo , Oñate Vergara Eider , Pacaud Jordi , Pacreau Marie L , Panning Marcus , Pariani Elena , Pekova Lili , Pellegrinelli Laura , Petrovec Miroslav , Pietsch Corinna , Pilorge Léa , Piñeiro Luis , Piralla Antonio , Poljak Mario , Prochazka Birgit , Rabella Nuria , Rahamat-Langendoen Janette C , Rainetova Petra , Reynders Marijke , Riezebos-Brilman Annelies , Roorda Lieuwe , Savolainen-Kopra Carita , Schuffenecker Isabelle , Smeets Leo C , Stoyanova Asya , Stefic Karl , Swanink Caroline , Tabain Irena , Tjhie Jeroen , Thouault Luc , Tumiotto Camille , Uceda Renteria Sara , Uršič Tina , Vallet Sophie , Van Ranst Marc , Van Wunnik Peter , Verweij Jaco J , Vila Jorgina , Wintermans Bas , Wollants Elke , Wolthers Katja C , Xavier López-Labrador F , Fischer Thea Kolsen , Harvala Heli , Benschop Kimberley S M 
Published: March 2024

Abstract
Enterovirus D68 (EV-D68) infections are associated with severe respiratory disease and acute flaccid myelitis (AFM). The European Non-Polio Enterovirus Network (ENPEN) aimed to investigate the epidemiological and genetic characteristics of EV-D68 infections and its clinical impact during the fall-winter season of 2021–2022. From 19 European countries, 58 institutes reported 10 481 (6.8%) EV-positive samples of which 1004 (9.6%) were identified as EV-D68 (including 852 respiratory samples). Clinical data were reported for 969 cases; 78.9% of infections were reported in children (0–5 years); and 37.9% of cases were hospitalized. Acute respiratory distress was commonly noted (93.1%) followed by fever (49.4%). Neurological problems were observed in 6.4% of cases including 6 diagnosed with AFM. Phylodynamic/Nextstrain and phylogenetic analyses based on 694 sequences showed the emergence of 2 novel B3-derived lineages, with no regional clustering. In conclusion, we describe a large-scale European EV-D68 upsurge with severe clinical impact and the emergence of B3-derived lineages.