Simoes, Margarida PiresHodcroft, Emma BSimmonds, PeterAlbert, JanAlidjinou, Enagnon KAmbert-Balay, KatiaAndrés, CristinaAntón, AndrésAuvray, ChristelleBailly, Jean-LucBaldanti, FaustoBastings, CapserBeard, StuartBerengua, CarlaBerginc, NatasaBloemen, MandyBlomqvist, SoileBosma, FroukjeBöttcher, SindyBubba, LauraBuderus, StafanCabrerizo, MariaCalvo, CristinaCelma, CristinaCeriotti, FerruccioClark, GemmaCosta, InësCoste-Burel, MarianneCouderé, KarenCremer, JeroenDel Cuerpo Casas, MargaritaDaehne, Theode Beer, Jessicade Ceano-Vivas, MariaDe Gascun, Cilliande Rougemont, AlexisDean, JonathanDembinski, Jennifer LDiedrich, SabineDiez-Domingo, JavierDillner, LenaDorenberg, Dagny HDucancelle, AlexandraDudman, SusanneDyrdak, RobertEis-Huebinger, Anna-MariaFalces-Romero, IkerFarkas, AgnesFeeney, SusanFernandez-Garcia, Maria DFlipse, JackyFranck, Kristina TGalli, CristinaGarrigue, IsabelleGeeraedts, FelixGeorgieva, IrinaGiardina, FedericaGuiomar, RaquelHauzenberger, ElenorHeikens, EstherHenquell, CécilleHober, DidierHönemann, MarioHowson-Wells, HannahHruškar, ŽeljkaIkonen, NiinaImbert, BerthemarieJansz, Arjan RJeannoël, MarionJiřincová, HelenaJosset, LaurenceKeeren, KathrinKramer-Lindhout, NaomieKrokstad, SidselLazrek, MounaLe Guillou-Guillemette, HélèneLefeuvre, CarolineLind, AndreasLunar, Maja MMaier, MelanieMarque-Juillet, StéphanieMcClure, C PatrickMcKenna, JamesMeijer, AdamMenasalvas Ruiz, AnaMengual-Chuliá, BeatrizMidgley, SofieMirand, AudreyMolenkamp, RichardMontes, MilagrosaMoreno-Docón, AntonioMorley, UrsulaMurk, Jean-LucNavascués-Ortega, AnaNijhuis, RoelNikolaeva-Glomb, LubomiraNordbø, Svein ANumanovic, SanelaOggioni, MassimoOñate Vergara, EiderPacaud, JordiPacreau, Marie LPanning, MarcusPariani, ElenaPekova, LiliPellegrinelli, LauraPetrovec, MiroslavPietsch, CorinnaPilorge, LéaPiñeiro, LuisPiralla, AntonioPoljak, MarioProchazka, BirgitRabella, NuriaRahamat-Langendoen, Janette CRainetova, PetraReynders, MarijkeRiezebos-Brilman, AnneliesRoorda, LieuweSavolainen-Kopra, CaritaSchuffenecker, IsabelleSmeets, Leo CStoyanova, AsyaStefic, KarlSwanink, CarolineTabain, IrenaTjhie, JeroenThouault, LucTumiotto, CamilleUceda Renteria, SaraUršič, TinaVallet, SophieVan Ranst, MarcVan Wunnik, PeterVerweij, Jaco JVila, JorginaWintermans, BasWollants, ElkeWolthers, Katja CXavier López-Labrador, FFischer, Thea KolsenHarvala, HeliBenschop, Kimberley S M2025-01-032025-01-032024-10-163854749910.1093/infdis/jiae154https://rivm.openrepository.com/handle/10029/628069Enterovirus 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.en© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.European Non-Polio Enterovirus Network (ENPEN)acute flaccid myelitis (AFM)enterovirus D68 (EV-D68)nonpolio enterovirus (NPEV)respiratory infectionEpidemiological and Clinical Insights into the Enterovirus D68 Upsurge in Europe 2021-2022 and Emergence of Novel B3-Derived Lineages, ENPEN Multicentre Study.ArticleJ Infect Dis 2024; 230(4):e917-e9287637136