key: cord-1010620-0sn7itog authors: Benschop, Kimberley SM; Albert, Jan; Anton, Andres; Andrés, Cristina; Aranzamendi, Maitane; Armannsdóttir, Brynja; Bailly, Jean-Luc; Baldanti, Fausto; Baldvinsdóttir, Guðrún Erna; Beard, Stuart; Berginc, Natasa; Böttcher, Sindy; Blomqvist, Soile; Bubba, Laura; Calvo, Cristina; Cabrerizo, Maria; Cavallero, Annalisa; Celma, Cristina; Ceriotti, Ferruccio; Costa, Inês; Cottrell, Simon; del Cuerpo, Margarita; Dean, Jonathan; Dembinski, Jennifer L; Diedrich, Sabine; Diez-Domingo, Javier; Dorenberg, DagnyHaug; Duizer, Erwin; Dyrdak, Robert; Fanti, Diana; Farkas, Agnes; Feeney, Susan; Flipse, Jacky; De Gascun, Cillian; Galli, Cristina; Georgieva, Irina; Gifford, Laura; Guiomar, Raquel; Hönemann, Mario; Ikonen, Niina; Jeannoël, Marion; Josset, Laurence; Keeren, Kathrin; López-Labrador, F Xavier; Maier, Melanie; McKenna, James; Meijer, Adam; Mengual-Chuliá, Beatriz; Midgley, Sofie E; Mirand, Audrey; Montes, Milagrosa; Moore, Catherine; Morley, Ursula; Murk, Jean-Luc; Nikolaeva-Glomb, Lubomira; Numanovic, Sanela; Oggioni, Massimo; Palminha, Paula; Pariani, Elena; Pellegrinelli, Laura; Piralla, Antonio; Pietsch, Corinna; Piñeiro, Luis; Rabella, Núria; Rainetova, Petra; Uceda Renteria, Sara Colonia; Romero, María P; Reynders, Marijke; Roorda, Lieuwe; Savolainen-Kopra, Carita; Schuffenecker, Isabelle; Soynova, Aysa; Swanink, Caroline MA; Ursic, Tina; Verweij, Jaco J; Vila, Jorgina; Vuorinen, Tytti; Simmonds, Peter; Fischer, Thea K; Harvala, Heli title: Re-emergence of enterovirus D68 in Europe after easing the COVID-19 lockdown, September 2021 date: 2021-11-11 journal: Euro Surveill DOI: 10.2807/1560-7917.es.2021.26.45.2100998 sha: 7ea7fc5584d7f40cb832e3cdf1f8173a3e5ded78 doc_id: 1010620 cord_uid: 0sn7itog We report a rapid increase in enterovirus D68 (EV-D68) infections, with 139 cases reported from eight European countries between 31 July and 14 October 2021. This upsurge is in line with the seasonality of EV-D68 and was presumably stimulated by the widespread reopening after COVID-19 lockdown. Most cases were identified in September, but more are to be expected in the coming months. Reinforcement of clinical awareness, diagnostic capacities and surveillance of EV-D68 is urgently needed in Europe. We report a rapid increase in enterovirus D68 (EV-D68) infections, with 139 cases reported from eight European countries between 31 July and 14 October 2021. This upsurge is in line with the seasonality of EV-D68 and was presumably stimulated by the widespread reopening after COVID-19 lockdown. Most cases were identified in September, but more are to be expected in the coming months. Reinforcement of clinical awareness, diagnostic capacities and surveillance of EV-D68 is urgently needed in Europe. A total of 36 institutions including 19 public health and 17 hospital laboratories from 18 European countries responded to the ENPEN alert (Table 1) . We requested data on EV-D68 cases and detection methods. The 19 public health laboratories from 13 countries indicated that they would identify EV-D68 infections either via their EV surveillance (n = 14), surveillance focusing on influenza-like illness (ILI) and/ or acute respiratory infection (ARI; n = 8), or via surveillance for acute flaccid paralysis (AFP) (n = 6). Two laboratories (in the Czech Republic and Germany) had not included respiratory samples in their EV surveillance. Data on screening and typing were supplied by 33 laboratories. All except one of the 14 hospital laboratory tested respiratory samples for EV-D68. The use of EV-D68-specific PCR was reported by 13 of 33 laboratories, and genetic characterisation by sequencing was applied in most laboratories (28/33, Table 2 ). A total of 139 EV-D68 cases were identified between 31 July and 14 October 2021 by 12 laboratories in eight countries (Table 1 ). Most EV-D68-positive samples were collected in September (99/139, 71%, Figure) . Screening and typing of samples collected in October is ongoing. Denominator data were available from 24 laboratories reporting 66 of 139 EV-D68 cases. Since the beginning of 2021, these laboratories identified 1,964 EV-positive samples by screening 56,401 samples by EV PCR (some also detecting and hence including rhinoviruses in these reports). While the number of samples tested monthly remained unchanged (on average 6,113 samples screened monthly between January and July, 5,170 in August and 6,353 in September), an increase in the positivity rate was noted (overall 2.5% in January through July, 4.5% in August and 8.2% in September). A total of 967 samples were typed as EV and 36 as EV-D68. The proportion of samples identified as EV-D68 increased from 0.2% in January through July (1/409) and 0.9% in August (2/208) to 14% in September (33/236; p < 0.0001 by chi-squared test). An additional 30 EV-D68-positive samples were identified by screening of 8,243 respiratory samples by EV-D68-specific PCR in 13 laboratories. Of these, none was identified before August despite screening of 5,088 samples since January (monthly average: 727 samples). Three EV-D68 positive samples were identified in August (3/739; 0.4%) and 27 in September and October (27/1,289; 2%) demonstrating a recent but significant increase in the EV-D68 positivity rate (p < 0.0001 by chi-squared test). Demographic information was collected for all reported EV-D68 cases (Table 3 ). Most were males (88/139; 63%) and younger than 5 years (120/139; 86%), with a median age of 3 years (range: newborns to 72 years). Clinical symptoms were reported for 120 cases, with most exhibiting respiratory symptoms (n = 116; 97%). Although five cases had neurological symptoms, none was diagnosed with AFP or acute flaccid myelitis (AFM). Thirty of 49 cases with data on hospitalisation were hospitalised. Pre-existing conditions were reported for 20 of 45 cases with available information, predominantly in older age groups (2/14 < 2 years, 18/31 > 2 years). Viral co-infection was reported for 16 cases; the most common co-detection was rhinovirus (n = 9). To date, genotyping of 20 EV-D68 positive samples has shown all strains to be genotype B3 (data not shown). Enterovirus D68 (EV-D68) infections have been linked to AFP/AFM since a large outbreak associated with respiratory and neurological symptoms in children was described in North America in 2014 [1, 2] . Although regular EV-D68 upsurges have been reported in Europe since 2010 [2] [3] [4] [5] [6] [7] , they largely ceased during the coronavirus disease (COVID-19) pandemic. Here we report EV-D68 circulation across Europe for the first time following the COVID-19 pandemic, with case numbers already exceeding what was reported during the most recent EV-D68 upsurge in 2019 [7] . Although EV-D68 circulation in Europe has largely followed a biennial epidemic pattern confined to the autumn season of even-numbered years, the autumn of 2019 showed an unexpected upsurge of EV-D68 infections leading to 93 reported cases, two with AFM, in five European countries [7] . EV-D68 has largely been detected through ILI/ARI sentinel surveillance because of its respiratory signature and in EV surveillance systems which have included respiratory samples since the occurrence of the first large outbreak of EV-D68 in Europe and North America where these samples were recommended [8, 9] . Several institutes have additionally included EV-D68-specific PCR for their respiratory surveillance. The timing of this increase in the number of EV-D68 infections is consistent with the known seasonality of EV, with numbers usually peaking in September and October [10] . However, this marked upsurge is likely to have been further precipitated by the widespread relaxation of COVID-19 mitigation measures such as travel restrictions, school closures, use of face masks and physical distancing. The findings are indeed consistent with the widespread resurgence of other community-transmitted respiratory infections, whose circulation in most of Europe had until recently largely ceased [11, 12] . The interruption in the transmission of respiratory and enteric viruses, including EV-D68, has probably created large cohorts of susceptible young children without prior exposure or immunity to any such virus, potentially creating the conditions for largescale outbreaks of severe respiratory disease in this age group this winter. As circulation of EV diminished during the lockdown, many of the surveillance systems not related to SARS-CoV-2 were temporarily discontinued or received fewer specimens because testing facilities prioritised SARS- the zero-reporting noted by two countries in this study was due to the exclusion of respiratory samples from their EV surveillance, an important reminder that a respiratory sample is needed for the detection of EV-D68 (even in cases of AFM) as the virus is only rarely detected in faecal or cerebrospinal fluid samples [9] . Our data clearly demonstrate that EV-D68 is now circulating in Europe, mostly affecting children or those with underlying conditions. Most paediatric cases presented with respiratory symptoms. Although no AFM cases were reported, we should be alert to the possibility of EV-D68-associated AFM cases occurring in the coming months following the rise in EV-D68 cases most evident in Wales, Belgium, France and Spain. The same trends were noted during the North American outbreak in 2014 where the majority of the initial cases were associated with respiratory diseases and neurological cases were only observed with a delay of a few weeks [1] . We recommend sequence analysis of EV-D68 to determine the relatedness of viruses circulating in Europe, and their potential link to a novel B3 subclade reported in 2019 [7] . The existing surveillance systems as well as laboratory and clinical networks relating to EV-D68 should be activated as this infection can have severe consequences [17] [18] [19] [20] . Re-emergence of EV-D68, and its known association with several neurological infections, is a reminder that the surveillance for EV infections is important. This study shows that EV-D68 cases can be identified through a combination of ILI/ARI sentinel surveillance and EV surveillance expanded to include respiratory samples. It calls for continued careful monitoring and vigilant testing of respiratory samples. 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Front Neurol The authors wish to thank the European Society for Clinical Virology for hosting the European Non-Polio Enterovirus Network (ENPEN). The authors would also like to thank everybody who contributed to the collection, testing and reporting of clinical and virological data presented in this study. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY 4.0) Licence. You may share and adapt the material, but must give appropriate credit to the source, provide a link to the licence and indicate if changes were made.Any supplementary material referenced in the article can be found in the online version.