Change in Age profile of Respiratory Syncytial Virus disease over the course of annual epidemics: a multi-national study.

OBJECTIVES: We aimed to study whether the percentwise age distribution of RSV cases changes over time during annual epidemics. METHODS: We used surveillance data (2008-2019) from the Netherlands, Lyon (France), Portugal, Singapore, Ecuador, South Africa, and New Zealand. In each country, every season was divided into "epidemic quarters", i.e. periods corresponding to each quartile of RSV cases. Multinomial logistic regression models were fitted to evaluate whether the likelihood of RSV cases being aged <1 or ≥5 years (vs. 1 to <5) changed over time within a season. RESULTS: In all countries, RSV cases were significantly more likely to be aged <1 year in the 4th vs. 1st epidemic quarter; the relative risk ratio [RRR] ranged between 1.35 and 2.56. Likewise, RSV cases were significantly more likely to be aged ≥5 years in the 4th vs. 1st epidemic quarter (except in Singapore); the RRR ranged from 1.75 to 6.70. The results did not change when stratifying by level of care or moving the lower cut-off to 6 months. CONCLUSIONS: The age profile of RSV cases shifts within a season, with infants and adolescents, adults, and the elderly constituting a higher proportion of cases in the later phases of annual epidemics. These findings may have implications for RSV prevention policies with newly approved vaccines.

Global analysis of respiratory viral circulation and timing of epidemics in the pre-COVID-19 and COVID-19 pandemic eras, based on data from the Global Influenza Surveillance and Response System (GISRS).

INTRODUCTION: The COVID-19 pandemic significantly changed respiratory viruses' epidemiology due to non-pharmaceutical interventions and possible viral interactions. This study investigates whether the circulation patterns of respiratory viruses have returned to pre-pandemic norms by comparing their peak timing and duration during the first three SARS-CoV-2 seasons to pre-pandemic times. METHODS: GISRS data from 194 countries (2014-2023) was analyzed for epidemic peak timing and duration, focusing on pre-pandemic and pandemic periods across both hemispheres and the intertropical belt. Analysis was restricted to countries meeting specific data thresholds to ensure robustness. RESULTS: In 2022/23, the Northern hemisphere experienced earlier influenza and RSV peaks by 1.9 months (p<0.001). The duration of influenza epidemics increased by 2.2 weeks (p<0.001), with RSV showing a similar trend. The Southern hemisphere's influenza peak shift was not significant (p=0.437). Intertropical regions presented no substantial change in peak timing but experienced a significant reduction in duration for hMPV and adenovirus (7.2 and 6.5 weeks shorter, p<0.001). CONCLUSIONS: The pandemic altered the typical patterns of influenza and RSV, with earlier peaks in 2022 in temperate areas. These findings highlight the importance of robust surveillance data to inform public health strategies on evolving viral dynamics in the years to come.

COVID-19 vaccine effectiveness against symptomatic infection with SARS-CoV-2 BA.1/BA.2 lineages among adults and adolescents in a multicentre primary care study, Europe, December 2021 to June 2022.

BackgroundScarce European data in early 2021 suggested lower vaccine effectiveness (VE) against SARS-CoV-2 Omicron lineages than previous variants.AimWe aimed to estimate primary series (PS) and first booster VE against symptomatic BA.1/BA.2 infection and investigate potential biases.MethodsThis European test-negative multicentre study tested primary care patients with acute respiratory symptoms for SARS-CoV-2 in the BA.1/BA.2-dominant period. We estimated PS and booster VE among adults and adolescents (PS only) for all products combined and for Comirnaty alone, by time since vaccination, age and chronic condition. We investigated potential bias due to correlation between COVID-19 and influenza vaccination and explored effect modification and confounding by prior SARS-CoV-2 infection.ResultsAmong adults, PS VE was 37% (95% CI: 24-47%) overall and 60% (95% CI: 44-72%), 43% (95% CI: 26-55%) and 29% (95% CI: 13-43%) < 90, 90-179 and ≥ 180 days post vaccination, respectively. Booster VE was 42% (95% CI: 32-51%) overall and 56% (95% CI: 47-64%), 22% (95% CI: 2-38%) and 3% (95% CI: -78% to 48%), respectively. Primary series VE was similar among adolescents. Restricting analyses to Comirnaty had little impact. Vaccine effectiveness was higher among older adults. There was no signal of bias due to correlation between COVID-19 and influenza vaccination. Confounding by previous infection was low, but sample size precluded definite assessment of effect modification.ConclusionPrimary series and booster VE against symptomatic infection with BA.1/BA.2 ranged from 37% to 42%, with similar waning post vaccination. Comprehensive data on previous SARS-CoV-2 infection would help disentangle vaccine- and infection-induced immunity.

Delineating immune variation between adult and children COVID-19 cases and associations with disease severity.

The SARS-CoV-2 pandemic has emphasized the need to explore how variations in the immune system relate to the severity of the disease. This study aimed to explore inter-individual variation in response to SARS-CoV-2 infection by comparing T cell, B cell, and innate cell immune subsets among primary infected children and adults (i.e., those who had never experienced SARS-CoV-2 infection nor received vaccination previously), with varying disease severity after infection. We also examined immune subset kinetics in convalescent individuals compared to those with persistent infection to identify possible markers of immune dysfunction. Distinct immune subset differences were observed between infected adults and children, as well as among adult cases with mild, moderate, and severe disease. IgM memory B cells were absent in moderate and severe cases whereas frequencies of B cells with a lack of surface immunoglobulin expression were significantly higher in severe cases. Interestingly, these immune subsets remained stable during recovery implying that these subsets could be associated with underlying baseline immune variation. Our results offer insights into the potential immune markers associated with severe COVID-19 and provide a foundation for future research in this area.

Interim 2023/24 influenza A vaccine effectiveness: VEBIS European primary care and hospital multicentre studies, September 2023 to January 2024.

Influenza A viruses circulated in Europe from September 2023 to January 2024, with influenza A(H1N1)pdm09 predominance. We provide interim 2023/24 influenza vaccine effectiveness (IVE) estimates from two European studies, covering 10 countries across primary care (EU-PC) and hospital (EU-H) settings. Interim IVE was higher against A(H1N1)pdm09 than A(H3N2): EU-PC influenza A(H1N1)pdm09 IVE was 53% (95% CI: 41 to 63) and 30% (95% CI: -3 to 54) against influenza A(H3N2). For EU-H, these were 44% (95% CI: 30 to 55) and 14% (95% CI: -32 to 43), respectively.

Influenza vaccine effectiveness in Europe: Results from the 2022-2023 VEBIS (Vaccine Effectiveness, Burden and Impact Studies) primary care multicentre study.

Background: Influenza A(H3N2) viruses dominated early in the 2022-2023 influenza season in Europe, followed by higher circulation of influenza A(H1N1)pdm09 and B viruses. The VEBIS primary care network estimated the influenza vaccine effectiveness (VE) using a multicentre test-negative study. Materials and Methods: Primary care practitioners collected information and specimens from patients consulting with acute respiratory infection. We measured VE against any influenza, influenza (sub)type and clade, by age group, by influenza vaccine target group and by time since vaccination, using logistic regression. Results: We included 38 058 patients, of which 3786 were influenza A(H3N2), 1548 influenza A(H1N1)pdm09 and 3275 influenza B cases. Against influenza A(H3N2), VE was 36% (95% CI: 25-45) among all ages and ranged between 30% and 52% by age group and target group. VE against influenza A(H3N2) clade 2b was 38% (95% CI: 25-49). Overall, VE against influenza A(H1N1)pdm09 was 46% (95% CI: 35-56) and ranged between 29% and 59% by age group and target group. VE against influenza A(H1N1)pdm09 clade 5a.2a was 56% (95% CI: 46-65) and 79% (95% CI: 64-88) against clade 5a.2a.1. VE against influenza B was 76% (95% CI: 70-81); overall, 84%, 72% and 71% were among 0-14-year-olds, 15-64-year-olds and those in the influenza vaccination target group, respectively. VE against influenza B with a position 197 mutation of the hemagglutinin (HA) gene was 79% (95% CI: 73-85) and 90% (95% CI: 85-94) without this mutation. Conclusion: The 2022-2023 end-of-season results from the VEBIS network at primary care level showed high VE among children and against influenza B, with lower VE against influenza A(H1N1)pdm09 and A(H3N2).

High quality of SARS-CoV-2 molecular diagnostics in a diverse laboratory landscape through supported benchmark testing and External Quality Assessment.

A two-step strategy combining assisted benchmark testing (entry controls) and External Quality Assessments (EQAs) with blinded simulated clinical specimens to enhance and maintain the quality of nucleic acid amplification testing was developed. This strategy was successfully applied to 71 diagnostic laboratories in The Netherlands when upscaling the national diagnostic capacity during the SARS-CoV-2 pandemic. The availability of benchmark testing in combination with advice for improvement substantially enhanced the quality of the laboratory testing procedures for SARS-CoV-2 detection. The three subsequent EQA rounds demonstrated high quality testing with regard to specificity (99.6% correctly identified) and sensitivity (93.3% correctly identified). Even with the implementation of novel assays, changing workflows using diverse equipment and a high degree of assay heterogeneity, the overall high quality was maintained using this two-step strategy. We show that in contrast to the limited value of Cq value for absolute proxies of viral load, these Cq values can, in combination with metadata on strategies and techniques, provide valuable information for laboratories to improve their procedures. In conclusion, our two-step strategy (preparation phase followed by a series of EQAs) is a rapid and flexible system capable of scaling, improving, and maintaining high quality diagnostics even in a rapidly evolving (e.g. pandemic) situation.

Impact of Subgroup Distribution on Seasonality of Human Respiratory Syncytial Virus: A Global Systematic Analysis.

BACKGROUND: Previous studies reported inconsistent findings regarding the association between respiratory syncytial virus (RSV) subgroup distribution and timing of RSV season. We aimed to further understand the association by conducting a global-level systematic analysis. METHODS: We compiled published data on RSV seasonality through a systematic literature review, and unpublished data shared by international collaborators. Using annual cumulative proportion (ACP) of RSV-positive cases, we defined RSV season onset and offset as ACP reaching 10% and 90%, respectively. Linear regression models accounting for meteorological factors were constructed to analyze the association of proportion of RSV-A with the corresponding RSV season onset and offset. RESULTS: We included 36 study sites from 20 countries, providing data for 179 study-years in 1995-2019. Globally, RSV subgroup distribution was not significantly associated with RSV season onset or offset globally, except for RSV season offset in the tropics in 1 model, possibly by chance. Models that included RSV subgroup distribution and meteorological factors explained only 2%-4% of the variations in timing of RSV season. CONCLUSIONS: Year-on-year variations in RSV season onset and offset are not well explained by RSV subgroup distribution or meteorological factors. Factors including population susceptibility, mobility, and viral interference should be examined in future studies.

Effectiveness of Immunization Products Against Medically Attended Respiratory Syncytial Virus Infection: Generic Protocol for a Test-Negative Case-Control Study.

Monitoring the real-life effectiveness of respiratory syncytial virus (RSV) products is of major public health importance. This generic protocol for a test-negative design study aims to address currently envisioned approaches for RSV prevention (monoclonal antibodies and vaccines) to study effectiveness of these products among target groups: children, older adults, and pregnant women. The generic protocol approach was chosen to allow for flexibility in adapting the protocol to a specific setting. This protocol includes severe acute respiratory infection (SARI) and acute respiratory infection (ARI), both due to RSV, as end points. These end points can be applied to studies in hospitals, primarily targeting patients with more severe disease, but also to studies in general practitioner clinics targeting ARI.

Respiratory Syncytial Virus European Laboratory Network 2022 Survey: Need for Harmonization and Enhanced Molecular Surveillance.

Respiratory syncytial virus (RSV) is a common pathogen causing mostly cold-like symptoms, but in very young infants and elderly individuals it can lead to severe disease and even death. There are currently promising developments both in vaccine development and in therapeutics that are expected to be approved soon. To get an impression within European countries of the laboratory diagnostics and surveillance activities, in anticipation of these developments, we queried the members of the European Respiratory Syncytial Virus Laboratory Network (RSV-LabNet, under the umbrella of the PROMISE project) via an online survey. The answers from the consortium members showed scattered monitoring and the application of a broad array of techniques in the laboratories. A majority of the members expressed strong interest in harmonization and collaboration for setting up surveillance programs and the need for sharing laboratory protocols. The additional value of RSV whole-genome sequencing is broadly appreciated, but implementation requires further development and closer collaboration. The RSV-LabNet can have an important responsibility in establishing contacts and exchange of expertise and providing a platform for communication to advance diagnostics, preparedness, and surveillance.

Seasonal and inter-seasonal RSV activity in the European Region during the COVID-19 pandemic from autumn 2020 to summer 2022.

Background: The emergence of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in early 2020 and subsequent implementation of public health and social measures (PHSM) disrupted the epidemiology of respiratory viruses. This work describes the epidemiology of respiratory syncytial virus (RSV) observed during two winter seasons (weeks 40-20) and inter-seasonal periods (weeks 21-39) during the pandemic between October 2020 and September 2022. Methods: Using data submitted to The European Surveillance System (TESSy) by countries or territories in the World Health Organization (WHO) European Region between weeks 40/2020 and 39/2022, we aggregated country-specific weekly RSV counts of sentinel, non-sentinel and Severe Acute Respiratory Infection (SARI) surveillance specimens and calculated percentage positivity. Results for both 2020/21 and 2021/22 seasons and inter-seasons were compared with pre-pandemic 2016/17 to 2019/20 seasons and inter-seasons. Results: Although more specimens were tested than in pre-COVID-19 pandemic seasons, very few RSV detections were reported during the 2020/21 season in all surveillance systems. During the 2021 inter-season, a gradual increase in detections was observed in all systems. In 2021/22, all systems saw early peaks of RSV infection, and during the 2022 inter-seasonal period, patterns of detections were closer to those seen before the COVID-19 pandemic. Conclusion: RSV surveillance continued throughout the COVID-19 pandemic, with an initial reduction in transmission, followed by very high and out-of-season RSV circulation (summer 2021) and then an early start of the 2021/22 season. As of the 2022/23 season, RSV circulation had not yet normalised.

Inference of age-dependent case-fatality ratios for seasonal influenza virus subtypes A(H3N2) and A(H1N1)pdm09 and B lineages using data from the Netherlands.

Background: Despite the known relatively high disease burden of influenza, data are lacking regarding a critical epidemiological indicator, the case-fatality ratio. Our objective was to infer age-group and influenza (sub)type specific values by combining modelled estimates of symptomatic incidence and influenza-attributable mortality. Methods: The setting was the Netherlands, 2011/2012 through 2019/2020 seasons. Sentinel surveillance data from general practitioners and laboratory testing were synthesised to supply age-group specific estimates of incidence of symptomatic infection, and ecological additive modelling was used to estimate influenza-attributable deaths. These were combined in an Bayesian inferential framework to estimate case-fatality ratios for influenza A(H3N2), A(H1N1)pdm09 and influenza B, per 5-year age-group. Results: Case-fatality estimates were highest for influenza A(H3N2) followed by influenza B and then A(H1N1)pdm09 and were highest for the 85+ years age-group, at 4.76% (95% credible interval [CrI]: 4.52-5.01%) for A(H3N2), followed by influenza B at 4.08% (95% CrI: 3.77-4.39%) and A(H1N1)pdm09 at 2.51% (95% CrI: 2.09-2.94%). For 55-59 through 85+ years, the case-fatality risk was estimated to double with every 3.7 years of age. Conclusions: These estimated case-fatality ratios, per influenza sub(type) and per age-group, constitute valuable information for public health decision-making, for assessing the retrospective and prospective value of preventative interventions such as vaccination and for health economic evaluations.

Pediatric acute flaccid myelitis: Evaluation of diagnostic criteria and differentiation from other causes of acute flaccid paralysis.

BACKGROUND: Acute flaccid paralysis (AFP) is characterized by rapidly progressive limb weakness with low muscle tone. It has a broad differential diagnosis, which includes acute flaccid myelitis (AFM), a rare polio-like condition that mainly affects young children. Differentiation between AFM and other causes of AFP may be difficult, particularly at onset of disease. Here, we evaluate the diagnostic criteria for AFM and compare AFM to other causes of acute weakness in children, aiming to identify differentiating clinical and diagnostic features. METHODS: The diagnostic criteria for AFM were applied to a cohort of children with acute onset of limb weakness. An initial classification based on positive diagnostic criteria was compared to the final classification, based on application of features suggestive for an alternative diagnosis and discussion with expert neurologists. Cases classified as definite, probable, or possible AFM or uncertain, were compared to cases with an alternative diagnosis. RESULTS: Of 141 patients, seven out of nine patients initially classified as definite AFM, retained this label after further classification. For probable AFM, this was 3/11, for possible AFM 3/14 and for uncertain 11/43. Patients initially classified as probable or possible AFM were most commonly diagnosed with transverse myelitis (16/25). If the initial classification was uncertain, Guillain-Barré syndrome was the most common diagnosis (31/43). Clinical and diagnostic features not included in the diagnostic criteria, were often used for the final classification. CONCLUSION: The current diagnostic criteria for AFM usually perform well, but additional features are sometimes required to distinguish AFM from other conditions.

A Comprehensive Sampling Study on SARS-CoV-2 Contamination of Air and Surfaces in a Large Meat Processing Plant Experiencing COVID-19 Clusters in June 2020.

OBJECTIVE: We aimed to assess SARS-CoV-2 contamination of air and surfaces to gain insight into potential occupational exposure in a large meat processing plant experiencing COVID-19 clusters. Methods: Oro-nasopharyngeal SARS-CoV-2 screening was performed in 76 workers. Environmental samples ( n = 275) including air, ventilation systems, sewage, and swabs of high-touch surfaces and workers' hands were tested for SARS-CoV-2 RNA by real-time quantitative polymerase chain reaction. Results: Twenty-seven (35.5%) of the (predominantly asymptomatic) workers tested positive with modest to low viral loads (cycle threshold ≥ 29.7). Six of 203 surface swabs, 1 of 12 personal air samples, and one of four sewage samples tested positive; other samples tested negative. Conclusions: Although one third of workers tested positive, environmental contamination was limited. Widespread SARS-CoV-2 transmission via air and surfaces was considered unlikely within this plant at the time of investigation while strict COVID-19 control measures were already implemented.

Influenza vaccine effectiveness against influenza A subtypes in Europe: Results from the 2021-2022 I-MOVE primary care multicentre study.

BACKGROUND: In 2021-2022, influenza A viruses dominated in Europe. The I-MOVE primary care network conducted a multicentre test-negative study to measure influenza vaccine effectiveness (VE). METHODS: Primary care practitioners collected information on patients presenting with acute respiratory infection. Cases were influenza A(H3N2) or A(H1N1)pdm09 RT-PCR positive, and controls were influenza virus negative. We calculated VE using logistic regression, adjusting for study site, age, sex, onset date, and presence of chronic conditions. RESULTS: Between week 40 2021 and week 20 2022, we included over 11 000 patients of whom 253 and 1595 were positive for influenza A(H1N1)pdm09 and A(H3N2), respectively. Overall VE against influenza A(H1N1)pdm09 was 75% (95% CI: 43-89) and 81% (95% CI: 45-93) among those aged 15-64 years. Overall VE against influenza A(H3N2) was 29% (95% CI: 12-42) and 25% (95% CI: -41 to 61), 33% (95% CI: 14-49), and 26% (95% CI: -22 to 55) among those aged 0-14, 15-64, and over 65 years, respectively. The A(H3N2) VE among the influenza vaccination target group was 20% (95% CI: -6 to 39). All 53 sequenced A(H1N1)pdm09 viruses belonged to clade 6B.1A.5a.1. Among 410 sequenced influenza A(H3N2) viruses, all but eight belonged to clade 3C.2a1b.2a.2. DISCUSSION: Despite antigenic mismatch between vaccine and circulating strains for influenza A(H3N2) and A(H1N1)pdm09, 2021-2022 VE estimates against circulating influenza A(H1N1)pdm09 were the highest within the I-MOVE network since the 2009 influenza pandemic. VE against A(H3N2) was lower than A(H1N1)pdm09, but at least one in five individuals vaccinated against influenza were protected against presentation to primary care with laboratory-confirmed influenza.

Emergence and Potential Extinction of Genetic Lineages of Human Metapneumovirus between 2005 and 2021.

Human metapneumovirus (HMPV) is one of the leading causes of respiratory illness (RI), primarily in infants. Worldwide, two genetic lineages (A and B) of HMPV are circulating that are antigenically distinct and can each be further divided into genetic sublineages. Surveillance combined with large-scale whole-genome sequencing studies of HMPV are scarce but would help to identify viral evolutionary dynamics. Here, we analyzed 130 whole HMPV genome sequences obtained from samples collected from individuals hospitalized with RI and partial fusion (n = 144) and attachment (n = 123) protein gene sequences obtained from samples collected from patients with RI visiting general practitioners between 2005 and 2021 in the Netherlands. Phylogenetic analyses demonstrated that HMPV continued to group in the four sublineages described in 2004 (A1, A2, B1, and B2). However, one sublineage (A1) was no longer detected in the Netherlands after 2006, while the others continued to evolve. No differences were observed in dominant (sub)lineages between samples obtained from patients with RI being hospitalized and those consulting general practitioners. In both populations, viruses of lineage A2 carrying a 180-nucleotide or 111-nucleotide duplication in the attachment protein gene became the most frequently detected genotypes. In the past, different names for the newly energing lineages have been proposed, demonstrating the need for a consistent naming convention. Here, criteria are proposed for the designation of new genetic lineages to aid in moving toward a systematic HMPV classification. IMPORTANCE Human metapneumovirus (HMPV) is one of the major causative agents of human respiratory tract infections. Monitoring of virus evolution could aid toward the development of new antiviral treatments or vaccine designs. Here, we studied HMPV evolution between 2005 and 2021, with viruses obtained from samples collected from hospitalized individuals and patients with respiratory infections consulting general practitioners. Phylogenetic analyses demonstrated that HMPV continued to group in the four previously described sublineages (A1, A2, B1, and B2). However, one sublineage (A1) was no longer detected after 2006, while the others continued to evolve. No differences were observed in dominant (sub)lineages between patients being hospitalized and those consulting general practitioners. In both populations, viruses of lineage A2 carrying a 180-nucleotide or 111-nucleotide duplication in the attachment protein gene became the most frequently detected genotypes. These data were used to propose criteria for the designation of new genetic lineages to aid toward a systematic HMPV classification.

Sensitivity of Detection and Variant Typing of SARS-CoV-2 in European Laboratories.

The molecular detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is key for clinical management and surveillance. Funded by the European Centre for Disease Prevention and Control, we conducted an external quality assessment (EQA) on the molecular detection and variant typing of SARS-CoV-2 that included 59 European laboratories in 34 countries. The EQA panel consisted of 12 lyophilized inactivated samples, 10 of which were SARS-CoV-2 variants (Alpha, Beta, Gamma, Delta, Epsilon, Eta, parental B.1 strain) ranging from 2.5 to 290.0 copies/µL or pooled respiratory viruses (adenovirus, enterovirus, influenza virus A, respiratory syncytial virus, or human coronaviruses 229E and OC43). Of all participants, 72.9% identified the presence of SARS-CoV-2 RNA correctly. In samples containing 25.0 or more genome copies/µL, SARS-CoV-2 was detected by 98.3% of the participating laboratories. Laboratories applying commercial tests scored significantly better (P < 0.0001, Kruskal-Wallis test) than those using in-house assays. Both the molecular detection and the typing of the SARS-CoV-2 variants were associated with the RNA concentrations (P < 0.0001, Kruskal-Wallis test). On average, only 5 out of the 10 samples containing different SARS-CoV-2 variants at different concentrations were correctly typed. The identification of SARS-CoV-2 variants was significantly more successful among EQA participants who combined real-time reverse transcription polymerase chain reaction (RT-PCR)-based assays for mutation detection and high-throughput genomic sequencing than among those who used a single methodological approach (P = 0.0345, Kruskal-Wallis test). Our data highlight the high sensitivity of SARS-CoV-2 detection in expert laboratories as well as the importance of continuous assay development and the benefits of combining different methodologies for accurate SARS-CoV-2 variant typing.

Epidemiology of acute flaccid myelitis in children in the Netherlands, 2014 to 2019.

BackgroundAcute flaccid myelitis (AFM) is a polio-like condition affecting mainly children and involving the central nervous system (CNS). AFM has been associated with different non-polio-enteroviruses (EVs), in particular EV-D68 and EV-A71. Reliable incidence rates in European countries are not available.AimTo report AFM incidence in children in the Netherlands and its occurrence relative to EV-D68 and EV-A71 detections.MethodsIn 10 Dutch hospitals, we reviewed electronic health records of patients diagnosed with a clinical syndrome including limb weakness and/or CNS infection and who were < 18 years old when symptoms started. After excluding those with a clear alternative diagnosis to AFM, those without weakness, and removing duplicate records, only patients diagnosed in January 2014-December 2019 were retained and further classified according to current diagnostic criteria. Incidence rates were based on definite and probable AFM cases. Cases' occurrences during the study period were co-examined with laboratory-surveillance detections of EV-D68 and EV-A71.ResultsAmong 143 patients included, eight were classified as definite and three as probable AFM. AFM mean incidence rate was 0.06/100,000 children/year (95% CI: -0.03 to 0.14). All patient samples were negative for EV-A71. Of respiratory samples in seven patients, five were EV-D68 positive. AFM cases clustered in periods with increased EV-D68 and EV-A71 detections.ConclusionsAFM is rare in children in the Netherlands. The temporal coincidence of EV-D68 circulation and AFM and the detection of this virus in several cases' samples support its association with AFM. Increased AFM awareness among clinicians, adequate diagnostics and case registration matter to monitor the incidence.