Genome Sequences of Rare Human Enterovirus Genotypes Recovered from Clinical Respiratory Samples in Bern, Switzerland

Grädel, Carole; Ireddy, N. R.; Koch, Michel C.; Baumann, Christian; Miani, Miguel Angel Terrazos; Barbani, Maria Teresa; Steinlin-Schopfer, Jacqueline; Suter‐Riniker, Franziska; Leib, Stephen L.; Ramette, Alban

doi:10.1128/mra.00276-22

Cited by 6 publications

(4 citation statements)

References 22 publications

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“…Enteroviruses are a very diverse and variable genus, characterized by worldwide distribution. Research on enteroviruses has continued to grow, particularly due to regional outbreaks over the last 20 years [6,12,[15][16][17][18][19][20][21][22][23]. Virus genotyping is likely to be of increasing interest in the coming years, particularly because of the increase in viral re-emergence due to continued population growth, urbanization, and increased global travel [36].…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, Europe has seen an increase in severe cases of AFM since 2016 coinciding with enterovirus D68 positivity [10][11][12][13][14], while Asia and the Pacific have experienced major outbreaks of enterovirus A71 causing hand, foot, and mouth disease [6,7,10]. Due to the higher number of severe cases, the interest in enterovirus surveillance and epidemiological studies has increased dramatically [6,12,[15][16][17][18][19][20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

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Retrospective Genotyping of Enteroviruses Using a Diagnostic Nanopore Sequencing Workflow

van Ackeren,

Schmutz,

Pichler

et al. 2024

Pathogens

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Enteroviruses are among the most common viruses pathogenic to humans. They are associated with various forms of disease, ranging from mild respiratory illness to severe neurological diseases. In recent years, an increasing number of isolated cases of children developing meningitis or encephalitis as a result of enterovirus infection have been reported, as well as discrete enterovirus D68 outbreaks in North America in 2014 and 2016. We developed an assay to rapidly genotype enteroviruses by sequencing a region within the VP1 gene using nanopore Flongles. We retrospectively analyzed enterovirus-/rhinovirus-positive clinical samples from the Zurich, Switzerland area mainly collected during two seasons in 2019/2020 and 2021/2022. Respiratory, cerebrospinal fluid, and stool samples were analyzed. Whole-genome sequencing was performed on samples with ambiguous genotyping results and enterovirus D68-positive samples. Out of 255 isolates, a total of 95 different genotypes were found. A difference in the prevalence of enterovirus and rhinovirus infections was observed for both sample type and age group. In particular, children aged 0–4 years showed a higher frequency of enterovirus infections. Comparing the respiratory seasons, a higher prevalence was found, especially for enterovirus A and rhinovirus A after the SARS-CoV-2 pandemic. The enterovirus genotyping workflow provides a rapid diagnostic tool for individual analysis and continuous enterovirus surveillance.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Retrospective Genotyping of Enteroviruses Using a Diagnostic Nanopore Sequencing Workflow

van Ackeren,

Schmutz,

Pichler

et al. 2024

Pathogens

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“…Reinfections by different strains may be common later in life [25]. Data from Switzerland are scanty, but the isolation of EV-D68 from Swiss patients has recently been reported [25,26]. Most infections solely induce an acute respiratory syndrome, but EV-D68 is -or has recently become [27] -neurotropic and has clearly been linked to acute flaccid myelitis epidemiologically [10], virologically [28], immunologically [29] and in animal models [30].…”

Section: Discussionmentioning

confidence: 99%

Acute flaccid myelitis in Switzerland – association with enterovirus D68

Bigi¹,

Ramette²,

Barbani³

et al. 2023

Swiss Med Wkly

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Poliomyelitis-like acute flaccid myelitis associated with enterovirus D68 (EV-D68) has emerged globally during the past decade. Here we describe the first documented case reported from Switzerland, and a second, suspected case occurring in temporal association. AFM occurs primarily in children, is usually heralded by a febrile, respiratory prodrome followed by acute-onset, usually asymmetrical, limb weakness with some predilection for the upper extremities, and respiratory muscle compromise in one third of reported cases. There is no specific therapy and the majority of cases result in permanent neurological sequelae. A comprehensive diagnostic workup and timely reporting to the health authorities are essential. Surveillance of respiratory and stool samples for EV-D68 and other neurotropic enteroviruses is in place in several European countries and warrants consideration in Switzerland. This could entail the extension of the poliomyelitis surveillance program of the Federal Office of Public Health by monitoring and enteroviral typing of respiratory samples from patients with acute flaccid paralysis.

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“…This report aims to assist the implementation of viral metagenomics for pathogen detection in clinical diagnostic settings by providing insight into the efficacy of platforms and key protocol steps. Gradel et al 20 Bigi et al 21 Gradel et al 22 Rodriguez et al 23 Penner et al 24 Morfopoulou et al 25 Atkinson et al2023 18 Alawi et al 26 Kufner et al 5 Narat et al 27 Vallet et al 28 Garzaro 29 and Aboudar et al 30 Cinek et al 31 Mourik et al 19 Carbo et al 11 Reyes et al 32 De Kleine et al 33 Vanmechelen et al 34 Wollants et al 35 Vanmechelen et al 36 Van Boheemen et al 6 Pichler et al 37 a; pre-nucleic acid extraction enrichment was applied to the ATCC Virome Mix dilutions containing whole viruses. WTA; whole transcriptome amplification, SISPA; sequence-independent, single-primer amplification.…”

Section: Sensitivity Specificity and Roc Curvesmentioning

confidence: 99%

Multicenter benchmarking of short and long read wet lab protocols for clinical viral metagenomics

Lopez-Labrador,

Huber,

Sidorov

et al. 2024

Preprint

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Metagenomics is gradually being implemented for diagnosing infectious diseases. However, in-depth protocol comparisons for viral detection have been limited to individual sets of experimental workflows and laboratories. In this study, we present a benchmark of metagenomics protocols used in clinical diagnostic laboratories initiated by the European Society for Clinical Virology (ESCV) Network on NGS (ENNGS).A mock viral reference panel was designed to mimic low biomass clinical specimens. The panel was used to assess the performance of twelve metagenomic wet-lab protocols in use in the diagnostic laboratories of participating ENNGS member institutions. Both Illumina and Nanopore, shotgun and targeted capture probe protocols were included. Performance metrics sensitivity, specificity, and quantitative potential were assessed using a central bioinformatics pipeline.Overall, viral pathogens with loads down to 104copies/ml (corresponding to C values of 31 in our assays) were detected by all the evaluated metagenomic wet-lab protocols. In contrast, lower abundant mixed viruses of CTvalues of 35 and higher were detected only by a minority of the protocols. Considering the reference panel as the gold standard, optimal thresholds to define a positive result were determined per protocol, based on the horizontal genome coverage. Implementing these thresholds, sensitivity and specificity of the protocols ranged from 67 to 100% and 87 to 100%, respectively.A variety of metagenomic protocols are currently in use in clinical diagnostic laboratories. Detection of low abundant viral pathogens and mixed infections remains a challenge, implying the need for standardization of metagenomic analysis for use in clinical settings.

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Genome Sequences of Rare Human Enterovirus Genotypes Recovered from Clinical Respiratory Samples in Bern, Switzerland

Cited by 6 publications

References 22 publications

Retrospective Genotyping of Enteroviruses Using a Diagnostic Nanopore Sequencing Workflow

Retrospective Genotyping of Enteroviruses Using a Diagnostic Nanopore Sequencing Workflow

Acute flaccid myelitis in Switzerland – association with enterovirus D68

Multicenter benchmarking of short and long read wet lab protocols for clinical viral metagenomics

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