Enteroviruses (EV) can cause severe neurological and respiratory infections, and occasionally lead to devastating outbreaks as previously demonstrated with EV-A71 and EV-D68 in Europe. However, these infections are still often underdiagnosed and EV typing data is not currently collected at European level. In order to improve EV diagnostics, collate data on severe EV infections and monitor the circulation of EV types, we have established European non-polio enterovirus network (ENPEN). First task of this cross-border network has been to ensure prompt and adequate diagnosis of these infections in Europe, and hence we present recommendations for non-polio EV detection and typing based on the consensus view of this multidisciplinary team including experts from over 20 European countries. We recommend that respiratory and stool samples in addition to cerebrospinal fluid (CSF) and blood samples are submitted for EV testing from patients with suspected neurological infections. This is vital since viruses like EV-D68 are rarely detectable in CSF or stool samples. Furthermore, reverse transcriptase PCR (RT-PCR) targeting the 5'noncoding regions (5'NCR) should be used for diagnosis of EVs due to their sensitivity, specificity and short turnaround time. Sequencing of the VP1 capsid protein gene is recommended for EV typing; EV typing cannot be based on the 5'NCR sequences due to frequent recombination events and should not rely on virus isolation. Effective and standardized laboratory diagnostics and characterisation of circulating virus strains are the first step towards effective and continuous surveillance activities, which in turn will be used to provide better estimation on EV disease burden.

Summary The significantly higher mortality rates seen in the elderly compared with young children during the coronavirus disease 2019 (Covid‐19) pandemic is likely to be driven in part by an impaired immune response in older individuals. Cytomegalovirus (CMV) seroprevalence approaches 80% in the elderly. CMV has been shown to accelerate immune ageing by affecting peripheral blood T cell phenotypes and increasing inflammatory mediated cytokines such as IL‐6. The elderly with pre‐existing but clinically silent CMV infection may therefore be particularly susceptible to severe Covid‐19 disease and succumb to a cytokine storm which may have been promoted by CMV. Here, we evaluate the potential role of CMV in those with severe Covid‐19 disease and consider how this relationship can be investigated in current research studies.

Targeted salivary screening for cCMV within the NHSP is feasible, acceptable and detects infants with cCMV-related SNHL who could benefit from early treatment.

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ObjectivesThis study aimed to prospectively collect detailed clinical information for all enterovirus (EV) and human parechovirus (HPeV) meningitis cases in infants aged <90 days in the UK and Ireland.Participants, design and settingProspective, active national surveillance during July 2014 to July 2015 through the British Paediatric Surveillance Unit. Reporting paediatricians completed questionnaires requesting information on clinical presentation, investigations, management and outcomes at hospital discharge and after 12 months.Main outcome measuresTo describe the clinical burden of EV and HPeV meningitis in infants aged <90 days.ResultsDuring the 13-month surveillance period, 703 cases (668 EV, incidence0.79/1,000 live- births; 35 HPeV, 0.04/1,000 live-births) were identified. The most common clinical presentations were fever (EV: 570/668(85%); HPeV: 28/35(80%)), irritability (EV: 441/668(66%); HPeV: 23/35(66%)) and reduced feeding (EV: 363/668(54%); HPeV 23/35(66%)). Features of circulatory shock were present in 27% (182/668) of EV and 43% (15/35) of HPeV cases. Overall, 11% (76/668) of EV and 23% (8/35) of HPeV cases required intensive care support. Nearly all cases (678/703, 96%) were confirmed by cerebrospinal fluid (CSF) PCR, with 52% (309/600) having normal CSF white cell count for age. Two infants with EV meningitis died (2/668, 0.3%) and four survivors (4/666, 0.6%) had long-term complications at 12 months’ follow-up. Infants with HPeV meningitis survived without sequelae. Overall 189 infants had a formal hearing test and none had sensorineural hearing loss.ConclusionThe incidence of laboratory-confirmed EV/HPeV meningitis in young infants is more than twice that for bacterial meningitis. Less than 1% will develop severe neurological complications or die of their infection. Further studies are required to formally assess long-term neurodevelopmental sequelae.

HPeV may cause severe disease and long-term neurological sequelae in young infants. HPeV should be considered in infants with clinical features of sepsis/meningitis with normal CSF microscopy. Prospective observational studies are warranted to better define the epidemiology of infection and thus inform future treatment trials.

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The costs of targeted screening for cCMV using salivary swabs integrated within NHSP resulted in an estimate of cost per case that compares favourably with other screening programmes. This could be used in future studies to estimate the full economic value in terms of incremental costs and incremental health benefits.