Neurological manifestations of SARS-CoV-2 infection in hospitalised children and adolescents in the UK: a prospective national cohort study

Background: The spectrum of neurological and psychiatric complications associated with paediatric SARS-CoV-2 infection is poorly understood. We aimed to analyse the range and prevalence of these complications in hospitalised children and adolescents. Methods: We did a prospective national cohort study in the UK using an online network of secure rapid-response notification portals established by the CoroNerve study group. Paediatric neurologists were invited to notify any children and adolescents (age <18 years) admitted to hospital with neurological or psychiatric disorders in whom they considered SARS-CoV-2 infection to be relevant to the presentation. Patients were excluded if they did not have a neurological consultation or neurological investigations or both, or did not meet the definition for confirmed SARS-CoV-2 infection (a positive PCR of respiratory or spinal fluid samples, serology for anti-SARS-CoV-2 IgG, or both), or the Royal College of Paediatrics and Child Health criteria for paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). Individuals were classified as having either a primary neurological disorder associated with COVID-19 (COVID-19 neurology group) or PIMS-TS with neurological features (PIMS-TS neurology group). The denominator of all hospitalised children and adolescents with COVID-19 was collated from National Health Service England data. Findings: Between April 2, 2020, and Feb 1, 2021, 52 cases were identified; in England, there were 51 cases among 1334 children and adolescents hospitalised with COVID-19, giving an estimated prevalence of 3·8 (95% CI 2·9–5·0) cases per 100 paediatric patients. 22 (42%) patients were female and 30 (58%) were male; the median age was 9 years (range 1–17). 36 (69%) patients were Black or Asian, 16 (31%) were White. 27 (52%) of 52 patients were classified into the COVID-19 neurology group and 25 (48%) were classified into the PIMS-TS neurology group. In the COVID-19 neurology group, diagnoses included status epilepticus (n=7), encephalitis (n=5), Guillain-Barré syndrome (n=5), acute demyelinating syndrome (n=3), chorea (n=2), psychosis (n=2), isolated encephalopathy (n=2), and transient ischaemic attack (n=1). The PIMS-TS neurology group more often had multiple features, which included encephalopathy (n=22 [88%]), peripheral nervous system involvement (n=10 [40%]), behavioural change (n=9 [36%]), and hallucinations at presentation (n=6 [24%]). Recognised neuroimmune disorders were more common in the COVID-19 neurology group than in the PIMS-TS neurology group (13 [48%] of 27 patients vs 1 [<1%] of 25 patients, p=0·0003). Compared with the COVID-19 neurology group, more patients in the PIMS-TS neurology group were admitted to intensive care (20 [80%] of 25 patients vs six [22%] of 27 patients, p=0·0001) and received immunomodulatory treatment (22 [88%] patients vs 12 [44%] patients, p=0·045). 17 (33%) patients (10 [37%] in the COVID-19 neurology group and 7 [28%] in the PIMS-TS neurology group) were discharged with disability; one (2%) died (who had stroke, in the PIMS-TS neurology group). Interpretation: This study identified key differences between those with a primary neurological disorder versus those with PIMS-TS. Compared with patients with a primary neurological disorder, more patients with PIMS-TS needed intensive care, but outcomes were similar overall. Further studies should investigate underlying mechanisms for neurological involvement in COVID-19 and the longer-term outcomes. Funding: UK Research and Innovation, Medical Research Council, Wellcome Trust, National Institute for Health Research

Autism and measles, mumps and rubella vaccine: no epidemiological evidence for a causal association

Background: We undertook an epidemiological study to investigate whether measles, mumps, and rubella (MMR) vaccine may be causally associated with autism. Methods: Children with autism born since 1979 were identified from special needs/disability registers and special schools in eight North Thames health districts, UK. Information from clinical records was linked to immunisation data held on the child health computing system. We looked for evidence of a change in trend in incidence or age at diagnosis associated with the introduction of MMR vaccination to the UK in 1988. Clustering of onsets within defined postvaccination periods was investigated by the case-series method. Findings: We identified 498 cases of autism (261 of core autism, 166 of atypical autism, and 71 of Asperger's syndrome). In 293 cases the diagnosis could be confirmed by the criteria of the International Classification of Diseases, tenth revision (ICD10: 214 [82%] core autism, 52 [31%] atypical autism, 27 [38%] Asperger's syndrome). There was a steady increase in cases by year of birth with no sudden "step-up" or change in the trend line after the introduction of MMR vaccination. There was no difference in age at diagnosis between the cases vaccinated before or after 18 months of age and those never vaccinated. There was no temporal association between onset of autism within 1 or 2 years after vaccination with MMR (relative incidence compared with control period 0.94 [95% CI 0.60-1.47] and 1.09 [0.79-1.52]). Developmental regression was not clustered in the months after vaccination (relative incidence within 2 months and 4 months after MMR vaccination 0.92 [0.38-2.21] and 1.00 [0.52-1.95]). No significant temporal clustering for age at onset of parental concern was seen for cases of core autism or atypical autism with the exception of a single interval within 6 months of MMR vaccination. This appeared to be an artifact related to the difficulty of defining precisely the onset of symptoms in this disorder. Interpretation: Our analyses do not support a causal association between MMR vaccine and autism. If such an association occurs, it is so rare that it could not be identified in this large regional sampl

Food industry by-products applied as pumpkin-based foodstuff preservatives

Pumpkin is traditionally cultivated and consumed worldwide, being the fruit and its by-products recognized by their nutritional and health benefits. In the current pandemic scenario and towards a circular economy, the development of a healthy and green technological food product was proposed using pumpkin pulp enriched with bioactive compounds obtained from pumpkin by-products.The authors are grateful to the Foundation for Science and Technology (FCT, Portugal) for financial support through national funds FCT/MCTES to CIMO (UIDB/00690/2020); national funding by FCT, P.I., through the institutional scientific employment program-contract for C. Pereira and L. Barros contracts and A.K. Molina and M.G. Leichtweis PhD grants (2020.06231.BD and 2020.06706.BD, respectively). The project is funded by the General Secretariat for Research and Technology of the Ministry of Development and Investments and FCT, P.I. under the PRIMA Programme. PRIMA is an Art.185 initiative supported and co-funded under Horizon 2020, the European Union’s Programme for Research and Innovation (PRIMA Section 2 - Multi-topic 2019: PulpIng (PRIMA/0007/2019 and Prima2019-08).info:eu-repo/semantics/publishedVersio

Care and three-year outcomes of children with Benign Epilepsy with Centro-Temporal Spikes in England.

PURPOSE: Benign Epilepsy with Centro-Temporal Spikes (BECTS) is a pediatric epilepsy with typically good seizure control. Although BECTS may increase patients' risk of developing neurological comorbidities, their clinical care and short-term outcomes are poorly quantified. METHODS: We retrospectively assessed adherence to National Institute for Health and Care Excellence (NICE) guidelines relating to specialist referral, electroencephalogram (EEG) conduct and annual review in the care of patients with BECTS, and measured their seizure, neurodevelopmental and learning outcomes at three years post-diagnosis. RESULTS: Across ten centers in England, we identified 124 patients (74 male) diagnosed with BECTS between 2015 and 2017. Patients had a mean age at diagnosis of 8.0 (95% CI = 7.6-8.4) years. 24/95 (25%) patients were seen by a specialist within two weeks of presentation; 59/100 (59%) received an EEG within two weeks of request; and 59/114 (52%) were reviewed annually. At three years post-diagnosis, 32/114 (28%) experienced ongoing seizures; 26/114 (23%) had reported poor school progress; 15/114 (13%) were diagnosed with a neurodevelopmental disorder (six autism spectrum disorder, six attention-deficit/hyperactivity disorder); and 10/114 (8.8%) were diagnosed with a learning difficulty (three processing deficit, three dyslexia). Center-level random effects models estimated neurodevelopmental diagnoses in 9% (95% CI: 2-16%) of patients and learning difficulty diagnoses in 7% (95% CI: 2-12%). CONCLUSIONS: In this multicenter work, we found variable adherence to NICE guidelines in the care of patients with BECTS and identified a notable level of neurological comorbidity. Patients with BECTS may benefit from enhanced cognitive and behavioral assessment and monitoring

Neurological and Psychiatric Manifestations of COVID-19 in UK Children: A Prospective National Cohort Study

Background: The spectrum of neurological and psychiatric complications associated with COVID-19 is poorly understood in children.Methods: Children and adolescents (Findings: Fifty-two cases were identified, among 1334 children hospitalised with COVID-19 giving an estimated incidence of 3.8 per 100 children. Twenty-seven (52%) had a primary neurological or psychiatric disorder, 25 (48%) had features associated with PIMS-TS. The median (range) age was 9 (1-17) years. Thirty-six (69%) were from Black or Asian backgrounds. In the primary neurology/psychiatry disorder group, diagnoses included seven with status epilepticus, five encephalitis, five Guillain-Barré syndrome, three acute demyelinating syndromes, two chorea, two psychosis, two encephalopathy, one transient ischaemic attack. The PIMS-TS neurology group more often had multiple features, which included encephalopathy (22, 88%), peripheral nervous system involvement (10, 40%), behavioural change (9, 36%), hallucinations (6, 24%). A recognised neuro-immune disorder was more common in the primary neurology than the PIMS-TS neurology group (13/27 [48%] vs 1/25 [0.04%], p=0.0003). More patients in the PIMS-TS neurology group were admitted to intensive care (20/25 [80%] vs 6/27 [22%], p=0.0001) and received immunomodulatory treatment (22/25 [88%] vs 12/27 [44%]), p=0.045). Seventeen (33%) were discharged with disability; one PIMS-TS child with stroke died.Interpretation: This first nation-wide study of the neurological and psychiatric manifestations of COVID-19 in children identified key differences between those with a primary disorder versus those with PIMS-TS. More PIMS-TS children needed intensive care, but outcomes were similar overall. Further studies must investigate underlying mechanisms and longer-term outcomes.Funding Statement: BDM and GB are supported to conduct COVID-19 neuroscience research by the UKRI/MRC (MR/V03605X/1); for additional neurological inflammation research due to viral infection BDM is also supported by grants from the MRC/UKRI (MR/V007181//1), MRC (MR/T028750/1) and Wellcome (ISSF201902/3). SR is also supported by Wellcome to conduct paediatric neuroinfectious research (203919/Z/16/Z). IG is supported by NIHR. TS is supported by the National Institute for Health Research (NIHR) Health Protection Research Unit in Emerging and Zoonotic Infections (Grant Nos. IS-HPU-1112-10117 and NIHR200907), NIHR Global Health Research Group on Brain Infections (No. 17/63/110), the UK Medical Research Council’s Global Effort on COVID-19 Programme (MR/V033441/1), and the European Union's Horizon 2020 research and innovation program ZikaPLAN (Preparedness Latin America Network), grant agreement No. 734584. MG is supported to conduct neuroscience and infection research internationally by MRC Newton Fund (MR/S019960/1), MRC DPFS (MR/R015406/1) and NIHR (153195 17/60/67, 126156 17/63/11 and 200907).Declaration of Interests: None.Ethics Approval Statement: The study was approved by the University of Liverpool Institute of Infection Veterinary and Ecological Sciences Ethics Committee (UoL #7725/2020) and the University of Southampton Faculty of Medicine Ethics Committee (ERGO #56504). The electronic CRF was hosted on ALEA (www.aleaclinical.eu) and managed by the Clinical Information Research Unit

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic : an international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Delaying surgery for patients with a previous SARS-CoV-2 infection

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