SARS-CoV-2 Antibody Response Following COVID-19 Infection or Vaccination in Children and Young People with Multiple Sclerosis on Disease Modifying Treatment

Background: Currently there are no published data regarding SARS-CoV-2 vaccine efficacy in paediatric-onset multiple sclerosis (MS) on disease-modifying treatments (DMTs). In adults, DMTs such as SIP-inhibitors (e.g., Fingolimod) and anti-CD20 therapies (e.g., Ocrelizumab) have been found to diminish SARS-CoV-2 vaccine efficacy. Objective(s): To ascertain whether young people with MS on DMTs generate a protective B-and/or T-cell response following SARS-CoV-2 vaccination or wild type (WT) infection. Method(s): Five millilitre additional blood was taken from MS patients during routine surveillance phlebotomy. Vaccination status and exposure to WT COVID was recorded. Serum samples measured SARS-CoV-2 antibodies using MSD quantitative assay. Multiplex T-cell stimulation assay was used to measure T-cell activity and T-cell response to SARS-CoV-2 Spike peptide was analysed. Result(s): Thirty-one MS patients (M:F 5:26;11-18 years) were included. DMTs included Ocrelizumab (n = 26);Fingolimod (n = 2);other DMT (n = 3). Vaccination status was confirmed in 12 children. 26/31 patients demonstrated protective B-cell responses, of which 10 were vaccinated +/- previous infection;six previously infected with unconfirmed vaccine status;and 10 had no infection/vaccine data available. Of the five patients with no B-cell response two were vaccinated. Six patients had impaired T-cell proliferation but 5/6 generated a B-cell response. T-cell proliferation upon exposure to Spike peptide was seen in 10 children'3/10 were vaccinated and 9/10 were being treated with Ocrelizumab. Patients on Fingolimod had impaired T-cell activity and no response to SARS-CoV-2 peptides, despite one being vaccinated and having a B-cell response. Conclusion(s): Fingolimod appeared to impair T-cell responses, however, only two patients were on this treatment. Those on Ocrelizumab have some protection following vaccination or WT exposure with 5/26 patients showing an impaired B-cell response but partial preservation of T-cell responses. While vaccination prior to starting DMT is ideal, some protection will be generated whilst on treatment.

NEUROLOGIC AND RADIOGRAPHIC FINDINGS ASSOCIATED WITH PAEDIATRIC INFLAMMATORY MULTISYSTEM SYNDROME TEMPORALLY ASSOCIATED WITH SARS-COV-2 (PIMS-TS)

Objective Our aim was to report neurological manifestations of children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). Methods Patients (<18yrs) presenting to Great Ormond Street Hospital between March 1, 2020, and June 21, 2020 fulfilling RCPCH PIMS-TS criteria, were included. Clinical and paraclinical features were retrieved retrospectively from electronic patient records. Results New-onset neurological symptoms/signs were reported in 23/45 (51.1%);headaches (n=16), encephalopathy (n=7), dysarthria/ dysphonia (n=6), hallucinations (n=4), ataxia (n=4), peripheral nerve involvement (n=3), and seizures (n=1). Five (21.7%) patients had CSF analysis;1 patient had 118 leukocytes in CSF. Splenium signal changes were seen in 4/14 patients who had brain MRI. A mild excess of slow activity was found in 10/10 who had an EEG and mild myopathic and neuropathic changes were seen 4/5 who underwent nerve conduction studies and electromyography. Children with neurological involvement had higher peak inflammatory markers and were more likely to be ventilated and require inotropic support in PICU (p<0.05). Conclusions Children with PIMS-TS presented with new neurological symptoms involving both the central and peripheral nervous systems, in the absence of respiratory symptoms. Neurological symptoms were seen more frequently in more severe presentations.

Risk of COVID-19 in children treated for demyelinating disorders in the UK

Objective: Paediatric neurologists are concerned about the risk of COVID-19 in children with demyelinating disorders receiving immunomodulatory treatment. To investigate this, we collected data via the UK Childhood Neuro-Inflammatory Disorders (UK-CNID) network of the British Paediatric Neurology Association (BPNA). Methods: Survey of paediatric neurologists managing unvaccinated UK children (<18 years) with a demyelinating disorder (multiple sclerosis [MS];neuromyelitis optica spectrum disorder [NMOSD] and myelin oligodendrocyte glycoprotein antibody disease [MOGAD]) on immunomodulatory therapy with SARS-CoV-2 infection confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) of nasopharyngeal swabs between March and December 2020. Results: Of 151 UK children (MS 98, MOGAD 37, NMOSD 16) with a median age of 9 years (range 6-18y), with a demyelinating disorder, nine (6.0%) had a positive PCR for SARS-CoV-2. Five had MS and four MOGAD. Four were from south Asian or south-east Asian, four were White and one was mixed White and south Asian. Seven children had COVID-19 symptoms;two were asymptomatic. Two required a brief hospital admission for typical COVID-19 respiratory symptoms and the remaining five had mild symptoms including fever, rash, cough and headache. One with MOGAD, treated with azathioprine, developed transverse myelitis 12 days after COVID-19 onset. She recovered fully with a course of corticosteroids. MS patients were on following disease modifying therapies;dimethylfumarate (n=2), fingolimod (n=1);natalizumab (n=1) and ocrelizumab (n=1). MOGAD cases were on the following immune therapy: combination of oral prednisolone and intravenous immunoglobulin (n=2), prednisolone steroids (n=1) and azathioprine (n=1). Conclusions: In contrast to adult patients, who often have underlying co-morbidities and advanced neurological disabilities, we have identified that children treated for demyelinating disorders appear to have a milder COVID-19 course. Whilst the number of children treated for demyelinating disorders that developed COVID-19 is low, the overall mild course described may provide reassurance to neurologists, patients and family members.

Neurological and radiological findings associated with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in children

Background: Neurological manifestations have been reported both in adults and children with coronavirus disease 2019 (COVID-19). Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) is a recently described severe post-infectious immune-mediated disorder. Objective: Our aim was to report neurological manifestations of children with PIMS-TS. Methods: Patients (<18y) presenting to Great Ormond Street Hospital between April 4, 2020, and May 1, 2021 fulfilling PIMS-TS criteria, were included. Clinical and paraclinical features were retrieved retrospectively from electronic patient records. Results: Data was available for 125 patients who presented during the study period. Median age was 10 years (IQR 7, 12), 71 (56.8%) were male and 96 (76.8%) were of non-white ethnicities. New-onset neurological symptoms were reported in 73/125 (58.4%);headaches (n=47), encephalopathy (n=41), hallucinations (n=15), ataxia (n=12), dysarthria/dysphonia (n=12), peripheral nerve involvement (n=3), and seizures (n=1). Thirteen patients had CSF examined;one patient had 118 leukocytes in CSF. Abnormalities were noted in 16/32 patients with neuroimaging, with splenium of the corpus callosum signal changes most commonly seen in 9 patients. An excess of slow activity was found in 78/98 who had an EEG;38 mild, 34 moderate and 7 had severe encephalopathy on EEG. Myopathic and neuropathic changes were seen in 7/12 who underwent nerve conduction studies and electromyography (EMG). Children with neurological involvement had higher peak inflammatory markers and were more likely to be ventilated and require inotropic support in PICU (p<0.05). Conclusions: Children with PIMS-TS presented with new neurological symptoms involving both the central and peripheral nervous systems, in the absence of respiratory symptoms. Neurological symptoms were seen more frequently in more severe presentations.