key: cord-1054199-yfzlbk46 authors: Aubart, M.; Roux, C.J.; Durrleman, C.; Gins, C.; Hully, M.; Kossorotoff, M.; Gitiaux, C.; Levy, R.; Moulin, F.; Debray, A.; Belhadjer, Z.; Georget, E.; Kom Tchameni, R.; Blanc, P.; Wehbi, S.; Mazeghrane, M.; Tencer, J.; Gajdos, V.; Rouget, S.; De Pontual, L.; Basmaci, R.; Yacouben, K.; Angoulvant, F.; Leruez-Ville, M.; Sterlin, D.; Rozenberg, F.; Robert, M.; Zhang, S.Y.; Boddaert, N.; Desguerre, I. title: Neuro-inflammatory disease following SARS-CoV-2 infection in children date: 2022-05-14 journal: J Pediatr DOI: 10.1016/j.jpeds.2022.05.018 sha: 9b67ea1278de0b97f9968f923b4413ae27de77cb doc_id: 1054199 cord_uid: yfzlbk46 OBJECTIVE: To describe neurologic, radiologic and laboratory features in children with central nervous system (CNS) inflammatory disease complicating SARS-CoV-2 infection. STUDY DESIGN: We focused on CNS inflammatory diseases in children referred from 12 hospitals in the Paris area to Necker-Enfants Malades Reference Centre. RESULTS: We identified 19 children who had a history of SARS-CoV-2 infection and manifest a variety of CNS inflammatory diseases: encephalopathy, cerebellar ataxia, ADEM, neuromyelitis optica spectrum disorder (NMOSD) or optic neuritis. All patients had a history of SARS-CoV-2 exposure, and all tested positive for circulating antibodies against SARS-CoV-2. At the onset of the neurologic disease, SARS-CoV-2 PCR results (nasopharyngeal swabs) were positive in 8 children. Cerebrospinal fluid was abnormal in 58% (11/19), MRI was abnormal in 74% (14/19). We identified an autoantibody co-trigger in 4 children (MOG and AQP4 antibodies) representing 21%. No autoantibody was found in the 6 children whose CNS inflammation was accompanied by a multisystem inflammatory syndrome in children (MIS-C). Overall, 89% of patients (17/19) received anti-inflammatory treatment, primarily high-pulse methylprednisolone. All patients had a complete long-term recovery and, to date, no patient with autoantibodies presented with a relapse. CONCLUSION: SARS2-CoV-2 represents a new trigger of post infectious CNS inflammatory diseases in children. 1 Aubart M 1,2 *, Roux CJ 3 , Durrleman C 1 , Gins C 1 , Hully M 1 , Kossorotoff M 1 , Gitiaux C 4,5 , Levy R 3 , Moulin F 6 , Debray A 7 , Belhadjer Z 8 , Georget E 9 , Kom Tchameni R 10 , Blanc P 11 , Wehbi S 12 , Mazeghrane M 13 , Tencer J 14 , Gajdos V 15 , Rouget S 16 Coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was declared a world pandemic in March 2020 [1] . In adults, infection ranges from asymptomatic infection to severe respiratory failure. Since the beginning of the COVID-19 pandemic, there are increasing reports of neurologic complications, including non specific headache, delirium, dizziness and stroke [2] [3] [4] [5] . Severe inflammatory central nervous system (CNS) events, such as encephalitis, acute disseminated encephalomyelitis (ADEM), optic neuritis are rare, but have also been reported in case reports or small series of cases [5, 6] . there are case reports of positive MOG (myelinoligodendrocyte) antibodies (9 adults and 3 children with encephalomyelitis or optic neuritis) [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] . The disease course in children with SARS-CoV-2 infection generally is less severe [20] [21] . Approximately 10% of infected adults develop hypoxemic pneumonia and about 3% develop acute respiratory distress syndrome (ARDS), however, respiratory symptoms are less frequent in children. In contrast, multisystem inflammatory syndrome in children (MIS-C) is now well-described as a SARS-CoV-2-related condition with estimated prevalence of 1-2 per 10,000 infected children [22, 23] . Some patients with MIS-C present with a neurologic inflammatory disease among other clinical symptoms. However, data focusing on neurologic issues in children with SARS-CoV-2 infection are limited [5, 6] . We report a case series of 19 children who presented with neurologic symptoms in association with SARS-CoV-2 infection and had a final diagnosis of neurologic inflammatory disease with or without associated MIS-C. We performed a monocentric retrospective chart review of pediatric patients referred to Necker-Enfants malades Hospital in Paris, France, between January 1, 2020, and July, 1, 2021. Inclusion criteria were: age under 18 years, neurologic signs and positive testing for SARS-CoV-2 infection by reverse transcription PCR (RT-PCR) performed <6 weeks before onset of neurological symptoms or a seroconversion following the symptoms with a prior history of SARS-CoV-2 exposure. MIS-C was defined according to the 2020 World Health Organization definition [24] . Data were collected by screening of clinical, laboratory and radiologic records. For the study and to ensure homogeneity, one physician and one radiologist reassessed clinical and radiological data retrospectively. SARS-CoV-2 PCR testing was performed on nasopharyngeal swab specimens using the Abbott real Time Anti-aquaporin 4 (AQP-4) and anti-myelin oligodendrocyte glycoprotein (MOG) antibodies were detected in serum using a cell-based assay by indirect immunofluorescence, following manufacturers' instructions (Euroimmun). The biological activity of alpha IFN (IU/mL) in CSF was measured as the protection conferred by serial CSF dilutions to cultured cells towards vesicular stomatitis virus (VSV), as previously described [25] . Brain magnetic resonance imaging (MRI) and spine MRI were performed in all the patients, including systematically three-dimensional T1-weighted imaging, T2 and T2-FLAIR weighted imaging, Diffusion weigthed imaging, sagittal T2-weighted imaging of the spine and post-contrast T1-weighted imaging of both brain and spine. Assistance Publique-Hôpitaux de Paris (N°1980120). All patients received a written information regarding the use of their clinical data for scientific studies and publications according to national legislation. Descriptive statistics were used for all study variables and expressed as median and range values, and categorical data were expressed as proportions (%). From January 1, 2020 to July 1st, 2021, 21 children with a CNS inflammatory encephalopathy in the context of SARS-CoV-2 infection were referred to Necker-Enfants malades Hospital in Paris from 12 Pediatric Departments in the Paris area. Admission of two of these children was related to a severe co- presented with fever, abdominal pain, diarrhea, headache, and/or asthenia (including all the patients with MIS-C). A MIS-C phenotype (according to WHO definition [24] ) was present in 6 children, with fever, laboratory evidence of systemic inflammation, and symptoms of myocardial dysfunction occurring a median of 3.5 days after the onset of general symptoms (3) (4) (5) . 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