Neuroinflammatory Disease following Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Children

Melodie Aubart¹, Charles-Joris Roux², Chloé Durrleman³, Clarisse Gins³, Marie Hully³, Manoelle Kossorotoff³, Cyril Gitiaux⁴, Raphaël Levy², Florence Moulin⁵, Agathe Debray⁶, Zahra Belhadjer⁷, Emilie Georget⁸, Temi Kom⁹, Philippe Blanc¹⁰, Samer Wehbi¹¹, Mustapha Mazeghrane¹², Jeremie Tencer¹³, Vincent Gajdos¹⁴, Sebastien Rouget¹⁵, Loic De Pontual¹⁶, Romain Basmaci¹⁷, Karima Yacouben¹⁸, Francois Angoulvant¹⁹, Marianne Leruez-Ville²⁰, Delphine Sterlin²¹, Flore Rozenberg²², Matthieu P Robert²³, Shen-Ying Zhang²⁴, Nathalie Boddaert², Isabelle Desguerre³

Affiliations

¹ Pediatric Neurology Department, Necker-Enfants malades Hospital, APHP, University of Paris-Cité, Paris, France; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, French Institute of Health and Medical Research U1163, University of Paris-Cité, Imagine Institute, Paris, France. Electronic address: melodie.aubart@aphp.fr.
² Pediatric Radiology Department, Necker-Enfats malades Hospital, APHP, University of Paris-Cité, Paris, France.
³ Pediatric Neurology Department, Necker-Enfants malades Hospital, APHP, University of Paris-Cité, Paris, France.
⁴ Pediatric Neurophysiology Department, Necker-Enfants malades Hospital, APHP, University of Paris-Cité, Paris, France; French Institute of Health and Medical Research U955-Team 10, Department of Neurosciences, Mondor Biomedical Research Institute, Paris-Est University, Créteil, France.
⁵ Intensive Care Unit, Necker-Enfants malades Hospital, APHP, University of Paris-Cité, Paris, France.
⁶ Pediatic Department, Necker-Enfants malades Hospital, APHP, University of Paris-Cité, Paris, France.
⁷ Pediatric Cardiology Department, Necker-Enfants malades Hospital, APHP, University of Paris-Cité, Paris, France.
⁸ Pediatic Department, Villeneuve Saint Georges Hospital, Villeneuve Saint Geroges, France.
⁹ Pediatic Department, Louis Pasteur Hospital, Le Coudray, France.
¹⁰ Pediatic Department, Poissy Intercommunal Hospital Center, Poissy, France.
¹¹ Pediatic Department, Andre Mignot Hospital, Versailles, France.
¹² Pediatic Department, Andre Gregoire Hospital, Montreuil, France.
¹³ Pediatic Department, Delafontaine Hospital, Saint Denis, France.
¹⁴ Pediatic Department, Antoine Béclère Hospital, APHP, Paris-Saclay University, Clamart, France.
¹⁵ Pediatic Department, Sud Francilien Hospital, Corbeil-Essone, France.
¹⁶ Pediatric Department, Jean Verdier Hospital, APHP, University of Paris-Cité, Bondy, France.
¹⁷ Pediatric Department, Louis Mourier Hospital, APHP, University of Paris-Cité, Colombes, France.
¹⁸ Pediatric Hematology Department, Robert Debre Hospital, APHP, University of Paris-Cité, Paris, France.
¹⁹ Pediatric Department, Robert Debre Hospital, APHP, University of Paris-Cité, Paris, France.
²⁰ Laboratory of Virology, Necker-Enfants malades Hospital, APHP, University of Paris-Cité, Paris, France.
²¹ Immunology Department, Pitié-Salpétrière Hospital, Sorbonne University, APHP, Paris, France.
²² Laboratory of Virology, Cochin Hospital, APHP, University of Paris-Cité, Paris, France.
²³ Ophthalmology Department, Necker-Enfants Hospital, APHP, University of Paris-Cité, Paris, France.
²⁴ Laboratory of Human Genetics of Infectious Diseases, Necker Branch, French Institute of Health and Medical Research U1163, University of Paris-Cité, Imagine Institute, Paris, France; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.

PMID: 35577119
PMCID: PMC9106400
DOI: 10.1016/j.jpeds.2022.05.018

Neuroinflammatory Disease following Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Children

Melodie Aubart et al. J Pediatr. 2022 Aug.

. 2022 Aug:247:22-28.e2.

doi: 10.1016/j.jpeds.2022.05.018. Epub 2022 May 14.

Authors

Affiliations

¹ Pediatric Neurology Department, Necker-Enfants malades Hospital, APHP, University of Paris-Cité, Paris, France; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, French Institute of Health and Medical Research U1163, University of Paris-Cité, Imagine Institute, Paris, France. Electronic address: melodie.aubart@aphp.fr.
² Pediatric Radiology Department, Necker-Enfats malades Hospital, APHP, University of Paris-Cité, Paris, France.
³ Pediatric Neurology Department, Necker-Enfants malades Hospital, APHP, University of Paris-Cité, Paris, France.
⁴ Pediatric Neurophysiology Department, Necker-Enfants malades Hospital, APHP, University of Paris-Cité, Paris, France; French Institute of Health and Medical Research U955-Team 10, Department of Neurosciences, Mondor Biomedical Research Institute, Paris-Est University, Créteil, France.
⁵ Intensive Care Unit, Necker-Enfants malades Hospital, APHP, University of Paris-Cité, Paris, France.
⁶ Pediatic Department, Necker-Enfants malades Hospital, APHP, University of Paris-Cité, Paris, France.
⁷ Pediatric Cardiology Department, Necker-Enfants malades Hospital, APHP, University of Paris-Cité, Paris, France.
⁸ Pediatic Department, Villeneuve Saint Georges Hospital, Villeneuve Saint Geroges, France.
⁹ Pediatic Department, Louis Pasteur Hospital, Le Coudray, France.
¹⁰ Pediatic Department, Poissy Intercommunal Hospital Center, Poissy, France.
¹¹ Pediatic Department, Andre Mignot Hospital, Versailles, France.
¹² Pediatic Department, Andre Gregoire Hospital, Montreuil, France.
¹³ Pediatic Department, Delafontaine Hospital, Saint Denis, France.
¹⁴ Pediatic Department, Antoine Béclère Hospital, APHP, Paris-Saclay University, Clamart, France.
¹⁵ Pediatic Department, Sud Francilien Hospital, Corbeil-Essone, France.
¹⁶ Pediatric Department, Jean Verdier Hospital, APHP, University of Paris-Cité, Bondy, France.
¹⁷ Pediatric Department, Louis Mourier Hospital, APHP, University of Paris-Cité, Colombes, France.
¹⁸ Pediatric Hematology Department, Robert Debre Hospital, APHP, University of Paris-Cité, Paris, France.
¹⁹ Pediatric Department, Robert Debre Hospital, APHP, University of Paris-Cité, Paris, France.
²⁰ Laboratory of Virology, Necker-Enfants malades Hospital, APHP, University of Paris-Cité, Paris, France.
²¹ Immunology Department, Pitié-Salpétrière Hospital, Sorbonne University, APHP, Paris, France.
²² Laboratory of Virology, Cochin Hospital, APHP, University of Paris-Cité, Paris, France.
²³ Ophthalmology Department, Necker-Enfants Hospital, APHP, University of Paris-Cité, Paris, France.
²⁴ Laboratory of Human Genetics of Infectious Diseases, Necker Branch, French Institute of Health and Medical Research U1163, University of Paris-Cité, Imagine Institute, Paris, France; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.

PMID: 35577119
PMCID: PMC9106400
DOI: 10.1016/j.jpeds.2022.05.018

Abstract

Objective: To describe neurologic, radiologic and laboratory features in children with central nervous system (CNS) inflammatory disease complicating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Study design: We focused on CNS inflammatory diseases in children referred from 12 hospitals in the Paris area to Necker-Sick Children 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, acute disseminated encephalomyelitis, neuromyelitis optica spectrum disorder, 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) and magnetic resonance imaging was abnormal in 74% (14/19). We identified an autoantibody co-trigger in 4 children (myelin-oligodendrocyte and aquaporin 4 antibodies), representing 21% of the cases. No autoantibody was found in the 6 children whose CNS inflammation was accompanied by a multisystem inflammatory syndrome in children. 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.

Conclusions: SARS2-CoV-2 represents a new trigger of postinfectious CNS inflammatory diseases in children.

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Figures

**Figure 1**
Demyelinating disorders in MRI in children associated with SARS-COV-2. MOGAD (top row). **A-C,** Multifocal and asymmetric cortical T2-fluid-attenuated inversion recovery (FLAIR) hyperintensities **A, B,** readily appreciated on coronal T2-weighted images, C. MOGAD (middle row). **D-F**, Small multiple white matter lesions, supratentorial and infratentorial on T2-FLAIR weighted images. MOGAD (middle row). **G-I,** Large confluent white matter lesions G, with substantia nigra involvement H, and small cerebellar lesions on T2-FLAIR-weighted images. AQP4-neuromyelitis optica spectrum disorder—bottom row. **J-L,** Prechiasmatic right optic nerve hyperintensity on axial T2-FLAIR J, with focal enhancement on axial K, and coronal L, contrast-enhanced T1-weighted images, suggesting right optic neuritis.

**Figure 2**
Other MRI inflammatory disorders in children associated with SARS-COV-2. Cytotoxic lesions of corpus callosum syndrome (CLOCCs) (top row). **A-C,** Well-limited restricted diffusion in the splenium of corpus callosum with low apparent diffusion coefficient values **A, B,** and T2 fluid-attenuated inversion recovery (FLAIR) hyperintensity C, suggestive of CLOCCs after SARS-CoV-2 infection. Cerebellitis (bottom row). **D-E,** Large and asymmetric cortical and white matter T2-FLAIR hyperintensities of the cerebellum D, with high blood flow on an arterial spin labeling sequence E, suggesting acute cerebellitis. Bilateral facial neuritis (bottom row). F, Bilateral enhancement of the meatal segment of facial nerves in internal auditory canal, bilaterally.

See this image and copyright information in PMC

References

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Neuroinflammatory Disease following Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Children

Affiliations

Neuroinflammatory Disease following Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Children

Authors

Affiliations

Abstract

Figures

References

MeSH terms

Substances

Supplementary concepts

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous