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Grace Y. Gombolay, Email: ggombol@emory.edu

The authors would like to thank research coordinators including Marco Benoit, Felicia Glover, Austin Lu, Lisa Macoy, Amber Samuel, Ashley Tippett, and Kathy Stephens, along with Children's Healthcare of Atlanta Research Laboratory along with the Emory Children's Clinical and Translational Discovery Core and patients and their families.

B.N., S.A.L, B.S., V.P., L.H., S.B., B.P., K.W., and L.W. have no disclosures. E.J.A. has received personal fees from AbbVie, Pfizer, and Sanofi Pasteur for consulting, and his institution receives funds to conduct clinical research unrelated to this manuscript from MedImmune, Regeneron, PaxVax, Pfizer, GSK, Merck, Novavax, Sanofi-Pasteur, Janssen, and Micron. He also serves on a safety monitoring board for Sanofi-Pasteur and Kentucky BioProcessing, Inc. C.A.R.’s institution has received funds to conduct clinical research unrelated to this manuscript from BioFire Inc, GSK, MedImmune, Micron, Janssen, Merck, Moderna, Novavax, PaxVax, Pfizer, Regeneron, Sanofi-Pasteur. She is co-inventor of patented RSV vaccine technology unrelated to this manuscript, which has been licensed to Meissa Vaccines, Inc. G.Y.G. receives salary support from the Centers for Disease Control and Prevention for surveillance for acute flaccid myelitis.

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Research Funding:

This work was funded by institutional funding from Emory University and Children's Center for Infections and Vaccines.

This study was supported in part by the Emory Multiplexed Immunoassay Core (EMIC), which is subsidized by the Emory University School of Medicine and is one of the Emory Integrated Core Facilities. Additional support was provided by the National Center for Georgia Clinical & Translational Science Alliance of the National Institutes of Health under Award Number UL1TR002378. The content is solely the responsibility of the authors and does not necessarily reflect the official views of the National Institutes of Health.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Clinical Neurology
  • Neurosciences & Neurology
  • Pediatric COVID-19
  • SARS-CoV-2
  • Coronavirus
  • Cytokines
  • Chemokines
  • Cerebrospinal fluid
  • Psychiatric symptoms

Cerebrospinal fluid cytokine, chemokine, and SARS-CoV-2 antibody profiles in children with neuropsychiatric symptoms associated with COVID-19

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Journal Title:

MULTIPLE SCLEROSIS AND RELATED DISORDERS

Volume:

Volume 55

Publisher:

, Pages 103169-103169

Type of Work:

Article | Final Publisher PDF

Abstract:

Background: Neuropsychiatric symptoms and CSF cytokine, chemokine, and SARS-COV-2 antibody profiles are unknown in pediatric patients with COVID-19 or multisystem inflammatory syndrome (MIS-C), (NP-COVID-19). Methods: Children at a single pediatric institution quaternary referral center with laboratory-confirmed COVID-19 or MIS-C and neuropsychiatric symptoms were included in this retrospective case series. Clinical symptoms, ancillary testing data, treatments and outcomes are described. Multiplexed electrochemiluminescence assays for cytokines, chemokines and SARS-CoV-2 antibodies were tested in the CSF NP-COVID-19 patients compared to five controls and were analyzed using the Student's t-test. Results: Three of five NP-COVID-19 patients had psychiatric symptoms, and two patients had encephalopathy and seizures. All patients had full or near resolution of neuropsychiatric symptoms by discharge. One patient received intravenous steroids for treatment for psychiatric symptoms; 3/5 other patients received immunotherapy for MIS-C, including IVIG, high-dose steroids, anakinra, and tocilizumab. Pro-inflammatory chemokines, including MIG, MPC, MIP-1β, and TARC were significantly elevated in NP-COVID-19 patients compared to controls. Two of five patients had elevated CSF neurofilament light chain. CSF SARS-CoV-2 antibody titers to the full-length spike, receptor binding domain and N-terminal domain were significantly elevated. SARS-CoV-2 antibody titers strongly correlated with pro-inflammatory chemokines/cytokines, including IL-1β, IL-2, IL-8, TNF-α, and IFN-γ (P≤0.05 for all). Conclusions: A spectrum of neuropsychiatric clinical manifestations can occur in children with SARS-CoV-2 infection. CSF pro-inflammatory chemokines and SARS-CoV-2 antibodies may serve as biomarkers of SARS-CoV-2 mediated NP-COVID-19. Additional study is required to understand the pathophysiologic mechanisms of neuroinflammation in children with COVID-19 and MIS-C.

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© 2021 Elsevier B.V. All rights reserved.

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