CSF cytokines/chemokines are unknown in pediatric COVID-19.
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We discuss neurological and psychiatric symptoms in five children with COVID-19.
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CSF chemokines and SARS-CoV-2 antibodies are elevated.
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SARS-CoV-2 antibodies strongly correlate with pro-inflammatory CSF cytokines.
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.
