Frontiers in Immunology (Feb 2024)

Central nervous system immune-related disorders after SARS-CoV-2 vaccination: a multicenter study

  • Alberto Vogrig,
  • Alberto Vogrig,
  • Sara Tartaglia,
  • Sara Tartaglia,
  • Marta Dentoni,
  • Marta Dentoni,
  • Martina Fabris,
  • Francesco Bax,
  • Marco Belluzzo,
  • Lorenzo Verriello,
  • Daniele Bagatto,
  • Matteo Gastaldi,
  • Pierluigi Tocco,
  • Marco Zoccarato,
  • Luigi Zuliani,
  • Andrea Pilotto,
  • Andrea Pilotto,
  • Andrea Pilotto,
  • Alessandro Padovani,
  • Alessandro Padovani,
  • Alessandro Padovani,
  • Macarena Villagrán-García,
  • Macarena Villagrán-García,
  • Vincent Davy,
  • Gian Luigi Gigli,
  • Gian Luigi Gigli,
  • Jérôme Honnorat,
  • Jérôme Honnorat,
  • Mariarosaria Valente,
  • Mariarosaria Valente

DOI
https://doi.org/10.3389/fimmu.2024.1344184
Journal volume & issue
Vol. 15

Abstract

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BackgroundCOVID-19 vaccines have been approved due to their excellent safety and efficacy data and their use has also permitted to reduce neurological complications of SARS-CoV-2. However, clinical trials were underpowered to detect rare adverse events. Herein, the aim was to characterize the clinical spectrum and immunological features of central nervous system (CNS) immune-related events following SARS-CoV-2 vaccination.MethodsMulticenter, retrospective, cohort study (December 1, 2020-April 30, 2022). Inclusion criteria were (1) de novo CNS disorders developing after SARS-CoV-2 vaccination (probable causal relationship as per 2021 Butler criteria) (2); evidence for an immune-mediated etiology, as per (i) 2016 Graus criteria for autoimmune encephalitis (AE); (ii) 2015 Wingerchuk criteria for neuromyelitis optica spectrum disorders; (iii) criteria for myelitis.ResultsNineteen patients were included from 7 tertiary referral hospitals across Italy and France (one of them being a national referral center for AE), over almost 1 year and half of vaccination campaign. Vaccines administered were mRNA-based (63%) and adenovirus-vectored (37%). The median time between vaccination and symptoms onset was 14 days (range: 2-41 days). CSF was inflammatory in 74%; autoantibodies were detected in 5%. CSF cytokine analysis (n=3) revealed increased CXCL-10 (IP-10), suggesting robust T-cell activation. The patients had AE (58%), myelitis (21%), acute disseminated encephalomyelitis (ADEM) (16%), and brainstem encephalitis (5%). All patients but 2 received immunomodulatory treatment. At last follow-up (median 130 days; range: 32-540), only one patient (5%) had a mRS>2.ConclusionCNS adverse events of COVID-19 vaccination appear to be very rare even at reference centers and consist mostly of antibody-negative AE, myelitis, and ADEM developing approximately 2 weeks after vaccination. Most patients improve following immunomodulatory treatment.

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