Fatal neuromyelitis optica after COVID-19 vaccination

Abstract

We read with interest the report by Motahharynia and coworkers (Motahharynia et al., 2022Motahharynia A. Naghavi S. Shaygannejad V. Adibi I. Fulminant neuromyelitis optica spectrum disorder (NMOSD) following COVID-19 vaccination: a need for reconsideration?.Mult. Scler. Relat. Disord. 2022; 104035https://doi.org/10.1016/j.msard.2022.104035Abstract Full Text Full Text PDF Scopus (2) Google Scholar) that showed a new-onset Neuromyelitis Optica diagnosis with a fatal outcome after COVID-19 vaccination. The authors report a 70-year-old woman who exhibited neurological symptoms (numbness and weakness in her left limbs) seven days after receiving the third dose of a SARS-CoV-2 inactivated vaccine (Sinovac: CoronaVac). She rapidly progressed to paraplegia, while spinal cord magnetic resonance imaging showed an extensive hemorrhagic lesion in the cervical cord (C1-C7). Cerebrospinal fluid analysis was unremarkable (including the absence of oligoclonal bands), but the patient tested positive for anti-Aquaporin-4. Unfortunately, the patient was refractory to all therapeutic interventions (methylprednisolone pulse therapy, plasma exchange and cyclophosphamide) and died two months after hospitalization (Motahharynia et al., 2022Motahharynia A. Naghavi S. Shaygannejad V. Adibi I. Fulminant neuromyelitis optica spectrum disorder (NMOSD) following COVID-19 vaccination: a need for reconsideration?.Mult. Scler. Relat. Disord. 2022; 104035https://doi.org/10.1016/j.msard.2022.104035Abstract Full Text Full Text PDF Scopus (2) Google Scholar). Neuromyelitis Optica Spectrum Disorder (NMOSD) is rare autoimmune neuro-inflammatory disease that affects the central nervous system (CNS) with predilection for causing lesions in the optic nerves/spinal cord. Usually, the median age for onset is 40-years, although the disease can occur at any age as proposed in this report. CNS-damage during NMOSD is mainly attributed to the presence of autoantibodies such as specific NMO-IgG against astrocyte-end-feet Aquaporin-4 (anti-AQP4) in association with complement system, innate cells (e.g., eosinophils/neutrophils) and pro-inflammatory cytokines (Jarius et al., 2020Jarius S. Paul F. Weinshenker B.G. Levy M. Kim H.J. Wildemann B. Neuromyelitis optica, Nature Reviews Disease Primers. Springer US, 2020https://doi.org/10.1038/s41572-020-0214-9Crossref Scopus (120) Google Scholar). Considering the accumulated reports during the pandemic, we speculate that antiviral immune responses against SARS-CoV-2 natural infection/immunization may trigger CNS-damage in some individuals. Here, we hypothesize that repetition of vaccination with the same vaccine type (inactivated SARS-CoV-2) evoked a robust antiviral immune response including, among others: (I) effector or even senescent/exhausted CD8+ T lymphocytes with massive cytotoxic capacity (e.g., granzymes); (II) pro-inflammatory cytokines derived from CD4+ Th1 (IFN-γ, TNF-α) and Th17 (IL-17, IL-22); (III) neutrophil extracellular traps (NETs) and pro-inflammatory cytokines (e.g., IL-1, IL-6, TNF-α) derived from innate immune cells. All of these components are known to promote blood-brain barrier disruption. In parallel to neutralizing antibodies against SARS-CoV-2, autoreactive clones of B cells may differentiate in plasma cells and release anti-AQP4 due to loss of peripheral autotolerance. Furthermore, it is not possible so far to exclude that neutralizing antibodies against SARS-CoV-2 may also exhibit cross-reactivity with self-antigens in the CNS. More broadly, post-COVID syndrome as well as manifestations after COVID-19 vaccination may share common immunological features (summarized in Fig. 1). The increasing number of reports suggest the occurrence of new-onset/exacerbating NMOSD and related disorders, such as Multiple Sclerosis, in the context of SARS-CoV-2 natural infection/immunization (Finsterer, 2022Finsterer J. Neuromyelitis optica complicating COVID vaccinations.Mult. Scler. Relat. Disord. 2022; 62103809https://doi.org/10.1016/j.msard.2022.103809Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar; Fragoso et al., 2022Fragoso Y.D. Gomes S. Gonçalves M.V.M. Mendes Junior E. Oliveira B.E.S. Rocha d. Santos C.F. dos G.A.C. Tauil C.B. Araujo R.V. Peron J.P.S. New relapse of multiple sclerosis and neuromyelitis optica as a potential adverse event of AstraZeneca AZD1222 vaccination for COVID-19.Mult. Scler. Relat. Disord. 2022; 57: 1-5https://doi.org/10.1016/j.msard.2021.103321Abstract Full Text Full Text PDF Scopus (8) Google Scholar; Khayat-Khoei et al., 2022Khayat-Khoei M. Bhattacharyya S. Katz J. Harrison D. Tauhid S. Bruso P. Houtchens M.K. Edwards K.R. Bakshi R. COVID-19 mRNA vaccination leading to CNS inflammation: a case series.J. Neurol. 2022; 269: 1093-1106https://doi.org/10.1007/s00415-021-10780-7Crossref PubMed Scopus (32) Google Scholar). Despite the need for continuous massive vaccination against SARS-CoV-2, which proved to be effective and safe, we should be aware of rare, aggressive and even fatal CNS-manifestations such as NMOSD in a small proportion of individuals. V.O.B. and C.L.Y. wrote the manuscript. Was in accordance with ethical guidelines. Not applicable. Not applicable. Not applicable. The author declares no conflicts of interest.