A Single-Health System Case Series of New-Onset CNS Inflammatory Disorders Temporally Associated With mRNA-Based SARS-CoV-2 Vaccines

Abstract

Background: Since 2020, over 250 million doses of mRNA-based SARS-CoV-2 vaccines have been administered in the United States and hundreds of millions worldwide between the Pfizer-BioNTech and Moderna SARS-CoV-2 vaccines. To date, there have been rare reports associating mRNA-based SARS-CoV-2 vaccines with episodes of inflammatory and autoimmune CNS disorders. We report a case series of five patients with new-onset neurological disorders of inflammatory or immunological origin temporally associated with these vaccines.

Methods: A case-series of five patients within a single 23-hospital health system who developed new-onset CNS inflammatory disease within 2 weeks of receiving a dose of an mRNA-based SARS-CoV-2 vaccine.

Results: Five cases of post-vaccination CNS disorders of immune origin (fatal ADEM; n = 1, new-onset NMOSD; n = 2, new-clinical onset MS-like syndrome but with preexisting clinically silent mild demyelination; n = 1, meningoencephalitis; n = 1) observed within 2 weeks of inoculation with either the first or second dose of mRNA-based SARS-CoV-2 vaccines (Moderna = 3, Pfizer = 2).

Discussion: To our knowledge, these are among the emerging cases of CNS adverse events of immunological or inflammatory origin. These findings should be interpreted with great caution as they neither prove a mechanistic link nor imply a potential long-term increased risk in post-vaccination CNS autoimmunity. Larger prospective studies assessing the potential association between mRNA-based vaccination and the development of neurological adverse events of suspected immune origin, particularly among those with underlying CNS or systemic autoimmune disorders, are needed. The use of mRNA-based SARS-CoV-2 vaccines should continue to be strongly encouraged given their high efficacy in overcoming this pandemic.

Keywords: ADEM; CNS inflammation; COVID-19 vaccination; mRNA vaccine; multiple sclerosis.

Figure 1

Case 1: Initial MRI brain on hospital day 5 demonstrated diffusion restriction in the right dorsal medulla (A) with corresponding T2 FlAIR hyperintensity (B), faint T2 hyperintensities in the left pons (C), midbrain (D), and thalamus (E), and minimal T2 sulcal hyperintensity without contrast enhancement (F). Repeat MRI brain on hospital day 17 showing significant progression of these abnormalities (G–L).

Figure 2

Case 1 Pathology: Hematoxylin and Eosin staining shows lymphohistocytic infiltrate in the brain tissue (200 X) (A). LFB staining demonstrates demyelination (200 X) (B). CD68 immunohistochemical stain shows numerous histiocytes (200 X) (C). CD3 immunohistochemical stain reveals scattered T-lymphocytes (200 X) (D). CD20 immunohistochemical stain demonstrate rare B-lymphocytes (200 X) (E). GFAP immunohistochemical stain shows reactive astrocytes (200 X) (F).

Figure 3

Case 2: Thalamic T2 FlAIR hyperintensity (A), T1 shortening (B) with subtle contrast enhancement (C) and diffusion restriction (D). Centrally located T2 hyperintensity spanning the length of the thoracic cord (E,F) without evidence of contrast enhancement (G,H).

Figure 4

Case 2 Pathology: Hematoxylin and Eosin staining shows lymphohistocytic infiltrate in the brain tissue (200 X) (A). LFB staining demonstrates demyelination (200 X) (B). CD163 immunohistochemical stain shows numerous histiocytes (200 X) (C). CD3 immunohistochemical stain reveals scattered T-lymphocytes (200 X) (D). CD20 immunohistochemical stain demonstrates rare B-lymphocytes (200 X) (E). GFAP immunohistochemical stain shows reduced astroglial density in the center of the lesion (200 X) (F). Neurofilament protein reveals the preservation of axons (200 X) (G).

Figure 5

Case 3: Sagittal (A) and Axial (C) MRI T2 STIR demonstrating central gray-matter predominant hyperintensity spanning the T2–T9 vertebrae; Sagittal (B) and Axial (D) MRI T1 with gadolinium study demonstrating centrally enhancement spanning T5–T7 levels. The brain, cervical and lumbar cord were spared and thus not pictured.

Figure 6

Case 4: Contrast MR brain demonstrating numerous T2 hyperintense lesions involving both the white and gray matter, many of which, but not all, had corresponding complete and incomplete ring enhancement [(A–D), arrows pointing to non-enhancing lesions]. Contrast MR cervical spine demonstrates multiple abnormal T2-hyperintense signal lesions (E) with enhancement (F) of the spinal cord, most prominent at the level of the C2 and C3 vertebrae.