Neurological autoimmune diseases following vaccinations against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): A follow-up study

Abstract

Background and purpose: Population-based studies suggest severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines may trigger neurological autoimmunity including immune-mediated thrombotic thrombocytopenia. Long-term characterization of cases is warranted to facilitate patient care and inform vaccine-hesitant individuals.

Methods: In this single-center prospective case study with a median follow-up of 387 days long-term clinical, laboratory and imaging characteristics of patients with neurological autoimmunity diagnosed in temporal association (≤6 weeks) with SARS-CoV-2 vaccinations are reported.

Results: Follow-up data were available for 20 cases (central nervous system demyelinating diseases n = 8, inflammatory peripheral neuropathies n = 4, vaccine-induced immune thrombotic thrombocytopenia n = 3, myositis n = 2, myasthenia n = 1, limbic encephalitis n = 1, giant cell arteritis n = 1). Following therapy, the overall disability level improved (median modified Rankin Scale at diagnosis 3 vs. 1 at follow-up). The condition of two patients worsened despite immunosuppressants possibly related to their autoimmune diagnoses (limbic encephalitis n = 1, giant cell arteritis n = 1). At 12 months' follow-up, 12 patients achieved complete clinical remissions with partial responses in five and stable disease in one case. Correspondingly, autoimmune antibodies were non-detectable or titers had significantly lowered in all, and repeat imaging revealed radiological responses in most cases. Under vigilant monitoring 15 patients from our cohort underwent additional SARS-CoV-2 vaccinations (BNT162b2 n = 12, mRNA-1273 n = 3). Most patients (n = 11) received different vaccines than prior to diagnosis of neurological autoimmunity. Except for one short-lasting relapse, which responded well to steroids, re-vaccinations were well tolerated.

Conclusions: In this study long-term characteristics of neurological autoimmunity encountered after SARS-CoV-2 vaccinations are defined. Outcome was favorable in most cases. Re-vaccinations were well tolerated and should be considered on an individual risk/benefit analysis.

Keywords: COVID-19; Guillain-Barré syndrome; autoimmune; cerebral venous sinus thrombosis; multiple sclerosis; myelitis; myositis.

FIGURE 1

Magnetic resonance imaging (MRI) findings during follow‐up. MRI obtained at diagnosis of neurological autoimmunity (a), (c), (e), (h), (k) after SARS‐CoV‐2 vaccination and at follow‐up (b), (d), (f), (g), (i), (j), (l) are shown including cases of inflammatory myopathy (a) and (b), L5 radiculitis (c) and (d), vaccine‐induced thrombotic thrombocytopenia (VITT) (e)–(j) and acute myelitis (k), (l). (a), (b) Axial T2‐weighted (T2w) and fat suppressed (fs) MRI of left pelvic and proximal thigh musculature are shown. (a) T2w hyperintensities of left iliopsoas (red *) and sartorius (red bracket) muscles consistent with an inflammatory myopathy (b) completely resolved (blue * and bracket) under steroid therapy over 11 months. (c), (d) Axial T2w fs MR neurography of the lumbosacral plexus at the level of the pelvis revealed T2w hyperintense L5 nerve root enlargement ((c) violet arrowhead) in line with an L5 radiculitis with subtotal remission 9 months later ((d) orange arrowhead) following immunosuppressive therapy. Normal appearance of right S1 nerve root ((c) violet arrow). (e)–(j) Axial reconstructions of contrast‐enhanced MR venography (e)–(g) and T2w axial MRI (h)–(j) are shown. (e) At diagnosis of VITT, complete thrombotic occlusion of the left hypoplastic sigmoid sinus (green arrowhead) and a non‐occlusive thrombus in the right sigmoid sinus (green arrow) were noted. Following therapy, marked regression ((f) 3 weeks after diagnosis) and complete resolution of thrombotic occlusions ((g) 9 months after diagnosis) were observed. CVST resulted in congestive intraparenchymal bleeding in the left temporal lobe at diagnosis (h) with associated midline shift and small intraventricular hemorrhage. Following decompressive craniotomy brain parenchyma protrusion and unchanged midline shift was noted ((i) 3 weeks after diagnosis). Nine months after onset, complete resorption of hemorrhage and a residual left temporal parenchymal defect with ex vacuo hydrocephalus was found (j). (k), (l) Axial T2w MRI of the spinal cord revealed a delineated central T2w hyperintensity with concomitant mild swelling at the level of the first thoracal vertebral body in line with acute myelitis (k). One year after therapy, marked regression of the spinal cord lesion and complete remission of spinal cord swelling were evident (l).

FIGURE 2

Modified Rankin Scale (mRS) during follow‐up. mRS values are shown for the entire cohort (a) and its largest subgroups (b)–(d): (b) CNS demyelinating disorders, (c) inflammatory neuropathies, (d) VITT before, at diagnosis and at 12 months’ follow‐up. Median mRS of the entire cohort and its subgroups improved after immunosuppressive therapy.

FIGURE 3

Re‐vaccination of patients with neurological autoimmunity after COVID‐19 vaccinations. Re‐vaccination data are summarized for the entire cohort (a) and its largest subgroups (b)–(d): (b) CNS demyelinating disorders; (c) inflammatory neuropathies; (d) VITT. Vaccines administered before diagnosis of neurological autoimmunity are shown along the x‐axis whereas different colors indicate vaccine types selected for re‐vaccinations. Following ChAdOx1 vaccinations most patients received mRNA‐based vaccines whereas re‐vaccination hesitancy was high after BNT162b2 vaccinations (a)–(d).