Neurological autoimmune diseases following vaccinations against SARS-CoV-2: a case series

Abstract

Background and purpose: Population-based studies suggest that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines may trigger immune-mediated thrombotic thrombocytopenia (VITT) raising concerns for other autoimmune responses. The aim was to characterize neurological autoimmunity after SARS-CoV-2 vaccinations.

Methods: In this single-centre prospective case study patients with neurological autoimmunity in temporal association (≤6 weeks) with SARS-CoV-2 vaccinations and without other triggers are reported. Clinical, laboratory and imaging data were collected with a median follow-up of 49 days.

Results: In the study period 232,603 inhabitants from the main catchment area of our hospital (Rhein-Neckar-Kreis, county) received SARS-CoV-2 vaccinations. Twenty-one cases (new onset n = 17, flares n = 4) diagnosed a median of 11 days (range 3-23) following SARS-CoV-2 vaccinations (BNT162b2 n = 12, ChAdOx1 n = 8, mRNA-1273 n = 1) were identified. Cases included VITT with cerebral venous sinus thrombosis (n = 3), central nervous system demyelinating diseases (n = 8), inflammatory peripheral neuropathies (n = 4), myositis (n = 3), myasthenia (n = 1), limbic encephalitis (n = 1) and giant cell arteritis (n = 1). Patients were predominantly female (ratio 3.2:1) and the median age at diagnosis was 50 years (range 22-86). Therapy included administration of steroids (n = 15), intravenous immunoglobulins in patients with Guillain-Barré syndrome or VITT (n = 4), plasma exchange in cases unresponsive to steroids (n = 3) and anticoagulation in VITT. Outcomes were favourable with partial and complete remissions achieved in 71% and 24%, respectively. Two patients received their second vaccination without further aggravation of autoimmune symptoms under low-dose immunosuppressants.

Conclusions: In this study various neurological autoimmune disorders encountered following SARS-CoV-2 vaccinations are characterized. Given the assumed low incidence and mostly favourable outcome of autoimmune responses, the benefits of vaccinations outweigh the comparatively small risks.

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

FIGURE 1

Spectrum of autoimmunity and intervals to symptom onset and hospital admission. (a) The box diagram shows neurological autoimmune diseases encountered at our institution following SARS‐CoV‐2 vaccinations. Conditions included CNS demyelinating disorders (CNS DD), inflammatory demyelinating peripheral neuropathies (IDP), vaccine‐induced immune thrombotic thrombocytopenia (VITT), myositis, giant cell arteritis (GCA), myasthenia gravis (MG) and limbic encephalitis (LE). Different grey tones indicate new onset (dark grey) or flare (light grey) of autoimmunity. (b) Inverted Kaplan–Meier curves highlight the interval from vaccination to autoimmune symptom onset (solid line, median 11 days) and hospital admission (dotted line, median 17 days)

FIGURE 2

Radiological findings in patients with autoimmunity following SARS‐CoV‐2 vaccinations. (a), (b) Four days prior to the onset of supraventricular tachycardia symptoms: aside from a hypoplastic left sigmoid sinus findings are unremarkable in contrast‐enhanced magnetic resonance venography (CE‐MRV) (a) and axial fluid attenuated inversion recovery (FLAIR) sequence (b). (c) Follow‐up CE‐MRV reveals an occlusive thrombus of the left sigmoid sinus and a non‐occlusive thrombus of the right transverse sinus (yellow arrows). (d) The corresponding axial FLAIR sequence shows resulting congestive bleeding in the left temporal and occipital lobe. (e) Coronal T2‐weighted (T2w) and (f) gadolinium contrast‐enhanced (Gd CE) T1w orbital sequences reveal T2w hyperintensity (e) (blue arrow) and associated mild contrast enhancement of the left optic nerve (f) (green arrow) consistent with optic neuritis. (g), (h) Axial, fat saturated, Gd CE T1w saturated images at the level of the left lower leg 6 weeks before (g) and 7 days after (h) vaccination demonstrate progressive contrast uptake of the left soleus muscle indicating reactivation of focal myositis. (i) Coronal T2w MRI reveals hyperintense enlargement of the right L5 nerve root (orange bracket) consistent with L5 radiculitis. (j), (k) Axial T2w sequence with spectral fat saturation at the level of the distal right thigh (j) and right lower leg (k) are shown. Somatotopic L5 lesion pattern with hyperintense, fascicular enlargement of the common peroneal nerve and the ventral section of the tibial nerve (j) (orange arrows) and subsequent denervation oedema of the fibularis longus, extensor digitorum longus, tibialis anterior and posterior muscles (k) are evident. (l) Coronal FLAIR sequence demonstrates bilateral hippocampal hyperintensities (red arrows) and mild swelling in line with limbic encephalitis [Color figure can be viewed at wileyonlinelibrary.com]