Case report: Bilateral panuveitis resembling Vogt-Koyanagi-Harada disease after second dose of BNT162b2 mRNA COVID-19 vaccine

Abstract

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a serious pandemic. COVID-19 vaccination is urgent needed for limiting SARS-CoV-2 outbreaks by herd immunity. Simultaneously, post-marketing surveillance to assess vaccine safety is important, and collection of vaccine-related adverse events has been in progress. Vision-threatening ophthalmic adverse events of COVID-19 vaccines are rare but are a matter of concern. We report a 45-year-old Japanese male with positive for HLA-DR4/HLA-DRB1*0405, who developed bilateral panuveitis resembling Vogt-Koyanagi-Harada (VKH) disease after the second dose of Pfizer-BioNTech COVID-19 mRNA (BNT162b2) vaccine. Glucocorticosteroid (GC) therapy combined with cyclosporine A (CsA) readily improved the panuveitis. The immune profile at the time of onset was analyzed using CyTOF technology, which revealed activations of innate immunity mainly consisting of natural killer cells, and acquired immunity predominantly composed of B cells and CD8⁺ T cells. On the other hand, the immune profile in the remission phase was altered by GC therapy with CsA to a profile composed primarily of CD4⁺ cells, which was considerably similar to that of the healthy control before the vaccination. Our results indicate that BNT162b2 vaccine may trigger an accidental immune cross-reactivity to melanocyte epitopes in the choroid, resulting in the onset of panuveitis resembling VKH disease.

Keywords: BNT162b2 vaccine; Vogt-Koyanagi-Harada disease; covid-19 mRNA vaccines; cyTOF; heat map; multiplex bead analysis; uveitis.

Figure 1

Fundus findings of panuveitis at the time of onset. Color fundus photographs show bullous SRDs in the posterior retina (areas of orange dotted circles), redness and swelling of the optic disc (white arrows) in (A) the right eye and (B) the left eye. EDI-OCT images reveal SRDs (yellow asterisks), cystoid spaces in the neurosensory layer of the retina (white asterisks), choroidal thickening (blue dotted lines) in (C) the right eye and (D) the left eye. FA images indicate multiple punctate fluorescein leaks (yellow arrowheads) and pooling (yellow asterisks) consistent with the SRD locations, and hyperfluorescence of the optic disc in (E) the right eye and (F) the left eye. IA images present dark patches (blue arrowheads) in (G) the right eye and (H) the left eye. The time of photography after administration of FA or IA is indicated in the lower right corner. Scale bars (white vertical bar) in (C, D), 200 μm. EDI-OCT; enhanced depth imaging optical coherence tomography; FA, fluorescein angiography; IA, indocyanine green angiography; SRD, serous retinal detachment.

Figure 2

Hierarchical cluster analysis of cellular phenotypes in the patient and the healthy control. In the heatmap, the vertical axis shows 37 types of immune cells in peripheral blood mononuclear cells. The horizonal axis shows four samples: Pre-P; patient not receiving GC therapy at the time of onset, Post-C; healthy control one month after the third dose of BNT162b2 vaccine, Pre-C; healthy control before BNT162b2 vaccination, Post-P; patient receiving GC therapy combined with CsA in the inactive phase. Hierarchical cluster analysis was performed using Euclidean distance as a distance measure and Ward’s method for hierarchical clustering (21). Color scale: low values, red; middle to high values, black to green.