Recovery from antibody-mediated biliary ductopenia and multiorgan inflammation after COVID-19 vaccination

Abstract

The coronavirus disease 2019 (COVID-19) pandemic has caused significant morbidity and mortality. Spike messenger RNA (mRNA)-based vaccines against severe acute respiratory syndrome coronavirus 2 may contribute to immune-mediated injuries. Here we present a case of a previously healthy 47-year-old man, who developed progressive jaundice 2 weeks after receiving his 3^rd COVID-19 vaccination (1^st mRNA-based vaccine). Apart from elevated serum total bilirubin levels (peaked at >70 mg/dL), deteriorating renal (blood urea nitrogen: peak, 108.5 mg/dL; creatinine: peak, 6 mg/dL) and exocrine pancreas (amylase: peak, 1717 U/L; lipase: peak, 5784 U/L) profiles were also seen. Vanishing bile duct syndrome characterized by ductopenia and cholangiocyte vacuolation, positive C4d deposition, and high titer of anti-angiotensin II type 1 receptor antibody consistently explain the overall antibody-mediated pathogenesis resembling antibody-mediated "rejection" in the solid organ transplant setting. Corticosteroids and plasmapheresis were administered, leading to gradual resolution of the symptoms, and the jaundice completely resolved 2 months later. In conclusion, we reported a case of antibody-mediated multiorgan injury after an mRNA COVID-19 vaccine, characterized by severe cholangiopathy. The patient recovered with corticosteroids and plasmapheresis, and long-term follow-up is necessary.

Fig. 1. Laboratory trends in a case of post-COVID-19 vaccination severe jaundice and multiorgan inflammation.

Hemogram (A), kidney (B), liver (C), pancreas (D), inflammation (E), and antibodies (anti-SARS-CoV-2 Spike antibody & angiotensin II receptor type 1 (AT1R) antibody) (F). Day 0 is the date of admission and doses and duration of medications are at top. Improvement was noted after starting steroids and plasma exchange (D7). Hb drop was noted after liver biopsy (D5). Reference of positivity: anti-SARS-CoV-2 Spike antibody (≥0.8 U/mL, quantitative Roche Elecsys® Anti-SARS-CoV-2 S assay), angiotensin II receptor type 1 (AT1R) antibody (>17 U/mL, enzyme immuno-assay (EIA), CellTrend GmbH). Normal ranges of laboratory testes other than antibodies were presented in Supplementary Table S1. ALT alanine transaminase, AST aspartate transaminase, BUN blood urea nitrogen, Cre creatinine, CRP C-reactive protein, D-bil direct bilirubin, Hb hemoglobin, PLT platelet, T-bil total bilirubin, WBC white blood cell.

Fig. 2. Liver biopsy in a case of post-COVID-19 vaccination severe jaundice and multiorgan inflammation.

Histopathological (A, B) and immunohistopathological (C) examinations of liver biopsy. A Marked centrilobular cholestasis. B Mild lymphocytic (square) and neutrophilic (circle) infiltration in the portal areas with bile duct damage and cholangiocyte vacuolation (black arrows). C Positive C4d deposition in portal venous and capillary endothelial cells (black arrows). 200X.