Fulminant Antibody-Mediated Rejection in a Stable Lung Transplant Recipient Post COVID-19 Vaccination

INTRODUCTION: Vaccination against COVID-19 in immunocompetent individuals has demonstrated high efficacy in disease prevention while significantly reducing severe infections and hospitalizations. COVID-19 vaccination is endorsed in immunosuppressed recipients of solid organ transplant. Trials have examined safety data in this population, with no published reports of increased risk of antibody-mediated rejection (AMR). We present a case of probable mRNA vaccine induced AMR in a previously stable lung transplant recipient. CASE REPORT: A 27-year-old bilateral lung transplant recipient for cystic fibrosis related lung had grade 2 rejection with class II antibodies 2 months post-transplant that was treated with methylprednisolone with good response. He was then event free for over two years. He developed acute onset of dyspnea, dry cough, non-pleuritic chest pain, and general malaise 24 hours after receiving his second dose of the Pfizer mRNA vaccine. Over the subsequent 3 weeks, he deteriorated with worsening exertional dyspnea and desaturation. He was admitted to hospital with rapidly progressive type 1 respiratory failure. A CT angiogram of the chest demonstrated findings consistent with organizing pneumonia versus opportunistic infection. Bronchoscopy was negative for infectious etiology. He was treated with a methylprednisolone pulse to treat the organizing pneumonia seen on imaging and potential AMR. He required intubation and mechanical ventilation on post admission day (PAD) 4. Human leukocyte antigen testing demonstrated de novo class II donor specific antibody (DR12) and possible weak class I reactivity. With declining status and refractory hypoxemia, 5 cycles plasma exchange (PLEX) alternating with thymoglobulin were administered. He became dependent on extracorporeal membrane oxygenation with poor lung compliance. Antibody levels decreased but remained elevated. Subsequent therapy included thymoglobulin (total dose 7mg/kg), 5 additional cycles of PLEX, and intravenous immunoglobulin and Dartinumab on PAD 38. He died PAD 47 when life sustaining measures were removed due complications from Clostridium difficile infection. SUMMARY: This case of probable AMR post mRNA vaccination in a lung transplant recipient raises clinical suspicion for a serious adverse event and contributes to safety data for this select population.