Relationship Between Covid-19 And Donor Specific Antibodies In Orthotopic Heart Transplant Recipients

ABSTRACT

Introduction: De novo donor specific antibodies (DSAs) are associated with increased risk of antibody-mediated rejection (AMR) and worse prognosis in patients after orthotopic heart transplant (OHT). Viral infections have the potential to induce or reactivate the production of DSAs, yet the development of DSAs after infection by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has not been reported. In this observational study, we describe DSA titers after Coronavirus Disease 2019 (COVID-19) infection and relationship with AMR and graft dysfunction in a large OHT cohort at a tertiary academic medical center. Hypothesis: We predicted that COVID-19 infection would be associated with development of de novo DSAs or increase in pre-existing DSAs. Method(s) We retrospectively analyzed all adult OHT patients followed at Washington University School of Medicine in St. Louis between 4/1/2020-12/31/2021. COVID-19 infection was defined by positive antigen or PCR test in setting of clinical exposure or symptoms. Patients were considered fully vaccinated 2 weeks after 2 doses of the BNT162b (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccines or after a single dose of the AD26.COV2.S (Johnson & Johnson) vaccine. De novo DSAs were defined as newly detected MHC I or II antibody greater than 2000 mean fluorescence intensity (MFI) by single antigen beads or newly elevated antibody against angiotensin-II type 1 receptor (AT1R). In patients with pre-existing DSAs, a significant increase was defined by an MFI value that increased by 20% or more compared to their baseline value prior to SARS-CoV-2 infection. Result(s) A total of 577 patients were followed during the study period and 117 cases of COVID-19 infection were identified. Baseline characteristics of COVID-19 positive patients are shown in Figure. Overall, 10% of patients infected with SARS-CoV-2 infection developed de novo DSAs or an increase in pre-existing DSAs, with unvaccinated patients having a higher incidence compared to vaccinated patients (15% vs. 2%, p=0.02). MHC class II-specific antibodies were the most common DSAs detected. There was a trend towards higher incidence of AMR in unvaccinated patients, although mortality and long-term graft dysfunction were similar. Conclusion(s) Unvaccinated patients had a higher incidence of developing de novo or an increase in pre-existing DSAs after SARS-CoV-2 infection. Future studies are necessary to investigate the long-term consequences of COVID-19 in the OHT population.Copyright © 2022