Subclinical Myocardial Leukocyte Infiltration after COVID-19 Vaccination in HeartTransplant Recipients

ABSTRACT

Background: mRNA-based COVID-19 vaccines have been reported to rarely cause myocarditis. Although myocardial biopsy is considered gold standard in the diagnosis of myocarditis, no standardized study following COVID-19 vaccination in humans was performed so far. Since heart transplant (HTX) recipients frequently undergo routine myocardial biopsy, we here aimed to investigate effects of COVID-19 vaccination by analyzing myocardial inflammation by state-of-the-art quantitative immunohistochemistry. Method(s) Consecutive patients after HTX who underwent routine endomyocardial biopsies at a median of 167 days before and 136 days after their first COVID-19 vaccination with a mRNA vaccine were included and divided into groups with and without inflammatory response following vaccination, defined as increased number of CD3+ lymphocytes >14/mm2. Patients with histological signs of rejection (ISHLT Grade >1) or >14 CD3+ lymphocytes/mm2 at baseline were excluded. Afterward clinical characteristics of patients with inflammatory response were screened for signs of myocarditis. Result(s) The final analysis included 46 patients with a median age of 63 years and a time post-HTX of 2.4 years. Immunosuppressive therapy remained unchanged between biopsies. 36 (78%) patients remained below the cut-off of 14 CD3+ lymphocytes/mm2. However, in 10 (22%) recipients, we detected significant leucocyte infiltration by quantitative analysis of endomyocardial biopsies following vaccination (4 vs. 33.7 leucocytes/mm2, p = 0.001). Groups did not differ in age (63 vs. 57 years, p = 0.21), body mass index (25 vs. 24 kg/m2, p = 0.24), NYHA-class (>=2 in 19 vs. 10%, p = 0.4), NTProBNP levels (592 vs. 514 ng/L, p = 0.55) or myocardial CD3+ cell count (4.9 vs. 2.6 cells/mm2, p = 0.07) before vaccination. Patients with leucocyte infiltration remained clinical inapparent with stable NYHA class (>=2 in 10 vs. 20%, p = 0.99) and depicted no increased NT-ProBNP levels (514 vs. 478 ng/L, p = 0.03). No hospitalizations due to suspected myocarditis were reported. Conclusion(s) For the first time, we report subclinical myocardial leucocyte infiltration following COVID-19 mRNA vaccination in every fifth patients without clinical consequences during the short observation period.