ABSTRACT
Background: Both mRNA-based Covid-19 vaccines, BNT162b2 (BioNTech/Pfzer) and mRNA-1273 (Moderna), efectively decrease the risk for severe Covid-19 disease in the general population. However, vaccination success is less likely in immunocompromised individuals. Methods: To assess the rate of humoral response to a full (two-fold) primary mRNA vaccination, defned by manufacturer cut-of > = 7.1 BAU/ml (SARS-CoV-2 IgG II Quant assay, Abbott), and identify clinical and laboratory parameters associated with failed humoral response in recipients of an allogeneic hemat-opoietic stem cell transplant (HSCT), 167 HSCT recipients were evaluated in this single-center retrospective study. Variables studied included time since HSCT to vaccination, time between vaccination to titer measurement, age of recipient and donor, ongoing anti-tumor therapy, individual immunosuppressives, type of GHVD-prophylaxis, sex, donor/recipient relationship, and vaccine type, and the immunologic parameters (assessed closely to vaccination), CD4, CD8, CD19, and NK blood-cell counts, immunoglobulin levels (IgA, IgG, and IgM), both by univariate and multivariate analyses. Results: Tirty-seven HSCT recipients (22 %) developed no detectable antibody-response. Median time from HSCT to vaccination was 10.2 months (range, 2.5-88.9) in non-responders, while it was 35.3 months (3.0-215.1) in responders (p < 0.001). By multivariable analysis, a higher CD19 (B cell) count was associated with humoral vaccination response adjusted odds ratio (aOR) 3.3 per 100 B-cells/mcl (CI 95 % [1.78-6.20], p < 0.001). Concurrent immunosuppression with mycophenolate mofetil (MMF) plus/minus a calcineurin inhibitor decreased the probability of response (aOR 0.04, CI 95 % [0.01-0.24], p < 0.001). Conclusions: Our fndings may contribute to a more profound understanding of risk factors for failure of mRNA-based SARS-CoV-2 vaccination in HSCT recipients.