*Purpose: Transplant recipients have worse CoVID-19 survival compared to the general population, and thus are recommended to be vaccinated and boosted. Determinants of vaccination efficacy have not been well studied in heart transplant patients.

*Methods: This was a prospective study of heart transplant recipients vaccinated against SARS-CoV-2 with one of the 2-dose mRNA vaccine series. Antibodies (Ab) were quantified by anti-Spike ELISA pre- and post-vaccination. Clinical data was extracted from electronic medical records. Differences in Ab detection and timing of Abs were assessed for statistical significance using Fisher’s exact tests for categorical variables and t-tests for continuous variables.

*Results: Of the total 54 participants recruited from Jan 2021 to present, 6 patients were Ab positive prior to vaccination and 11 did not provide a pre-vaccination sample but were Ab positive post-vaccination. Almost half of participants (48%, n=26) received a booster 3^rd dose. The mean age at vaccination was 58 ± 11, 20% (n=11) were female, 70% (n=38) were Caucasian, and median time since transplant was 4 years (interquartile range: 2-11 years). Of the 37 Ab-negative individuals enrolled, none developed detectable Abs after a single vaccine dose and only 9 (24%) developed Abs after the 2nd vaccine dose. Interestingly in this small group, 6/9 (66%) of participants had delayed seroconversion of approximately 3 months. Unexpectedly, hyperlipidemia was positively associated with a detectable antibody response (p = 0.05) after the 2^nd dose. There was also a trend toward higher age (p=0.06) and BMI (p=0.08) being associated with lack of response to the 2-dose series. Importantly, of the 28 patients who had no Ab response to the 2-dose vaccination regimen, 11/17 (65%) became Ab positive after the booster, increasing the vaccine response rate in this pre-vaccine Ab-negative group to 20/37 (54%). Looking at the total cohort of 54 participants, the overall positivity rate regardless of antigen sources (i.e., including those previously infected or for whom no pre-vaccine sample is available) is 68.5% (37/54) with a trend suggesting that absence of Ab response may be associated with prednisone treatment (p=0.06).

*Conclusions: Heart transplant recipients exhibit a low response rate to the initial 2-dose mRNA vaccines (24%), but the 3^rd dose induces a response in the majority of those who failed to respond to the 2-dose series increasing overall response to over 50%. Similar to observations in the general public, non-response tended to be associated with older age and higher BMI. However, further/larger studies are needed to identify key determinants of vaccine efficacy in this population to guide management.

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