ABSTRACT
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. Method(s): 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. Result(s): 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 3rd 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 2nd 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). Conclusion(s): Heart transplant recipients exhibit a low response rate to the initial 2-dose mRNA vaccines (24%), but the 3rd 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.
ABSTRACT
Purpose: Heart transplant recipients have worse survival with COVID-19 than the general population, highlighting the importance of vaccination in these patients. The impact of vaccination on rejection in transplant recipients is not well studied. This study examines the association of vaccination for COVID-19 with changes in markers for and evidence of transplant rejection. Method(s): A retrospective analysis of heart transplant recipients vaccinated for COVID-19 was conducted at a major tertiary care center in the American Midwest. Serial antibody responses were drawn after vaccination to assess vaccine response. Data from routine transplant surveillance was extracted from the electronic medical record. Markers of rejection included Allomap, Allosure, donor specific antibodies (DSA), and endomyocardial biopsies. Only patients with comparative data within 365 days of their first COVID-19 vaccination were included for analysis. Numerical data was assessed using descriptive statistics. Categorical variables were analyzed using Fisher's exact tests. Result(s): Between January 1, 2021 and September 30, 2021, 51 heart transplant recipients had COVID-19 antibody levels checked post-vaccination. There was an increase in the mean Allomap (31.19 +/- 5.27 vs 32.14 +/- 4.30), Allosure (0.04 +/- 0.08 vs 0.11 +/- 0.12%), and biopsy C4d% (3.33 +/- 8.16 vs 10.00 +/- 12.65%) levels post-vaccination compared to those pre-vaccination. Both positive and negative responders to vaccination showed this numerical increase in markers of rejection. There was no change in biopsy grades for acute cellular rejection, nor any changes in class I DSA positivity. One patient who had a positive antibody response to the vaccine had a de novo class II DSA post vaccination. No patients in this cohort had an episode of treated rejection post vaccination. Conclusion(s): Heart transplant recipients receiving COVID-19 vaccination have numerical increases in markers of rejection like Allomap, Allosure, and biopsy C4d%. These subtle changes may suggest a difference in the immunologic environment but are of unclear significance. There was no change in biopsy proven ACR or treated episodes of rejection. Further studies are warranted to investigate the effect of COVID-19 vaccination on transplant rejection. (Table Presented).