Background SARS-CoV-2 vaccination in solid organ transplant (SOT) is associated with poorer antibody response (AbR) compared to non-SOT recipients. However, its impact on the risk of breakthrough infection (BI) should yet be assessed. Methods Single-center prospective longitudinal cohort study enrolling adult SOT recipients who received SARS-CoV2 vaccination during 1-year period from February 2021, and followed-up to April 30th 2022. Patients were tested for AbR at multiple timepoints. Primary endpoint was BI (laboratory confirmed SARS-CoV2 infection ≥14 days after 2nd dose). Immunization (positive AbR) was considered an intermediate state between vaccination and BI. Probabilities of being in vaccination, immunization and BI states were obtained for each type of graft and vaccination sequence with multistate survival analysis, then multivariable logistic regression was performed to analyse the risk of BI in AbR levels. Results 614 SOT (275 kidney, 163 liver, 137 heart, 39 lung) recipients were included. Most patients (84.7%) received three vaccine doses, the first two consisted of BNT162b2 and mRNA-1273 in 73.5% and 26.5% of cases, respectively; while at the third dose mRNA-1273 was administered in 59.8% of patients. Overall, 75.4% of patients reached immunization and 18.4% developed BI. Heart transplant recipients showed lowest probability of immunization (0.418) and highest of BI (0.323), all-mRNA-1273 vaccine-sequence showed higher probability of immunization (0.732) and lowest of BI (0.098). Risk of BI was higher for non-high-level AbR, younger age and shorter time from transplant. Conclusions SOT patients with non-high-level AbR, shorter time from transplantation, and heart recipients are at highest risk of BI.

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Background: Every year the number of heart transplant recipients increases but the number of patients in the heart transplant waiting list (HTx WL) does not slow down. However, there are no data on those excluded from HTx WL. The aim was to study clinical differences of chronic heart failure (CHF) patients who excluded from a HTx WL and estimate their survival. Methods: We retrospectively analyzed HTx WL data that was collected from 2010 to 2020 and included 280 patients: 47.4±12.8 year-old, male -210 (75%). We estimated the number of excluded patients, causes of the exclusion and patients' clinical characteristics. Data was analyzed by using the SPSS 21.0. Results: During 10-year follow-up 53 patients (class III by NYHA, class 2 UNOS) excluded from HTx WL: 66% (n=35; 55.4±12.5 year-old; n=33male) -improved (group 1), 9% (n=5; 50 [37;56] year-old; male) refused after the inclusion for their personal reasons (group 2) and 25% (n=13; 58 [46;63] year-old; n=12 -male) -due to diagnosed contraindications (group 3). Most common cause of CHF was ischaemic heart disease (49%, 60% and 69%, respectively). Patients excluded from HTx WL due to their improvement in 17 [8;43] days. LVEF were 21 [17;24] %, 13 [10;17] % and 18 [16;28] %, respectively, (p1,2=0.013) and PASP -44±20 mm Hg, 45 [43;47] mm Hg and 59 [40;67] mm Hg, respectively, (p1,2=0.02). VO2peak was <10-12 ml/kg/min. There was a high incidence of pulmonary hypertension (PHT) in the group 3, including irreversible. NT-proBNP levels were 2556 [1698;3680] pg/ml, 9212 [6226;14508] pg/ml and 3054 [1751;4304] pg/ml, respectively, (p1,2=0.005, p2,3=0.03). After the inclusion in HTx WL, patients completed the SF-36 questionnaire and results did not show significant differences between the groups (p>0.05). One year survival after exclusion was 86% in the group 1, 20% -group 2 and 38% -group 3. Two years after the exclusion 2 patients were put back on HTx WL and then successfully underwent heart transplantation. Mortality of excluded individuals was associated with a higher level of PAWP (r=0.72, p=0.01), a low level of venous oxygen saturation of the central venous blood (r=-0.86, p=0.02), heart rate (r=0.61, p=0.03) and QRS width (r=0.52, p=0.04). Conclusion:In 10 years 19% of patients were excluded from HTx WL, most of them due to the improvement and this one had a higher survival. Most of patients excluded due to irreversible PHT but those who decided to refuse had the lower LVEF. Clinical characteristics, except LVEF and right heart failure, were similar between excluded ones.

Patients with heart transplantation (HT) have an increased risk of COVID-19 disease and the efficacy of vaccines on antibody induction is lower, even after three or four doses. The aim of our study was to assess the efficacy of four doses on infections and their interplay with immunosuppression. We included in this retrospective study all adult HT patients (12/21–11/22) without prior infection receiving a third or fourth dose of mRNA vaccine. The endpoints were infections and the combined incidence of ICU hospitalizations/death after the last dose (6-month survival rate). Among 268 patients, 62 had an infection, and 27.3% received four doses. Following multivariate analysis, three vs. four doses, mycophenolate (MMF) therapy, and HT < 5 years were associated with an increased risk of infection. MMF ≥ 2000 mg/day independently predicted infection, together with the other variables, and was associated with ICU hospitalization/death. Patients on MMF had lower levels of anti-RBD antibodies, and a positive antibody response after the third dose was associated with a lower probability of infection. In HT patients, a fourth dose of vaccine against SARS-CoV-2 reduces the risk of infection at six months. Mycophenolate, particularly at high doses, reduces the clinical effectiveness of the fourth dose and the antibody response to the vaccine.