Fifth bivalent omicron BA.4/BA.5 vaccination neutralization of SARS-CoV-2 in heart transplant recipients.

In 2022, the antigenically divergent SARS-CoV-2 omicron variants (BA.1, BA.2, BA.4, BA.5) outcompeted previous variants and continued to cause substantial numbers of illnesses and deaths. We evaluated the safety and immunogenicity of the bivalent original/omicron BA.4/BA.5 Pfizer/BioNTech vaccine administered as a fifth dose to heart transplant recipients (HTxRs). We compared neutralization (using live virus assays) of SARS-CoV-2-infected cells in serum samples from HTxRs who had previously received 4 doses of the monovalent BNT162b2 vaccine with samples from HTxRs with breakthrough infection after 4 monovalent BNT162b2 doses. The fifth vaccination induced high neutralization efficiency against the wild-type virus and omicron BA.1, BA.2, BA.4, and BA.5 variants, with significantly higher neutralization efficiency being induced in HTxRs with breakthrough infection than in those without. Neutralizing titers in those with breakthrough infection were sustained above the level induced by the fifth dose in the uninfected. We conclude that the fifth bivalent vaccine is immunogenic, including to variants, with higher vaccine immunogenicity conferred by breakthrough infection. Nevertheless, the clinical protection conferred by the fifth dose is yet to be determined. The sustained neutralization responses in those with breakthrough infection support the notion of delaying booster in those with natural breakthrough infection.

Kinetics of cellular and humoral responses to third BNT162B2 COVID-19 vaccine over six months in heart transplant recipients - implications for the omicron variant.

BACKGROUND: The durability of the immune response following the 3-dose BNT162b2 vaccination is unknown. The complexity of the situation is enhanced by the threat that highly transmissible variants may further accelerate the decline in the protection afforded by mRNA vaccines. METHODS: One hundred and three 3-dose-vaccinated heart transplant recipients were longitudinally assessed for the kinetics of variant-specific neutralization (Cohort 1, n = 60) and SARS-CoV-2-specific-T-cell response (Cohort 2, n = 54) over 6 months. Neutralization and T-cell responses were compared between paired samples at 2 time points, using the Kruskal-Wallis test followed by Dunn's multiple comparison test for continuous variables and McNemar's test for dichotomous variables. The Bonferroni method of p values adjustment for multiple comparison was applied. RESULTS: The third dose induced high neutralization of the wild-type virus and delta variant (geometric mean titer [GMT], 137.2 [95% CI, 84.8-221.9] and 80.6, [95% CI, 49.3-132.0], respectively), and to a lesser degree of the omicron variant (GMT, 10.3 [95% CI, 5.9-17.9]). At 6 months, serum neutralizing activity declined but was still high for the wild-type virus and for the delta variant (GMTs 38.1 [95% CI, 21.2-69.4], p = 0.011; and 28.9 [95% CI, 16.6-52.3], p = 0.022, respectively), but not for the omicron variant (GMT 5.9 [95% CI, 3.4-9.8], p = 0.463). The percentages of neutralizing sera against the wild-type virus, delta and omicron variants increased from 70%, 65%, and 38%, before the third dose, to 93% (p < 0.001), 88% (p < 0.001), and 48% (p = 0.021) at 3 weeks after, respectively; and remained high through the 6 months for the wild-type (80%, p = 0.06) and delta (77%, p = 0.102). The third dose induced the development of a sustained SARS-CoV-2-specific-T-cell population, which persisted through 6 months. CONCLUSIONS: The third BNT162b2 dose elicited a durable SARS-CoV-2-specific T-cell response and induced effective and durable neutralization of the wild-type virus and the delta variant, and to a lesser degree of the omicron variant.

Fourth BNT162b2 vaccination neutralization of omicron infection after heart transplantation.

We investigated changes in receptor-binding domain IgG and neutralizing antibodies against the omicron and delta variants, vs the wild-type virus, in response to a fourth BNT162b2 dose in 90 heart transplant (HT) recipients. The fourth dose induced anti-RBD IgG antibodies and a higher neutralization efficiency against the wild-type virus and the variants; however, neutralization efficiency against the omicron variant was lower than that against the delta variant (the latter demonstrating efficacy similar to that against the wild-type virus). Notably, while IgG anti-RBD antibodies were detectable in >80% of the HT recipients, only about half demonstrated neutralization efficiency against the omicron variant. A SARS-CoV-2-specific-T-cell response following the fourth dose was evident in the majority of transplant recipients. Boosting vulnerable groups improves antibody responses (including neutralizing responses) and cellular immunity, but the incomplete immunological response, particularly for omicron, suggests continued preventive measures and optimization of vaccination strategies that elicit strong, and long-lasting immune responses, in this high-risk population, should remain a priority.

Third dose of the BNT162b2 vaccine in heart transplant recipients: Immunogenicity and clinical experience.

BACKGROUND: The repeated waves of the COVID-19 pandemic have highlighted the necessity to optimize vaccine responses in immunocompromised populations. We investigated the safety and immunogenicity of a third, booster, dose of the Pfizer BNT162b2 vaccine in heart transplant (HT) patients. METHODS: The cohort comprised 96 adult HT patients who received a third homologous dose of the BNT162b2 vaccine 168 days after the second dose. The vaccine-induced antibody responses of both receptor-binding domain (RBD) IgG and neutralizing antibodies were assessed in all patients, with a positive antibody response being defined as the presence of either IgG anti-RBD or neutralizing antibodies. For a subset of patients, T cell response was also studied. RESULTS: The third dose was associated with a low rate of adverse events, mostly mild pain at the injection site. No serious adverse events were recorded, and there were no episodes of rejection. At 18 days following the third dose of the vaccine, the positive antibody response increased from 23% to 67%, with a corresponding increase in neutralizing capacity. The third dose elicited SARS-CoV-2 neutralization titers >9-fold and IgG anti-RBD antibodies >3-fold of the range achieved after the two primary doses. Mycophenolate use, lower eGFR and higher C-reactive protein were independently associated with a reduced likelihood of generating an immune response. Importantly, a specific T-cell response following the third dose was evident in the majority of transplant recipients. CONCLUSIONS: An homologous third booster dose of the BNT162b2 vaccine gave overall consistent tolerability and a good safety profile, while eliciting humoral and cellular immune responses.

BNT162b2 vaccination in heart transplant recipients: Clinical experience and antibody response.

BACKGROUND: Data on the safety and efficacy of SARS-CoV-2 vaccines in immunocompromised populations are sparse. METHODS: We conducted a prospective study of 77 heart transplant (HT) recipients vaccinated with two doses of BNT162b2 vaccine and monitored for adverse events following both doses, the receptor-binding domain (RBD) IgG response, and neutralizing antibodies. RESULTS: BNT162b2 vaccination was associated with a low rate of adverse events, characterized mostly by pain at the injection site. By a mean 41 days post second dose there were no clinical episodes of rejection, as suggested by a troponin leak or allograft dysfunction. At a mean 21 days following the second dose, IgG anti-RBD antibodies were detectable in 14 (18%) HT recipients. Immune sera neutralized SARS-CoV-2 pseudo-virus in 8 (57%) of those with IgG anti-RBD antibodies. Immunosuppressive regimen containing mycophenolic acid was associated with lower odds of an antibody response (OR = 0.12, p = 0.042). CONCLUSIONS: Whether a longer time-frame for observation of an antibody response is required after vaccination in immunosuppressed individuals remains unknown.

Acute pulmonary embolism following acute type A aortic dissection in a patient with COVID-19.

Acute aortic dissection and acute pulmonary embolism (PE) are life-threatening emergencies that can mimic each other at presentation. Immediate and accurate diagnosis of these scenarios is crucial to initiate the appropriate interventions. In this case report we present a 73-year-old patient, who was admitted to our Medical Center with acute type A aortic dissection. She was tested for coronavirus disease 2019 (COVID-19) infection and was found to be positive. During her admission in the COVID-19 designated intensive care unit, she diagnosed with acute PE in the main right and left pulmonary arteries. She underwent surgery that included bilateral pulmonary embolectomy and aortic dissection repair. The patient was discharged from our hospital on the ninth postoperative day without any complications. Frequency of simultaneous presentation of acute aortic dissection and acute PE is increased with a history of coagulation abnormalities as seen in patients with COVID-19.

The impact of COVID-19 pandemic on cardiac surgery in Israel.

BACKGROUND: Ever since the coronavirus disease 2019 (COVID-19) has become a pandemic, worldwide efforts are being made to "flatten the curve". Israel was amongst the first countries to impose significant restrictions. As a result, cardiac surgeons have been required to scale down their routine practice, resulting in a significant reduction in the number of cardiac surgeries. The aim of this study is to characterize the impact of COVID-19 on cardiac surgery in Israel. METHODS: This is a retrospective observational study performed in two cardiac surgery departments in Israel and includes all patients who underwent cardiac surgery in March and April during the years 2019 and 2020. The patient cohort was divided into two groups based on the year of operation. Analysis of the patients' baseline characteristics, operative data, and postoperative outcome, was performed. RESULTS: The 2019 group (n = 173), and the 2020 group (n = 108) were similar regarding their baseline characteristics, previous medical history, and rates of previous revascularization interventions. However, compared to the 2019 group, patients in the 2020 group were found to be more symptomatic (NYHA class IV; 2.4% vs. 6.2%, p = 0.007). While all patients underwent similar procedures, patients in the 2020 group had significantly longer procedural time (p < 0.001). In-hospital mortality rate was found to be significantly higher in group 2020 (13% vs. 5.2%, p = 0.037). CONCLUSIONS: While the number of patients undergoing cardiac surgery declined during the outbreak period, the rate of surgical mortality increased. One explanation for this might be delayed hospital arrival.