ABSTRACT
The cellular responses to the BNT162b2 vaccine and their correlation with antibody titer and gender determinants are critical to assess. We aimed to evaluate the cellular response kinetics, correlating it with gender and antibody titer.Peripheral Blood Mononuclear Cells (PBMC) were stimulated with SARS-CoV-2 Spike protein, and the IFN-gamma was evaluated by Elispot assay at 5 different timepoints, for up to 9 months after the BNT162b2 vaccine. 107 healthcare workers were divided into 4 age groups: <40 and >40 years for men, based on the gradual decline of testosterone with aging;<48 and >48 years for women based on the decrease of estrogen with menopause. Furthermore, seropositive individuals were analyzed at baseline to avoid confounding factors caused by the previous infection with SARS-CoV-2. We also analyzed pre-pandemic samples as controls to consider the cross-reactivity toward other coronaviruses. Among seronegative at baseline, the T-cell response against Sprotein changed from a median of 2 spot forming cells (SFC)/400.000 PBMC (Interquartile range, IQR, 0-17) before vaccination to a median of 42 (17.5-78.0) after the second dose. Then, it progressively decreased to 13 (0-34) at 6 months after vaccination and 11 (0-31) after 9 months. At all timepoints, the differences were statistically significant compared to baseline values. Moreover, the results obtained after the second dose were significantly higher than those observed at any other time point. Indeed, a significant correlation was observed between T-cell response and anti-S antibody titer (p<0.001), previously analyzed, even if it was weak in magnitude (r=0.314). Natural seropositive showed higher T cell response at baseline than seronegative ones (median: 2 vs. 29, p=0.003), even if there were no significant differences in response at later time points. Our data suggest that T-cell reactiveness is poorly impacted by sex and age, whereas age was significantly associated with anti-S antibody titer. T-cell response declines 9 months later administration, indicating a waning of immune response over time. So, the positive correlation with the antibody titer confirms a linkage between different arms of adaptive responses and potentially converts future vaccinations into a tailored process.
ABSTRACT
Development of endomyocardial biopsy for acute rejection monitoring in the early Seventies, and above all use of cyclosporine in the clinical practice starting from 1980, introduced the modern era of heart transplantation. Following the initial positive outcomes, the first Italian transplant was performed in Padua by V.Gallucci on November 15th 1985. This pioneering success was rapidly repeated in Pavia, where M.Viganò performed the second transplant on Novembre 17th. Recipient was 20 years old man, suffering from dilated cardiomyopathy, on urgent transplant list. Cardiac index was 1.38 l/min/m2 and pulmonary vascular resistance 1.6 WU. Donor was a 14 years old boy died of brain injury. Total ischemic time was 125 minutes. Induction immunosuppression consisted of horse anti-lymphocyte immunoglobulins, whereas maintenance therapy included cyclosporine, azathioprine and steroids. Postoperative course was complicated by pericardial effusion and cholestatic jaundice. Later pulmonary aspergillosis occurred and due to the profound immunodepression was complicated by fungal localization at L2 vertebral body. The infection was treated with surgical removal of the secondary localization and amphotericin B administration. On December 6th severe acute rejection was found at biopsy and treated with i.v. steroid pulse. Length of ICU and hospital stay was 28 and 72 days, respectively. In 1998 HCV infection was detected and eradicated in 2017 with elbasvir/grazoprevir therapy. Complications of long term immunosuppressive treatment included dyslipidemia, myeloma and basal cell carcinoma. Due to long-term calcineurin inhibitors therapy progressive chronic renal failure occurred, leading to replacement therapy in 2015 and kidney transplantation in 2016. In 2015 the patient underwent percutaneous coronary intervention with stents implantation in two marginal branches and in the anterior descending artery in 2021. Everolimus was introduced to slow down progression of cardiac allograft vasculopathy. In 2020 he suffered from Covid-19, but the course of infection was uneventful being cough the only symptom. We report the eldest survivor after heart transplant in Europe. Our case demonstrates that despite early and long-term complications of immunosuppressive therapy, a careful and patient tailored management allowed an amazing outcome. Nowadays heart transplant remains the best treatment for end stage heart failure and allows to resume a nearly normal quality of life.