ABSTRACT
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is the standard of care for the prevention of COVID-19 disease, with a positive impact in countries in which vaccination has been promoted. Since the emergence of variants of concern (VOCs) European Medicines Agency (EMA) recommended an extra dose of the COVID-19 vaccines Comirnaty (BioNTech/Pfizer) and Spikevax (Moderna) for patients with severely weakened immune system and booster doses for subjects with normal immune system to ensure a lasting response. Although Vaccination triggers both humoral and cellular immune response, COVID-19 vaccination efficacy is evaluated by measuring antibodies only, whereas adaptative cellular immunity is unexplored. Our aim is to test this new kit QuantiFERON SARS-CoV-2 to evaluate the immune response after three doses of BNT162b vaccine in healthy donors compared to two cohort of fragile patients: Common Variable Immunodeficiency (CVID) patients and Kidney Transplant Recipients (KTR) patients. Method(s): Blood samples were collected from eight health care workers in our department, fourteen CVID patients and eight KTR patients. All the individuals recruited were naive to SARS-COV2 and immunized by three doses of BNT162b vaccine. We examined humoral responses to vaccinations using the LIAISON DIASORIN SARSCOV-2 S1/S2 IgG. Next blood from all participants was subjected to the novel Interferon gamma (INF-gamma) Release Assay (IGRA) from Qiagen, measuring INF-gamma release induced by two proprietary SARS-CoV-2 peptide pools (Ag1 and Ag2) encompassing the spike protein and designed to stimulate CD4+ and CD8+ T cells and induce the releases of INF-gamma. Result(s): Using LIAISON SARS-COV-2 S1/S2 IgG assay from DIASORIN we confirm that in healthy subjects BNT162b third dose had successfully mounted humoral immune response with a S1/S2 IgG mean of 17100 BAU/ml. Conversely, the CVID group and KTR group shown a statistically significant reduction of IGg levels with a mean of 978 BAU/ml and 1029 respectively. Notably seven patients (five CVID and two KTR) presented IGg levels below the cut-off (33,8 BAU/ml). Next, we evaluated the INF-gamma response to SARS-CoV-2 Ag1 and Ag2 founding seven non-reactive subjects (three CVID and four KTR). Surprisingly three of non-reactive patients shown a good humoral response, whereas three patients with a negative humoral immune response shown reactiveness to IGRA assay. Conclusion(s): Assessing cellular immunity for SARSCOV-2 in addition to humoral immunity is important taking into account that cellular immunity plays a pivotal role against the virus and likely its variants. Some patients with weakened immune response have no correlation between humoral and cellular immunity, suggesting that the evaluation of T cell responses could be a more sensitive clinical marker of immunization. In this scenario the evaluation of cellular immunity might be informative for clinicians to identify patients more susceptible to a severe COVID-19 disease.
ABSTRACT
Background: Thymic epithelial tumors (TETs) are rare malignancies associated with dysregulation of the immune system with humoral and cell mediated immunity abnormalities. Anti-syndrome coronavirus type 2 (SARSCoV- 2) vaccine is effective at preventing COVID-19 morbidity and mortality. No published data are available regarding the post-vaccine immunization in TET patients (pts). The aim of our study was to evaluate the immunization in TET pts, who received the third mRNA vaccine dose and who did not achieve seroconversion after the previous two doses. Method(s): Starting from November 2021 to March 2022, 23 consecutive TET patients (pts) found to be serologically negative after two doses of SARS-Cov-2 mRNA vaccine (BNT162b2 by Pfizer-BioNTech) were enrolled at the Rare Tumors Coordinating Center of Campania Region (CRCTR-Naples, Italy). SARS-CoV-2 spike-binding IgG antibody serological levels were centrally analyzed by chemiluminescent immunoassay (CLIA) at two different time-points: T0 (before the third dose) and T1 (one month after the third dose). Cut-off for Ab titers positivity was >25 AU/mL. Result(s): Among the 23 enrolled pts, 10 (43,5%) were female and 13 (56,5%) males;17 pts had thymoma and 6 thymic carcinoma. Autoimmune disorders were detected in 20 TET pts (87%), of whom 3 (15%) suffered from Myasthenia Gravis, 8 (40%) from Good's Syndrome, 7 (35%) from both diseases, and 2 (10%) from other autoimmune disorders. By the time of third vaccine dose 2 pts had died, 2 pts were lost to follow up, 5 pts had suffered from SARS-CoV-2 infection. Of the remaining 14 pts, 7 achieved seroconversion whereas 7 maintained negative serological antibody titers. Two of these 7 pts had SARSCoV- 2 infection after the third dose. Interestingly, among these 7 pts who did not develop positive antibody titers, 6 had active cancer disease and only one was diseasefree. Moreover, 6 out of these 7 pts suffered from Good's Syndrome. On the other hand, among the 7 pts who developed positive antibody titers, only 3 had active disease. Conclusion(s): Our preliminary results showed that TET pts who did not achieve seroconversion even after the third SARS-Cov-2 vaccine dose in most cases had active cancer disease. If confirmed on larger cohorts of patients, these data may have important clinical implications and may help to better identify fragile pts who could benefit the most from prophylactic therapy with monoclonal antibodies.
ABSTRACT
Background: Thymic epithelial tumors (TET) are rare malignancies associated with dysregulation of the immune system and humoral and cell mediated immunity abnormalities. Anti-syndrome coronavirus type 2 (SARS-CoV-2) vaccine is effective at preventing COVID-19 morbidity and mortality. No published data are available regarding the immunization in TET patients (pts). The aim of this study was to evaluate the immunization in TET pts who received two doses of mRNA vaccine, by longitudinal serological detection of SARS-COV-2 spike-binding IgG antibody. Methods: Starting from April 2021 to October 2021, consecutive TET pts referred to the Rare Tumors Coordinating Center of Campania Region (CRCTR - Naples, Italy) were enrolled. All study subjects received two doses of COVID-19 mRNA vaccine (BNT162b2 by Pfizer-BioNTech). SARS-CoV-2 spike-binding IgG antibody (Ab) serological levels were analyzed by centralized chemiluminescent immunoassay (CLIA) at different time-points, including before 1st vaccine dose (T0) and 1 month after 2nd dose (T2). Cut-off for Ab titers positivity was > 25 AU/mL. Results: Forty pts were enrolled;23 (57.5%) were female and 17 (42.5%) male. Eleven pts (27.5%) suffered from thymic carcinoma, 28 (70%) thymoma, and 1 (2.5%) thymic hyperplasia. At the time of study enrollment, 20 pts (50%) had no evidence of disease (NED) and were in followup;the remaining 20 pts had evidence of disease (ED) by imaging and were receiving systemic treatment (55% oral low-dose etoposide-based therapy, 40% somatostatin analogs + prednisone, 5% supportive care). Immune system disorders were diagnosed in 29 TET pts (72.5%): 19 pts (47.5%) had Good's Syndrome (GS) and 10 (25%) other immune disorders. At T0, all enrolled pts had negative Ab titers and no prior SARS-CoV-2 infection. At T2, Ab data were available for 37 pts (92.5%): 18 pts (48.7%) had positive Ab titers, whereas 19 (51.3%) did not achieve seroconversion. Among pts with ED, seroconversion was achieved only in 2 cases (11.8%). Lack of seroconversion at T2 was significantly associated with ED (Fisher's exact test p: 0.0001) and with the presence of GS (Fisher's exact test p: 0.0489). No significant association of seroconversion with other immune disorders and disease features was found. Conclusions: Our data showed that TET pts with ED had substantially higher probability of impaired seroconversion after SARS-COV-2 vaccine as compared with NED pts. We warrant further studies to evaluate the role of disease status, anti-tumor treatments and immune disorders in post-vaccine immunization of TET pts.
ABSTRACT
Introduction: In the context of the Italian SARS-CoV-2 vaccination program, liver transplant (LT) recipients were prioritized for vaccine administration, although the lower response to vaccines is a well known problem in this population. Aim: We aimed to evaluate immunogenicity of BNT162b2 mRNA vaccine in LT recipients and healthy controls and to identify factors associated with negative response to vaccine. Materials and Methods: We prospectively evaluated a cohort of adult LT patients the humoral response (with anti-Spike protein IgG-LIAISON SARS-CoV-2 S1/S2-IgG chemiluminescent assay) at 1 and 3 months after 2-dose vaccination. A group of 307 vaccinated healthcare workers, matched by age and sex, served as controls. Results: Overall, 492 LT patients were enrolled (75.41% male, median age 64.85 years). Detectable antibodies were observed in the 75% of patients with a median value of 73.9 AU/mL after 3 months from 2-dose vaccination. At multivariable analysis, older age (>40years, p=0.016), shorter time from liver transplantation (<5years, p=0.004), and immunosuppression with antimetabolites (p=0.029) were significantly associated with non-response to vaccination. Moreover, the LT recipients showed antibody titers statistically lower than the control group (103 vs 261 AU/ml, p<0.0001) (fig. 1). Finally, both in controls and LT patients we found a trend of inverse correlation between age and antibody titers (correlation coefficient: -0.2023 and -0.2345, respectively). Conclusions: Three months after vaccination, LT recipients showed humoral response in 75% of cases. Older age, shorter time from transplantation and use of antimetabolites were factors associated with non-response to vaccination and needed to be kept under close monitoring.