ABSTRACT
Purpose: Short-term adaptive immune memory has been reported among immunocompetent (IC) and convalescent Solid Organ Transplant (SOT) individuals following SARS-CoV-2 infection as well as after active vaccination. However, quality and longevity of anti-viral immune memory comparisons between natural and active immunization has not been thoroughly assessed among SOT. Method(s): SARS-CoV-2-specific adaptive immune memory was assessed at different compartments (serological, memory B cells [mBC] and cytokine [Th1: IFN-gamma, IL-2, IFN-gamma/IL-2 and Th2: IL-21 and IL-5] producing T cells) by ELISA and FluoroSpotbased assays, respectively, in 41 convalescent patients with severe COVID-19 (22 SOT and 19 IC) and 39 vaccinated patients (19 SOT and 20 IC) with a mRNA-based vaccine) at different time-points post immunization (T1=21days after infection/1st dose;T2=3months after infection/2nd dose;T3=6months after infection/2nd dose). Additionally, a group of convalescent mild (19 SOT and 19 IC) and asymptomatic patients (9 SOT and 10 IC) were also evaluated at T3. Result(s): Overall, statistically significant higher immune responses in all immune compartments were observed in convalescent patients than among those after vaccination. After vaccination, low seropositivity rates (5,88%) were observed among SOT after 1st dose, whereas seroconversion was fully achieved in IC patients and SOT with severe COVID-19 (p<0.001). Similarly, while the presence of mBc after vaccination progressively increased over time, it was less pronounced and significantly delayed among SOT than convalescent patients in all time points (p<0.001 T1, T2 and T3). SARS-CoV-2-specific Th1 and Th2 frequencies were significantly higher among vaccinated IC patients than SOT, being these responses significantly lower than those observed in convalescent among SOTT and IC patients (p<0.001 T1, T2 and T3). At 6 months after vaccination, IgG titers, mBc frequencies and Th1/ Th2 T-cell responses after two-dose vaccination in SOT mimicked those observed in convalescent SOT with an asymptomatic/mild clinical COVID-19 infection. Conclusion(s): The type of immunization against SARS-CoV-2, either natural or active after vaccination, clearly differentiates the quality and length of adaptive immune memory, with a clear weaker immune response observed among SOT.
ABSTRACT
BACKGROUND AND AIMS: COVID-19 in kidney transplants has a high risk of complications and mortality, especially in older recipients diagnosed during the early period after transplantation. Management of immunosuppression has been challenging during the pandemic. We investigated the impact of induction immunosuppression, either basiliximab or thymoglobulin, on the clinical evolution of kidney transplants developing COVID-19 during the early period after transplantation. METHOD: Kidney transplant recipients with <6 months with a functioning graft diagnosed of COVID-19 from the initial pandemic outbreak (March 2020) until 31 July 2021 from different Spanish centres participating in a nationwide registry. RESULTS: A total of 127 patients from 17 Spanish centres developed COVID-19 during the first 6 months after transplantation, 73 (57.5%) received basiliximab and 54 (42.5%) thymoglobulin. Demographics were not different between groups, but patients receiving thymoglobulin were more sensitized (cPRA of 32.7% ± 40.8% versus 5.6% ± 18.5%) and more frequently re-transplanted (30% versus 4%). Recipients older than 65 years treated with thymoglobulin showed the highest rate of acute respiratory distress syndrome [64.7% versus 37.1% for older recipients receiving thymoglobulin and basiliximab (P < .05), and 23.7% and 18.9% for young recipients receiving basiliximab and thymoglobulin (P > .05)] and the poorest survival [mortality rate of 64.7% and 42.9% for older recipients treated with thymoglobulin and basiliximab, respectively (P < .05), and 8.1% and 10.5% for young recipients treated with thymoglobulin and basiliximab (P > .05)]. Older recipients treated with thymoglobulin showed the poorest survival in the Cox's regression model adjusted for comorbidities. CONCLUSION: Thymoglobulin should be used with caution in older recipients during the present pandemic era.
ABSTRACT
Purpose: The emerged COVID-19 pandemic caused by SARS-CoV-2 has paralyzed the world, due to its high infectivity and fatal outcomes, especially among more vulnerable individuals. While description of protective humoral and T-cell immune responses has been reported among immunocompetent (IC) individuals, its characterization and determinants of poorer outcomes among the at-risk Solid Organ Transplant (SOT) patient population has not been thoroughly investigated. Methods: SARS-CoV-2-specific serological and functional T-cell immune responses against main immunogenic antigens were tracked in 28 SOT recipients during acute infection and over the following 40 days of convalescence and were compared to 16 IC patients admitted with similar moderate/severe COVID-19. Results: We show a more severe polyfunctional T-cell and serological impairment in SOT at the infection onset as compared to IC individuals, especially against membrane antigen. Worse clinical outcomes (need of mechanical ventilation or death) more frequently occurred within SOT and were associated with a significantly impaired Th1 polarized immune response to antigens spike and membrane. Nonetheless, SOT achieved robust serological and functional Th1 and Th2 immune responses at convalescence, similarly to those of IC patients. Conclusions: Our data show a delay of serological and functional T-cell immune activation to SARS-CoV-2 in SOT, which may entail poorer clinical outcomes.
ABSTRACT
BACKGROUND AND AIMS: Immunosuppressed patients such as kidney transplant recipients (KTs) have increased mortality risk in the setting of coronavirus disease 2019 (COVID-19). The role and management of chronic immunosuppressive therapies during COVID-19 must be characterized. METHOD: Herein, we report the follow-up of a cohort of 47 KTs admitted at two Spanish Kidney Transplant Units who survived COVID-19. The impact of the management of immunosuppression during COVID-19 on graft function and immunologic events was evaluated. RESULTS: At least one immunosuppressive agent was withdrawn in 83% of patients, with antimetabolites being the most frequent. Steroids were generally not stopped and the dose was even increased in 15% of patients as part of the treatment of COVID-19. Although immunosuppressive drugs were suspended during a median time of 17 days, no rejection episodes neither de novo donor specific antibodies were observed up to 3 months after discharge, and no significant changes occurred in calculated panel reactive antibodies. Acute graft dysfunction was common (55%) and the severity was related to tacrolimus trough levels, which were higher in patients receiving antivirals. At the end of follow-up, all patients recovered baseline kidney function. CONCLUSION: Our observational study suggests that immunosuppression in KTs hospitalized due to COVID-19 could be safely minimized.