Low switched memory B cells are associated with no humoral response after SARS-CoV-2 vaccine boosters in kidney transplant recipients.

Introduction: The humoral response after SARS-CoV-2 vaccination and boosters in kidney transplant recipients (KTRs) is heterogeneous and depends on immunosuppression status. There is no validated immune measurement associated with serological response in clinical practice. Multicolor flow cytometric immunophenotyping could be useful for measuring immune response. This study aimed to study B- and T-cell compartments through Standardized EuroFlow PID Orientation after SARS-CoV-2 vaccination and their association with IgG SARS-CoV-2 seropositivity status after two doses or boosters. Methods: We conducted a multicenter prospective study to evaluate humoral response after SARS-CoV-2 vaccination in KTRs. Heterologous regimen: two doses of inactivated SARS-CoV-2 and two boosters of BNT162b2 mRNA (n=75). Homologous vaccination: two doses of BNT162b2 mRNA and one BNT162b2 mRNA booster (n=13). Booster doses were administrated to KTRs without taking into account their IgG SARS-CoV-2 seropositivity status. Peripheral blood samples were collected 30 days after the second dose and after the last heterologous or homologous booster. A standardized EuroFlow PID Orientation Tube (PIDOT) and a supervised automated analysis were used for immune monitoring cellular subsets after boosters. Results: A total of 88 KTRs were included and divided into three groups according to the time of the first detected IgG SARS-CoV-2 seropositivity: non-responders (NRs, n=23), booster responders (BRs, n=41), and two-dose responders (2DRs, n=24). The NR group was more frequent on mycophenolate than the responder groups (NRs, 96%; BRs, 80%; 2DRs, 42%; p=0.000). Switched memory B cells in the 2DR group were higher than those in the BR and NR groups (medians of 30, 17, and 10 cells/ul, respectively; p=0.017). Additionally, the absolute count of central memory/terminal memory CD8 T cells was higher in the 2DR group than in the BR and NR groups. (166, 98, and 93 cells/ul, respectively; p=0.041). The rest of the T-cell populations studied did not show a statistical difference. Conclusion: switched memory B cells and memory CD8 T-cell populations in peripheral blood were associated with the magnitude of the humoral response after SARS-CoV-2 vaccination. Boosters increased IgG anti-SARS-CoV-2 levels, CM/TM CD8 T cells, and switched MBCs in patients with seropositivity after two doses. Interestingly, no seropositivity after boosters was associated with the use of mycophenolate and a lower number of switched MBCs and CM/TM CD8 T cells in peripheral blood.

Comparison of antibody response to SARS-CoV-2 after two doses of inactivated virus and BNT162b2 mRNA vaccines in kidney transplant.

BACKGROUND: Antibody response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after mRNA or adenoviral vector-based vaccines is weak in kidney transplant (KT) patients. However, few studies have focused on humoral response after inactivated virus-based vaccines in KT. Here, we compare antibody response following vaccination with inactivated virus (CoronaVac®) and BNT162b2 mRNA. METHODS: A national multicentre cross-sectional study was conducted. The study group was composed of patients from all KT centres in Uruguay, vaccinated between 1 and 31 May 2021 (CoronaVac®, n = 245 and BNT162b2, n = 39). The control group was constituted of 82 healthy individuals. Participants had no prior confirmed coronavirus disease 2019 (COVID-19) test. Blood samples were collected between 30 and 40 days after the second dose. Serum-specific immunoglobulin G (IgG) antibodies against the receptor-binding domain (RBD) of SARS-CoV-2 Spike protein were determined using the COVID-19 IgG QUANT ELISA Kit. RESULTS: Only 29% of KT recipients showed seroconversion (36.5% BNT162b2, 27.8% inactivated virus, P = 0.248) in comparison with 100% in healthy control with either vaccine. Antibody levels against RBD were higher with BNT162b mRNA than with inactivated virus [median (interquartile range) 173 (73-554) and 29 (11-70) binding antibody units (BAU)/mL, P < 0.034] in KT and 10 times lower than healthy control [inactivated virus: 308 (209-335) and BNT162b2: 2638 (2608-3808) BAU/mL, P < 0.034]. In multivariate analysis, variables associated with negative humoral response were age, triple immunosuppression, estimated glomerular filtration rate and time post-KT. CONCLUSION: Seroconversion was low in KT patients after vaccination with both platforms. Antibody levels against SARS-CoV-2 were lower with inactivated virus than BNT162b mRNA. These findings support the need for strategies to improve immunogenicity in KT recipients after two doses of either vaccine.

A US Student Reflects on Her Cuban Medical Education.

At first I was skeptical about the opportunity for international candidates to study medicine for free in Cuba… Now, four years into my medical studies I believe living and studying in Cuba has shaped who I am and given me a host of applicable lessons of personal and academic growth. I am convinced that no other school would have offered me the support system, challenges and wisdom this experience entails. ELAM not only represents the place where I am getting my medical education; it is a place where I have found a family, become bilingual and made extraordinary memories.

Diez años del Registro Uruguayo de Peritonitis en Diálisis Peritoneal

La peritonitis es una complicación grave de la diálisis peritoneal (DP), por lo que interesa conocer la incidencia y sensibilidad antibiótica de los gérmenes causantes. En Uruguay, desde el 1° de enero de 2004, se realiza un registro nacional de las peritonitis en DP, gérmenes, sensibilidad y evolución. Método: se analizaron los registros desde el 1° de enero de 2004 al 31 de diciembre de 2013. El registro fue aprobado por comités de ética institucionales. Resultados: en el período se registraron 850 peritonitis, con una incidencia que descendió de 0,49/paciente-año (2004-2005) a 0,37/paciente-año (2013). La incidencia de Staphylococcus aureus y Staphylococcus coagulasa negativo (SCoN) fue menor en 2009-2013 vs 2004-2005 (0,2 vs 0,12 peritonitis/paciente-año, test Poisson p<0,05). En 2009-2013: 14/54 S. aureus y 26/71 SCoN fueron meticilinorresistente, similar al período previo. El 98% de los gérmenes gramnegativos fueron sensibles a amikacina. En 145/467 (31%) episodios no se identificó germen. Se logró cura primaria en 71% de las peritonitis por grampositivos y en 45% por gramnegativos (chi2 p<0,05). En 2013 se observó mayor incidencia de peritonitis en los centros en los que no se controló el estado de portador nasal. Comentarios y conclusiones: se justifica implementar el control de portador de Staphylococcus aureus. La incidencia de peritonitis por S. aureus y SCoN meticilinorresistentes, la incidencia sostenida de gérmenes gramnegativos (con peor evolución), y el elevado porcentaje de cultivos sin desarrollo justifica mantener el protocolo antibiótico empírico inicial con vancomicina y amikacina. El descenso de la incidencia de S. aureus + SCoN podría ser atribuido a una mejor educación de los pacientes en DP.(AU)

Abstract Peritonitis is a severe complication of peritoneal dialysis (PD), so it is important to learn about the incidence and antibiotic sensitivity of the germs that cause it. In Uruguay, since January 1, 2004, a national record is kept for peritonitis in PD, germs, sensitivity and evolution. Method: the records from January 1, 2004 through December 31, 2013 were analyzed. The registry was approved by institutional ethical committes. Results: during the above mentioned period, 850 cases of peritonitis were recorded, and incidence dropped from 0.49/patient-year (2004-2005) to 0.37/patient-year (2013). Incidence of Staphylococcus aureus and coagulase-negative staphylococci (SCoN) was lower in 2009-2013 vs 2004-2005 (0.2 vs 0.12 peritonitis/patient-year, test Poisson p<0.05). In 2009-2013: 14/54 S. aureus and 26/71 SCoN were methicillin-resistant, similar to the previous period. 98% of Gram-negative were sensitive to amikacin. No germ was identified in 145/467 (31%) of episodes. Primary cure was achieved in 71% of peritonitis for Gram-positive and 45% for Gram-negative bacteria (chi2 p<0.05). In 2013 a greater incidence of peritonitis was observed in those centers where the nasal carriage was not controlled. Comments and conclusions: controlling Staphylococcus aureus nasal carriages is worth doing. The incidence of peritonitis by methicillin-resistant S. aureus y SCoN, the sustained incidence of Gram-negative germs (with a worse evolution), and the high percentage of cultures with no development justify keeping the initial empirical antibiotic protocol with vancomycin and amikacin. Reduction in the incidence of S. aureus + SCoN could be explained by a greater education in PD patients.(AU)

Resumo A peritonite é uma complicação grave da diálise peritoneal (DP), sendo, portanto, importante conhecer a incidência e a sensibilidade antibiótica dos gérmens causadores. No Uruguai, desde 1 de janeiro de 2004, realiza-se um registro nacional das peritonites em DP, com dados sobre gérmens, sensibilidade e evolução. Método: foram analisados os registros do período 1 de janeiro de 2004 - 31 de dezembro de 2013. O registro foi aprovado pelos comitês de ética das instituições envolvidas. Resultados: foram registradas 850 peritonites no período estudado; a incidência diminuiu de 0,49/paciente-ano no período 2004-2005 a 0,37/paciente-ano em 2013. A incidência de Staphylococcus aureus e Staphylococcus coagulase negativo (SCoN) foi menor no período 2009-2013 comparada com 2004-2005 (0,2 vs 0,12 peritonite/paciente-ano, teste de Poisson p<0,05). No período 2009-2013: 14/54 S. aureus e 26/71 SCoN foram resistentes à meticilina, similar ao período prévio. 98% dos gérmens gramnegativos eram sensíveis a amicacina. Não se pode identificar o gérmen em 145/467 (31%) episódios. Em 71% das peritonites por grampositivos e em 5% por gramnegativos (chi2 p<0,05) foi possível obter cura primária. Em 2013 foi observada uma maior incidência de peritonite nos centros em que não se realizava controle de portador nasal. Comentários e conclusões: justifica-se a realização de controle de portador de Staphylococcus aureus. A incidência de peritonite por S. aureus e SCoN resistentes à meticilina, a incidência constante de gérmens gramnegativos (com pior evolução), e a alta porcentagem de cultivos sem crescimento justificam manter o protocolo antibiótico empírico inicial com vancomicina e amicacina. A redução da incidência de S. aureus + SCoN poderia ser atribuída a melhor educação dos pacientes em DP.(AU)

Diez años del Registro Uruguayo de Peritonitis en Diálisis Peritoneal / Ten years of the Uruguayan Registry of Peritonitis in Peritoneal Dialysis

La peritonitis es una complicación grave de la diálisis peritoneal (DP), por lo que interesa conocer la incidencia y sensibilidad antibiótica de los gérmenes causantes. En Uruguay, desde el 1° de enero de 2004, se realiza un registro nacional de las peritonitis en DP, gérmenes, sensibilidad y evolución. Método: se analizaron los registros desde el 1° de enero de 2004 al 31 de diciembre de 2013. El registro fue aprobado por comités de ética institucionales. Resultados: en el período se registraron 850 peritonitis, con una incidencia que descendió de 0,49/paciente-año (2004-2005) a 0,37/paciente-año (2013). La incidencia de Staphylococcus aureus y Staphylococcus coagulasa negativo (SCoN) fue menor en 2009-2013 vs 2004-2005 (0,2 vs 0,12 peritonitis/paciente-año, test Poisson p<0,05). En 2009-2013: 14/54 S. aureus y 26/71 SCoN fueron meticilinorresistente, similar al período previo. El 98% de los gérmenes gramnegativos fueron sensibles a amikacina. En 145/467 (31%) episodios no se identificó germen. Se logró cura primaria en 71% de las peritonitis por grampositivos y en 45% por gramnegativos (chi2 p<0,05). En 2013 se observó mayor incidencia de peritonitis en los centros en los que no se controló el estado de portador nasal. Comentarios y conclusiones: se justifica implementar el control de portador de Staphylococcus aureus. La incidencia de peritonitis por S. aureus y SCoN meticilinorresistentes, la incidencia sostenida de gérmenes gramnegativos (con peor evolución), y el elevado porcentaje de cultivos sin desarrollo justifica mantener el protocolo antibiótico empírico inicial con vancomicina y amikacina. El descenso de la incidencia de S. aureus + SCoN podría ser atribuido a una mejor educación de los pacientes en DP.

Abstract Peritonitis is a severe complication of peritoneal dialysis (PD), so it is important to learn about the incidence and antibiotic sensitivity of the germs that cause it. In Uruguay, since January 1, 2004, a national record is kept for peritonitis in PD, germs, sensitivity and evolution. Method: the records from January 1, 2004 through December 31, 2013 were analyzed. The registry was approved by institutional ethical committes. Results: during the above mentioned period, 850 cases of peritonitis were recorded, and incidence dropped from 0.49/patient-year (2004-2005) to 0.37/patient-year (2013). Incidence of Staphylococcus aureus and coagulase-negative staphylococci (SCoN) was lower in 2009-2013 vs 2004-2005 (0.2 vs 0.12 peritonitis/patient-year, test Poisson p<0.05). In 2009-2013: 14/54 S. aureus and 26/71 SCoN were methicillin-resistant, similar to the previous period. 98% of Gram-negative were sensitive to amikacin. No germ was identified in 145/467 (31%) of episodes. Primary cure was achieved in 71% of peritonitis for Gram-positive and 45% for Gram-negative bacteria (chi2 p<0.05). In 2013 a greater incidence of peritonitis was observed in those centers where the nasal carriage was not controlled. Comments and conclusions: controlling Staphylococcus aureus nasal carriages is worth doing. The incidence of peritonitis by methicillin-resistant S. aureus y SCoN, the sustained incidence of Gram-negative germs (with a worse evolution), and the high percentage of cultures with no development justify keeping the initial empirical antibiotic protocol with vancomycin and amikacin. Reduction in the incidence of S. aureus + SCoN could be explained by a greater education in PD patients.

Resumo A peritonite é uma complicação grave da diálise peritoneal (DP), sendo, portanto, importante conhecer a incidência e a sensibilidade antibiótica dos gérmens causadores. No Uruguai, desde 1 de janeiro de 2004, realiza-se um registro nacional das peritonites em DP, com dados sobre gérmens, sensibilidade e evolução. Método: foram analisados os registros do período 1 de janeiro de 2004 - 31 de dezembro de 2013. O registro foi aprovado pelos comitês de ética das instituições envolvidas. Resultados: foram registradas 850 peritonites no período estudado; a incidência diminuiu de 0,49/paciente-ano no período 2004-2005 a 0,37/paciente-ano em 2013. A incidência de Staphylococcus aureus e Staphylococcus coagulase negativo (SCoN) foi menor no período 2009-2013 comparada com 2004-2005 (0,2 vs 0,12 peritonite/paciente-ano, teste de Poisson p<0,05). No período 2009-2013: 14/54 S. aureus e 26/71 SCoN foram resistentes à meticilina, similar ao período prévio. 98% dos gérmens gramnegativos eram sensíveis a amicacina. Não se pode identificar o gérmen em 145/467 (31%) episódios. Em 71% das peritonites por grampositivos e em 5% por gramnegativos (chi2 p<0,05) foi possível obter cura primária. Em 2013 foi observada uma maior incidência de peritonite nos centros em que não se realizava controle de portador nasal. Comentários e conclusões: justifica-se a realização de controle de portador de Staphylococcus aureus. A incidência de peritonite por S. aureus e SCoN resistentes à meticilina, a incidência constante de gérmens gramnegativos (com pior evolução), e a alta porcentagem de cultivos sem crescimento justificam manter o protocolo antibiótico empírico inicial com vancomicina e amicacina. A redução da incidência de S. aureus + SCoN poderia ser atribuída a melhor educação dos pacientes em DP.