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.

Recomendaciones sobre la vacunación contra SARS-CoV-2 / COVID-19 en pacientes con enfermedad renal y trasplante renal / Recommendations for the SARS-CoV-2 vaccination of patients with kidney disease and transplant recipients / Recomendações sobre vacinação contra SARS-CoV-2 / COVID-19 em pacientes com doença renal e transplante renal

Resumen: Este documento de recomendaciones tiene como objetivo orientar a médicos nefrólogos y no nefrólogos que asisten a pacientes con enfermedad renal crónica (ERC) en todas las etapas de la misma, en el proceso de vacunación contra el SARS-CoV-2. Como consecuencia de la situación epidemiológica y de los tiempos del proceso de elaboración de las vacunas disponibles, no se ha generado evidencia lo suficientemente potente, por lo que las recomendaciones no se acompañan del nivel de evidencia. Se fundamenta la necesidad de priorizar la vacunación en este grupo de pacientes en el mayor riesgo de adquirir la infección por SARS-CoV-2, desarrollar la enfermedad COVID-19 con mayor gravedad y presentar una mortalidad más elevada que la población general. Las recomendaciones se organizan por grupos de pacientes considerando pacientes con ERC no dialítica, diálisis y trasplante renal, y pacientes bajo tratamiento inmunosupresor.

Summary The objective of this document containing recommendations is to provide guidelines for nephrologists and non-nephrologists who assist patients with chronic kidney disease (CKD) at all stages of the disease on the vaccination process against SARS-CoV-2. As a consequence of the current epidemiological situation and the timing of the COVID-19 vaccine development -for available vaccines- there is no solid evidence, and thus, recommendations are not accompanied by the due medical proof. The need to prioritize vaccination in this group of patients is based on the increased risk of acquiring the SARS-CoV-2 infection, developing the COVID-19 disease with greater severity and presenting higher mortality rates than the general population. The recommendations are organized by groups of patients, considering patients with non-dialytic CKD, dialysis and kidney transplantation, and patients under immunosuppressive treatment.

Resumo: O objetivo deste documento de recomendações é orientar os nefrologistas e não nefrologistas que atendem pacientes com doença renal crônica (DRC) em todas as fases da doença, no processo de vacinação contra a SARS-CoV-2. Como consequência da situação epidemiológica e do momento do processo de produção das vacinas disponíveis, não foram geradas evidências suficientemente potentes, de modo que as recomendações não são acompanhadas de seu nível de evidência. A necessidade de priorizar a vacinação neste grupo de pacientes baseia-se no maior risco de adquirir a infecção pelo SARS-CoV-2, desenvolver a doença COVID-19 com maior gravidade e apresentar mortalidade superior à da população em geral. As recomendações são organizadas por grupos de pacientes, considerando pacientes com DRC não dialítica, em diálise, com transplante renal, e pacientes em tratamento imunossupressor.

Online Continuing Medical Education for the Latin American Nephrology Community.

A continuing medical education (CME) course was implemented for Latin American nephrologists in 2013. The topic was Immunopathology in native and transplanted kidneys. The course was given in Spanish and Portuguese. The activities included a distance education seven-week asynchronous online modality with multiple educational strategies. Thirty hours of study workload were estimated to complete the course. Four hundred and ninety-eight physicians coming from 18 countries registered for the course; 442 of them participated in it. Of those who participated, 51% received a certificate of completion and 29% a certificate of participation. Sixty-five percent of registrants participated in the case discussions. Eighty-six percent were very satisfied and 13% were satisfied. Lack of time to devote to the course was the main limitation expressed (62%), while Internet access or difficulties in the use of technology were considered by only 12 and 6% of participants, respectively. There was a significant increase in knowledge between before and after the course; the average grade increased from 64 to 83%. In conclusion, technology-enabled education demonstrated potential to become an instrument for Latin American nephrologists.

Sepsis caused by New Delhi metallo-ß-lactamase (blaNDM-1) and qnrD-producing Morganella morganii, treated successfully with fosfomycin and meropenem: case report and literature review.

OBJECTIVES: The objective of this study was to describe the microbiological characteristics of an extensively drug-resistant (XDR) isolate of Morganella morganii obtained from a patient with sepsis of urinary origin and to describe the patient's clinical characteristics. We further aimed to perform a literature review of the situation in Latin America regarding Gram-negative bacillus (GNB) carriers of New Delhi metallo-ß-lactamase (NDM-1) and qnr genes and current reports on the treatment of infections caused by XDR enterobacteria, with particular attention to colistin-resistant isolates. METHODS: The patient's clinical data were obtained from his medical history. Microbiological identification and susceptibility testing were done using the VITEK 2 Compact System. Resistance genes were detected by PCR and sequencing. RESULTS: Blood and urine cultures grew an M. morganii isolate (Mm4232) harboring NDM-1 and qnrD1. The patient was treated successfully with fosfomycin and double doses of meropenem. There are no previous reports of the use of fosfomycin and meropenem to treat infections by XDR enterobacteria harboring NDM-1 carbapenemase. CONCLUSIONS: This is the first report of qnrD1 in South America. We consider that this report could be helpful to physicians implementing treatments for infections caused by XDR GNB, including colistin-carbapenem-resistant GNB.

Infecciones bacterianas en pacientesreceptores de trasplante renal y reno-páncreas: alta incidencia de microorganismos multirresistentes / Bacterial infections in kidney and kidney-pancreas transplant recipients: high incidence of multi-resistant microorganisms

Introducción: las infecciones bacterianas en los receptores de trasplante renal (TR) y reno-páncreas (TRP) son frecuentes y constituyen una de las principales causas de muerte eneste grupo de pacientes. Es imperativo identificar el perfil de estos microorganismos para realizar un mejor abordaje terapéutico empírico.Objetivo: conocer la etiología y las características de las infeccionesbacterianas tanto a nivel comunitario como nosocomial en un grupo de pacientes que recibieron TR y TRP, y fueron asistidos en el Hospital de Clínicas entre noviembre de 1987 y noviembre de 2010. Material y método: estudio retrospectivo de la evolución detodos los pacientes con TR y TRP que ingresados al Hospital de Clínicas hayan presentado por lo menos un episodio infeccioso de etiología bacteriana, sea comunitaria o nosocomial. Se definió como microorganismo multirresistente (MO-MR) si se trató de un SAMR, EVR o un BGN resistente por lo menos a tres grupos de antimicrobianos. Resultados: en el período de estudio, 122 pacientes recibieron un TR o TRP (seis pacientes fueron trasplantados en un centro diferente al Hospital de Clínicas). De aquellos, 64 (52,5%) desarrollaron por lo menos un episodio de infección bacteriana; 34 de sexo femenino (53,1%), con una edad media de 37,7 ± 11,4 años. Treinta y nueve recibieron un TR (60,1%) y 25 (39,1%) un TRP. La mediana de seguimiento fue de cinco meses (P25 = 1, P75 = 25). Hubo 138 episodios de infección bacteriana (2,07 episodios/paciente), de los cuales 76 fueron comunitarias y 62 nosocomiales. El foco más frecuente en ambos fue urinario (63,2% y 53,2%, respectivamente), seguido del respiratorio en las comunitarias (13%). El microorganismo predominante fue E. coli, seguido de Klebsiella spp. y Enterococcus spp. De un total de 103 microorganismos aislados 46 (44,7%) presentaron multirresistencia (con Klebsiella spp. y Acinetobacter baumannii como agentes más frecuentes)...

Introduction: bacterial infections in kidney (KTX) and kidney-pancreas transplant (KPTX) recipients are frequent and constitute one of the leading causes of death in this group of patients. The profile of these microorgapatients with KTX and KPTX who were admitted at the Clinicas Hospital and presented at least one bacterial etiology infection episode, community and hospital-acquired.A multidrug-resistant (MDR) microorganism was defined if it were resistant to MRSA,VREor a gramnegative bacilli resistant to at least three groups of antimicrobial agents.Results: during the period of study 122 patients receivedKTXorKPTX(six patientswere transplanted in a centerdifferent form the Clinicas Hospital). Out of these patients, 64 (52.5%) developed at least one bacterial infectionepisode; 34 of them were women (53.1%), average age was 37.7± 11.4 years old. Thirty nine patients receivedKTX (60.1%) and 25 (39.1%) KPTX. Median follow up was fivemonths (P25 = 1, P75 = 25). There were 138 bacterial infection episodes (2.07 episodes/patient), 76 of which were community acquired and 62 were hospital acquired. In both cases, themost frequent center of infectionwas the urinary system (63.2% and 53.2% respectively), followed respiratory infections in the community acquired infections (13%). E. coli was the predominant microorganism,followed by Klebsiella spp. and Enterococcus spp. Out of 103 microorganisms isolated, 46 (44.7%) evidencedmultidrug-resistance - Klebsiella spp. and Acinetobacterbaumannii being the most frequent agents)...

Introdução: as infecções bacterianas em receptores de transplante renal (TR) e reno-pancreáticos (TRP) são frequentes sendo uma das principais causas de mortneste grupo de pacientes. É fundamental identificar o perfil destes micro-organismos para uma melhor abordagemterapêutica empírica. Objetivo: conhecer a etiologia e as característicasdas infecções bacterianas tanto comunitárias como hospitalaresem um grupo de pacientes que receberam TR e TRP, e que foram atendidos no Hospital das Clínicas noperíodo novembro 1987 - novembro 2010. Material e método: estudo retrospectivo da evolução de todos os pacientes com TR e TRP que internadosno Hospital das Clínicas apresentaram ao menosumepisodio infeccioso de etiologia bacteriana comunitária ouhospitalar. Definiu-se como micro-organismo multirresistente (MO-MR) quando se tratava de um SAMR, EVR ou um BGN resistente ao menos a três grupos de antimicrobianos. Resultados: no período estudado, 122 pacientes receberamumTRouTRP(seis pacientes foram transplantados emumcentro diferente ao doHospital das Clínicas).Do total de pacientes, 64 (52,5%) apresentaram ao menos um episodio de infecção bacteriana; 34 de sexo feminino(53,1%), commédia de idade de 37,7 ± 11,4 anos. Trinta e nove receberam um TR (60,1%) e 25 (39,1%) umTRP. Amediana do seguimento foi de cincomeses (P25 = 1, P75 = 25). Foram registrados 138 episódios de infecção bacteriana (2,07 episódios/paciente), dos quais 76 foram de origem comunitária e 62 hospitalares. Emambos os grupos o foco mais frequente foi urinário (63,2% e 53,2%, respectivamente), seguido do respiratório da comunidade (13%). Omicro-organismo predominante foi E. coli, seguido por Klebsiella spp. e Enterococcus spp. Do total de 103 micro-organismos isolados 46 (44,7%) apresentaram multirresistencia(sendo Klebsiella spp. e Acinetobacter baumannii os agentes mais frequentes)...