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.

Hantavirus antibodies among phyllostomid bats from the arc of deforestation in Southern Amazonia, Brazil.

In order to determine whether southern Amazonian bats could harbour hantaviruses we, serologically and molecularly, screened blood, saliva, excreta and organ tissues of 47 bats captured from September to December 2015. We found that only phyllostomid bats presented antibodies against hantavirus. The seropositive bats belonged to two species of Phyllostomid bats: the greater spear-nosed bat Phyllostomus hastatus (omnivorous) and the gnome fruit-eating bat Dermanura gnoma. The overall seroprevalence was of 4.2%. Therefore, we show here that hantaviruses are circulating among phyllostomid bats in the Amazonian arc of deforestation.

Correlação entre índice de massa corporal (IMC) e velocidade em saltos alternados em crianças / Correlation between body mass index (BMI) and speed in alternated jumps in children

A obesidade infantil vem em uma crescente pelo mundo inteiro e acredita-se que pode ser desecandeada pelo efeito negativo que os baixos níveis da coordenação motora podem causar sobre os níveis de atividade física e aptidão física durante a infância. Estudos analisaram a relação entre coordenação motora e composição corporal, e apontaram uma carência nas investigações sobre a influência do peso corporal em tarefas motoras específicas. Mediante ao exposto, o objetivo do presente estudo foi analisar a relação entre o Índice de Massa Corporal (IMC) e a velocidade em saltos alternados em crianças. Participaram do estudo 98 escolares com idade entre 6 e 10 anos. Para avaliação da velocidade de saltos alternados utilizou-se de uma das provas do teste Teste de Coordenação Corporal para Crianças (Köperkoordination Test für Kinder - KTK) que avalia saltos laterais por meio de teste específico. A análise estatística foi realizada por meio do programa R- Plus, o qual foi aplicado o teste de Mann-Whitney para verificar as diferenças do quociente motor (QM) entre meninos e meninas, Spearman para correlação entre o QM e IMC; e ANOVA para as diferenças entre a classificação do peso e o QM, sendo adotado nível de significância de 5% (p <0,05). Os resultados demonstraram não haver diferença estatística significativa entre os sexos para as variáveis analisadas. Entretanto, os meninos atingiram valores maiores para idade, IMC e QM. Na correlação entre o IMC e QM dos saltos laterais das crianças avaliadas, houve correlação negativa fraca, demonstrando que o IMC não teve grande influência no desempenho motor dos saltos quando analisado ambos os gêneros juntos. Tais resultados demonstram não haver correlação do IMC e a habilidade de saltos laterais em crianças com IMC elevado quando analisados de maneira geral. Porém, quando analisado por gênero, os meninos demonstram uma relação inversamente proporcional de IMC e saltos laterais o que não observou-se nas meninas.

Child obesity has been rising worldwide and is believed to be triggered by the negative effect that low levels of motor coordination can cause on the levels of physical activity and physical fitness during childhood. Studies analyzed the relationship between motor coordination and body composition, and pointed to a lack of research on the influence of body weight on specific motor tasks. The purpose of this study was to analyze the relationship between Body Mass Index (BMI) and the speed in alternate jumps in children. A total of 98 students aged 6 to 10 years took part in the study. In order to evaluate the speed in alternate jumps, one of the Köperkoordination Test für Kinder (KTK) tests that evaluates side jumps by means of a specific test was used. Statistical analysis was performed using the R-Plus program, which applied the Mann-Whitney test to verify the motor quotient (QM) differences between boys and girls, the Spearman test for correlation between QM and BMI; and ANOVA for the differences between weight classification and QM; as well as adopting a 5% (p <0.05) significance level. The results showed that there were no significant statistical differences between the sexes for the analyzed variables; however, boys scored higher values for age, BMI and QM. A weak negative correlation was observed between BMI and QM for the lateral jumps of the assessed children, demonstrating that the BMI did not have a great influence on the motor performance of the jumps when both genders were analyzed together. These results show that there is no correlation between BMI and lateral jumping skills in children with high BMI when analyzed in general, but when analyzed by gender, boys demonstrate an inversely proportional relation of BMI and lateral jumps, which was not observed in girls.

Deep brain stimulation reverses anhedonic-like behavior in a chronic model of depression: role of serotonin and brain derived neurotrophic factor.

BACKGROUND: Deep brain stimulation (DBS) is being investigated as a treatment for major depression, but its mechanisms of action are still unknown. We have studied the effects of ventromedial prefrontal cortex (vmPFC) stimulation in a chronic model of depression and assessed the involvement of the serotonergic system and brain derived neurotrophic factor (BDNF) in a DBS response. METHODS: Rats were subjected to chronic unpredictable mild stress during 4 weeks. Decline in preference for sucrose solutions over water, an index suggested to reflect anhedonic-like behavior, was monitored on a weekly basis. The outcome of chronic vmPFC stimulation alone (8 hours/day for 2 weeks) or combined with serotonin-depleting lesions was characterized. BDNF levels were measured in the hippocampus. RESULTS: Stress induced a significant decrease in sucrose preference as well as hippocampal BDNF levels as compared with those recorded in control subjects. vmPFC stimulation completely reversed this behavioral deficit and partially increased BDNF levels. In contrast, DBS did not improve stress-induced anhedonic-like behavior in animals bearing serotonin-depleting raphe lesions with associated normal hippocampal BDNF levels. CONCLUSIONS: vmPFC stimulation was effective in a chronic model of depression. Our results suggest that the integrity of the serotonergic system is important for the anti-anhedonic-like effects of DBS but question a direct role of hippocampal BDNF.

Chronic mild stress induces widespread decreases in thyroid hormone alpha1 receptor mRNA levels in brain--reversal by imipramine.

While considerable clinical evidence implicates thyroid hormones (THs) in depressive illness, the specific nature of this involvement remains unclear. The alpha1 subtype (TR-alpha1) is the most abundant TH receptor in brain. Here we investigated changes in TR-alpha1 mRNA in the chronic mild stress (CMS) model of depression. Rats were exposed to a CMS schedule for 3 weeks, which resulted in a progressive decreases in sucrose preference (an index of anhedonia). They were then treated daily with either imipramine (IMI, 10mg/kg) or vehicle (VEH) for 2 weeks before being sacrificed for quantitative in situ hybridization analyses of TR-alpha1 mRNA throughout the brain. Results indicated that CMS followed by VEH induced widespread decreases in TR-alpha1 mRNA in brain. In contrast, CMS-exposed rats receiving IMI for the last 2 weeks prior to sacrifice showed full recovery of sucrose preference. Furthermore, brain TR-alpha1 mRNA levels in these animals were similar to those of non-stressed controls receiving either SAL or IMI. These results reveal that TR-alpha1 mRNA brain levels are very sensitive to CMS effects. The reversal of both anhedonic and TR-alpha1 effects of CMS by IMI suggests that TR-alpha1 may play a role both in stress-induced depressive symptoms and in their reversal by antidepressant interventions.