Hybrid Immunity Protects against Antibody Fading after SARS-CoV-2mRNA Vaccination in Kidney Transplant Recipients, Dialysis Patients, and Medical Personnel: 9 Months Data from the Prospective, Observational Dia-Vacc Study.

(1) Background: Compared to medical personnel, SARS-CoV-2mRNA vaccination-related positive immunity rates, levels, and preservation over time in dialysis and kidney transplant patients are reduced. We hypothesized that COVID-19 pre-exposure influences both vaccination-dependent immunity development and preservation in a group-dependent manner. (2) Methods: We evaluated 2- and 9-month follow-up data in our observational Dia-Vacc study, exploring specific cellular (interferon-γ release assay = IGRA) and/or humoral immune responses (IgA/IgG/RBD antibodies) after two SARS-CoV-2mRNA vaccinations in 2630 participants, including medical personnel (301-MP), dialysis patients (1841-DP), and kidney transplant recipients (488-KTR). Study participants were also separated into COVID-19 pre-exposure (hybrid immunity) positive (n = 407) versus negative (n = 2223) groups. (3) Results: COVID-19 pre-exposure improved most vaccination-related positive immunity rates in KTR and DP at 2 months but not in MP, where rates reached almost 100% independent of hybrid immunity. In the COVID-19-negative study, patients' immunity faded between two and nine months, evaluated via the percentage of patients with an RBD antibody decrease >50%, and was markedly group- (MP-17.8%, DP-52.2%, and KTR-38.6%) and vaccine type-dependent. In contrast, in all patient groups with COVID-19, pre-exposure RBD antibody decreases of >50% were similarly rare (MP-4.3%, DP-7.2%, and KTR-0%) but still vaccine type-dependent, with numerically reduced numbers in mRNA-1273- versus BNT162b2mRNA-treated patients. Multivariable regression analysis of RBD antibody changes between two and nine months by interval scale categorization confirmed COVID-19 pre-exposure as a factor in inhibiting strong RBD Ab fading. COVID-19 pre-exposure in MP and DP also numerically reduced T-cell immunity fading. In DP, symptomatic (versus asymptomatic) COVID-19 pre-exposure was identified as a factor in reducing strong RBD Ab fading after vaccination. (4) Conclusions: After mRNA vaccination, immunity positivity rates in DP and KTR but not MP, as well as immunity preservation in MP/DP/KTR, are markedly improved via prior COVID-19 infection. In DP, prior symptomatic compared to asymptomatic COVID-19 disease was particularly effective in blocking immunity fading after mRNA vaccination.

9-Month observational Dia-Vacc study of vaccine type influence on SARS-CoV-2 immunity in dialysis and kidney transplant patients.

BACKGROUND: SARS-CoV-2mRNA vaccination related seroconversion rates are reduced in dialysis and kidney transplant patients. METHODS: We evaluated nine months follow up data in our observational Dia-Vacc study exploring specific cellular (interferon-γ release assay) or/and humoral immune responses after 2x SARS-CoV-2mRNA vaccination in 880 participants including healthy medical personnel (125-MP), dialysis patients (595-DP), kidney transplant recipients (111-KTR), and apheresis patients (49-AP) with positive seroconversion (de novo IgA or IgG antibody positivity by ELISA) after eight weeks. FINDINGS: Nine months after first vaccination, receptor binding domain (RBD) antibodies were still positive in 90 % of MP, 86 % of AP, but only 55 %/48 % of DP/KTR, respectively. Seroconversion remained positive in 100 % of AP and 99·2 % of MP, but 86 %/81 % of DP/KTR, respectively. Compared to MP, DP but not KTR or AP were at risk for a strong RBD decline, while KTR kept lowest RBD values over time. By multivariate analysis, BNT162b2mRNA versus 1273-mRNA vaccine type was an independent risk factor for a strong decline of RBD antibodies. Within the DP group, only time on dialysis was another (inverse) risk factor for the DP group. Compared to humoral immunity, T-cell immunity decline was less prominent. INTERPRETATION: While seroconverted KTR reach lowest RBD values over time, DP are at specific risk for a strong decline of RBD antibodies after successful SARS-CoV-2mRNA vaccination, which also depends on the vaccine type being used. Therefore, booster vaccinations for DP should be considered earlier compared to normal population.

Anti-SARS-CoV-2 Revaccination Success in Kidney Transplant Recipients With No Initial Humoral Response Is Linked to Primary Vaccine Type.

Background: While anti-SARS-CoV-2 vaccination success in kidney transplant recipients (KTR) after two doses and 1273-mRNA was associated with higher seroconversion rates compared to BNT162b2-mRNA in our "DIA-Vacc Study" (NCT04799808), it remains unclear whether this may also be the case in non-responding KTR after a third vaccination dose. Materials and Methods: Non-responding KTR (after two mRNA vaccinations) were investigated 4.5-6 months after study enrollment at first vaccination. One hundred sixty-six of 193 received a third vaccination between 3.5 and 5 months after the initial study enrollment and were always investigated 4 weeks later, exploring humoral immune response (ELISA) and specific cellular responses (interferon-γ release assay). Sixty-seven of 193 measurements in KTR were done immediately before the third vaccination or in KTR without further vaccination at 4.5-6 months. Results: Of 193 KTR with no initial immune response 4 weeks after the second vaccination, 106/87 were immunized twice with 1273-mRNA/BNT162b2-mRNA, respectively. Additional mRNA booster vaccination led to positive seroconversion rates of 30-50%, while 16% of the initial non-responders demonstrated a delayed seroconversion without any booster vaccination. Using logistic regression analysis, a positive IgG response after the third vaccination was 23% more likely if the primary vaccine type was 1273-mRNA compared to BNT162b2-mRNA (OR = 4.420, 95% CI [1.208-16.173], p = 0.025). Primary vaccine type, a weak anti-SpikeS1 IgG response 4 weeks after second vaccination (3.2-35.2 BAU/ml, p < 0.001) and a lack of MMF/MPA as part of the immunosuppressive treatment (trend, p = 0.06) but no other variables studied correlated with seroconversion success. Conclusion: This observational study adds important evidence toward using 1273-mRNA as the primary mRNA vaccine type for immunosuppressed KTR.

Risk of strong antibody decline in dialysis and transplant patients after SARS-CoV-2mRNA vaccination: Six months data from the observational Dia-Vacc study.

Background: Vulnerable dialysis and kidney transplant patients show impaired seroconversion rates compared to medical personnel eight weeks after SARS-CoV-2mRNA vaccination. Methods: We evaluated six months follow up data in our observational Dia-Vacc study exploring specific cellular (interferon-γ release assay) or/and humoral immune responses after 2x SARS-CoV-2mRNA vaccination in 1205 participants including medical personnel (125 MP), dialysis patients (970 DP) and kidney transplant recipients (110 KTR) with seroconversion (de novo IgA or IgG antibody positivity by ELISA) after eight weeks. Findings: Six months after vaccination, seroconversion remained positive in 98% of MP, but 91%/87% of DP/KTR (p = 0·005), respectively. Receptor binding domain-IgG (RBD-IgG) antibodies were positive in 98% of MP, but only 68%/57% of DP/KTR (p < 0·001), respectively. Compared to MP, DP and KTR were at risk for a strong IgG or RBD-IgG decline (p < 0·001). Within the DP but not KTR group male gender, peritoneal dialysis, short time on dialysis, BNT162b2mRNA vaccine, immunosuppressive drug use and diabetes mellitus were independent risk factors for a strong decline of IgG or RBD antibodies. The percentage of cellular immunity decline was similar in all groups. Interpretation: Both vulnerable DP and KTR groups are at risk for a strong decline for IgG and RBD antibodies. In KTR, antibody titres peak at a markedly lower level and accelerated antibody decline is mixed with a delayed/increasing IgG, RBD-IgG, or cellular immune response in a 16% fraction of patients. In both populations, immune monitoring should be used for early timing of additional booster vaccinations. Funding: This study was funded by the Else Kröner Fresenius Stiftung, Bad Homburg v. d. H., grant number Fördervertrag EKFS 2021_EKSE.27.

Humoral and cellular immunity to SARS-CoV-2 vaccination in renal transplant versus dialysis patients: A prospective, multicenter observational study using mRNA-1273 or BNT162b2 mRNA vaccine.

BACKGROUND: Dialysis and kidney transplant patients are vulnerable populations for COVID-19 related disease and mortality. METHODS: We conducted a prospective study exploring the eight week time course of specific cellular (interferon-γ release assay and flow cytometry) or/and humoral immune responses (ELISA) to SARS-CoV-2 boost vaccination in more than 3100 participants including medical personnel, dialysis patients and kidney transplant recipients using mRNA vaccines BNT162b2 or mRNA-1273. RESULTS: SARS-CoV-2-vaccination induced seroconversion efficacy in dialysis patients was similar to medical personnel (> 95%), but markedly impaired in kidney transplant recipients (42%). T-cellular immunity largely mimicked humoral results. Major risk factors of seroconversion failure were immunosuppressive drug number and type (belatacept, MMF-MPA, calcineurin-inhibitors) as well as vaccine type (BNT162b2 mRNA). Seroconversion rates induced by mRNA-1273 compared to BNT162b2 vaccine were 97% to 88% (p < 0.001) in dialysis and 49% to 26% in transplant patients, respectively. Specific IgG directed against the new binding domain of the spike protein (RDB) were significantly higher in dialysis patients vaccinated by mRNA-1273 (95%) compared to BNT162b2 (85%, p < 0.001). Vaccination appeared safe and highly effective demonstrating an almost complete lack of symptomatic COVID-19 disease after boost vaccination as well as ceased disease incidences during third pandemic wave in dialysis patients. CONCLUSION: Dialysis patients exhibit a remarkably high seroconversion rate of 95% after boost vaccination, while humoral response is impaired in the majority of transplant recipients. Immunosuppressive drug number and type as well as vaccine type (BNT162b2) are major determinants of seroconversion failure in both dialysis and transplant patients suggesting immune monitoring and adaption of vaccination protocols.

[Identification of Good-Practice Projects in Promoting Physical Activity - Methods, Pitfalls and Sampled Outcomes]. / Identifikation von Beispielen guter Praxis der Bewegungsförderung ­ Methoden, Fallstricke und ausgewählte Ergebnisse.

The aim of this paper is to identify and show examples of good practice of public health promotion. For this, uniform quality criteria were worked out under consideration of national and international scientific literature.For the identification of examples of good practice, a comparison of different quality criteria was carried out and combined with each other in a first step. In the following step, examples of good practice were identified after a comprehensive search. The choice of the "good-practice" projects is exemplary and lays no claim to completeness.6 main quality criteria (QC) of programs promoting physical activity could be identified in the national and international context. The analysis showed altogether 10 projects which can exemplarily be classified as examples of good practice of the target groups of children and teenagers, adults, older people and people with pre-existing illnesses. These projects, however, show major differences in their (methodological) quality.The analysis reports a lack of "Good-Practice" examples. Deficits lie mainly in documentation and sustainability. Because of incomplete documentation, an assessment as a "Good-Practice" example is only possible to a limited extent; a lot of information, particularly in the evaluation, is missing.

Limited Accuracy of Colour Doppler Ultrasound Dynamic Tissue Perfusion Measurement in Diabetic Adults.

Dynamic tissue perfusion measurement (DTPM) is a pre-described and available method in pediatric ultrasound to quantify tissue perfusion in renal Doppler ultrasound by particular video analysis software. This study evaluates DTPM during single and between repeated visits after 6 months, calibrates repeated DTPM within different region of interest (ROI) and compares DTPM with kidney function markers in adult patients with early diabetic nephropathy (n = 17). During repeated measurements, no association of readings at the same patients in the same (n = 3 readings) as well as repeated visit (n = 2 visits) could be retrieved. No association between DTPM, MDRD-GFR, albuminuria, age and duration of diabetes was observed. These negative results are presumably related to inconsistency of DTPM due to non-fixed ROI position as could be shown in calibrating series. Further development of the method should be performed to enable reproducible DTPM readings in adults.

Cohort profile: the Motorik-Modul Longitudinal Study: physical fitness and physical activity as determinants of health development in German children and adolescents.

The Motorik-Modul (MoMo) Longitudinal Study aims to contribute to long-term improvement in the health of German children and adolescents by focusing on: (i) the development of physical fitness and physical activity (including period effects); (ii) the individual and physical/social environmental determinants of the development of physical fitness and physical activity; and (iii) the impact of physical fitness and physical activity on the development of physical and mental health. The MoMo Longitudinal Study began with a nationwide representative sample of 4529 children and adolescents who ranged in age from 4-17 years at the study baseline (2003-2006). The first survey wave of the MoMo Longitudinal Study was conducted between 2009 and 2012, with two subsequent survey waves to be conducted between 2014 and 2016 and 2018 and 2020, respectively. The MoMo Longitudinal Study includes a physical fitness test profile, a physical activity questionnaire, and subjective and objective measures of health from the German Health Interview and Examination Survey (KiGGS). Data access is provided on request (alexander.woll@kit.edu). For further information, including a complete list of publications please visit www.motorik-modul.de.