Background: Kidney failure patients on dialysis or after renal transplantation have a high risk for severe COVID-19 infection and vaccination against SARS-CoV-2 is the only expedient prophylaxis. Generally, immune responses are attenuated in kidney failure patients, however, systematic analyses of immune responses to SARS-CoV-2 vaccination in dialysis patients and in kidney transplant recipients (KTR) are still missing. Methods: In this prospective multicentric cohort study, antibody responses COVID-19 mRNA vaccines (BNT162b2; Biontech/Pfizer or mRNA-1273; Moderna) were measured in 32 dialysis patients and in 28 KTRs. SARS-CoV-2-specific antibodies and neutralization capacity were evaluated and compared to controls (n=78) in a similar age-range. Results: After the first vaccination, SARS-CoV-2-specific antibodies were nearly undetectable in kidney failure patients. After the second vaccination, 93% of the controls and 88% of dialysis patients but only 37% of KTRs developed SARS-CoV-2-specific IgG above cut-off. Moreover, mean IgG levels were significantly lower in KTRs (54±93 BAU/ml) compared to dialysis patients (503±481 BAU/ml, p<0.01). Both KTRs as well as dialysis patients had significantly lower IgG levels compared to controls (1992±2485 BAU/ml; p<0.001 and p<0.01). Importantly, compared to controls, neutralizing antibody titers were significantly lower in KTRs and dialysis patients. After the second vaccination, 76% of KTRs did not show any neutralization capacity against SARS-CoV-2 suggesting impaired seroprotection. Conclusions: Kidney failure patients show a significantly weaker antibody response compared to controls. Most strikingly, only one out four KTRs developed neutralizing antibodies against SARS-CoV-2 after two doses of vaccine. These data suggest that vaccination strategies need modification in immune transplant and dialysis patients.

Modification of vaccination strategies is necessary to improve the immune response to SARS‐CoV‐2 vaccination in kidney transplant recipients (KTRs). This multicenter observational study analyzed the effects of the third SARS‐CoV‐2 vaccination in previously seronegative KTRs with the focus on temporary mycophenolate mofetil (MMF) dose reduction within propensity matched KTRs. 56 out of 174 (32%) previously seronegative KTRs became seropositive after the third vaccination with only three KTRs developing neutralizing antibodies against the omicron variant. Multivariate logistic regression revealed that initial antibody levels, graft function, time after transplantation and MMF trough levels had an influence on seroconversion ( P < .05). After controlling for confounders, the effect of MMF dose reduction before the third vaccination was calculated using propensity score matching. KTRs with a dose reduction of ≥33% showed a significant decrease in MMF trough levels to 1.8 (1.2–2.5) μg/ml and were more likely to seroconvert than matched controls ( P = .02). Therefore, a MMF dose reduction of 33% or more before vaccination is a promising approach to improve success of SARS‐CoV‐2 vaccination in KTRs.

Background: Modification of vaccination strategies is needed to improve the immune response to SARS-CoV-2 vaccination in kidney transplant recipients (KTRs). Methods: This multicenter observational study aimed to determine antibody kinetics among 60 seropositive KTRs and analyzed the effects of the third vaccination against SARS-CoV-2 in 174 previously seronegative KTRs. We investigated whether mycophenolate mofetil (MMF) dose reduction by 25-50% prior the third vaccination influences vaccination success. Results: 18 of 60 (30%) seropositive KTRs became seronegative in the serological assay within six months. Loss of antibodies was predicted by low initial antibody levels (<≤>206.8 BAU/ml), older age, and impaired graft function. A third vaccination in previously seronegative KTRs induced seroconversion in 56 of 174 (32.1%) KTRs with median antibody levels 119 (76-353) BAU/ml and median neutralizing capacity titer of 1:10 (0-1:40). Multivariate logistic regression revealed that initial antibody levels (OR 1.39, 95% CI 1.09-1.76), graft function (OR 0.05, 95% CI 0.01-0.39), time after transplantation (OR 1.04, 95% CI 1.02-1.07) and MMF trough levels (OR 0.43, 95% CI 0.21-0.88) correlated with seroconversion, p<0.05. After controlling for these confounders, the effect of MMF dose reduction was calculated using propensity score matching. KTRs in the MMF reduction group had significantly lower MMF serum concentrations prior to the third vaccination and were more likely to develop antibody levels <≥>35.2 BAU/ml than their matched KTRs (p=0.02). Conclusions: Temporary reduction in MMF dose might be a promising approach to improve the immune response in KTRs.

Vaccination against SARS-CoV-2 is an important prophylactic measure in kidney transplant recipients (KTRs), however, the immune response is often impaired. Here, we examined the T cell immune response against SARS-CoV-2 in 148 KTRs after three or four vaccine doses including 35 KTRs with subsequent SARS-CoV-2 infection. The frequency of spike-specific T cells was lower in KTRs compared to immunocompetent controls and correlated with the level of spike-specific antibodies. Positive predictors for detection of vaccine-induced T cells were detection of spike-specific antibodies, heterologous immunization with mRNA and a vector vaccine and longer time past transplant. In vaccinated KTRs with subsequent SARS-CoV-2 infection, the T-cell response was greatly enhanced and was significantly higher than in vaccinated KTRs without SARS-CoV-2 infection. Overall, the data show a correlation between impaired humoral and T-cell immunity to SARS-CoV-2 vaccination and provide evidence for greater robustness of hybrid immunity in KTRs.

ZusammenfassungZur arthroskopischen Synovialektomie der Metacarpophalangealgelenke (MCP-Gelenke) sind bisher kaum Arbeiten erschienen. Sie berichten jedoch über vielversprechende Ergebnisse. Ziel der vorliegenden Arbeit ist die Auswertung der subjektiven Ergebnisse nach arthroskopischer Synovialektomie bei Patienten mit rheumatoider Arthritis. Von 2009 bis 2013 wurden 137 arthroskopische Synovialektomien der MCP- und der proximalen Interphalangealgelenke (PIP) bei 77 Patienten mit rheumatoider Arthritis durchgeführt. Nach Berücksichtigung der Ausschlusskriterien verblieben 41 Patienten, bei denen ein oder mehrere MCP-Gelenke oder zusätzlich ein PIP-Gelenk behandelt wurden. Telefonisch konnten 39 Patienten mit 76 MCP-Gelenken nach durchschnittlich 22,7 (9–42) Monaten retrospektiv zu Schmerzreduktion, Funktionsverbesserung und Zufriedenheit mit dem Eingriff befragt werden. 37 Patienten mit 74 operierten Gelenken waren mit dem Eingriff zufrieden und würden ihn erneut durchführen lassen. Die Verringerung des Ruhe- und Bewegungsschmerzes war signifikant, ohne dass hierbei ein Zusammenhang mit dem präoperativen Röntgenstadium festzustellen war. Intraoperativ konnte in allen Fällen eine Synovialitis bestätigt werden. Die Ergebnisse der vorgelegten Arbeit zeigen, dass mit der arthroskopischen Synovialektomie der MCP-Gelenke bei rheumatoider Arthritis eine hohe Patientenzufriedenheit erreicht werden kann. Voraussetzung für die Indikation ist ein intakter Bandapparat der MCP-Gelenke ohne biomechanische Veränderungen.