ABSTRACT
BackgroundModification of vaccination strategies is needed to improve the immune response to SARS-CoV-2 vaccination in kidney transplant recipients (KTRs). MethodsThis 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. Results18 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). ConclusionsTemporary reduction in MMF dose might be a promising approach to improve the immune response in KTRs.
ABSTRACT
Background: The Seraph®100 Microbind Affinity Blood Filter® is a hemofiltration device that is licensed for pathogen reduction in the blood. This includes several viruses. Removal of the nucleocapsid of the SARS-CoV-2 virus by the Seraph®100 has been recently demonstrated. As viral load has repeatedly been shown to correlate with adverse outcome in severe coronavirus disease 2019 (COVID-19), the aim of this registry was to evaluate safety and efficacy of Seraph®100 treatment for COVID-19.Methods: An online registry in which main patient charcteristics, treatment coordinates and outcome parameters was documented without reimbursement. So far 12 hospitals in 4 countries on 2 continents took part in the registry. 75 treatment sessions in 60 patients were documented in the registry. Results: Adverse effects of the Seraph® 100 treatment were reported in 2 (2.6 %) of the 75 treatments. Eight (10.6 %) of all the procedures ended prematurely due to circuit failure / clotting. Half of the treatments (47.6 %) were performed as hemoperfusion only. 21.6 % of the treatments were performed in conjuction with intermittent hemodialysis. Median treatment time was 4.21 [4.00 - 8.06] h. Anticoagulation was performed using citrate in 20.6 % of treatments. Patients that died despite treatment with the Seraph® 100 filter had a higher rate of bacterial superinfection, higher level of inflammatory laboratory markers (procalcitonin and ferritin) and higher d-dimer levels. While predicted survival rate in ICU patients was >80 %, the observed survival rate was 47.6 %. In non-ICU patients, 4 C score predicted a survival rate of 31.4-34.9 % while the observed survival rate was 22.2 %.Conclusion: Seraph® 100 treatment was well tolerated and circuit failure rate was significantly lower than reported for KRT in COVID-19 patients. All patients that died despite of Seraph® 100 treatment had serious pre-existing medical conditions, coexisting bacterial infections and more pronounced systemic signs of inflammation. Compared to the calculated mortality using established scores, the observed mortality in the Seraph® 100 treated patients was lower.Trial registration:ClinicalTrials.gov Identifier: NCT04361500