COVID‐19 is associated with increased morbidity and mortality in transplant recipients. There are no efficacy data available regarding these patients with any of the available SARS‐CoV‐2 vaccines. We analyzed the humoral response following full vaccination with the BNT162b2 (Pfizer‐BioNTech) in 136 kidney transplant recipients, and compared it to 25 controls. In order to exclude prior exposure to the virus, only participants with negative serology to SARS‐CoV‐2 nucleocapsid protein were included. All controls developed a positive response to spike protein, while only 51 of 136 transplant recipients (37.5%) had positive serology (p < .001). Mean IgG anti‐spike level was higher in the controls (31.05 [41.8] vs. 200.5 [65.1] AU/mL, study vs. control, respectively, p < .001). Variables associated with null humoral response were older age (odds ratio 1.66 [95% confidence interval 1.17–2.69]), high‐dose corticosteroids in the last 12 months (1.3 [1.09–1.86]), maintenance with triple immunosuppression (1.43 [1.06–2.15]), and regimen that includes mycophenolate (1.47 [1.26–2.27]). There was a similar rate of side effects between controls and recipients, and no correlation was found between the presence of symptoms and seroconversion. Our findings suggest that most kidney transplant recipients remain at high risk for COVID‐19 despite vaccination. Further studies regarding possible measures to increase recipient's response to vaccination are required.
Background and aims Two SARS-CoV-2 mRNA vaccines were approved to prevent COVID-19 infection, with reported vaccine efficacy of 95%. Liver transplant (LT) recipients are at risk for lower vaccine immunogenicity and were not included in the registration trials. We assessed vaccine immunogenicity and safety in this special population. Methods LT recipients followed at the Tel-Aviv Sourasky Medical Center and healthy volunteers were tested for SARS-CoV-2 IgG antibodies directed against the Spike-protein (S) and Nucleocapsid-protein (N) 10-20 days after receiving the second Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine dose. Information regarding vaccine side effects and clinical data was collected from patients and medical records. Results Eighty LT recipients were enrolled. Mean age was 60 years and 30% were female. Twenty-five healthy volunteer controls were younger (mean age 52.7 years, p=0.013) and mostly female (68%, p=0.002). All participants were negative for IgG N-protein serology, indicating immunity did not result from prior COVID-19 infection. All controls were positive for IgG S-protein serology. Immunogenicity among LT recipients was significantly lower with positive serology in only 47.5% (p<0.001). Antibody titer was also significantly lower in this group (mean 95.41 AU/mL vs. 200.5 AU/mL in controls, p<0.001). Predictors for negative response among LT recipients were older age, lower eGFR, and treatment with high dose steroids and MMF. No serious adverse events were reported in both groups. Conclusion LT recipients developed substantially lower immunological response to Pfizer-BioNTech SARS-CoV-2 mRNA-based vaccine. Factors influencing serological antibodies response include age, renal function and immunosuppressive medications. The findings require re-evaluation of vaccine regimens in this population. Lay summary Liver Transplant recipients had a substantially inferior immunity to the Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine. Less than half of the patients developed sufficient levels of antibodies against the virus, and in those who were positive , average antibody levels were two times less compared to healthy controls. Factors predicting non-response were older age, renal function and immunosuppressive medications.
Background and objectivesCoronavirus disease 2019 (COVID-19) is associated with higher morbidity and mortality in patients on maintenance hemodialysis. Patients on dialysis tend to have a reduced immune response to infection or vaccination. We aimed to assess, for the first time to the best of our knowledge, the humoral response following vaccination with the BNT162b2 vaccine in patients on maintenance hemodialysis and the factors associated with it.Design, setting, participants, & measurementsThe study included 56 patients on maintenance hemodialysis (dialysis group) and a control group composed of 95 health care workers. All participants had received two doses of the BNT162b2 (Pfizer-BioNTech) vaccine. The serology testing was done using Quant II IgG anti-Spike severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) assay by Abbott a median of 30 days after receipt of the second dose of the vaccine.ResultsAll subjects in the control group developed an antibody response compared with 96% (54 of 56) positive responders in the dialysis group. The IgG levels in the dialysis group (median, 2900; interquartile range, 1128–5651) were significantly lower than in the control group (median, 7401; interquartile range, 3687–15,471). A Mann–Whitney U test indicated that this difference was statistically significant (U=1238; P<0.001). There was a significant inverse correlation of age and IgG levels in both groups. The odds of being in the lower quartile were significantly higher for older individuals (odds ratio, 1.11 per year of age; 95% confidence interval, 1.08 to 1.20; P=0.004) and for the dialysis group compared with the control group (odds ratio, 2.7; 95% confidence interval, 1.13 to 7.51; P=0.05). Within the dialysis group, older age and lower lymphocyte count were associated with antibody response in the lower quartile (odds ratio, 1.22 per 1-year older; 95% confidence interval, 1.13 to 1.68; P=0.03 and odds ratio, 0.83 per 10-e3/µl-higher lymphocyte count; 95% confidence interval, 0.58 to 0.97; P=0.05).ConclusionsAlthough most patients on maintenance hemodialysis developed a substantial humoral response following the BNT162b2 vaccine, it was significantly lower than controls. Age was an important factor in the humoral response, regardless of chronic medical conditions.
Membranous nephropathy recurs in 48% of cases threatening the allograft. Treatment of early but progressive recurrence with anti-CD20 antibodies is quite effective achieving clinical remission and histologic resolution of MN.
The accepted use of left ventricular assist device (LVAD) technology as a good alternative for the treatment of patients with advanced heart failure together with the improved survival of patients on the device and the scarcity of donor hearts has significantly increased the population of LVAD supported patients. Device-related, and patient-device interaction complications impose a significant burden on the medical system exceeding the capacity of LVAD implanting centres. The probability of an LVAD supported patient presenting with medical emergency to a local ambulance team, emergency department medical team and internal or surgical wards in a non-LVAD implanting centre is increasing. The purpose of this paper is to supply the immediate tools needed by the non-LVAD specialized physician -ambulance clinicians, emergency ward physicians, general cardiologists, and internists -to comply with the medical needs of this fast-growing population of LVAD supported patients. The different issues discussed will follow the patient's pathway from the ambulance to the emergency department, and from the emergency department to the internal or surgical wards and eventually back to the general practitioner.
Objectives: Hyperuricemia provokes endothelial dysfunction (ECD). Decreased endothelial nitric oxide synthase (eNOS) activity is an important source of ECD. Cationic amino acid transporter-1 (CAT-1) is the specific arginine transporter for eNOS. We hypothesize that hyperuricemia inhibits arginine uptake. Methods: Experiments were performed in freshly harvested aortas from untreated animals and rats fed with oxonic acid (hyperuricemia), and compared to hyperuricemic rats treated with either allopurinol, benzbromarone or arginine. Results: Arginine transport was significantly decreased in hyperuricemia. Benzbromarone and arginine prevented the decrease in arginine transport in hyperuricemic rats while allopurinol did not. Arginine transport was significantly decreased in control rats treated with allopurinol. Blood pressure response to acetylcholine was significantly attenuated in hyperuricemic rats, an effect which was prevented in all other experimental groups. L-NAME inhibitable cGMP response to carbamyl-choline was significantly decreased in hyperuricemic rats and this was completely prevented by both benzbromarone and arginine, while allopurinol partially prevented the aforementioned phenomenon. Hyperuricemia induced a significant increase in protein nitration that was prevented by benzbromarone, allopurinol, and arginine. Protein abundance of CAT-1, PKCα, and phosphorylated PKCα remained unchanged in all experimental groups. Conclusions: In hyperuricemia, the decrease in aortic eNOS activity is predominantly the result of attenuated arginine uptake.
Background Little is known about vaccine efficacy and sustainability among people with HIV (PWH). We estimated humoral and cellular immune responses post-vaccination with BNT162b2 mRNA COVID-19 vaccine among PWH in Tel-Aviv medical center. Methods The vaccine humoral response was evaluated by measuring IgG titers of anti-spike receptor-binding domain antibodies (anti-RBD IgG). Cellular response was assessed by stimulating donor peripheral blood mononuclear cells with pooled complete S-peptide mix. Results 136 PWH who completed 2 doses of the SARS-CoV-2 vaccine were tested for anti-RBD IgG and compared with 61 vaccinated healthcare workers (HCW). The antibody titers were similar between the groups (median of 118 BAU/ml for PWH and 101.4 BAU/ml for HCW, p=0.231), although the mean time from 2 nd vaccine was 4.5 months in PWH and 6.7 months in HCW (P<0.0001). Longer time from 2 nd vaccine dose was associated with decreased antibody level, as were CD4 counts of <300 cells/µL compared with higher CD4 counts (25.1 BAU/ml vs. 119.3 BAU/ml, respectively, p=0.047). There was no difference in cellular immune response between vaccinated PWH, convalescent unvaccinated PWH and vaccinated HCW. Conclusions The humoral immune response of PWH was comparable to those of HCW after BNT162b2 mRNA vaccination. Cellular immune response did not differ between vaccinated PWH, convalescent PWH and vaccinated HCW. PWH with CD4 count of < 300 cells/µL (n=9) had lower antibody titers compared with patients with counts of >300 cells/µL (n=127).
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