Vaccination against COVID-19 in patients with end-stage renal disease (ESRD) on replacement therapy and kidney transplant recipients (KTRs) is particularly important due to the high mortality rate. ...Here, we tested the local and systemic immunity to the novel Pfizer BioNTech (BNT162b2) messenger RNA (mRNA) in ESRD, KTR patients, and healthy individuals (150 subjects). The ESRD group was divided into: hemodialysis (HD) and peritoneal dialysis (PD). We investigated the local and systemic immunity based on anti-N (nucleoprotein) and anti-S (spike1/2) Immunoglobulin A (IgA) and Immunoglobulin G (IgG) antibodies, respectively. Additionally, we performed an Interferon gamma (IFN-γ) release test Interferon-gamma release assay (IGRA) to monitor the cellular component of vaccine response. The control group had the highest level of anti-S IgG antibodies (153/2,080 binding antibody units (BAU)/ml) among all analyzed patients after the 1st and 2nd dose, respectively. The HD group (48/926 BAU/ml) had a diminished antibody level compared to PD (93/1,607 BAU/ml). Moreover, the seroconversion rate after the 1st dose was lower in HD than PD (56% vs. 86%). KTRs had extremely low seroconversion (33%). IgA-mediated immunity was the most effective in the control group, while other patients had diminished IgA production. We observed a lower percentage of vaccine responders based on the IFN-γ level in all research participants (100% vs. 85% in control, 100% vs. 80% in PD, 97% vs. 64% in HD). 63% of seropositive KTRs had a positive IGRA, while 28% of seronegative patients produced IFN-γ. Collectively, PD patients had the strongest response among ESRD patients. Two doses of the Pfizer vaccine are ineffective, especially in HD and KTRs. A closer investigation of ESRD and KTRs is required to set the COVID-19 vaccine clinical guidance.
Clinical Trial Registration Number
www.ClinicalTrials.gov
, identifier: NCT04 905 862
: The Pfizer-BioNTech (BNT162b2) COVID-19 mRNA vaccine has demonstrated excellent efficacy and safety in phase 3 trials. However, no dialyzed patients were included, and therefore safety data for ...this patient group is lacking. The aim of the study was to assess the safety and tolerances of vaccinations with BNT162b2 performed in chronically dialyzed patients.
: We performed a prospective cohort study including a group of 190 dialyzed patients (65% male) at median age 68.0 (55-74) years. 169 (89.0%) patients were treated with hemodialysis and 21 (11.0%) with peritoneal dialysis. The control group consisted of 160 people (61% male) without chronic kidney disease at median age 63 (range 53-77) years. Both groups were vaccinated with BNT162b2 with a 21-day interval between the first and the second dose. Solicited local and systemic reactogenicity, unsolicited adverse events and antipyretic and pain medication use were assessed with a standardized questionnaire. The toxicity grading scales were derived from the FDA Center for Biologics Evaluation and Research guidelines.
: 59.8% (dose 1), 61.4% (dose 2) and 15.9% (dose 1), 29.4% (dose 2) dialyzed patients reported at least one local and one systemic reaction respectively within seven days after the vaccination. Many local and systemic solicited reactions were observed less frequently in dialyzed patients than in the age and sex matched control group and much less frequently than reported in the pivotal study. They were mostly mild to moderate, short-lived, and more frequently reported in younger individuals and women. No related unsolicited adverse events were observed.
: We have shown here that BNT162b2, an mRNA vaccine from Pfizer-BioNTech against SARS-COV-2 is safe and well-tolerated by dialyzed patients. The results can be useful for the nephrological community to resolve patients' doubts and reduce their vaccine hesitancy.
The group most at risk of death due to COVID-19 are patients on maintenance hemodialysis (HD). The study aims to describe the clinical course of the early phase of SARS-CoV-2 infection and find ...predictors of the development of COVID-19 severe pneumonia in this population. This is a case series of HD nonvaccinated patients with COVID-19 stratified into mild pneumonia and severe pneumonia group according to the chest computed tomography (CT) pneumonia total severity score (TSS) on admission. Epidemiological, demographic, clinical, and laboratory data were obtained from hospital records. 85 HD patients with a mean age of 69.74 (13.19) years and dialysis vintage of 38 (14-84) months were included. On admission, 29.14% of patients had no symptoms, 70.59% reported fatigue followed by fever-44.71%, shortness of breath-40.0%, and cough-30.59%. 20% of the patients had finger oxygen saturation less than 90%. In 28.81% of patients, pulmonary parenchyma was involved in at least 25%. The factors associated with severe pneumonia include fever, low oxygen saturation and arterial partial pressure of oxygen, increased C-reactive protein and ferritin serum levels, low blood count of lymphocytes as well as chronic treatment with angiotensin converting enzyme inhibitors; while the chronic active vitamin D treatment was associated with mild pneumonia. In conclusion, even though nearly one-third of the patients were completely asymptomatic, while the remaining usually reported only single symptoms, a large percentage of them had extensive inflammatory changes at diagnosis with SARS-CoV-2 infection. We identified potential predictors of severe pneumonia, which might help individualize pharmacological treatment and improve clinical outcomes.
Background: The efficacy of SARS-CoV-2 vaccination among kidney transplant recipients (KTR) is low. The main goal of this study was to analyze factors that may influence the humoral response to ...vaccination. Methods: We analyzed the titer magnitude of IgG antibodies directed against spike (S)-SARS-CoV-2 antigen after the second dose of the mRNA vaccine in 142 infection naïve KTR (83 men, i.e., 58.4%) with a median age (IQR) of 54 (41–63), and 36 respective controls without chronic kidney disease. mRNA-1273 or BNT162b2 were applied in 26% and 74% of KTR, respectively. Results: S-specific immune response (seroconversion) was seen in 73 (51.41%) of KTR, and in all controls 36 (100%). Independent predictors of no response were elder age, shorter transplantation vintage, and a more than two-drug immunosuppressive protocol. In subgroup analyses, the seroconversion rate was highest among KTR without MMF/MPS treatment (70%), treated with no more than two immunosuppressants (69.2%), treated without corticosteroid (66.7%), younger patients aged <54 years (63.2%), and those vaccinated with the mRNA-1273 vaccine (62.16%). The independent predictors of higher S-antibody titer among responders were younger age, treatment with no more than two immunosuppressants, and the mRNA-1273 vaccination. Conclusions: Our study confirmed a low rate of seroconversion after vaccination with the mRNA vaccine in KTR. The major modifiable determinants of humoral response were the composition of the immunosuppressive protocol, as well as the type of vaccine. The latter could be taken into consideration when initial vaccination as well as booster vaccination is considered in KTR.
The immune response to the primary (two-dose) series of mRNA COVID-19 vaccines in kidney transplant recipients (KTRs) is very weak. We conducted a longitudinal observational study to compare the ...humoral response to a third, additional primary dose of mRNA vaccines between infection-naïve (IN-KTRs) and previously infected KTRs (PI-KTRs). Methods: We measured the levels of anti-spike (anti-s) IgG antibodies before and 14-21 days after the third dose and, in the secondary analysis, we compared the antibody response to BNT162b2 versus mRNA-1273. The reactogenicity assessment included solicited local and systemic reactions.
A total of 112 KTRs were enrolled, including 83 IN-KTR and 29 PI-KTR, among whom seroconversion in anti-s antibodies after the primary two-dose vaccination was achieved in 45.78% and 100% of cases, respectively. After three months, a waning antibodies titer by 67.4% (IN-KTR) and 7.5% (PI-KTR) was observed. After the third dose of the mRNA vaccine, 71.08% (59/83) of IN-KTR and 96.5% (28/29) of PI-KTR samples were seroconverted with a median anti-s titer of 468.0 (195.0-1620.0) BAU/mL and 1629.0 (1205-1815) BAU/mL, respectively. Of those IN-KTR in whom the primary vaccination failed, 46.67% (21/45) of patients achieved seroconversion after the third dose. No serious adverse events after the third dose were reported. In strata analyses, after the third dose, 66% (40/60) of patients vaccinated with BNT162b2 and 82.6% (19/23) of patients vaccinated with mRNA-1273 seroconverted with a median anti-s titer of 384.5 (144-837) BAU/mL and 1620 (671-2040) BAU/mL, respectively.
: The use of a third dose of mRNA vaccine may be of benefit for KTR, especially for those in whom the primary vaccination failed. Vaccines with a higher dose of mRNA and a longer interval between doses of the primary vaccination, such as mRNA-1273, seem to be the preparations of choice in immunocompromised individuals.
Introduction
Three-dose mRNA vaccination against COVID-19 is unable to elicit a sufficient immune response in immunocompromised subjects.
Material and methods
The aim of the study was to conduct a ...retrospective evaluation of the efficacy of a heterologous mRNA booster with mRNA-1273 in constantly seronegative kidney transplant recipients (KTRs) after three doses of the BNT162b2 mRNA vaccine. Twelve seronegative KTRs received a mRNA-1273 booster 5 months after the third dose of BNT162b2.
Results
A total of 5 out of 12 patients (41.7%) seroconverted, with a mean titer of 353 BAU/ml.
Conclusions
The administration of a heterologous mRNA vaccine as a booster may be an effective alternative for achieving post-vaccination immunity in seronegative KTRs.
Background Agents inhibiting the renin-angiotensin-aldosterone (RAAS) system have an important role in slowing the progression of chronic kidney disease. We evaluated the hypothesis that the addition ...of an aldosterone receptor antagonist to an angiotensin-converting enzyme (ACE) inhibitor and angiotensin II type 1 (AT-1) receptor blocker (ARB) (triple RAAS blockade) may provide an additional benefit compared with an ACE inhibitor and ARB (double RAAS blockade). Design Randomized open controlled crossover study. Setting & Participants 18 whites (7 women, 11 men) from the Outpatient Department of Nephrology with chronic nondiabetic proteinuric kidney diseases, mean age 42.4 ± 1.9 years (SEM). Interventions In the 8-week run-in period, all participants received the ACE inhibitor cilazapril (5 mg), the ARB telmisartan (80 mg), and the diuretic hydrochlorothiazide (12.5 mg) as double RAAS blockade to achieve the target blood pressure of less than 130/80 mm Hg. Participants were then randomly assigned to 2 treatment sequences, either the addition of spironolactone (25 mg) (triple RAAS blockade) through 8 weeks followed by double RAAS blockade through 8 weeks (sequence 1) or double RAAS blockade followed by triple RAAS blockade (sequence 2). Main Outcome Measures 24-hour urine protein excretion (primary end point) and markers of tubular injury and fibrosis (secondary end points). Analysis was performed using analysis of variance for repeated measurements. Results At baseline, mean serum creatinine level was 1.16 ± 0.09 mg/dL (103 ± 8 μmol/L), estimated glomerular filtration rate was 107.8 mL/min (95% confidence interval, 93 to 140.9 1.8 mL/s; 95% confidence interval, 1.55 to 2.35; Cockcroft-Gault formula), and 24-hour mean proteinuria was 0.97 ± 0.18 g. Mean urine protein excretion was 0.7 g/24 h (95% confidence interval, 0.48 to 0.92) less after triple RAAS blockade than after double RAAS blockade ( P = 0.01), without change in blood pressure. Urine excretion of N -acetyl-β- d -glucosaminidase ( P = 0.02) and amino-terminal propeptide of type III procollagen ( P = 0.05) also significantly decreased. Potassium levels increased significantly after triple therapy ( P = 0.02). However, no patient was withdrawn because of adverse effects. Limitations Absence of blinding, small sample size, short treatment period, absence of histological assessment. Conclusions Administration of an aldosterone receptor antagonist in addition to double RAAS blockade with an ACE inhibitor and ARB may slow the progression of chronic kidney disease. Additional studies are necessary to confirm this result.
Background: After recovery from COVID-19, patients frequently face so-called “Post-COVID-19 Syndrome” defined by clusters of persistent symptoms lasting for >12 weeks which may arise from any system ...in the body. The long-term health consequences of COVID-19 in maintenance hemodialyzed (HD) patients remain to be investigated. Methods: In this longitudinal cohort study we described the health consequences in HD patients requiring hospitalization due to COVID-19. They were interviewed three and six months (M3 and M6) after discharge with a series of standardized questionnaires. Results: Of 144 HD patients discharged from the 7th Naval Hospital in Gdansk, 79 participants were enrolled, 39 m (49.4%) and 40 f (50.6%) with a median age of 70.0 (64.0–76.5) and an HD vintage of 40 months (17.5–88). After discharge, 93.7% and 81% reported at least one persistent symptom at M3 and M6, respectively. The most common symptoms were fatigue or muscle weakness (60.76% and 47.04%) and palpitations (40.51% and 30.14%). Dyspnea with an mMRC scale grade of at least 1 was reported by 21.5% before infection, and by 43.03% and 34.25% at M3 and M6, respectively. A decrease in the quality of life was reported in all domains of the EQ-5D-5L questionnaire but mainly in the pain/discomfort and anxiety dimensions. Mean EQ-VAS scores were 69.05, 61.58 and 64.38, respectively. Conclusion: Our study showed that HD patients may still experience persistent symptoms six months after recovery from COVID-19, which can further reduce their already poor health-related quality of life. This study highlights the need for long-term follow-up on these patients for diagnostic and rehabilitation programs.
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