The RECOVAC IR study: the immune response and safety of the mRNA-1273 COVID-19 vaccine in patients with chronic kidney disease, on dialysis or living with a kidney transplant.
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ABSTRACT:
SUBMITTER: Kho MML
PROVIDER: S-EPMC8241423 | biostudies-literature | 2021 Aug
REPOSITORIES: biostudies-literature
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The RECOVAC IR study: the immune response and safety of the mRNA-1273 COVID-19 vaccine in patients with chronic kidney disease, on dialysis or living with a kidney transplant.
Kho Marcia M L MML Reinders Marlies E J MEJ Baan Carla C CC van Baarle Debbie D Bemelman Frederike J FJ Diavatopoulos Dimitri A DA Gansevoort Ron T RT van der Klis Fiona R M FRM Koopmans Marion P G MPG Messchendorp A Lianne AL van der Molen Renate G RG Remmerswaal Ester B M EBM Rots Nynke N Vart Priya P de Vries Rory D RD Hilbrands Luuk B LB Sanders Jan-Stephan F JF
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 20210801 9
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Project description:BackgroundThe immune response to COVID-19 vaccination is inferior in kidney transplant recipients (KTR), and to a lesser extent in patients on dialysis or with chronic kidney disease (CKD). We assessed the immune response 6 months after mRNA-1273 vaccination in kidney patients and compared this to controls.Methods152 participants with CKD stages G4/5 (eGFR <30 mL/min/1.73m2), 145 participants on dialysis, 267 KTR, and 181 controls were included. SARS-CoV-2 Spike S1-specific IgG antibodies were measured by fluorescent bead-based multiplex-immunoassay, neutralizing antibodies to ancestral, Delta and Omicron (BA.1) variants by plaque reduction, and T-cell responses by IFN-γ release assay.ResultsAt 6 months after vaccination S1-specific antibodies were detected in 100% of controls, 98.7% of CKD G4/5 patients, 95.1% of dialysis patients, and 56.6% of KTR. These figures were comparable to the response rates at 28 days, but antibody levels waned significantly. Neutralization of the ancestral and Delta variant was detected in most participants, whereas neutralization of Omicron was mostly absent. S-specific T-cell responses were detected 6 months in 75.0% of controls, 69.4% of CKD G4/5 patients, 52.6% of dialysis patients, and 12.9% of KTR. T-cell responses at 6 months were significantly lower than responses at 28 days.ConclusionsAlthough seropositivity rates at 6 months were comparable to that at 28 days after vaccination, significantly decreased antibody levels and T-cell responses were observed. The combination of low antibody levels, reduced T-cell responses, and absent neutralization of the newly-emerging variants indicates the need for additional boosts or alternative vaccination strategies in KTR.
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| S-EPMC8842265 | biostudies-literature
Project description:According to preliminary data, seroconversion after mRNA SARS-CoV-2 vaccination might be unsatisfactory in Kidney Transplant Recipients (KTRs). However, it is unknown if seronegative patients develop at least a cellular response that could offer a certain grade of protection against SARS-CoV-2. To answer this question, we prospectively studied 148 recipients of either kidney (133) or kidney-pancreas (15) grafts with assessment of IgM/IgG spike (S) antibodies and ELISpot against the nucleocapside (N) and the S protein at baseline and 2 weeks after receiving the second dose of the mRNA-1273 (Moderna) vaccine. At baseline, 31 patients (20.9%) had either IgM/IgG or ELISpot positivity and were considered to be SARS-CoV-2-pre-immunized, while 117 (79.1%) patients had no signs of either cellular or humoral response and were considered SARS-CoV-2-naïve. After vaccination, naïve patients who developed either humoral or cellular response were finally 65.0%, of which 29.9% developed either IgG or IgM and 35.0% S-ELISpot positivity. Factors associated with vaccine unresponsiveness were diabetes and treatment with antithymocytes globulins during the last year. Side effects were consistent with that of the pivotal trial and no DSAs developed after vaccination. In conclusion, mRNA-1273 SARS-CoV-2 vaccine elicits either cellular or humoral response in almost two thirds of KTRs.
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Project description:BackgroundDetermining the humoral immunogenicity of tozinameran (BNT162b2) in patients requiring chronic renal replacement therapy, and its impact on COVID-19 morbidity several months after vaccination, may guide risk assessment and changes in vaccination policy.MethodsIn a prospective post-vaccination cohort study with up to 5 months follow-up we studied outpatient dialysis and kidney transplant patients and respective healthcare teams. Outcomes were anti S1/S2 antibody responses to vaccine or infection, and infection rate during follow-up.ResultsOne hundred seventy-five dialysis patients (40% women, 65 ± 15 years), 252 kidney transplant patients (33% women, 54 ± 14 years) and 71 controls (65% women, 44 ± 14 years) were followed. Three months or longer after vaccination we detected anti S1/S2 IgG antibodies in 79% of dialysis patients, 42% of transplant recipients and 100% of controls, whereas respective rates after infection were 94%, 69% and 100%. Predictors of non-response were older age, diabetes, history of cancer, lower lymphocyte count and lower vitamin-D levels. Factors associated with lower antibody levels in dialysis patients were modality (hemodialysis vs peritoneal) and high serum ferritin levels. In transplant patients, hypertension and higher calcineurin or mTOR inhibitor drug levels were linked with lower antibody response. Vaccination was associated with fewer subsequent infections (HR 0.23, p < 0.05). Moreover, higher antibody levels (particularly above 59 AU/ml) were associated with fewer events, with a HR 0.41 for each unit increased in log10titer (p < 0.05).ConclusionsDialysis patients, and more strikingly kidney transplant recipients, mounted reduced antibody response to COVID-19 mRNA vaccination. Lesser humoral response was associated with more infections. Measures to identify and protect non-responsive patients are required.
| S-EPMC8731189 | biostudies-literature
Project description:BackgroundSolid organ transplant recipients (SOTRs) are at high risk for severe COVID-19.MethodsThis open-label, phase 3b trial evaluated mRNA-1273 in 137 kidney and 77 liver SOTRs and 20 immunocompetent participants. In part A, SOTRs received three 100-µg doses of mRNA-1273; immunocompetent participants received 2 doses. In part B, an additional 100-µg dose was offered ≥4 months after the primary series. Here, we report interim trial results.ResultsmRNA-1273 was well-tolerated in SOTRs. Four serious adverse events were considered vaccine related by the investigator in 3 SOTRs with preexisting comorbidities. No vaccine-related biopsy-proven organ rejection events or deaths were reported. mRNA-1273 elicited modest neutralizing antibody responses after dose 2 and improved responses after dose 3 in SOTRs. Post-dose 3 responses among liver SOTRs were comparable to post-dose 2 responses in immunocompetent participants. Post-additional dose responses were increased in SOTRs, regardless of primary series vaccination. In liver SOTRs, post-additional dose responses were ∼3-fold higher versus post-dose 2 but lower than immunocompetent participant responses. Most kidney SOTRs received multiple immunosuppressants and had reduced antibody responses versus liver SOTRs.ConclusionsmRNA-1273 was well-tolerated, and dose 3 and the additional dose improved antibody responses among SOTRs.Clinical trials registrationNCT04860297.
| S-EPMC11420796 | biostudies-literature
Project description:BackgroundVaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle-encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19.MethodsThis phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2.ResultsThe trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline. Symptomatic Covid-19 illness was confirmed in 185 participants in the placebo group (56.5 per 1000 person-years; 95% confidence interval [CI], 48.7 to 65.3) and in 11 participants in the mRNA-1273 group (3.3 per 1000 person-years; 95% CI, 1.7 to 6.0); vaccine efficacy was 94.1% (95% CI, 89.3 to 96.8%; P<0.001). Efficacy was similar across key secondary analyses, including assessment 14 days after the first dose, analyses that included participants who had evidence of SARS-CoV-2 infection at baseline, and analyses in participants 65 years of age or older. Severe Covid-19 occurred in 30 participants, with one fatality; all 30 were in the placebo group. Moderate, transient reactogenicity after vaccination occurred more frequently in the mRNA-1273 group. Serious adverse events were rare, and the incidence was similar in the two groups.ConclusionsThe mRNA-1273 vaccine showed 94.1% efficacy at preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.).
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Project description:Background: Providing holistic care to kidney patients is important; however, without full consideration of the perspectives of people living with a kidney transplant, the provision of truly 'holistic healthcare' cannot be possible. It is imperative to understand patient experiences by including kidney patients in key strategies and future renal service planning. Ignoring these important patient views means that there is a significant risk of inappropriate renal service provision and lack of adequate support, impacting overall health. The aim of this study was to develop an in-depth understanding of the lived experiences of kidney transplant recipients. Methods: A total of 23 participants were recruited between two regional nephrology units within the United Kingdom via clinical gatekeepers. In-depth interviews were undertaken. Interviews were digitally recorded, transcribed verbatim, and subjected to interpretative phenomenological analysis. Results: Two themes emerged: "managing ongoing fears of dialysis, distress, and COVID-19" and "dealing with difficult conversations". Conclusions: Renal healthcare professionals need to understand more than the biological impact of receiving a kidney transplant. Understanding the holistic and multidomain experiences that these participants experience will help healthcare professionals to recognize the needs of this group and ensure more responsive psychosocial care.
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Project description:BackgroundThe optimal timing of dialysis access placement in individuals with stage 5 CKD is challenging to estimate. Preemptive living donor kidney transplant (LDKT) is the gold-standard treatment for ESKD due to superior graft survival and mortality, but dialysis initiation is often required. Among LDKT recipients, we sought to determine which clinical characteristics were associated with preemptive transplant. Among non-preemptive LDKT recipients, we sought to determine what dialysis access was used, and their duration of use before receipt of living donor transplant.MethodsWe retrospectively extracted data on 569 LDKT recipients, >18 years old, who were transplanted between January 2014 and July 2019 at UCSF, including dialysis access type (arteriovenous fistula [AVF], arteriovenous graft [AVG], peritoneal dialysis catheter [PD], and venous catheter), duration of dialysis, and clinical characteristics.ResultsPreemptive LDKT recipients constituted 30% of our cohort and were older, more likely to be White, more likely to have ESKD from polycystic kidney disease, and less likely to have ESKD from type 2 diabetes. Of the non-preemptive patients, 26% used AVF, 0.5% used AVG, 32% used peritoneal catheter, 11% used venous catheter, and 31% used more than one access type. Median (IQR) time on dialysis for AVF/AVG use was 1.86 (0.85-3.32) years; for PD catheters, 1.12 (0.55-1.92) years; for venous catheters, 0.66 (0.23-1.69) years; and for multimodal access, 2.15 (1.37-3.72) years.ConclusionsWe characterized the dialysis access landscape in LDKT recipients. Venous catheter and PD were the most popular modality in the first quartile of dialysis, and patients using these modalities had shorter times on dialysis compared with those with an AVF. Venous catheter or PD can be considered a viable bridge therapy in patients with living donor availability given their shorter waitlist times. Earlier referral of patients with living donor prospects might further minimize dialysis need.
| S-EPMC9255866 | biostudies-literature
Project description:BackgroundDialysis and kidney transplant patients are vulnerable populations for COVID-19 related disease and mortality.MethodsWe 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.ResultsSARS-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.ConclusionDialysis 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.
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