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  • 1
    In: Nephrology Dialysis Transplantation, Oxford University Press (OUP), Vol. 37, No. 11 ( 2022-10-19), p. 2264-2274
    Abstract: Several guidelines recommend using the Clinical Frailty Scale (CFS) for triage of critically ill coronavirus disease 2019 (COVID-19) patients. This study evaluates the impact of CFS on intensive care unit (ICU) admission rate and hospital and ICU mortality rates in hospitalized dialysis patients with COVID-19. Methods We analysed data of dialysis patients diagnosed with COVID-19 from the European Renal Association COVID-19 Database. The primary outcome was ICU admission rate and secondary outcomes were hospital and ICU mortality until 3 months after COVID-19 diagnosis. Cox regression analyses were performed to assess associations between CFS and outcomes. Results A total of 1501 dialysis patients were hospitalized due to COVID-19, of whom 219 (15%) were admitted to an ICU. The ICU admission rate was lowest (5%) in patients & gt;75 years of age with a CFS of 7–9 and highest (27%) in patients 65–75 years of age with a CFS of 5. A CFS of 7–9 was associated with a lower ICU admission rate than a CFS of 1–3 [relative risk 0.49 (95% confidence interval 0.27–0.87)]. Overall, mortality at 3 months was 34% in hospitalized patients, 65% in ICU-admitted patients and highest in patients & gt;75 years of age with a CFS of 7–9 (69%). Only 9% of patients with a CFS ≥6 survived after ICU admission. After adjustment for age and sex, each CFS category ≥4 was associated with higher hospital and ICU mortality compared with a CFS of 1–3. Conclusions Frail dialysis patients with COVID-19 were less frequently admitted to the ICU. Large differences in mortality rates between fit and frail patients suggest that the CFS may be a useful complementary triage tool for ICU admission in dialysis patients with COVID-19.
    Type of Medium: Online Resource
    ISSN: 0931-0509 , 1460-2385
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 1465709-0
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  • 2
    In: Clinical Pharmacology & Therapeutics, Wiley, Vol. 114, No. 1 ( 2023-07), p. 118-126
    Abstract: Despite (repeated) boosting, kidney transplant recipients (KTRs) may remain at increased risk of severe COVID‐19 since a substantial number of individuals remain seronegative or with low antibody titers. In particular, mycophenolic acid use has been shown to affect antibody formation negatively and may be an important modifiable risk factor. We investigated the exposure–response relationship between mycophenolic acid 12‐hour area under the curve (AUC 0–12h ) exposure and seroconversion including antibody titers after vaccination using mRNA‐1273 SARS‐CoV‐2 vaccine (Moderna) in 316 KTRs from our center that participated in the national Dutch renal patients COVID‐19 vaccination – long term efficacy and safety of SARS‐CoV‐2 vaccination in kidney disease patients vaccination study. After two vaccination doses, 162 (51%) KTRs seroconverted. KTRs treated with mycophenolic acid showed less seroconversion and lower antibody titers compared with KTRs without mycophenolic acid (44% vs. 77%, and 36 binding antibody units (BAU)/mL vs. 340 BAU/mL; P   〈  0.001). The mean mycophenolic acid AUC 0–12h exposure was significantly lower in KTRs who seroconverted compared with KTRs who did not (39 vs. 29 mg⋅h/L; P   〈  0.001). High mycophenolic acid exposure (±90 mg⋅h/L) and no exposure to mycophenolic acid resulted in a seroconversion rate ranging from 10% to 80%. Every 10 mg⋅h/L increase in mycophenolic acid AUC 0–12h gave an adjusted odds ratio for seroconversion of 0.87 (95% confidence interval (CI), 0.79–0.97; P  = 0.010) and 0.89 (95% CI, 0.85–0.93; P   〈  0.001) for KTRs on dual and triple maintenance immunosuppressive therapy, respectively. Higher mycophenolic acid AUC 0–12h correlated with lower antibody titers (R = 0.44, P   〈  0.001). This study demonstrates the exposure–response relationship between gold standard mycophenolic acid exposure and antibody formation to support interventional studies investigating mycophenolic acid adjustment to improve antibody formation after further boosting.
    Type of Medium: Online Resource
    ISSN: 0009-9236 , 1532-6535
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2040184-X
    SSG: 15,3
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  • 3
    In: Nephrology Dialysis Transplantation, Oxford University Press (OUP), Vol. 38, No. Supplement_1 ( 2023-06-14)
    Abstract: Kidney transplant recipients (KTRs) remain at increased risk for severe COVID-19 after vaccination, most likely due to an impaired immune response. However, the exact clinical impact of this impaired response remains unclear. Therefore we analysed the relationship between antibody levels after vaccination and the occurrence and severity of COVID-19 in a large cohort of KTRs. Method All KTRs, living in the Netherlands, who received COVID-19 vaccination were invited to participate in this observational cohort study. At approximately 28 days after the 2nd vaccination blood samples were obtained by a home-based finger-prick method and analysed for IgG antibodies against the receptor-binding domain of the SARS-CoV-2 spike protein (anti-RBD IgG). Participants were classified as either seronegative or seropositive using an anti-RBD IgG threshold of 50 BAU/mL. Participants who previously experienced COVID-19 were excluded. Primary endpoint was the incidence of COVID-19 from the moment the blood sample for anti-RBD IgG measurement was obtained until 6 months thereafter. Multivariable Cox and logistic regression analyses were performed to analyse which factors affected the occurrence and the severity (i.e. hospitalization and/or death) of COVID-19. Results In total 12,159 KTR were approached of whom 3,828 agreed to participate. In 2,885 subjects successful antibody measurement was performed after the 2nd COVID-19 vaccination. Among those, 1,578 (54.7%) became seropositive, whereas 1,307 (45.3%) remained seronegative. During a follow-up of 6 months, seropositivity was associated with a lower risk for COVID-19 incidence, also after adjusting for age, sex, socio-economic status and adherence to COVID-19 restrictions (HR 0.48 (0.27-0.86), p = 0.01). COVID-19 was also significantly less severe in seropositive as compared to seronegative participants (OR 0.14 (0.03-0.67), p = 0.01). When studied on a continuous scale, we observed a log-linear relationship between antibody level and risk for COVID-19 incidence (HR 0.52 (0.31-0.89) per tenfold higher anti-RBD IgG antibody level, p = 0.02). A threshold above which optimal protection was offered could not be detected. A similar association was found for COVID-19 severity. Conclusion In conclusion, antibody level after COVID-19 vaccination is associated in a log-linear relationship with the occurrence and severity of COVID-19 in KTRs. Therefore higher antibody levels, and not only reaching seropositivity, should be the aim of COVID-19 vaccination in KTRs. Immunosuppressed patients who have no or low antibody levels after vaccination should be offered repeat vaccinations, whether or not via alternative vaccination strategies, or passive immunization.
    Type of Medium: Online Resource
    ISSN: 0931-0509 , 1460-2385
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1465709-0
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  • 4
    In: Nephrology Dialysis Transplantation, Oxford University Press (OUP), Vol. 37, No. Supplement_3 ( 2022-05-03)
    Abstract: during the COVID-19 pandemic, several guidelines have recommended the use of the Clinical Frailty Scale (CFS) for triage of critically ill patients with COVID-19 in case of shortage in ICU resources. However, no data on using CFS assessment for ICU triage for dialysis patients is yet available. This study evaluates whether CFS is associated with mortality rates in a cohort of hospitalized dialysis patients with COVID-19. METHOD the analyses are based on data of the European Renal Association COVID-19 Database (ERACODA). Dialysis patients who presented with COVID-19 between 1 February 2020 and 30 April 2021 and with complete information on CFS and vital status at 3 months were included. Study outcomes were hospital and ICU admission rates and hospital and ICU mortality at 3 months after hospital admission. Cox regression analyses were performed to assess the association of CFS category (≤5 versus ≥ 6) and study outcomes in line with Dutch ICU triage guidelines for COVID-19. Furthermore, additional subgroup analyses were performed to assess the association between CFS and 3-month mortality by age category ( & lt;65, 65–75 and  & gt;75 years). RESULTS among a total of 2206 dialysis patients (mean age = 67.2 (14.1) years, male sex = 61%), 1694 (77%) had CFS ≤ 5 and 514 (23%) had CFS ≥ 6. Hospitalization rate was comparable in patients with CFS ≤ 5 and in patients with CFS ≥ 6 (67 and 71%, respectively), whereas the rate of ICU admission was higher in patients with CFS ≤ 5 than in patients with CFS ≥ 6 (16 versus 9%, p = 0.001). Among 1501 hospitalized patients, 3-month mortality was 26% of patients with CFS ≤ 5 and 59% in patients with CFS ≥ 6 (P  & lt; 0.001). Multivariate analysis with adjustment for patient demographics, smoking status and BMI revealed that CFS ≥ 6 was associated with hospital mortality [aHR 2.27 (1.88–2.74) versus CFS ≤ 5; P  & lt; 0.001) with a significant interaction for age (P = 0.029). aHR was 4.00 (2.56–6.37; CFS ≥ 6 versus CFS ≤ 5; P  & lt; 0.001) in patients  & lt; 65 years, aHR was 1.87 (1.33–2.64; CFS ≥ 6 versus CFS ≤ 5; P  & lt; 0.001) in patients 65–75 years and aHR was 2.12 (1.64–2.75; CFS ≥ 6 versus CFS ≤ 5; P  & lt; 0.001) in patients & gt;75 years. Among 219 ICU admitted patients, 3-month mortality was 60% of the patients with CFS ≤ 5 and 91% in the patients with CFS ≥ 6, respectively. Multivariate analysis with adjustment for patient demographics, smoking status and BMI revealed that CFS ≥ 6 was associated with ICU mortality [aHR 1.80 (1.17–2.77); CFS ≥ 6 versus CFS ≤ 5; P = 0.002]. CONCLUSION more frail dialysis patients with CFS ≥ 6 who are hospitalized for COVID-19 were less often admitted to the ICU, but in case they were admitted to the ICU they have a very high mortality of 91% in this cohort study. In fit to mildly frail dialysis, patients who were admitted to the ICU, mortality rates are lower. The association between frailty and hospital mortality is interacted by age with the strongest association in patients younger than 65 years. These findings suggest that CFS may be a useful complementary triage tool for ICU admission of dialysis patients during the ongoing COVID-19 pandemic.
    Type of Medium: Online Resource
    ISSN: 0931-0509 , 1460-2385
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 1465709-0
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  • 5
    In: Clinical Kidney Journal, Oxford University Press (OUP), Vol. 16, No. 3 ( 2023-02-28), p. 528-540
    Abstract: Patients with chronic kidney disease (CKD) or kidney replacement therapy demonstrate lower antibody levels after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination compared with healthy controls. In a prospective cohort, we analysed the impact of immunosuppressive treatment and type of vaccine on antibody levels after three SARS-CoV-2 vaccinations. Methods Control subjects (n = 186), patients with CKD G4/5 (n = 400), dialysis patients (n = 480) and kidney transplant recipients (KTR) (n = 2468) were vaccinated with either mRNA-1273 (Moderna), BNT162b2 (Pfizer-BioNTech) or AZD1222 (Oxford/AstraZeneca) in the Dutch SARS-CoV-2 vaccination programme. Third vaccination data were available in a subgroup of patients (n = 1829). Blood samples and questionnaires were obtained 1 month after the second and third vaccination. Primary endpoint was the antibody level in relation to immunosuppressive treatment and type of vaccine. Secondary endpoint was occurrence of adverse events after vaccination. Results Antibody levels after two and three vaccinations were lower in patients with CKD G4/5 and dialysis patients with immunosuppressive treatment compared with patients without immunosuppressive treatment. After two vaccinations, we observed lower antibody levels in KTR using mycophenolate mofetil (MMF) compared with KTR not using MMF [20 binding antibody unit (BAU)/mL (3–113) vs 340 BAU/mL (50–1492), P  & lt; .001]. Seroconversion was observed in 35% of KTR using MMF, compared with 75% of KTR not using MMF. Of the KTR who used MMF and did not seroconvert, eventually 46% seroconverted after a third vaccination. mRNA-1273 induces higher antibody levels as well as a higher frequency of adverse events compared with BNT162b2 in all patient groups. Conclusions Immunosuppressive treatment adversely affects the antibody levels after SARS-CoV-2 vaccination in patients with CKD G4/5, dialysis patients and KTR. mRNA-1273 vaccine induces a higher antibody level and higher frequency of adverse events.
    Type of Medium: Online Resource
    ISSN: 2048-8505 , 2048-8513
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2656786-6
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  • 6
    In: Journal of Nephrology, Springer Science and Business Media LLC, Vol. 36, No. 7 ( 2023-08-22), p. 2037-2046
    Abstract: The mental health of dialysis patients during the COVID-19 pandemic may have been modulated by dialysis modality. Studies comparing mental health of in-center hemodialysis and peritoneal dialysis patients during the first 2 years of the pandemic are lacking. Methods We conducted repeated cross-sectional and multivariable regression analyses to compare the mental health of in-center hemodialysis and peritoneal dialysis patients from March 2019 until August 2021 using data from the Dutch nOcturnal and hoME dialysis Study To Improve Clinical Outcomes. The study period was divided into one pre-pandemic and six 3-month pandemic periods (period 1–period 6). Mental health was assessed with the Mental Component Summary score of the 12-item Short Form health survey and mental symptoms of the Dialysis Symptom Index. Results We included 1274 patients (968 on in-center hemodialysis and 306 on peritoneal dialysis). Mental Component Summary scores did not differ between in-center hemodialysis and peritoneal dialysis patients. In contrast, in-center hemodialysis patients more often reported nervousness during period 3 (27% vs 15%, P  = 0.04), irritability and anxiety during period 3 (31% vs 18%, P  = 0.03, 26% vs. 9%, P  = 0.002, respectively) and period 4 (34% vs 22%, P  = 0.04, 22% vs 11%, P  = 0.03, respectively), and sadness in period 4 (38% vs 26%, P  = 0.04) and period 5 (37% vs 22%, P  = 0.009). Dialysis modality was independently associated with mental symptoms. Conclusions In-center hemodialysis patients more often experienced mental symptoms compared to peritoneal dialysis patients from September 2020 to June 2021, which corresponds to the second lockdown of the COVID-19 pandemic. Mental health-related quality-of-life did not differ between in-center hemodialysis and peritoneal dialysis patients. Trial registration number Netherlands Trial Register NL6519, date of registration: 22 August, 2017. Graphical abstract
    Type of Medium: Online Resource
    ISSN: 1724-6059
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 1475007-7
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  • 7
    In: Nephrology Dialysis Transplantation, Oxford University Press (OUP), Vol. 38, No. Supplement_1 ( 2023-06-14)
    Abstract: Results from previous studies suggest that mental health of dialysis patients was unaffected during the first wave of the COVID-19 pandemic. However, the location of dialysis treatment might have had a different impact on patients during the ongoing COVID-19 pandemic, especially at time of restrictions. Studies comparing the mental health of ICHD and PD patients during the pandemic are scarce. Therefore, we aimed to assess whether dialysis modality differently affected the mental health of patients during the COVID-19 pandemic. Method This study used data of patients participating in the Dutch nOcturnal and hoME dialysis Study To Improve Clinical Outcomes (DOMESTICO). We conducted repeated cross-sectional analyses between ICHD and PD patients from the start of the COVID-19 pandemic in March 2020 until August 2021. For this, we divided the study period into six periods of three months. The year before the pandemic was used as reference period. Mental health-related quality of life (HRQOL) was assessed using the mental component summary (MCS) score of the 12-item Short Form (SF-12) health survey. The presence of mental symptoms was determined using the Dialysis Symptom Index (DSI). Both questionnaires were provided at start of dialysis, at 3 months, 6 months and each 6 months thereafter. Patients were included for analysis if a questionnaire was available in at least one period. MCS scores and the prevalence of mental symptoms between ICHD and PD patients were compared with Student's t-test and Chi-square test, respectively. Moreover, we performed multivariable regression analyses to adjust for possible confounders. Results For this analysis, 1274 patients (968 ICHD and 306 PD) were included. Mean age was 65±14 and 64±14 years, respectively. Most patients were male (ICHD: 68%, PD: 61%). Before the pandemic ICHD patients reported similar MCS scores, yet more often reported feeling nervous (32% vs. 22%, P = .03) and sad (40% vs. 29%, P = .03). During the pandemic, mean MCS scores also did not differ between ICHD and PD patients. In contrast, ICHD patients more often reported feeling nervous during period 3 (27% vs 15%, P = .04), feeling irritable and anxious during period 3 (31% vs 18%, P = .03, 26% vs. 9%, P = .002, resp.) and period 4 (34% vs 22%, P = .04, 22% vs 11%, P = .03, resp.), and feeling sad in period 4 (38% vs 26%, P = .04) and period 5 (37% vs 22%, P = .009). In a multivariable regression analysis, these differences persisted after correction for several confounders. Conclusion ICHD patients experienced more mental symptoms compared to PD patients in the period September 2020 to June 2021, which corresponds with the second lockdown of the COVID-19 pandemic. This higher prevalence of specific mental symptoms in ICHD patients was not reflected by a decrease in mental HRQoL.
    Type of Medium: Online Resource
    ISSN: 0931-0509 , 1460-2385
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1465709-0
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  • 8
    In: Nephrology Dialysis Transplantation, Oxford University Press (OUP), Vol. 38, No. Supplement_1 ( 2023-06-14)
    Abstract: The prevalence of post-COVID-19 condition (PCC) is estimated to be 13% in healthy individuals. We analyzed the prevalence and disease burden of PCC in patients with chronic kidney disease (CKD) G4/5, dialysis patients and kidney transplant recipients (KTR). Method Patients participated in the RECOVAC study, in which SARS-CoV-2 antibodies were measured in CKD G4/5, dialysis patients and KTR after the second and third COVID-19 vaccination in the Netherlands. A questionnaire was sent to 4868 participants one year after initial vaccination asking for the presence of long-lasting symptoms after diagnosis in COVID-19 positive patients, or since the start of the pandemic in COVID-19 negative patients. PCC was defined according to the WHO clinical case definition. Blood samples at one month after the second and third vaccination were analysed with anti-RBD IgG ELISA. COVID-19 diagnosis was assessed by questionnaire or positive anti-nucleocapsid IgG antibodies. Logistic regression analysis was used to compare the presence of one or more long-lasting symptoms between COVID-19 positive and negative patients. In COVID-19 positive patients, we likewise identified predictors of PCC by backward selection and estimated the association between log-transformed antibody levels and PCC. Results 2747 patients were included, of which 222 patients with CKD G4/5, 390 dialysis patients and 2135 KTR. PCC was present in 25%, 16%, and 21% of CKD G4/5 patients, dialysis patients and KTR with high or very high symptom burden in 57%, 61% and 71%, respectively. In COVID-19 negative patients, long-lasting symptoms were present in 15%, 13% and 18%, respectively. COVID-19 positive patients (n = 1004) were at higher odds of having one or more long-lasting symptoms compared with COVID-19 negative patients (n = 1743) (OR: 1.33 [1.09–1.61], p = .005). Predictors of PCC were chronic lung disease (adjusted OR 2.04 [1.18#x2013;3.50] , p = .01) and hospital/ICU admission (adjusted OR 5.03 [3.22-7.86], p & lt; .001). Log anti-RBD IgG antibody level was negatively associated with PCC (adjusted OR: 0.79 [0.66#x2013;0.94], p = .008). Conclusion Patients with CKD G4/5, dialysis patients and KTR are at risk for PCC with a high symptom burden, especially if antibody levels after COVID-19 vaccination are low.
    Type of Medium: Online Resource
    ISSN: 0931-0509 , 1460-2385
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1465709-0
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  • 9
    In: Nephrology Dialysis Transplantation, Oxford University Press (OUP), Vol. 37, No. Supplement_3 ( 2022-05-03)
    Abstract: Lower antibody responses after SARS-Cov-2 vaccination have been reported in patients with severely impaired kidney function or patients with kidney replacement treatment. We compared humoral responses and reported adverse events of three vaccines (mRNA-1273, BNT162b2 and AZD1222) in kidney transplant recipients (KTRs), dialysis patients, patients with CKD stages G4–G5 and control subjects without kidney disease. METHOD KTRs, dialysis patients and patients with CKD stages G4–G5 were vaccinated with either mRNA-1273, BNT162b2 or AZD1222 during the Dutch SARS-CoV-2 vaccination program. Control subjects were all vaccinated with mRNA-1273. Blood samples were obtained at 1 month after two vaccinations by home-based finger prick tests and were analysed for the presence of IgG antibodies against the receptor-binding domain of the spike protein of SARS-CoV-2 using the Sanquin anti-SARS-CoV-2 RBD IgG ELISA assay. Primary endpoints were the antibody titer and reported systemic adverse events (AEs) at 1 month after the second vaccination. Multivariate regression analysis was performed on the difference between vaccines with respect to antibody titer and AEs after correction for sex, ethnicity, BMI, eGFR, dialysis vintage, transplantation characteristics and use of immunosuppressive drugs. RESULTS A total of 2468 KTRs, 480 dialysis patients, 400 patients with CKD stages G4–G5 and 186 control subjects were enrolled. KTRs had lower antibody titers (66 [8–573] BAU/mL) in comparison to dialysis patients [1375 (431–2896) BAU/mL] , patients with CKD stages G4–G5 [2097 (828–4077) BAU/mL] and control subjects [3713 (2291–6451) BAU/mL] . mRNA-1273 demonstrated a higher antibody titer compared with BNT162b2 in KTR [72 (9–638) versus 21 (6–128) BAU/mL; P  & lt; .001), dialysis patients [1675 (573–3031) versus 636 (216–1416) BAU/mL; P  & lt; .001] and patients with CKD stages G4–G5 [2879 (1425–5311) versus 1063 (389–1939) BAU/mL; P  & lt; .001). In a similar pattern, mRNA-1273 demonstrated a higher antibody titer compared with AZD1222 (P  & lt; .001 in all groups). Multivariate analysis revealed that BNT162b2 and AZD1222 were significantly associated with lower antibody levels compared with mRNA-1273 in all 3 patient groups. BNT162b2 demonstrated less frequently systemic AEs compared with mRNA-1273 in KTRs (12% versus 27%; P  & lt; .001), dialysis patients (12% versus 29%; P = .007) and in patients with CKD G4–G5 (18% versus 67%, P  & lt; .001). AZD1222 demonstrated less systemic AEs compared with mRNA-1273 only in patients with CKD stages G4–G5 (39% versus 67%; P = .03). Multivariate analysis revealed that BNT162b2 was associated with fewer systemic AEs in only dialysis patients (P = .04) and patients with CKD stages G4–G5 (P = .02). CONCLUSION mRNA-1273 demonstrated significantly higher antibody levels at 1 month after 2 vaccinations as compared with BNT162b2 and AZD1222 in high-risk patients with kidney disease. BNT162b2 was associated with a fewer systemic AEs in dialysis patients and patients with CKD stages G4–G5, although these AEs were mild and self-limiting. mRNA-1273 may therefore be considered as the preferred SARS-CoV-2 vaccine in high-risk patients with kidney disease. Whether the higher antibody response following vaccination with mRNA-1273 sustains and results in a better protection against COVID-19 is yet to be analysed.
    Type of Medium: Online Resource
    ISSN: 0931-0509 , 1460-2385
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 10
    In: eClinicalMedicine, Elsevier BV, Vol. 62 ( 2023-08), p. 102103-
    Type of Medium: Online Resource
    ISSN: 2589-5370
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 2946413-4
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