HIGHER ANTIBODY RESPONSE AFTER 2 VACCINATIONS WITH MRNA-1273 AS COMPARED WITH BNT162B2 AND AZD1222 IN HIGH-RISK KIDNEY PATIENTS

BACKGROUND AND AIMS: 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 SARSCoV- 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 receptorbinding domain of the spike protein of SARS-CoV-2 using the Sanquin anti-SARSCoV- 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 < .001), dialysis patients [1675 (573-3031) versus 636 (216-1416) BAU/mL;P < .001] and patients with CKD stages G4-G5 [2879 (1425-5311) versus 1063 (389-1939) BAU/mL;P < .001). In a similar pattern, mRNA-1273 demonstrated a higher antibody titer compared with AZD1222 (P < .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 < .001), dialysis patients (12% versus 29%;P = .007) and in patients with CKD G4- G5 (18% versus 67%, P < .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.

Long-term efficacy and safety of SARS-CoV-2 vaccination in patients with chronic kidney disease, on dialysis or after kidney transplantation: a national prospective observational cohort study.

BACKGROUND: COVID-19 is associated with increased morbidity and mortality in patients with chronic kidney disease (CKD) stages G4-G5, on dialysis or after kidney transplantation (kidney replacement therapy, KRT). SARS-CoV-2 vaccine trials do not elucidate if SARS-CoV-2 vaccination is effective in these patients. Vaccination against other viruses is known to be less effective in kidney patients. Our objective is to assess the efficacy and safety of various types of SARS-CoV-2 vaccinations in patients with CKD stages G4-G5 or on KRT. METHODS: In this national prospective observational cohort study we will follow patients with CKD stages G4-G5 or on KRT (n = 12,000) after SARS-CoV-2 vaccination according to the Dutch vaccination program. Blood will be drawn for antibody response measurements at day 28 and month 6 after completion of vaccination. Patient characteristics and outcomes will be extracted from registration data and questionnaires during 2 years of follow-up. Results will be compared with a control group of non-vaccinated patients. The level of antibody response to vaccination will be assessed in subgroups to predict protection against COVID-19 breakthrough infection. RESULTS: The primary endpoint is efficacy of SARS-CoV-2 vaccination determined as the incidence of COVID-19 after vaccination. Secondary endpoints are the antibody based immune response at 28 days after vaccination, the durability of this response at 6 months after vaccination, mortality and (serious) adverse events. CONCLUSION: This study will fulfil the lack of knowledge on efficacy and safety of SARS-CoV-2 vaccination in patients with CKD stages G4-G5 or on KRT. TRIAL REGISTRATION: The study protocol has been registered in clinicaltrials.gov ( NCT04841785 ). Current knowledge about this subject COVID-19 has devastating impact on patients with CKD stages G4-G5, on dialysis or after kidney transplantation. Effective SARS-CoV-2 vaccination is very important in these vulnerable patient groups. Recent studies on vaccination in these patient groups are small short-term studies with surrogate endpoints. Contribution of this study Assessment of incidence and course of COVID-19 after various types of SARS-CoV-2 vaccination during a two-year follow-up period in not only patients on dialysis or kidney transplant recipients, but also in patients with CKD stages G4-G5. Quantitative analysis of antibody response after SARS-CoV-2 vaccination and its relationship with incidence and course of COVID-19 in patients with CKD stages G4-G5, on dialysis or after kidney transplantation compared with a control group. Monitoring of (serious) adverse events and development of anti-HLA antibodies. Impact on practice or policy Publication of the study design contributes to harmonization of SARS-CoV-2 vaccine study methodology in kidney patients at high-risk for severe COVID-19. Data on efficacy of SARS-CoV-2 vaccination in patients with CKD will provide guidance for future vaccination policy.

Impact of the COVID-19 pandemic on symptoms of anxiety and depression and health-related quality of life in older patients with chronic kidney disease.

BACKGROUND: Older patients with advanced chronic kidney disease are at increased risk for a severe course of the coronavirus disease-2019 (COVID-19) and vulnerable to mental health problems. We aimed to investigate prevalence and associated patient (demographic and clinical) characteristics of mental wellbeing (health-related quality of life [HRQoL] and symptoms of depression and anxiety) before and during the COVID-19 pandemic in older patients with advanced chronic kidney disease. METHODS: An ongoing Dutch multicentre prospective cohort study enrols patients of ≥70 years with an eGFR < 20 mL/min/1.73m2 from October 2018 onward. With additional questionnaires during the pandemic (May-June 2020), disease-related concerns about COVID-19 and general anxiety symptoms were assessed cross-sectionally, and depressive symptoms, HRQoL, and emotional symptoms longitudinally. RESULTS: The 82 included patients had a median age of 77.5 years (interquartile range 73.9-82.1), 77% were male and none had tested positive for COVID-19. Cross-sectionally, 67% of the patients reported to be more anxious about COVID-19 because of their kidney disease, and 43% of the patients stated that their quality of life was reduced due to the COVID-19 pandemic. Compared to pre-COVID-19, the presence of depressive symptoms had increased (11 to 22%; p = .022) and physical HRQoL declined (M = 40.4, SD = 10.1 to M = 36.1, SD = 10.4; p < .001), particularly in males. Mental HRQoL (M = 50.3, SD = 9.6 to M = 50.4, SD = 9.9; p = .913) and emotional symptoms remained similar. CONCLUSIONS: Older patients with advanced chronic kidney disease suffered from disease-related anxiety about COVID-19, increased depressive symptoms and reduced physical HRQoL during the COVID-19 pandemic. The impact of the pandemic on this vulnerable patient group extends beyond increased mortality risk, and awareness of mental wellbeing is important. TRIAL REGISTRATION: The study is registered at the Netherlands Trial Register (NTR), trial number NL7104. Date of registration: 06-06-2018.

Impact of the COVID-19 pandemic on symptoms of anxiety and depression and health-related quality of life in older patients with chronic kidney disease

BACKGROUND AND AIMS: Older patients with advanced chronic kidney disease (CKD) are at increased risk for a severe course of the coronavirus disease-2019 (COVID-19) and vulnerable to mental health problems. We aimed to investigate prevalence and associated patient (demographic and clinical) characteristics of mental wellbeing (health-related quality of life [HRQoL] and symptoms of depression and anxiety) before and during the COVID-19 pandemic in older patients with advanced CKD. METHOD: An ongoing Dutch multicentre prospective cohort study enrols patients of ≥70 years with an eGFR <20 mL/min/1.73m2 from October 2018 onward. With additional questionnaires during the pandemic (May-June 2020), disease-related concerns about COVID-19 and general anxiety symptoms were assessed crosssectionally, and depressive symptoms, HRQoL, and emotional symptoms longitudinally. RESULTS: The 82 included patients had a median age of 77.5 years (inter-quartile range 73.9-82.1), 77% was male and none had tested positive for COVID-19. Crosssectionally, 67% of the patients reported to be more anxious for COVID-19 because of their kidney disease, and 43% of the patients stated that their quality of life was reduced due to the COVID-19 pandemic (Figure 1). Higher COVID-19-related stress was associated with a lower education level (p=0.036), and patients who reported to feel more down due to COVID-19 were more often female (p=0.020). Anxiety scores were higher among females compared to males (median 4.0 [IQR 3.0-9.0] versus 2.0 [0.0- 6.0], p=0.020), and weakly associated to a decline in eGFR (correlation coefficient 0.197, p=0.023). MO505 Figure 1: Respondents' agreement to the COVID-19 related statements. Questions were scored on a scale from 1 'totally disagree' to 5 'totally agree'. Mean score for question 1 was 3.6 (IQR 2.8-5.0) n=82, question 2 mean 2.7 (IQR 1.0-4.0) n=82, question 3 mean 2.3 (IQR 1.0-4.0) n=82, question 4 mean 2.7 (IQR 1.0-4.0) n=81.Compared to pre-COVID-19, presence of depressive symptoms had increased (11% to 22%;p=0.022) and physical HRQoL declined (40.4610.1 to 36.1610.4, p<0.001). Mental HRQoL (50.369.6 to 50.469.9;p=0.913) and emotional symptoms remained similar. Males showed a greater decline in physical HRQoL (mean -5.3, SD 8.5) compared to females (mean -0.9, SD 5.7;p=0.039). CONCLUSION: Our findings show that older patients with advanced CKD suffered from disease-related anxiety for COVID-19, increased depressive symptoms, and reduced physical HRQOL during the COVID-19 pandemic. The impact of the pandemic on this vulnerable patient group extends beyond increased mortality risk, and awareness of mental health problems during the pandemic is essential. More indepth investigation on disease-related COVID-19 concerns and its implications for the CKD population is needed.