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Background: The fatality rates and factors associated with death from coronavirus disease 2019 (COVID-19) in hemodialysis patients have been extensively investigated. However, data on peritoneal dialysis (PD) patients remain scarce. Materials and methods: In this nationwide cohort study, we assessed the 28-day COVID-19-related fatality rate in PD patients between August 2021 and July 2022 using data from the InCov19-PD registry. Predictors associated with death were evaluated using a multivariable Cox regression model. Changes in functional status before and during COVID-19 were also examined. Results: A total of 1,487 eligible participants were evaluated. During the study period, 196 participants died within 28 days after COVID-19 diagnosis (case fatality rate: 13%). In a multivariable Cox regression model, an increased risk of death within 28 days after COVID-19 diagnosis among PD patients was independently associated with functional impairment during COVID-19 [adjusted hazard ratio (HR) 2.46, 95% confidence interval (CI) 1.59-3.81], SARS-CoV-2 infection with the Delta variant (HR 2.23, 95% CI 1.55-3.21), and the need for respiratory support (HR 7.13, 95% CI 3.74-13.57) (p < 0.01 for all). Conversely, the number of COVID-19 vaccines administered (HR 0.69, 95% CI 0.55-0.87; p = 0.001) and receiving corticosteroid therapy during COVID-19 (HR 0.72, 95% CI 0.54-0.97; p = 0.03) were associated with a decreased risk of death within 28 days after COVID-19 diagnosis. The number of functionally independent PD patients dropped from 94% at baseline to 63% during COVID-19 (p < 0.01). Conclusions: The COVID-19-related 28-day fatality rate was high among PD patients. The predictors of COVID-19-related death in PD patients were similar to those in hemodialysis patients. During COVID-19, PD patients commonly experienced functional deterioration.
ABSTRACT
Background The fatality rates and factors associated with death from coronavirus disease 2019 (COVID-19) in hemodialysis patients have been extensively investigated. However, data on peritoneal dialysis (PD) patients remain scarce. Materials and methods In this nationwide cohort study, we assessed the 28-day COVID-19-related fatality rate in PD patients between August 2021 and July 2022 using data from the InCov19-PD registry. Predictors associated with death were evaluated using a multivariable Cox regression model. Changes in functional status before and during COVID-19 were also examined. Results A total of 1,487 eligible participants were evaluated. During the study period, 196 participants died within 28 days after COVID-19 diagnosis (case fatality rate: 13%). In a multivariable Cox regression model, an increased risk of death within 28 days after COVID-19 diagnosis among PD patients was independently associated with functional impairment during COVID-19 [adjusted hazard ratio (HR) 2.46, 95% confidence interval (CI) 1.59–3.81], SARS-CoV-2 infection with the Delta variant (HR 2.23, 95% CI 1.55–3.21), and the need for respiratory support (HR 7.13, 95% CI 3.74–13.57) (p < 0.01 for all). Conversely, the number of COVID-19 vaccines administered (HR 0.69, 95% CI 0.55–0.87;p = 0.001) and receiving corticosteroid therapy during COVID-19 (HR 0.72, 95% CI 0.54–0.97;p = 0.03) were associated with a decreased risk of death within 28 days after COVID-19 diagnosis. The number of functionally independent PD patients dropped from 94% at baseline to 63% during COVID-19 (p < 0.01). Conclusions The COVID-19-related 28-day fatality rate was high among PD patients. The predictors of COVID-19-related death in PD patients were similar to those in hemodialysis patients. During COVID-19, PD patients commonly experienced functional deterioration.
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BACKGROUND AND AIMS Patients with end-stage kidney disease (ESKD) are at risk of coronavirus disease 2019 infection and its associated complications. A previous study demonstrated that patients with ESKD on dialysis generated suboptimal humoral immune response (HIR) and lower seroconversion rate after two-dose inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination as compared to healthy individuals. In this study, we examined HIR of the additional dose of ChAdOx1 nCoV-19 vaccine following a standard two-dose inactivated whole-virus SARS-CoV-2 vaccination in patients on dialysis, and compared to those of healthy controls. METHOD We recruited 59 patients with ESKD [31 patients on haemodialysis (HD) and 28 on peritoneal dialysis (PD)) and 16 healthy controls who received two doses of inactivated SARS-CoV-2 vaccine (V2) from Ramathibodi hospital and Banphaeo General Hospital, Bangkok, Thailand, from July 2021 to September 2021. All participants were administered a third dose of the ChAdOx1nCoV-19 vaccine (V3) with a 6-week interval between the V2 to V3. HIR was measured 2 weeks after V2 and V3 using SARS-CoV-2 immunoglobulin G (IgG) assay, which detects antibodies against the S1 receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. Median anti-RBD IgG titer and seroconversion rate, defined as anti-RBD IgG titre ≥ 7.1 BAU/mL, were compared among ESKD patients and to those of healthy controls using the Kruskal–Wallis H test and the chi-squared test, respectively. RESULTS Baseline characteristics of patients on HD, PD and healthy controls are shown in Table 1. Demographic characteristics and baseline laboratory parameters were comparable between the HD and PD groups, except for a lower mean serum albumin level in the PD group (P < .001). None of the healthy controls were immunocompromised or receiving immunosuppressive therapies.Table 1.Clinical characteristics, n (%) HD (n = 31)PD (n = 28)Controls (n = 16)Age, years45 (10)41 (12)41 (9)Male, n (%) 23 (74)17 (61)5 (31)Body mass index, kg/m226 (5)24 (4)27 (6)Charlson Comorbidity Index, median (IQR) 3 (3–5)2.5 (2–4)0Comorbidities, n (%) Diabetes mellitus HypertensionCardiovascular disease 14 (45)24 (77)7 (23)7 (25)25 (89)2 (7)1 (6)2 (13)0 Causes of ESKD, n (%) Diabetic nephropathy Hypertensive nephropathy Others Unknown6 (19)3 (10)5 (16)14 (45)5 (18)8 (29)8 (29)7 (25)NADialysis vintage, months, median (IQR)33 (17–84)34 (7–57)NATotal Kt/Vurea1.6 (0.3)2.0 (0.4)NALaboratories White blood cells, × 109/L Absolute lymphocyte count, × 109/L Haemoglobin, g/dL Ferritin, ng/mL, median (IQR) Albumin, g/L6.9 (1.9)1.6 (0.5)11 (2)301 (119–441)40 (4)7.3 (2.8)1.5 (0.8)10 (2)367 (156–751)33 (4)*7.7 (2.4)2.2 (0.9)NANANA *P < .05. At 2 weeks after V3, the median anti-RBD IgG titres were significantly increased in all groups compared to those levels after V2 (85[33–412] versus 1566 [861–3083] BAU/mL for patients on HD, 81 [15–144] versus 913 [293–1359] BAU/mL for patients on PD and 250 [92–603] versus 2210 [1531–2782] BAU/mL for healthy controls;P < .001 for all groups). Comparing antibody levels between groups after V3, patients on PD generated significantly lower anti-RBD IgG titer than patients on HD (P = .02) and healthy controls (P < .01) (Figure 1A). The seroconversion rate of the HD and PD groups improved from 94% and 82% after V2 to 100% after V3 in both groups (P = .16 and P = .03, respectively) (Figure 1B). All patients on dialysis who had anti-RBD IgG < 7.1 BAU/mL after V2 (7/59 patients) seroconverted after the additional dose of ChAdOx1 nCoV-19 vaccine. CONCLUSION We suggest that an additional ChAdOx1 nCoV-19 vaccine after a primary two doses inactivated SARS-CoV-2 vaccination could improve seroconversion rate and magnitude of humoral immune response in patients on dialysis. The durability of the immune response to this vaccination regimen requires further study.
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Immunogenicity following an additional dose of Coronavirus disease 2019 (COVID-19) vaccine was investigated in an extended primary series among kidney transplant (KT) recipients. Eighty-five KT participants were randomized to receive either an mRNA (M group; n = 43) or viral vector (V group; n = 42) vaccine. Among them, 62% were male, with a median (IQR) age of 50 (43-59) years and post-transplantation duration of 46 (26-82) months. At 2 weeks post-additional dose, there was no difference in the seroconversion rate between the M and V groups (70% vs. 65%, p = .63). A median (IQR) of anti-RBD antibody level was not statistically different between the M group compared with the V group (51.8 [5.1-591] vs. 28.5 [2.9-119.3] BAU/ml, p = .18). Furthermore, the percentage of participants with positive SARS-CoV-2 surrogate virus neutralization test results was not statistically different between groups (20% vs. 15%, p = .40). S1-specific T cell and RBD-specific B cell responses were also comparable between the M and V groups (230 [41-420] vs. 268 [118-510], p = .65 and 2 [0-10] vs. 2 [0-13] spot-forming units/106 peripheral blood mononuclear cells, p = .60). In conclusion, compared with an additional dose of viral vector COVID-19 vaccine, a dose of mRNA COVID-19 vaccine did not elicit significantly different responses in KT recipients, regarding either humoral or cell-mediated immunity. (TCTR20211102003).
Subject(s)
COVID-19 , Kidney Transplantation , Viral Vaccines , Male , Humans , Middle Aged , Female , COVID-19 Vaccines , SARS-CoV-2 , RNA, Messenger/genetics , Leukocytes, Mononuclear , COVID-19/epidemiology , COVID-19/prevention & control , Transplant Recipients , Antibodies, ViralABSTRACT
The durability of a three-dose extended primary series of COVID-9 vaccine in dialysis patients remains unknown. Here, we assessed dynamic changes in SARS-CoV-2-specific humoral and cell-mediated immunity at baseline, 3 months, and 6 months after the extended primary series in 29 hemodialyzed (HD), 28 peritoneal dialyzed (PD) patients, and 14 healthy controls. Participants received two doses of inactivated SARS-CoV-2 vaccine followed by a dose of ChAdOx1 nCoV-19 vaccine. At 6 months, median anti-RBD IgG titers (IQR) significantly declined from baseline in the HD (1741 (1136-3083) BAU/mL vs. 373 (188-607) BAU/mL) and PD (1093 (617-1911) BAU/mL vs. 180 (126-320) BAU/mL) groups, as did the mean percent inhibition of neutralizing antibodies (HD: 96% vs. 81%; PD: 95% vs. 73%) (all p < 0.01). Age and post-vaccination serological response intensity were predictors of early humoral seroprotection loss. In contrast, cell-mediated immunity remained unchanged. In conclusion, humoral immunity declined substantially in dialysis patients, while cell-mediated immunity remained stable 6 months after the extended heterologous primary series of two inactivated SARS-CoV-2/ChAdOx1 nCoV-19 vaccine. A booster dose could be considered in dialysis patients 3 months after this unique regimen, particularly in the elderly or those with a modest initial humoral response.
ABSTRACT
Vaccination with inactivated SARS-CoV-2 virus produces suboptimal immune responses among kidney transplant (KT), peritoneal dialyzed (PD), and hemodialyzed (HD) patients. Participants were vaccinated with two-dose inactivated SARS-CoV-2 vaccine (V2) and a third dose of ChAdOx1 nCoV-19 vaccine (V3) at 1-2 months after V2. We enrolled 106 participants: 31 KT, 28 PD, and 31 HD patients and 16 controls. Among KT, PD, and HD groups, median (IQR) of anti-receptor binding domain antibody levels were 1.0 (0.4-26.8), 1092.5 (606.9-1927.2), and 1740.9 (1106-3762.3) BAU/mL, and percent neutralization was 0.9 (0-9.9), 98.8 (95.9-99.5), and 99.4 (98.8-99.7), respectively, at two weeks after V3. Both parameters were significantly increased from V2 across all groups (p < 0.05). Seroconversion and neutralization positivity rates in PD, HD, and control groups were 100% but were impaired in KT patients (39% and 16%, respectively). S1-specific T-cell counts were increased in PD and HD groups (p < 0.05) but not in KT patients. The positive S1-specific T-cell responder rate was > 90% in PD, HD, and control groups, which was higher than that in KT recipients (74%, p < 0.05). The heterologous inactivated virus/ChAdOx1 nCoV-19 vaccination strategy elicited greater immunogenicity among dialysis patients; however, inadequate responses remained among KT recipients (TCTR20210226002).
Subject(s)
COVID-19 Vaccines/immunology , Kidney Transplantation , Renal Dialysis , SARS-CoV-2/immunology , Antibodies, Viral/blood , COVID-19 Vaccines/administration & dosage , HumansABSTRACT
Immunogenicity following inactivated SARS-CoV-2 vaccination among solid organ transplant recipients has not been assessed. Seventy-five patients (37 kidney transplant [KT] recipients and 38 healthy controls) received two doses, at 4-week intervals, of an inactivated whole-virus SARS-CoV-2 vaccine. SARS-CoV-2-specific humoral (HMI) and cell-mediated immunity (CMI) were measured before, 4 weeks post-first dose, and 2 weeks post-second dose. The median (IQR) age of KT recipients was 50 (42-54) years and 89% were receiving calcineurin inhibitors/mycophenolate/corticosteroid regimens. The median (IQR) time since transplant was 4.5 (2-9.5) years. Among 35 KT patients, the median (IQR) of anti-RBD IgG level measured by CLIA after vaccination was not different from baseline, but was significantly lower than in controls (2.4 [1.1-3.7] vs. 1742.0 [747.7-3783.0] AU/ml, p < .01) as well as percentages of neutralizing antibody inhibition measured by surrogate viral neutralization test (0 [0-0] vs. 71.2 [56.8-92.2]%, p < .01). However, the median (IQR) of SARS-CoV-2 mixed peptides-specific T cell responses measured by ELISpot was significantly increased compared with baseline (30 [4-120] vs. 12 [0-56] T cells/106 PBMCs, p = .02) and not different from the controls. Our findings revealed weak HMI but comparable CMI responses in fully vaccinated KT recipients receiving inactivated SARS-CoV-2 vaccination compared to immunocompetent individuals (Thai Clinical Trials Registry, TCTR20210226002).
Subject(s)
COVID-19 , Kidney Transplantation , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Immunity, Cellular , Middle Aged , SARS-CoV-2 , Transplant Recipients , VaccinationABSTRACT
INTRODUCTION: Patients with end-stage kidney disease (ESKD) are at risk of severe coronavirus disease and mortality. Immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inactivated whole-virus vaccine in patients with ESKD has never been explored. METHODS: We conducted a prospective cohort study of 60 patients with ESKD and 30 healthy controls. All participants received two doses of an inactivated whole-virus SARS-CoV-2 vaccine (Sinovac Biotech Ltd) 4 weeks apart. SARS-CoV-2-specific humoral and cell-mediated immune responses were investigated and referenced with healthy controls. RESULTS: After two doses, an anti-receptor-binding domain immunoglobulin G of 50 AU/ml or greater was present in 53 of 60 patients (88%) in the ESKD group and all participants (100%) in the control group (P = 0.05). The percentage of patients with ESKD and controls with neutralizing antibodies of 35% threshold or greater was 58% and 88%, respectively (P = 0.01). Furthermore, the proportion of patients with ESKD and S1-specific T cell response was comparable with controls (82% vs. 77%, P = 0.45). Old age, high ferritin level, and low absolute lymphocyte count were independently associated with poor humoral immune responses. CONCLUSIONS: Patients with ESKD could develop similar SARS-CoV-2-specific cell-mediated immune responses compared to healthy controls, although suboptimal humoral immune responses were observed following two doses of SARS-CoV-2 vaccination. Therefore, patients with ESKD and the abovementioned factors are at risk of generating inadequate humoral immune responses, and a vaccine strategy to elicit greater immunogenicity among these relatively immunocompromised patients is warranted. (Thai Clinical Trials Registry, TCTR20210226002).