The Effect of a Booster Dose mRNA Vaccine on COVID-19 Infection in Kidney Transplant Recipients after Inactivated or Viral Vector Vaccine Immunization.

The mortality rate after novel coronavirus infection, which causes severe acute respiratory distress syndrome (SARS-CoV-2), is much higher in kidney transplant recipients (KTRs) compared to the general population. Seroconversion after vaccination is also lower, and breakthrough infection is much higher. Many studies reported seroconversion rate after a booster (third) dose of vaccine but clinical outcomes received less attention. Here, we reported the impact of an mRNA vaccine booster dose on clinical outcomes of KTRs with SARS-CoV-2 infection. A total of 183 KTRs with SARS-CoV-2 infection were identified. Of 183 KTRs, 146 KTRs had sufficient data for analysis and were included in this study. Forty-eight patients (32.9%) received zero to 1 doses of vaccine (Group 1), thirty-one (21.2%) received two doses (Group 2), and sixty-seven (45.9%) received a booster dose (Group 3). Pneumonia developed in 50%, 23%, and 10% in Group 1, 2, and 3 (p < 0.001). Hospital admission requirement was 81%, 48%, and 12% (p < 0.001). Mortality rate was 26%, 3%, and 3% (p = 0.001). A multivariate analysis showed that only diabetes adversely affects mortality while the booster dose of the vaccine significantly reduced mortality. The booster dose of the vaccine is strongly recommended in all KTRs especially those with diabetes. Our study also suggested the timing of the booster dose vaccine to be administered within 4 months after the second dose.

Humoral Immune Response of the Additional Chadox1 NCOV-19 Vaccine Following a Two-Dose Inactivated Whole-Virus SARS-COV-2 Vaccination in Patients on Dialysis

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.

Benefits of Inactivated Vaccine and Viral Vector Vaccine Immunization on COVID-19 Infection in Kidney Transplant Recipients.

The coronavirus virus disease 2019 (COVID-19) pandemic has impacted the global healthcare system. In Thailand, the first and most available vaccines were inactivated and viral vector vaccines. We reported the impact of those vaccines in preventing severe disease and death in kidney transplant recipients. This retrospective study comprised 45 kidney transplant recipients with COVID-19 infection, classified by vaccination status. Outcomes of interest were death, pneumonia, and allograft dysfunction. There were 23 patients in vaccinated group and 22 patients in unvaccinated group. All baseline characteristics were similar except mean age was older in vaccinated group, 55 vs. 48 years. Total 11 patients (24%) died (13% vaccinated vs. 36% unvaccinated RR, 0.56; 95% CI, 0.29-0.83; p = 0.03). Multivariate analysis showed that vaccination significantly decrease mortality (odds ratio, 0.54; 95% CI, 0.10-0.94; p = 0.03). Pneumonia developed equally in both groups (70%). There was a trend toward less oxygen requirement as well as ventilator requirement in vaccinated group. The rate of allograft dysfunction was similar (47%). Inactivated and viral vector COVID-19 vaccines have beneficial effect on mortality reduction in kidney transplant recipients. Even partial vaccination can exert some protection against death. However, full vaccination should be encouraged to achieve better prevention.

Immunogenicity of ChAdOx1 nCoV-19 vaccine after a two-dose inactivated SARS-CoV-2 vaccination of dialysis patients and kidney transplant recipients.

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).

SARS-CoV-2-specific humoral and cell-mediated immune responses after immunization with inactivated COVID-19 vaccine in kidney transplant recipients (CVIM 1 study).

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).