To the editor:
Patients with end-stage kidney disease (ESKD) are at greater risk for morbidity and mortality following coronavirus disease 2019 (COVID-19) than the general population.1 Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for this vulnerable population is the main priority to prevent COVID-19 and mitigate unfavorable or severe complications. However, the immune responses to vaccination in patients with ESKD may be altered by accumulation of uremic toxins and comorbidities.2 Currently, the effectiveness and safety profiles of immunization with SARS-CoV-2 vaccines in patients on maintenance dialysis remain poorly understood.
Several studies reported variable humoral and cellular responses to different platforms of the approved SARS-CoV-2 vaccine in chronic dialysis patients.3, 4, 5, 6, 7 Preliminary studies revealed that most patients with ESKD receiving maintenance dialysis developed decent seroconversion after the second vaccine dose. However, most immunogenicity and safety data against SARS-CoV-2 in these susceptible individuals mainly derived from the mRNA or adenoviral-vectored vaccines. Presently, the effects of immunization with an inactivated whole-virus SARS-CoV-2 vaccine among patients on maintenance dialysis have not been evaluated.
A pilot, multicenter, prospective study of patients with ESKD on maintenance dialysis who received a 2-dose immunization, administered at a 4-week interval, of an inactivated whole-virus SARS-CoV-2 vaccine, CoronaVac (Sinovac Biotech Ltd), was conducted from April 2021 to July 2021. SARS-CoV-2–specific humoral response was measured at baseline before administering the vaccine, 4 weeks after the first dose, and 2 weeks after the second dose, using a semiquantitative SARS-CoV-2 IgG assay (Abbott Diagnostics), which detects IgG antibodies against the receptor-binding domain (RBD) of the S1 spike antigen of SARS-CoV-2. The level of anti-RBD antibody was reported in arbitrary units per milliliter (AU/ml). Those humoral responses were also referenced to healthy controls. The study was approved by the Institutional Review Board of the Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand (MURA2021/242). All patients provided written informed consent before participation.
A total of 60 patients with ESKD on maintenance dialysis, and 30 healthy controls, aged between 18 and 59 years, were recruited into the study. A total of 29 and 31 patients received peritoneal dialysis (PD) and regular maintenance hemodialysis (HD) treatment, respectively. Of patients with ESKD, 67% were men, with a mean age (SD) of 42.1 (10.4) years. The median dialysis vintage for the PD and HD groups was 32.2 months (interquartile range, 7.0–55.1 months) and 32.6 months (interquartile range, 17.3–83.5 months; P = 0.35), respectively. The median Charlson Comorbidity Index scores of both groups were 3 (interquartile range, 2–4). A total of 45% in the HD group and 24% in the PD group carried underlying diabetes mellitus. The per-session average dialyzer urea clearance (Kt/Vurea) was 1.6 for the HD group, and the total average weekly Kt/Vurea was 2.0 for the PD group. A total of 36% of the HD group and 51% of the PD group used either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers as an antihypertensive medication, respectively. At 2 weeks after the second dose of vaccine, a median (95% confidence interval [CI]) of anti-RBD IgG antibody was significantly greater in the healthy controls than patients with ESKD: 1767 (95% CI, 312–7870) versus 590 (95% CI, 219–1427) AU/ml (P <0.01; Figure 1 ).
Figure 1.
A median with an interquartile range of anti–receptor-binding domain (RBD) IgG antibody in patients with end-stage kidney disease (ESKD) and healthy controls at 2 weeks after the second dose of inactivated whole-virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. ∗P < 0.05. AU, arbitrary unit.
In comparison, the median anti-RBD IgG antibody response elicited by a 2-dose form of an inactivated whole-virus SARS-CoV-2 vaccine was comparable between the HD and the PD groups: 601 (95% CI, 20–4145) versus 537 (95% CI, 20–1783) AU/ml (P = 0.10; Figure 2 ). Seroconversion rates, defined by anti-RBD IgG level >50 AU/ml, were slightly better in patients on maintenance HD in comparison to patients on PD treatment, at 94% and 83%, respectively (P = 0.25). There was also a marginally significant trend of greater seroconversion rates among healthy controls than patients with ESKD (100% vs. 88%; P = 0.051). There were 12 (60%) patients in the control group and 21 (35%) patients in the ESKD group who reported mild adverse reactions in the early postvaccination period. Those adverse reactions included low-grade fever, headache, myalgia, and pain around the injection site.
Figure 2.
A median with an interquartile range of anti–receptor-binding domain (RBD) IgG antibody in patients requiring maintenance hemodialysis (HD) and peritoneal dialysis (PD) treatment at 2 weeks after the second dose of inactivated whole-virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. AU, arbitrary unit; NS, not significant.
Our preliminary report suggests that patients with ESKD requiring maintenance dialysis raised satisfactory humoral seroconversion response rates at 2 weeks after the second dose of an inactivated whole-virus SARS-CoV-2 vaccine. However, patients with ESKD developed lower levels of anti-RBD antibodies compared with healthy individuals. Adverse reactions were infrequent and relatively mild. Although obtained in a small number of patients, these data suggest that the immune response to CoronaVac is comparable to that achieved with mRNA and adenoviral-vectored vaccines. Further study including neutralizing antibody and cell-mediated immunity, is encouraged to better explore immunogenicity in these specific populations (Thai Clinical Trials Registry, TCTR20210226002).
Acknowledgments
This study was granted by the National Research Council of Thailand (102912).
References
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