The RECOVAC Immune-response Study: The Immunogenicity, Tolerability, and Safety of COVID-19 Vaccination in Patients With Chronic Kidney Disease, on Dialysis, or Living With a Kidney Transplant

Abstract

Background: In kidney patients COVID-19 is associated with severely increased morbidity and mortality. A comprehensive comparison of the immunogenicity, tolerability, and safety of COVID-19 vaccination in different cohorts of kidney patients and a control cohort is lacking.

Methods: This investigator driven, prospective, controlled multicenter study included 162 participants with chronic kidney disease (CKD) stages G4/5 (eGFR < 30 mL/min/1.73m2), 159 participants on dialysis, 288 kidney transplant recipients, and 191 controls. Participants received 2 doses of the mRNA-1273 COVID-19 vaccine (Moderna). The primary endpoint was seroconversion.

Results: Transplant recipients had a significantly lower seroconversion rate when compared with controls (56.9% versus 100%, P < 0.001), with especially mycophenolic acid, but also, higher age, lower lymphocyte concentration, lower eGFR, and shorter time after transplantation being associated with nonresponder state. Transplant recipients also showed significantly lower titers of neutralizing antibodies and T-cell responses when compared with controls. Although a high seroconversion rate was observed for participants with CKD G4/5 (100%) and on dialysis (99.4%), mean antibody concentrations in the CKD G4/5 cohort and dialysis cohort were lower than in controls (2405 [interquartile interval 1287-4524] and 1650 [698-3024] versus 3186 [1896-4911] BAU/mL, P = 0.06 and P < 0.001, respectively). Dialysis patients and especially kidney transplant recipients experienced less systemic vaccination related adverse events. No specific safety issues were noted.

Conclusions: The immune response following vaccination in patients with CKD G4/5 and on dialysis is almost comparable to controls. In contrast, kidney transplant recipients have a poor response. In this latter, patient group development of alternative vaccination strategies are warranted.

Trial registration: ClinicalTrials.gov NCT04741386.

Graphical abstract

FIGURE 1.

Subject enrollment and outcomes. CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; COVID-19, coronavirus disease 2019; eGFR, estimated glomerular filtration rate.

FIGURE 2.

Proportion of responders (A) and SARS-CoV-2 Spike S1-specific IgG antibody levels (B) per study cohort at 28 d after second vaccination. A, Responders were defined as subjects with a S1-specific IgG antibody level ≥10 BAU/mL after first vaccination or second vaccination. B (left panel), Depicted are box and whisker plots together with outliers, with the box representing median and interquartile range, whiskers representing the 95% CI; (right panel) dot plot of S1-specific IgG antibody level of kidney transplant recipients only. Dotted horizontal line indicates threshold for definition of responder at ≥10 BAU/; P were calculated using Mann-Whitney U test and corrected for multiple testing by Bonferroni. BAU, binding antibody unit; CKD, chronic kidney disease; IgG, immunoglobulin G; KTR, kidney transplant recipient; N, number; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

FIGURE 3.

SARS-CoV-2 neutralizing antibody titer (PRNT₅₀). A, Data of a random subset of subjects included in 1 of the participating centers. Data are shown as box and whisker plots together with outliers, with the box representing median and interquartile range, whiskers representing the 95% confidence interval. P were calculated using Mann-Whitney U. B, S1 specific IgG antibody levels for all kidney transplant recipients included at that center (N = 69) and correlation with PRNT₅₀. Dotted vertical line indicates threshold for seroresponse, and horizontal line indicates the threshold for neutralizing capacity. Asterisks represent samples assumed not measurable. The solid line represents the regression line calculated for only subjects with seroconversion (S1-specific IgG response ≥10 BAU/mL) and a measurable T-cell response (PRNT₅₀ ≥20), with corresponding R and P calculated using Spearman correlation. CKD, chronic kidney disease; IgG, immunoglobulin G; KTR, kidney transplant recipient; N, number; PRNT₅₀, 50% plaque reduction neutralization test; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

FIGURE 4.

SARS-CoV-2-specific T-cell response in all subjects in 1 of the participating centers. A, Percentage of high T-cell response per group after vaccination (defined as antigen 1 and antigen 2 ≥0.149 IU/mL, ie, 3 times the background). B, Left panel shows individual IFNγ levels per group. Depicted are box and whisker plots together with outliers, with the box representing median and interquartile range, whiskers representing the 95% confidence interval. P were calculated using Mann-Whitney U. B, Right panel shows S1 specific IgG antibody levels vs T-cell response kidney transplant recipients (n = 68). Dotted vertical line indicates threshold for seroresponse and dotted horizontal line the threshold for cellular response. BAU, binding antibody unit; CKD, chronic kidney disease; IFNγ, interferon-gamma; IgG, immunoglobulin G; KTR, kidney transplant recipient; N, number; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

FIGURE 5.

Impact of the various immunosuppressive regimens on S1-specific IgG antibody level 28 d after the second vaccination. Regimens with <10 subjects were categorized as “Other.” BAU, binding antibody unit; IgG, immunoglobulin G; MMF, mycophenolate mofetil; N, number.

FIGURE 6.

Solicited adverse events after first and second vaccination per study cohort. CKD, chronic kidney disease; KTR, kidney transplant recipient.