FC001: Humoral Response to Third Dose of Sars-Cov-2 Vaccines in the CKD Spectrum: The Sencovac Study

Abstract

BACKGROUND AND AIMS There is incomplete information on the impact of a third dose of the SARS-CoV-2 vaccine in advance chronic kidney disease (CKD). The aim of the present analysis was to evaluate the kinetics of humoral response in the CKD spectrum (KT, HD, PD and ND-CKD) 6 months after completing the initial vaccine schedule. Some patients of each group received a third dose before 6 months, providing a pragmatic insight into real-world responses to different vaccine schedules in patients with advanced CKD not on dialysis, on dialysis or in KT recipients. METHOD The SENCOVAC study describes the humoral response and safety of different SARS-CoV-2 vaccines in a real-world setting in 3687 CKD patients: 787 kidney transplant (KT), 319 peritoneal dialysis (PD), 2297 haemodialysis (HD) and 284 non-dialysis-CKD (ND-CKD) patients. Anti-Spike antibodies were assessed in an efficacy analysis at 28 days (n = 1755), 3 months (n = 1386), and 6 months (n = 1018, of whom 628 had received a third vaccine dose). Adverse events (AEs) were registered during follow-up, including SARS-CoV-2 infections in the safety analysis. RESULTS Among the patients included in the efficacy analysis, KT recipients presented lower anti-Spike antibody titers than other CKD cohorts at 28 days and 3 months (P < .001 for all). A total of 943 patients [249 (26%) KT, 108 (11%) PD, 511 (54%) HD and 75 (8%) ND-CKD] had negative baseline anti-Spike antibodies. Again, at 28 days or 3 months, KT recipients developed lower anti-Spike antibody titers than PD (P < .001), HD (P < .001) and ND-CKD (P< .001) patients. At 6 months, patients that had received a third vaccine dose had higher anti-Spike antibody titers than those without the third dose [1837 (507–9726) UI/mL versus 80 (19–409) ml/UI; P < .001] and this was evident in all CKD cohorts. Anti-Spike titers after the third dose were higher in patients boosted with mRNA-1273 than with BNT162b2 [1710 (322–9615) versus 472 (34–2094); P < .001). At 6 months, in patients that had received a third dose, a positive humoral response (anti-Spike antibodies > 36 UI/mL) was achieved in 584 (93%): 94 (80%) of 118 KT recipients, 20 (100%) of 20 patients on PD, 436 (96%) of 455 patients on HD and 34 (97%) of 35 patients with ND-CKD (Fig. 1). Among patients without humoral response 3 months after completing the initial vaccination schedule, 72 (69%) seroconverted after the third dose (62% KT, 76% HD, 100% ND-CKD, all PD patients had a positive humoral response at 3 months). Independent predictors of a positive humoral response at 6 months were not-KT (HR for KT 0.26, P = .011), third dose (HR 22.9, P < .001), initial mRNA-1273 (HT 1.78, P = .017) and humoral response at 3 months (HR 26.2, P < .001). Breakthrough SARS-CoV-2 infections occurred in 1.1% of patients, and mortality was 14.6%, none after the third dose. CONCLUSION In the CKD spectrum, anti-Spike antibody titers continued to decrease from 3 to 6 months after complete vaccination, and KT recipients presented higher rates of negative humoral response at 6 months. A third dose of mRNA vaccine increased anti-Spike antibody titers but was still insufficient to spur a humoral immune response in at least 38% of KT recipients and 24% of patients on HD that lacked anti-SARS-CoV-2 antibodies 3 months post-initial vaccination. New strategies are urgently needed to protect CKD patients that remain negative for anti-SARS-CoV-2 antibodies, given the high mortality of breakthrough SARS-CoV-2 infections.

Vaccination in kidney disease: what did we learn from COVID-19 pandemic

“…Patients with non-dialysis kidney disease and on dialysis presented good antibody response to vaccination, especially after third and fourth doses. Kidney transplant recipients presented suboptimal response after all doses, with persistent negative seroconversion after third and fourth doses [58 ▪ ]. Similar findings were observed in a Dutch cohort comparing seroconversion in non-dialysis advanced kidney disease, dialysis patients and controls.…”

“…Immune response to SARS-CoV-2 vaccination across the kidney disease spectrum (CKD, dialysis and kidney transplant) has been assessed in two recent prospective studies [57 ▪ ,58 ▪ ]. The SENCOVAC study assessed humoral responses (antispike protein IgG antibodies) in nondialysis kidney disease, haemodialysis and transplant 28 days, 3 months, 6 months and 12 months after vaccination in a Spanish cohort.…”

Longitudinal SARS-CoV-2 neutralization of Omicron BA.1, BA.5 and BQ.1.1 after four vaccinations and the impact of break-through infections in hemodialysis patients

“…Low serum anti-spike concentrations have been associated with an increased risk of break-through infections in hemodialysis patients 17, 18 . We detected high surrogate NAb titers against the original Wuhan-strain in all our patients although absolute NAb values were significantly decreasing in SARS-CoV-2 naïve patients during the follow-up.…”

Short and mid‐term SARS‐CoV‐2 antibody response after inactivated COVID‐19 vaccine in hemodialysis and kidney transplant patients

“…Therefore, health authorities emphasize that vaccination approaches against COVID‐19 should be a priority in CKD and kidney recipients. However, the efficacy of COVID‐19 vaccines in immunocompromised kidney transplant patients was found to be significantly lower than in other populations 5,6 . At the beginning of the COVID‐19 pandemic, it was not understood how effective the vaccines were in these patient groups, as the phase III studies against COVID‐19 did not include CKD, dialysis, or kidney recipients and focused only on normal individuals.…”

“…With these measures, it has been clearly demonstrated that the COVID‐19 disease can be controlled after the emergence of different effective and safe vaccines in the normal population 3,4 . So far, messenger RNA (mRNA)‐based COVID‐19 vaccines have proven to be the most protective vaccine type against COVID‐19 disease in the normal population and in different chronic kidney diseases (CKDs) 3,5–7 . CKD and kidney transplantation are important independent risk factors for severe COVID‐19 disease 8–10 .…”