Humoral response after the fourth dose of the SARS-CoV-2 vaccine in the CKD spectrum: a prespecified analysis of the SENCOVAC study

Abstract

Background There is scarce evidence on fourth doses of SARS-CoV-2 vaccines in chronic kidney disease (CKD) patients. We have evaluated the humoral response and effectivity of the fourth dose in the CKD spectrum: non-dialysis CKD (ND-CKD), hemodialysis (HD), peritoneal dialysis (PD) and kidney transplant (KT) recipients. Methods This is a prespecified analysis of the prospective, observational, multicentric SENCOVAC study. In patients with CKD who had received a complete initial vaccination and one or two boosters and had anti-Spike antibody determinations 6 and 12 months after the initial vaccination, we analyzed factors associated to persistent negative humoral response and to higher anti-Spike antibody titers as well as the efficacy of vaccination on COVID-19 severity. Results Of 2186 patients (18% KT, 8% PD, 69% HD and 5% ND-CKD), 30% had received a fourth dose. The fourth dose increased anti-Spike antibody titers in HD (P = 0.001) and ND-CKD (P = 0.014) patients and seroconverted 72% of previously negative patients. Higher anti-Spike antibody titers at 12 months were independently associated to repeated exposure to antigen (fourth dose, previous breakthrough infections), previous anti-Spike antibody titers and not being a KT. Breakthrough COVID-19 was registered in 137 (6%) patients, of whom 5% required admission. Admitted patients had prior titers below 620 UI/ml and median values were lower (P = 0.020) than in non-admitted patients. Conclusions A fourth vaccine dose increased anti-Spike antibody titers or seroconverted many CKD patients, but those with the highest need for a vaccine booster (i.e. those with lower pre-booster antibody titers or KT recipients) derived the least benefit in terms of antibody titers. Admission for breakthrough COVID-19 was associated with low anti-Spike antibody titers.

Effectiveness, Immunogenicity and Harms of Additional SARS-CoV-2 Vaccine Doses in Kidney Transplant Recipients: A Systematic Review

“…As in our analysis the few participants with severe disease had low or absent immune responses, additional vaccine doses can provide efficient [72] protection from severe disease once a sufficient serologic response is reached. Recent studies confirm these findings [73,74].…”

Durable Anti-SARS-CoV-2 Antibody Response after mRNA-1273 Booster in Peritoneal Dialysis Patients during the Omicron Wave

“…Prior to SARS-CoV-2 infection, these PD patients had a lower antibody level compared with SARS-CoV-2 naive patients, but this difference did not reach statistical significance, probably due to the small number of patients in our cohort. This inverse relationship between antibody levels and risk for breakthrough infections has been widely reported [26,27,33,34]. In a study by Manley et al in 16,213 dialysis patients during the pre-Delta and Delta-variant-dominated periods, lower anti-spike IgG levels were associated with a higher risk for COVID-19 infections and COVID-19-related hospitalizations [26].…”

Comparative effectiveness of two- and three-dose COVID-19 vaccination schedules involving AZD1222 and BNT162b2 in people with kidney disease: a linked OpenSAFELY and UK Renal Registry cohort study

“…This likely reflects the greater baseline vulnerability of RRT recipients to COVID-19 4 alongside lower immunogenicity and absolute effectiveness per vaccine dose. 29 A recent randomised trial compared several strategies aiming to enhance immunogenicity among kidney transplant recipients who remain seronegative after multiple RNA vaccine doses, including administration of a double RNA vaccine dose, heterologous vaccination, and temporary discontinuation of immunosuppressive therapy before vaccination. However, these approaches induced seroconversion rates comparable to that of a standard RNA vaccine dose.…”