Lessons from SENCOVAC: a prospective study evaluating the response to SARS-CoV-2 vaccination in the CKD spectrum

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has negatively impacted on patients of the whole CKD spectrum, causing high rates of morbi-mortality. SARS-CoV-2 vaccines opened a new era, but patients with CKD (including kidney transplant, hemodialysis and peritoneal dialysis) were systematically excluded from pivotal clinical trials. The Spanish Society of Nephrology promoted the multicentric national SENCOVAC study aimed at assessing immunological responses after vaccination in patients with CKD. During the first year after vaccination, patients with non-dialysis CKD and those on hemodialysis and peritoneal dialysis presented good anti-Spike antibody responses to vaccination, especially after receiving the third and fourth doses. However, kidney transplant recipients presented suboptimal responses after any vaccination schedule (initial, third and fourth dose). Especially worrisome is the situation of a patients with a persistently negative humoral response that do not seroconvert after boosters. In this regard, monoclonal antibodies targeting SARS-CoV-2 have been approved for high-risk patients, although they may become obsolete as the viral genome evolves. The present report reviews the current status of SARS-CoV-2 vaccination in the CKD spectrum with emphasis on lessons learned from the SENCOVAC study. Predictors of humoral response, including vaccination schedules and types of vaccines, as well as the integration of vaccines, monoclonal antibodies and antiviral agents are discussed.

Fig. 1

Global prevalence of CKD and impact of CKD on COVID-19 mortality. (A) Global prevalence of CKD by age according to Global Burden of Disease (GBD) data. Gray lines represent individual countries. (B) According to these data, CKD accounts for the increased risk of severe COVID-19 in 5.1% of the global population, or 23% of the global population at increased risk of severe COVID-19, as represented in panel B, being the highest contributor to global risk. Data for (A) and (B) from Ref. . (C) Risk of COVID-19 death for selected preexistent conditions from Ref 8. Dialysis and transplantation were the conditions that most increased the risk of death from COVID-19 in the OpenSAFELY study. Additionally, the increased risk conveyed by CKD G4/G5 was still higher than that conveyed by several of the often-cited risk factors for severe CVOD-19, including diabetes, chronic heart disease and hypertension. Even CKD G3 conveyed a higher risk of COVID-19 death than heart disease or hypertension. The discontinuous horizontal blue line indicates neutral risk (Adj HR = 1.0).

Fig. 2

Design of the SENCOVAC study. Abbreviations: CKD: chronic kidney disease, CKD-EPI: Chronic Kidney Disease Epidemiology Collaboration, eGFR: estimated glomerular filtration rate, HD: hemodialysis, PD: peritoneal dialysis, KT: kidney transplant.

Fig. 3

Flow chart of the different humoral response assessment in SENCOVAC. Abbreviations: ND-CKD: non-dialysis chronic kidney disease, HD: hemodialysis, PD: peritoneal dialysis, KT: kidney transplant.

Fig. 4

Positive humoral response in each assessment of the SENCOVAC study across all the categories of the CKD spectrum from ref 26,27,38,42,55, 59. Positive immune response was defined as anti-Spike antibody titers above 36 IU/ml as positive, while ≤32 IU/ml were considered as negative, and between 32 and 36 IU/ml as equivocal, based on the manufacturer evaluation of serum from exposed and non-exposed individuals. Abbreviations: ND-CKD: non-dialysis chronic kidney disease, HD: hemodialysis, PD: peritoneal dialysis, KT: kidney transplant.