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Safety and immediate humoral response of COVID-19 vaccines in chronic kidney disease patients: the SENCOVAC study

Abstract Background Chronic kidney disease (CKD) patients are at high-risk for severe Covid-19. The multicentric, observational and prospective SENCOVAC study aims to describe the humoral response and safety of SARS-CoV-2 vaccines in CKD patients. Safety and immediate humoral response results are reported here. Methods Four cohorts of patients were included: kidney transplant (KT) recipients, haemodialysis (HD), peritoneal dialysis (PD) and non-dialysis CKD patients from 50 Spanish centres. Adverse events after vaccine doses were recorded. At baseline and on day 28 after the last vaccine dose, anti-Spike antibodies were measured and compared between cohorts. Factors associated with development of anti-Spike antibodies were analyzed. Results 1746 participants were recruited: 1116 HD, 171 PD, 176 non-dialysis CKD patients and 283 KT recipients. Most patients (98%) received mRNA vaccines. At least one vaccine reaction developed after the first dose in 763 (53.5%) and after the second dose in 741 (54.5%) of patients. Anti-Spike antibodies were measured in the first 301 patients. At 28 days, 95% of patients had developed antibodies: 79% of KT, 98% of HD, 99% of PD and 100% of non-dialysis CKD patients (p<0.001). In a multivariate adjusted analysis, absence of an antibody response was independently associated to KT (OR 20.56, p = 0.001) and to BNT162b2 vaccine (OR 6.03, p = 0.023). Conclusion The rate of anti-Spike antibody development after vaccination in KT patients was low but in other CKD patients it approached 100%; suggesting that KT patients require persistent isolation measures and booster doses of a Covid-19 vaccine. Potential differences between Covid-19 vaccines should be explored in prospective controlled studies.

The fast development and approval of SARS-CoV-2 vaccines has decreased the severity of the Covid-19 pandemic in countries with high immunization rates. However, there is concern regarding the humoral response of CKD patients to vaccination against SARS CoV-2. Data on KT patients is the most worrisome, with a seroconversion rate lower than 50% in the majority of published studies 4 . In addition, recent series have shown their limited development of anti-Spike antibodies, even after three vaccine doses 5 . In contrast, preliminary studies suggest that HD patients reach higher anti-Spike antibody levels after the administration of mRNA vaccines than KT patients, but lower than the general population 6 . Two recent reports involving peritoneal dialysis (PD) patients suggest that this population acquires similar humoral and cellular responses as HD infection.

Variables and outcomes
In this interim analysis, we assessed safety and the humoral response at 28 days after

Adverse events and vaccine reactions
After each vaccine dose, patients were asked to complete the adverse events questionnaire.
During the study all patients were followed, and any AE was registered. Serious AE were considered if they led to death, were life-threatening, needed hospitalization or caused disability, as considered by the investigators.

Ethical concerns
The study was approved by the Ethical Committee of Fundación Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz in February 2021.

Baseline characteristics
Among the 1746 participants in SENCOVAC, 1092 (62.5%) were male and the mean age was 63.6713.28 years ( were on PD. The distribution of the different types of vaccines differed between groups ( Table 1). KT recipients, HD and PD patients were more likely to receive mRNA-1273 and non-dialysis CKD patients BNT162b2 (p<0.001). Table 2 shows baseline characteristics for participants that received mRNA vaccines (BNT162b2 or mRNA-1273) in the safety and humoral response population populations. The analysis restricted to patients without anti-Spike antibodies at baseline is shown in Table 1S.

Local and systemic reactions after vaccination
The adverse reactions form after the first dose was completed by 1426 participants.
Among them, 763 (53.5%) patients developed at least one reaction. Reactions were more frequent in KT recipients, followed by PD and HD patients (p<0.001) (figure 1S).
Vaccine reactions was more frequent in younger patients (p<0.001 for all groups combined, not shown). Specifically, vaccine reactions were more frequent in younger KT recipients (p=0.016) and in younger persons with non-dialysis CKD (p=0.012) than in older participants from these groups (not shown). Previous Covid-19 infection was also associated with higher rates of reactions after the first dose (64% vs 53%) (p=0.038). The most frequent reaction was local pain (556, 73%), followed by general discomfort (163, 22%) and asthenia (160, 21%) (table 2S). mRNA-1273 vaccine was associated with higher rates of local pain, erythema, swelling, skin hypersensitivity, low-grade fever and fever, headache, asthenia, chills, and general discomfort. Among patients who were working, those who had received mRNA-1273 requested a work leave more frequently (p=0.015).
The adverse reactions form after the second dose was completed by 1359 patients.
Among them, 741 (54.5%) developed at least one reaction. Reactions were more frequent in KT patients (p=0.006) (figure 1S). Vaccine reactions to the second dose were also more frequent in younger patients (p<0.001 for all groups combined, not shown). Specifically, vaccine reactions were more frequent in younger KT patients (p=0.035) and in younger non-dialysis CKD patients (p=0.003) than in older participants from these groups (not shown). Previous Covid-19 infection was also associated with higher rates of reactions after the second dose (65% vs 53%) (p<0.001).
The most frequent reaction was local pain (493, 68%) followed by general discomfort (261, 36%) and asthenia (258, 36%) (table 3S).The second dose of mRNA-1273 produced more frequent local pain, erythema, swelling, itching, skin hypersensitivity, low-grade fever and fever, headache, asthenia, myalgia, chills, general discomfort and arthralgias than the other vaccines. Among patients who were working, those who had   To our knowledge, our study is the first to also analyse non-dialysis CKD patients in comparison with patients on kidney replacement therapy. Interestingly, and despite the low GFR of this subgroup, they displayed a very high rate of humoral response after completing the full vaccination schedule. Although uremia alters humoral immunity, our data suggest that, at least in the short-term, non-dialysis CKD patients have higher seroconversion rates than CKD patients on kidney replacement therapy 19