ABSTRACT
BACKGROUND AND AIMS: COVID-19 infection in solid organ transplant recipients (SOT) is associated with increased morbidity and mortality due to comorbidities and immunosuppression state (Chaudhry ZS et al, 2020). Although vaccines represent the greatest hope to control COVID-19 pandemic, several studies showed the low immunogenicity of a two-dose mRNA COVID-19 vaccine regimen in SOT as compared with general population (Boyarsky BJ et al, 2021). Based on this evidence, on September 2021, the Italian Medicine Agency (AIFA) authorized a third vaccine administration as additional primary dose to immunocompromised patients. The aim of this study is to evaluate the seroconversion rate after the third dose of BNT162b2 (Pfizer-BioNTech) SARS-CoV-2 mRNA vaccine in kidney transplant recipients (KTRs) and to investigate the baseline factors associated with the absence of the antibody response. METHOD: we performed a prospective and observational study on a monocentric cohort of 329 consecutive Caucasian KTRs given three doses of the BNT162b2 COVID-19 vaccine. Key exclusion criteria were a previous history of COVID-19 infection and transplantation or having underwent chemotherapy treatment within the last year. Antibody response against the spike protein was tested on blood sample collected before the administration of vaccine (T0), at 15 and 90 days after the second dose (T2 and T3, respectively) and one month after the third dose (T5). The level of antibodies was assessed using the Roche Elecsys anti-SARS-CoV-2 S enzyme immunoassay (positive cut-off ≥ 0.8 U/mL). A total of 22 patients were excluded from the analysis because categorized as SARS-CoV-2-pre-immunized according to the antibodies' baseline status (T0) above the positivity cut-off. The Local Ethics Committees approved the study protocol and written informed consent was obtained before enrolment. RESULTS: The study population of 307 KTRs was 57.10 ± 13.10 years, with a predominance of male sex (64.2%). Median time from transplantation to vaccine was 10 [IQR 5-17] years. Blood analysis at baseline revealed mean eGFR assessed by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation to be 56.95 ± 23.04 mL/min/1.73 m2. The standard immunosuppressive regimen consisted of glucocorticoids in all patients, calcineurin inhibitors (88.6% of patients), antimetabolites (73.3% of patients) and mTOR inhibitors (in 15.6% of patients). The first two doses were administered 21 days apart, and the third dose was administrated 172 ± 4 days after the second dose. In our cohort, 43.3% patients (133/307) responded to the vaccine at T2. The proportion of responders increased to 68.4% (186/272) at T3 (median antibody level: 5.2 [0.40-74.07]). One month after the third dose, a positive antibody titer was detected in 251 of 307 patients (81.8%) (median antibody titre: 1137.50 [9.32- 4189.75]). The response curve starting at T2 and increasing at T3 makes apparent that there is a distinctive kinetic of humoral response in immunocompromised patients compared to immunocompetent individuals (Walsh EE et al., 2020). A multivariate analysis showed that the negative response to the third primary dose was associated with antimetabolite immunosuppressants (P = .001), lower estimated glomerular filtration rate (P < .001) and female sex (P = .04) (Figure 1). No serious adverse events were reported. Neither De novo DSAs nor change in proteinuria were reported after vaccination. The limitation of this study is the absence of assays for cellular immune response. CONCLUSION: Although the exact threshold of antibody titer for protection against SARS-CoV-2 infection remains unclear, the ability of the additional mRNA COVID- 19 vaccine dose to increase both immune response (Figure 2A) and the prevalence of seroconversion rate (Figure 2B) associated with the acceptable safety profile supports its use after an initial 2-dose mRNA COVID-19 primary vaccine series in immunocompromised patients. (Table Presented).