Incidence and severity of covid-19 in relation to anti-rbd igg antibody level after covid-19 vaccination in kidney transplant recipients

Abstract Background and Aims Kidney transplant recipients (KTRs) remain at increased risk for severe COVID-19 after vaccination, most likely due to an impaired immune response. However, the exact clinical impact of this impaired response remains unclear. Therefore we analysed the relationship between antibody levels after vaccination and the occurrence and severity of COVID-19 in a large cohort of KTRs. Method All KTRs, living in the Netherlands, who received COVID-19 vaccination were invited to participate in this observational cohort study. At approximately 28 days after the 2nd vaccination blood samples were obtained by a home-based finger-prick method and analysed for IgG antibodies against the receptor-binding domain of the SARS-CoV-2 spike protein (anti-RBD IgG). Participants were classified as either seronegative or seropositive using an anti-RBD IgG threshold of 50 BAU/mL. Participants who previously experienced COVID-19 were excluded. Primary endpoint was the incidence of COVID-19 from the moment the blood sample for anti-RBD IgG measurement was obtained until 6 months thereafter. Multivariable Cox and logistic regression analyses were performed to analyse which factors affected the occurrence and the severity (i.e. hospitalization and/or death) of COVID-19. Results In total 12,159 KTR were approached of whom 3,828 agreed to participate. In 2,885 subjects successful antibody measurement was performed after the 2nd COVID-19 vaccination. Among those, 1,578 (54.7%) became seropositive, whereas 1,307 (45.3%) remained seronegative. During a follow-up of 6 months, seropositivity was associated with a lower risk for COVID-19 incidence, also after adjusting for age, sex, socio-economic status and adherence to COVID-19 restrictions (HR 0.48 (0.27-0.86), p = 0.01). COVID-19 was also significantly less severe in seropositive as compared to seronegative participants (OR 0.14 (0.03-0.67), p = 0.01). When studied on a continuous scale, we observed a log-linear relationship between antibody level and risk for COVID-19 incidence (HR 0.52 (0.31-0.89) per tenfold higher anti-RBD IgG antibody level, p = 0.02). A threshold above which optimal protection was offered could not be detected. A similar association was found for COVID-19 severity. Conclusion In conclusion, antibody level after COVID-19 vaccination is associated in a log-linear relationship with the occurrence and severity of COVID-19 in KTRs. Therefore higher antibody levels, and not only reaching seropositivity, should be the aim of COVID-19 vaccination in KTRs. Immunosuppressed patients who have no or low antibody levels after vaccination should be offered repeat vaccinations, whether or not via alternative vaccination strategies, or passive immunization.