Objectives Immunocompromised patients are at risk of severe coronavirus disease 2019 and are considered a high priority for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Humoral vaccination response is impaired in these patients when circulating B cells are lacking. We aimed to analyze B-cell subsets at the time of vaccination to identify potential predictors of humoral vaccination response. Methods Patients (n=120) receiving B-cell-depleting therapy (n=41), those suffering from inborn errors of immunity (n=25) and hematologic malignancies (n=56), and healthy controls (n=79) were vaccinated twice with BNT162b2 or mRNA 1273. B-cell subsets were analyzed prior to vaccination. Two independent anti-SARS-CoV-2 S immunoassays targeting the receptor-binding domain (RBD) or trimeric S protein (TSP) were performed three to four weeks after the second vaccination. Results Seroconversion occurred in 100% of the healthy controls, in contrast to 67% (RBD) and 82% (TSP) of the patients, while only 32% (RBD) and 22% (TSP) achieved antibody levels comparable to those of healthy controls. The number of circulating naive B cell was strongly associated with antibody levels (r=0.761, P<0.001) across all immunosuppressive treatments or conditions. In multivariable analysis, the number of naive B cells was an independent predictor for achieving antibody levels comparable to healthy controls, and receiver operating characteristic analysis predicted that at least six naive B cells per microL were required. Conclusions Assessing the abundance of naive B cells in immunocompromised patients could be useful in predicting the optimal vaccination response.
Association of Naive B Cells with Humoral Response to SARS-CoV-2 Vaccination