CD19+IgD+CD27-Naive B Cells as Predictors of Humoral Response to COVID 19 mRNA Vaccination in Immunocompromised Patients

Immunocompromised patients are considered high-risk and prioritized for vaccination against COVID-19. We aimed to analyze B-cell subsets in these patients to identify potential predictors of humoral vaccination response. Patients (n=120) suffering from hematologic malignancies or other causes of immunodeficiency and healthy controls (n=79) received a full vaccination series with an mRNA vaccine. B-cell subsets were analyzed prior to vaccination. Two independent anti-SARS-CoV-2 immunoassays targeting the receptor-binding domain (RBD) or trimeric S protein (TSP) were performed three to four weeks after the second vaccination. Seroconversion occurred in 100% of healthy controls, in contrast to 67% (RBD) and 82% (TSP) of immunocompromised patients, while only 32% (RBD) and 22% (TSP) achieved antibody levels comparable to those of healthy controls. The number of circulating CD19(+)IgD(+)CD27(-) naive B cells was strongly associated with antibody levels (rho=0.761, P<0.001) and the only independent predictor for achieving antibody levels comparable to healthy controls (OR 1.07 per 10-mu L increase, 95%CI 1.02-1.12, P=0.009). Receiver operating characteristic analysis identified a cut-off at >= 61 naive B cells per mu l to discriminate between patients with and without an optimal antibody response. Consequently, measuring of naive B cells in immunocompromised hematologic patients could be useful in predicting their humoral vaccination response.