Abstract
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- naïve B cells was strongly associated with antibody levels (ρ=0.761, P<0.001) and the only independent predictor for achieving antibody levels comparable to healthy controls (OR 1.07 per 10-µL increase, 95%CI 1.02–1.12, P=0.009). Receiver operating characteristic analysis identified a cut-off at ≥61 naïve B cells per µl to discriminate between patients with and without an optimal antibody response. Consequently, measuring of naïve B cells in immunocompromised hematologic patients could be useful in predicting their humoral vaccination response.
Highlights
Coronavirus disease 2019 (COVID-19) results in increased morbidity and mortality in immunocompromised patients [1,2,3]
Since the presence of B cells is a prerequisite for humoral vaccination responses, we investigated B cells overall and multiple B-cell subsets in immunocompromised patients and healthy controls prior to COVID-19 mRNA vaccination
Comparing the two immunoassays of Roche and DiaSorin, which distinctly correlated with each other, we found that only 67% and 82% of patients, respectively, mounted antibody levels within the quantification range of the two tests
Summary
Coronavirus disease 2019 (COVID-19) results in increased morbidity and mortality in immunocompromised patients [1,2,3]. Immunodeficiency can be primary (PID) due to underlying genetic causes such as common variable immunodeficiency or secondary (SID) resulting from hematologic malignancies (HM), immunosuppressive therapies, or hematopoietic stem cell transplantation (HSCT). In a recent study of 100 patients with COVID-19 disease, patients with PID and SID demonstrated higher morbidity and mortality than the general population, while the outcomes of individuals suffering from SID were the worst [1]. Risk of death was highest in patients with acquired bone marrow failure syndromes (53%, 95% CI: 34-72), followed by acute leukemias (41%, 95% CI: 30-52), myeloproliferative neoplasms (34%, 95% CI: 19-51), plasma cell dyscrasias (33%, 95% CI: 25-41), lymphomas (32%, 95% CI: 18-48), and chronic lymphocytic leukemias (CLL) (31%, 95% CI: 23-40), respectively
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