Altered immune response against SARS-CoV-2 infection in individuals with low-count monoclonal B-cell lymphocytosis

Altered immune response against SARS-CoV-2 infection in individuals with low-count monoclonal B-cell lymphocytosis

Guillermo Oliva Ariza

Centro de Investigación del Cáncer (Universidad de Salamanca-CSIC)

Date: 28/09/2023
Time: 12:30
CIC Lecture Hall
Host: Alberto Orfao

Monoclonal B-cell lymphocytosis (MBL) is a pre-malignant condition of chronic lymphocytic leukemia (CLL), which can be subdivided into low-count (MBLlo) and high-count (MBLhi) lymphocytosis. MBLlo is highly prevalent in the general adult population, but only a minority of MBLlo progresses into MBLhi/CLL. However, there is some evidence suggesting that MBLlo is associated with an underlying immunodeficiency, which might make MBLlo subjects more likely to develop severe infections and secondary tumors. After the COVID-19 outbreak, our laboratory had the opportunity to investigate the clinical impact of MBLlo in the context of the infection by a novel virus (SARS-CoV-2), aiming at confirming the hypothesis that MBLlo is a risk factor for developing more severe infection. For this purpose, we analyzed a large cohort of patients during the first two waves of the COVID-19 pandemic, to study the frequency of MBLlo among COVID-19 patients and its potential impact on disease severity; further, we investigated the kinetics of immune-cell and antibody responses in blood during active COVID-19, convalescent phase and later after infection (until week +43 after the disease onset) of MBLlo vs. age-matched non-MBL patients. We found that the frequency of MBLlo was higher among COVID-19 patients compared to the general population, and that MBLlo SARS-Cov-2 infected patients had clinical and biological features associated with more severe COVID-19. Consistent with these data, our results on the immune kinetics in blood revealed that MBLlo COVID-19 patients showed (vs. non-MBL patients) a delayed, but more pronounced, plasma cell and antibody humoral responses, together with a delayed dendritic-cell and innate-like T-cell responses, mimicking those previously described for severe COVID-19 disease in adults. Overall, our findings support MBLlo as a new independent risk condition for more severe COVID-19, and suggest that subjects with a MBLlo-associated impaired immunity are more likely prone to potentially suffer from other severe infections and immunodeficiency-related conditions.