High frequency of low-count monoclonal B-cell lymphocytosis in hospitalized COVID-19 patients

Abstract

[EN]Low-count monoclonal B-cell lymphocytosis (MBLlo) is associated with clinical and biological features typical of an underlying immunodeficiency, which may be a risk factor for developing more severe infections. Here we studied the frequency of MBLlo among COVID-19 patients and its potential impact on disease severity. The presence of MBLlo was investigated in blood of 249 COVID-19 patients vs. a pre-COVID-19 cohort of 728 individuas, using high-sensitivity flow cytometry; plasma levels of anti-SARS-CoV-2 antibodies were measured by ELISA. Overall, MBLlo was detected in 29% of COVID-19 patients (vs. 14% in the general pre-COVID-19 population; p<0.0001), particularly among hospitalized patients (40%; p<0.0001), with a tendency toward a predominance in men. MBLlo patients showed features of more severe COVID-19 than non-MBL cases, including more frequent (85% vs. 60%; p=0.0001) and longer (14 vs. 10 days; p=0.03) hospitalization, higher oxygen therapy (70% vs. 39%; p<0.0001) and need for intensive care (15% vs. 6%; p=0.02). Except for lower B-cell counts at recovery in MBLlo cases (p=0.04), similarly altered immune-cell profiles were observed in patients with and without MBLlo. In contrast, MBLlo patients showed a significantly higher percentage of detectable anti-SARS-CoV-2 IgM/IgG/IgA antibodies in plasma, associated with higher IgA SARS-CoV-2 specific antibody levels during acute infection. In conclusion, MBLlo is significantly more prevalent in COVID-19 patients vs. the general population, and it is associated with more severe COVID-19, further supporting the existence of a pre-established immunodeficiency already at early MBL stages.