Severity of SARS-CoV-2 infection is linked to double-negative (CD27¿ IgD¿) B cell subset numbers
                 
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    	© 2021, The Author(s), under exclusive licence to Springer Nature Switzerland AG.Objectives: The role of B cells in COVID¿19, beyond the production of specific antibodies against SARS-CoV-2, is still not well understood. Here, we describe the novel landscape of circulating double-negative (DN) CD27¿ IgD¿ B cells in COVID¿19 patients, representing a group of atypical and neglected subpopulations of this cell lineage. Methods: Using multiparametric flow cytometry, we determined DN B cell subset amounts from 91 COVID-19 patients, correlated those with cytokines, clinical and laboratory parameters, and segregated them by principal components analysis. Results: We detected significant increments in the DN2 and DN3 B cell subsets, while we found a relevant decrease in the DN1 B cell subpopulation, according to disease severity and patient outcomes. These DN cell numbers also appeared to correlate with pro- or anti-inflammatory signatures, respectively, and contributed to the segregation of the patients into disease severity groups. Conclusion: This study provides insights into DN B cell subsets¿ potential role in immune responses against SARS¿CoV¿2, particularly linked to the severity of COVID¿19. 
    
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