Abstract
Double Negative (DN) B cells constitute a B cell population that lacks expression of immunoglobulin D and CD27 memory marker. These cells expand in elderly healthy individuals, but also accumulate prematurely in autoimmune and infectious diseases. COVID-19 is a pandemic infectious disease caused by SARS-CoV-2, a coronavirus that was first observed in Wuhan, China in December 2019. In its more severe cases, COVID-19 causes severe pneumonia and acute respiratory syndrome with high morbidity and mortality. Recent studies have revealed that the extrafollicular DN2 B cell subset, previously described in lupus patients, does also expand in severe and/or critical groups of COVID-19 patients. These DN2 cells correlate with disease severity and laboratory parameters of inflammation. However, their exact role and function in COVID-19 require to be further investigated. In this review, we highlight the DN immune responses in both rheumatic diseases and COVID-19, and we point out the importance of clarifying DN's role in the immunopathology of the aforementioned infection, as it could probably enable better management of rheumatic diseases during the pandemic. Of note, the symptomatology of COVID-19, as well as the potential outcome of death, have given rise to a worldwide concern and scare of exposition to SARS-CoV-2, especially among the rheumatological patients who believe to be at higher risk due to their immunological background and the immunosuppressive therapies. Nevertheless, there is no convincing evidence so far that these patients are truly at higher risk than others.