Expansion of atypical memory B cells is a prominent feature of COVID-19

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an RNA virus responsible for a pandemic that causes asymptomatic or paucisymptomatic infection in most individuals but may be responsible for severe interstitial pneumonia, myocarditis, acute kidney injury, hepatitis, acute respiratory distress syndrome (ARDS), multiorgan failure (MOF), and death. 1 Patients with severe coronavirus disease (COVID-19) typically show signs of hyperinflammation characterized by an exuberant host immune response leading to a virus-driven cytokine release syndrome. 2 A hallmark of COVID-19 is lymphopenia, involving virtually all cell lineages, and a number of studies have provided evidence in support of altered innate and adaptive immune responses in COVID-19. 2 With respect to the latter, most studies focused on phenotypic and molecular T-cell alterations; however, little or no information is available for B cells, apart from the possible role of SARS-CoV-2specific neutralizing antibodies in controlling the infection and clinical outcome. An altered distribution of B-cell subsets is usually observed in chronic viral infections, including hepatitis C and B 3,4 and HIV. All were admitted to the hospital because of severe dyspnea requiring at least a Venturi type of mask for oxygen ventilation. Four patients required a ventilation upgrade to continuous positive airway pressure with high positive end-expiratory pressure or transfer to the ICU and intubation. Ten of these patients died because of ARDS and/or MOF. Follow-up peripheral blood mononuclear cells were available from seven recovered patients ~45 days after discharge. Seven convalescent (Conv) individuals who donated hyperimmune plasma because of serum high-titer neutralizing antibodies immediately after hospital discharge or after home quarantine were also investigated. Laboratory findings are reported in Supplementary Table Thirteen clinically healthy, SARS-CoV-2 RNA-negative subjects of the same age group as the patients served as controls (HD). The study was approved by the Institutional Review Board of Fondazione IRCCS Policlinico San Matteo (prot. N. 20200038910).