Single Cell Transcriptomic Re-analysis of Immune Cells in Bronchoalveolar Lavage Fluids Reveals the Correlation of B Cell Characteristics and Disease Severity of Patients with SARS-CoV-2 Infection

Abstract

The coronavirus disease 2019 (COVID-19) pandemic (severe acute respiratory syndrome coronavirus 2) is a global infectious disease with rapid spread. Some patients have severe symptoms and clinical signs caused by an excessive inflammatory response, which increases the risk of mortality. In this study, we reanalyzed scRNA-seq data of cells from bronchoalveolar lavage fluids of patients with COVID-19 with mild and severe symptoms, focusing on Ab-producing cells. In patients with severe disease, B cells seemed to be more activated and expressed more immunoglobulin genes compared with cells from patients with mild disease, and macrophages expressed higher levels of the TNF superfamily member B-cell activating factor but not of APRIL (a proliferation-inducing ligand). In addition, macrophages from patients with severe disease had increased pro-inflammatory features and pathways associated with Fc receptor-mediated signaling, compared with patients with mild disease. CCR2-positive plasma cells accumulated in patients with severe disease, probably because of increased CCL2 expression on macrophages from patients with severe disease. Together, these results support the hypothesis that different characteristics of B cells might be associated with the severity of COVID-19 infection.

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“…et al, 2021 ). Consistently, in the lung environment, both BAL macrophages from severe patients ( Liao et al, 2020 ; Kim C.W. et al, 2021 ) and airway macrophages from critical (according to WHO guidelines) cases ( Chua et al, 2020 ) exhibited proinflammatory characteristics ( Chua et al, 2020 ; Liao et al, 2020 ; Kim C.W.…”

“…Moreover, as previously observed for the mDCs, also COVID-19 patients CD14+ monocytes showed an impaired ability to answer to TLR stimulation, reinforcing the idea of an impaired innate response during COVID-19 disease ( Arunachalam et al, 2020 ). However, classical monocytes from severe (according to the National Early Warning Score) COVID-19 cases showed type I IFN response, and exacerbation of TNF/IL-1β-driven inflammation ( Lee et al, 2020 ; Kim C.W. et al, 2021 ).…”

“…This was demonstrated also from a functional point of view, with both somatic hypermutation in B cell receptor (BCR) and higher antibody titres correlating with disease severity ( Schultheiß et al, 2020 ; Okba et al, 2020 ). Thus, COVID-19 related B lymphocyte alterations determine not only disease severity but also the entity of long-term consequences and may have potential prognostic applications ( Detsika et al, 2021 ; Kim C.W. et al, 2021 ; Kos et al, 2021 ; Shuwa et al, 2021 ).…”

“…Dysregulation of B cell production, survival and turnover in older subjects affects the ability to respond to new antigens (thus influencing response to vaccination) and may cause the accumulation of class switched memory cells (IgD-CD27+), although the eventuality of such an effect is still a matter of debate ( Ventura et al, 2017 ; Aiello et al, 2019 ; Crooke et al, 2019 ; Hazeldine and Lord, 2020 ). Also, age-associated B cells (ABCs), defined as CD11b+CD11c+CD21low/-T-bet+, increase with age, and accounts for a reduction in the generation of new B cells, the release of pro-inflammatory cytokines and autoantibody production in autoimmune diseases ( Rubtsova et al, 2015 ; Hagen and Derudder, 2020 ; Pietrobon et al, 2020 ; Sachinidis et al, 2020 ; Kim C.W. et al, 2021 ).…”

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“…Patients with a mild case of COVID-19 have higher levels of immunoglobulins and more activation markers on B cells than patients with severe disease, but there are more CCR2 + plasma cells recruited to the lungs of patients with severe disease. Although B cell populations differ depending on the severity of the disease, it is not known whether these changes in cell populations affect the severity of the disease [ 31 ]. After acute infection, IgM appears first, followed about 4 weeks later by increasing levels of IgG, which may persist for 16–24 months [ 32 ].…”