Alterations of B cell responses to SARS-CoV-2 in Long COVID 2566

Description Long COVID (LC) is a debilitating condition characterized by neurological, respiratory and/or gastrointestinal symptoms persisting after the infection with SARS-CoV-2. It has been hypothesized that LC is caused by suboptimal immune responses failing to clear SARS-CoV-2. Memory B cells and antibody-secreting plasma cells with high affinity for viruses, which confer protection from infection and contribute to viral clearance, canonically originate from germinal center (GC) reactions in lymphoid organs. By using a Fine Needle Aspirate (FNA) approach, which we previously deployed to probe GC responses to vaccination (Lederer et al. Cell 2022), we collected biopsies from cervical lymph nodes of LC and healthy COVID-19 convalescents. High-parameter flow cytometry analysis of FNA samples showed that convalescents mounted efficient GC B cell responses to SARS-CoV-2 that correlated with the generation of neutralizing antibodies. Conversely, GC responses to SARS-CoV-2 were severely hindered in LC patients and linked to a decreased production of binding and neutralizing antibodies against SARS-CoV-2 that waned faster than in convalescents. CITE-seq analysis of FNA samples also revealed transcriptional alterations in GC B and memory B cells from LC patients that were coupled to inferior clonal expansion. Overall, the direct analysis of lymph nodes uncovered major abnormalities in B cell responses to SARS-CoV-2 that might be connected to the incomplete lack of viral clearance in LC. Funding Sources This work is supported by PolyBio Research Foundation and by NIH 2U19AI082630-16 grant Topic Categories Immune Mechanisms of Human Disease (HUM)