Long COVID B Cell Immunity
Perelman School of Medicine, University of Pennsylvania
MICHAELA LOCCI, Ph.D.
Associate Professor of Microbiology
Background & approach
Long COVID is a chronic, debilitating condition affecting neurological, respiratory, and gastrointestinal function following SARS-CoV-2 infection. A leading hypothesis is that suboptimal immune responses — particularly impaired clearance of the virus — underlie the condition. The Locci Lab is uniquely focused on this question at the level of lymphoid tissue, using fine needle aspirates and core biopsies of cervical lymph nodes to directly study germinal center (GC) B cell reactions in Long COVID patients and healthy convalescents.
Major findings over the past year
Severely compromised germinal center responses. Building on earlier work, the team has confirmed that GC responses against SARS-CoV-2 are profoundly impaired in Long COVID. Upon reinfection, healthy convalescents mount efficient GC B cell responses and produce neutralizing antibodies; Long COVID patients generate fewer binding and neutralizing antibodies, and responses wane faster.
Reduced somatic hypermutation in SARS-CoV-2-specific B cells. Extended single-cell transcriptional analysis of lymph node samples, now with antigen-specific resolution, has revealed a significant reduction in somatic hypermutation — a hallmark of impaired affinity maturation — specifically in SARS-CoV-2-targeted B cells from Long COVID patients.
Depletion of germinal-center-derived memory B cells. In-depth characterization of SARS-CoV-2-specific B cells found a significant reduction in GC-derived memory B cell populations in Long COVID, suggesting a failure to build durable humoral immunity.
Together, these findings demonstrate profound alterations in B cell responses against SARS-CoV-2 in Long COVID that may be central to disease pathogenesis and contribute to incomplete viral clearance.