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Authors: Woodruff, Matthew C et al
Abstract: A wide spectrum of clinical manifestations has become a hallmark of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) COVID-19 pandemic, although the immunological underpinnings of diverse disease outcomes remain to be defined. We performed detailed characterization of B cell responses through high-dimensional flow cytometry to reveal substantial heterogeneity in both effector and immature populations. More notably, critically ill patients displayed hallmarks of extrafollicular B cell activation and shared B cell repertoire features previously described in autoimmune settings. Extrafollicular activation correlated strongly with large antibody-secreting cell expansion and early production of high concentrations of SARS-CoV-2-specific neutralizing antibodies. Yet, these patients had severe disease with elevated inflammatory biomarkers, multiorgan failure and death. Overall, these findings strongly suggest a pathogenic role for immune activation in subsets of patients with COVID-19. Our study provides further evidence that targeted immunomodulatory therapy may be beneficial in specific patient subpopulations and can be informed by careful immune profiling.
Journal: Nature immunology
Curator: Hancock Lab
Reviewer: Aris Floratos
Author-provided data: ?

paper: Woodruff, M. C., Ramonell, R. P., Nguyen, D. C., Cashman, K. S., Saini, A. S., Haddad, N. S., ... & Sanz, I. (2020). Extrafollicular B cell responses correlate with neutralizing antibodies and morbidity in COVID-19. Nature immunology, 21(12), 1506-1516.
contributor: Matthew C. Woodruff
contributor_organization: Emory University


    • description: Patients with severe/critical COVID-19 show a robust activation of the extrafollicular B cell pathway – similar to responses seen in active and flaring autoimmune disease.
    • exact_source: Extrafollicular response signatures in COVID-19, and their comparison to patients with active lupus, are best highlighted in figures 3 and 4 (,
    • tissue: PBMC; B cell, CD19-positive
    • immune_exposure: COVID-19 infection
    • cohort: ICU patients. Ages 34-81. Clinical data presented in Data Table 2 (
    • comparison: ICU patients (severe/critical) versus outpatients (mild/moderate), active lupus patients, and healthy controls
    • repository_id: Flow data – (
    • platform: NA
    • response_components: NA
    • response_behavior: Antibody secreting cells up, DN2 B cells up, DN3 B cells up, Activated Naive B cells up