A wide clinical spectrum has become a hallmark of the SARS-CoV-2 (COVID-19) pandemic, although its immunologic underpinnings remain to be defined. We have performed deep 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 as previously described in autoimmune settings. Extrafollicular activation correlated strongly with large antibody secreting cell expansion and early production of high levels of SARS-CoV-2-specific antibodies. Yet, these patients fared poorly with elevated inflammatory biomarkers, multi-organ failure, and death. Combined, the findings strongly indicate a major pathogenic role for immune activation in subsets of COVID-19 patients. Our study suggests that, as in autoimmunity, targeted immunomodulatory therapy may be beneficial in specific patient subpopulations that can be identified by careful immune profiling.

中文翻译：

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重症 SARS-CoV-2 患者表现出滤泡外 B 细胞活化的狼疮样特征。

广泛的临床谱已成为 SARS-CoV-2 (COVID-19) 大流行的标志，尽管其免疫学基础仍有待确定。我们通过高维流式细胞术对 B 细胞反应进行了深入表征，以揭示效应子和未成熟群体的显着异质性。更值得注意的是，重症患者表现出滤泡外 B 细胞活化的标志，如先前在自身免疫环境中所述。滤泡外激活与大抗体分泌细胞扩增和高水平 SARS-CoV-2 特异性抗体的早期产生密切相关。然而，这些患者在炎症生物标志物升高、多器官衰竭和死亡方面表现不佳。综合起来，这些发现强烈表明免疫激活在 COVID-19 患者亚群中的主要致病作用。