Although critical illness has been associated with SARS-CoV-2-induced hyperinflammation, the immune correlates of severe COVID-19 remain unclear. Here, we comprehensively analyzed peripheral blood immune perturbations in 42 SARS-CoV-2 infected and recovered individuals. We identified extensive induction and activation of multiple immune lineages, including T cell activation, oligoclonal plasmablast expansion, and Fc and trafficking receptor modulation on innate lymphocytes and granulocytes, that distinguished severe COVID-19 cases from healthy donors or SARS-CoV-2-recovered or moderate severity patients. We found the neutrophil to lymphocyte ratio to be a prognostic biomarker of disease severity and organ failure. Our findings demonstrate broad innate and adaptive leukocyte perturbations that distinguish dysregulated host responses in severe SARS-CoV-2 infection and warrant therapeutic investigation.

尽管危重疾病与 SARS-CoV-2 诱导的过度炎症有关，但重症 COVID-19 的免疫相关性仍不清楚。在这里，我们全面分析了 42 名 SARS-CoV-2 感染者和康复者的外周血免疫扰动。我们发现了多种免疫谱系的广泛诱导和激活，包括 T 细胞激活、寡克隆浆母细胞扩增以及对先天淋巴细胞和粒细胞的 Fc 和运输受体调节，从而将重症 COVID-19 病例与健康供体或 SARS-CoV-2 康复者区分开来或中等严重程度的患者。我们发现中性粒细胞与淋巴细胞的比率是疾病严重程度和器官衰竭的预后生物标志物。我们的研究结果表明，广泛的先天性和适应性白细胞扰动可以区分严重 SARS-CoV-2 感染中失调的宿主反应，并值得进行治疗研究。