There is an urgent need to better understand the pathophysiology of Coronavirus disease 2019 (COVID-19), the global pandemic caused by SARS-CoV-2, which has infected more than three million people worldwide¹. Approximately 20% of patients with COVID-19 develop severe disease and 5% of patients require intensive care². Severe disease has been associated with changes in peripheral immune activity, including increased levels of pro-inflammatory cytokines^3,4 that may be produced by a subset of inflammatory monocytes^5,6, lymphopenia^7,8 and T cell exhaustion^9,10. To elucidate pathways in peripheral immune cells that might lead to immunopathology or protective immunity in severe COVID-19, we applied single-cell RNA sequencing (scRNA-seq) to profile peripheral blood mononuclear cells (PBMCs) from seven patients hospitalized for COVID-19, four of whom had acute respiratory distress syndrome, and six healthy controls. We identify reconfiguration of peripheral immune cell phenotype in COVID-19, including a heterogeneous interferon-stimulated gene signature, HLA class II downregulation and a developing neutrophil population that appears closely related to plasmablasts appearing in patients with acute respiratory failure requiring mechanical ventilation. Importantly, we found that peripheral monocytes and lymphocytes do not express substantial amounts of pro-inflammatory cytokines. Collectively, we provide a cell atlas of the peripheral immune response to severe COVID-19.

迫切需要更好地了解 2019 年冠状病毒病 (COVID-19) 的病理生理学，这是由 SARS-CoV-2 引起的全球大流行，已感染全球超过 300 万人¹。大约 20% 的 COVID-19 患者发展为重症，5% 的患者需要重症监护²。严重的疾病与外周免疫活动的变化有关，包括促炎细胞因子^3,4水平升高，这可能由炎症单核细胞^5,6的一个子集产生，淋巴细胞减少^7,8和 T 细胞耗竭^9,10. 为了阐明可能导致重症 COVID-19 的免疫病理学或保护性免疫的外周免疫细胞通路，我们应用单细胞 RNA 测序 (scRNA-seq) 分析了七名因 COVID-19 住院的患者的外周血单个核细胞 (PBMC) ，其中四人患有急性呼吸窘迫综合征和六名健康对照。我们确定了 COVID-19 中外周免疫细胞表型的重构，包括异质干扰素刺激的基因特征、HLA II 类下调和发展中的中性粒细胞群，这似乎与出现在需要机械通气的急性呼吸衰竭患者中的​​浆母细胞密切相关。重要的是，我们发现外周单核细胞和淋巴细胞不表达大量的促炎细胞因子。集体，