Coronavirus disease 2019 (COVID-19) is a mild to moderate respiratory tract infection, however, a subset of patients progress to severe disease and respiratory failure. The mechanism of protective immunity in mild forms and the pathogenesis of severe COVID-19 associated with increased neutrophil counts and dysregulated immune responses remain unclear. In a dual-center, two-cohort study, we combined single-cell RNA-sequencing and single-cell proteomics of whole-blood and peripheral-blood mononuclear cells to determine changes in immune cell composition and activation in mild versus severe COVID-19 (242 samples from 109 individuals) over time. HLA-DR^hiCD11c^hi inflammatory monocytes with an interferon-stimulated gene signature were elevated in mild COVID-19. Severe COVID-19 was marked by occurrence of neutrophil precursors, as evidence of emergency myelopoiesis, dysfunctional mature neutrophils, and HLA-DR^lo monocytes. Our study provides detailed insights into the systemic immune response to SARS-CoV-2 infection and reveals profound alterations in the myeloid cell compartment associated with severe COVID-19.

2019 年冠状病毒病 (COVID-19) 是一种轻度至中度呼吸道感染，但部分患者会进展为严重疾病和呼吸衰竭。轻度形式的保护性免疫机制以及与中性粒细胞计数增加和免疫反应失调相关的重症 COVID-19 的发病机制仍不清楚。在一项双中心、两队列研究中，我们结合了全血和外周血单核细胞的单细胞 RNA 测序和单细胞蛋白质组学，以确定轻度与重度 COVID-19 中免疫细胞组成和激活的变化（来自 109 个人的 242 个样本）随着时间的推移。在轻度 COVID-19 中，具有干扰素刺激基因特征的HLA-DR ^hi CD11c ^{hi炎症单核细胞升高。}严重的 COVID-19 的特点是出现中性粒细胞前体，作为紧急骨髓生成、功能障碍的成熟中性粒细胞和HLA-DR ^lo单核细胞的证据。我们的研究提供了对 SARS-CoV-2 感染的系统免疫反应的详细见解，并揭示了与严重的 COVID-19 相关的骨髓细胞区室的深刻变化。