Understanding the immunological characteristics of monocytes—including the characteristics associated with fibrosis—in severe coronavirus disease 2019 (COVID-19) is crucial for understanding the pathogenic mechanism of the disease and preventing disease severity. In this study, we performed single-cell transcriptomic sequencing of peripheral blood samples collected from six healthy controls and 14 COVID-19 samples including severe, moderate, and convalescent samples from three severely/critically ill and four moderately ill patients. We found that the monocytes were strongly remodeled in the severely/critically ill patients with COVID-19, with an increased proportion of monocytes and seriously reduced diversity. In addition, we discovered two novel severe-disease-specific monocyte subsets: Mono 0 and Mono 5. These subsets expressed amphiregulin (AREG), epiregulin (EREG), and cytokine interleukin-18 (IL-18) gene, exhibited an enriched erythroblastic leukemia viral oncogene homolog (ErbB) signaling pathway, and appeared to exhibit pro-fibrogenic and pro-inflammation characteristics. We also found metabolic changes in Mono 0 and Mono 5, including increased glycolysis/gluconeogenesis and an increased hypoxia inducible factor-1 (HIF-1) signaling pathway. Notably, one pre-severe sample displayed a monocyte atlas similar to that of the severe/critical samples. In conclusion, our study discovered two novel severe-disease-specific monocyte subsets as potential predictors and therapeutic targets for severe COVID-19. Overall, this study provides potential predictors for severe disease and therapeutic targets for COVID-19 and thus provides a resource for further studies on COVID-19.

了解 2019 年严重冠状病毒病 (COVID-19) 中单核细胞的免疫学特征——包括与纤维化相关的特征——对于了解该病的致病机制和预防疾病的严重程度至关重要。在这项研究中，我们对从 6 名健康对照者和 14 名 COVID-19 样本（包括来自 3 名重症/危重症患者和 4 名中度患者的重度、中度和恢复期样本）采集的外周血样本进行了单细胞转录组测序。我们发现，在 COVID-19 重症/危重症患者中，单核细胞发生强烈重塑，单核细胞比例增加，多样性严重降低。此外，我们还发现了两种新的严重疾病特异性单核细胞亚群：Mono 0 和 Mono 5。这些亚群表达双调蛋白（AREG )、上皮调节蛋白 ( EREG ) 和细胞因子白介素 18 ( IL-18 ) 基因，表现出丰富的成红细胞白血病病毒癌基因同系物 ( ErbB) 信号通路，并且似乎表现出促纤维化和促炎症特征。我们还发现了 Mono 0 和 Mono 5 的代谢变化，包括糖酵解/糖异生增加和缺氧诱导因子 1 (HIF-1) 信号通路增加。值得注意的是，一个预严重样本显示的单核细胞图谱与严重/危重样本相似。总之，我们的研究发现了两种新的严重疾病特异性单核细胞亚群作为严重 COVID-19 的潜在预测因子和治疗靶点。总的来说，这项研究为 COVID-19 的严重疾病和治疗靶点提供了潜在的预测因子，从而为 COVID-19 的进一步研究提供了资源。