The mortality risk of coronavirus disease 2019 (COVID-19) patients has been linked to the cytokine storm caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Understanding the inflammatory responses shared between COVID-19 and other infectious diseases that feature cytokine storms may therefore help in developing improved therapeutic strategies. Here, we use integrative analysis of single-cell transcriptomes to characterize the inflammatory signatures of peripheral blood mononuclear cells from patients with COVID-19, sepsis, and HIV infection. We identify ten hyperinflammatory cell subtypes in which monocytes are the main contributors to the transcriptional differences in these infections. Monocytes from COVID-19 patients share hyperinflammatory signatures with HIV infection and immunosuppressive signatures with sepsis. Finally, we construct a “three-stage” model of heterogeneity among COVID-19 patients, related to the hyperinflammatory and immunosuppressive signatures in monocytes. Our study thus reveals cellular and molecular insights about inflammatory responses to SARS-CoV-2 infection and provides therapeutic guidance to improve treatments for subsets of COVID-19 patients.

2019 年冠状病毒病 (COVID-19) 患者的死亡风险与严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 引起的细胞因子风暴有关。因此，了解 COVID-19 和其他以细胞因子风暴为特征的传染病之间共有的炎症反应可能有助于制定改进的治疗策略。在这里，我们使用单细胞转录组的综合分析来表征来自 COVID-19、败血症和 HIV 感染患者的外周血单个核细胞的炎症特征。我们确定了十种高炎症细胞亚型，其中单核细胞是这些感染中转录差异的主要贡献者。来自 COVID-19 患者的单核细胞与 HIV 感染具有高炎症特征，与败血症具有免疫抑制特征。最后，我们在 COVID-19 患者中构建了一个“三阶段”异质性模型，与单核细胞中的高炎症和免疫抑制特征相关。因此，我们的研究揭示了有关对 SARS-CoV-2 感染的炎症反应的细胞和分子见解，并为改善 COVID-19 患者亚群的治疗提供了治疗指导。