COVID-19 pathogenesis is associated with an exaggerated immune response. However, the specific cellular mediators and inflammatory components driving diverse clinical disease outcomes remain poorly understood. We undertook longitudinal immune profiling on both whole blood and peripheral blood mononuclear cells (PBMCs) of hospitalized patients during the peak of the COVID-19 pandemic in the UK. Here, we report key immune signatures present shortly after hospital admission that were associated with the severity of COVID-19. Immune signatures were related to shifts in neutrophil to T cell ratio, elevated serum IL-6, MCP-1 and IP-10, and most strikingly, modulation of CD14⁺ monocyte phenotype and function. Modified features of CD14⁺ monocytes included poor induction of the prostaglandin-producing enzyme, COX-2, as well as enhanced expression of the cell cycle marker K_i-67. Longitudinal analysis revealed reversion of some immune features back to the healthy median level in patients with a good eventual outcome. These findings identify previously unappreciated alterations in the innate immune compartment of COVID-19 patients and lend support to the idea that therapeutic strategies targeting release of myeloid cells from bone marrow should be considered in this disease. Moreover, they demonstrate that features of an exaggerated immune response are present early after hospital admission suggesting immune-modulating therapies would be most beneficial at early timepoints.

COVID-19 发病机制与过度的免疫反应有关。然而，驱动不同临床疾病结果的特定细胞介质和炎症成分仍然知之甚少。在英国 COVID-19 大流行高峰期间，我们对住院患者的全血和外周血单个核细胞 (PBMC) 进行了纵向免疫分析。在这里，我们报告了入院后不久出现的与 COVID-19 严重程度相关的关键免疫特征。免疫特征与中性粒细胞与 T 细胞比率的变化、血清 IL-6、MCP-1 和 IP-10 升高有关，最引人注目的是与 CD14 ⁺单核细胞表型和功能的调节有关。CD14 ^{+的修改功能}单核细胞包括产生前列腺素的酶COX-2的不良诱导，以及细胞周期标志物K _i -67的增强表达。纵向分析显示，患者的一些免疫特征恢复到健康的中位水平，最终结果良好。这些发现确定了 COVID-19 患者先天免疫区室中以前未被重视的改变，并支持这样一种观点，即在这种疾病中应考虑以骨髓释放骨髓细胞为目标的治疗策略。此外，他们证明了在入院后早期出现了过度免疫反应的特征，这表明免疫调节疗法在早期时间点最有益。