Coronavirus disease 2019 (COVID-19) manifests with a range of severities, but immune signatures of mild and severe disease are still not fully understood. Excessive inflammation has been postulated to be a major factor in the pathogenesis of severe COVID-19 and innate immune mechanisms are likely to be central in the inflammatory response. We used 40-plex mass cytometry and targeted serum proteomics to profile innate immune cell populations from peripheral blood of patients with mild or severe COVID-19 and healthy controls. Sampling at different stages of COVID-19 allowed us to reconstruct a pseudo-temporal trajectory of the innate immune response. Despite the expected patient heterogeneity, we identified consistent changes during the course of the infection. A rapid and early surge of CD169+ monocytes associated with an IFNy+MCP-2+ signature quickly followed symptom onset; at symptom onset, patients with mild and severe COVID-19 had a similar signature, but over the course of the disease, the differences between patients with mild and severe disease increased. Later in the disease course, we observed a more pronounced re-appearance of intermediate/non-classical monocytes and mounting systemic CCL3 and CCL4 levels in patients with severe disease. Our data provide new insights into the dynamic nature of the early inflammatory response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and identifies sustained pathological innate immune responses as a likely key mechanism in severe COVID-19, further supporting investigation of targeted anti-inflammatory interventions in severe COVID-19.

中文翻译：

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独特的先天免疫特征标志从轻度到严重COVID-19的发展

冠状病毒病2019（COVID-19）表现出一系列严重程度，但轻度和重度疾病的免疫特征仍未完全了解。据推测，过度炎症是严重COVID-19发病机理的主要因素，而先天免疫机制可能是炎症反应的中心。我们使用40重质谱细胞仪和靶向的血清蛋白质组学来分析轻度或重度COVID-19患者和健康对照者外周血的先天免疫细胞群。在COVID-19的不同阶段进行采样使我们能够重建先天免疫反应的伪时间轨迹。尽管预期的患者异质性，我们在感染过程中发现了一致的变化。症状发作后，与IFNγ+ MCP-2 +信号相关的CD169 +单核细胞迅速而迅速地激增。在症状发作时，轻度和重度COVID-19患者具有相似的特征，但在整个疾病过程中，轻度和重度患者之间的差异增加。在疾病过程的后期，我们观察到重症患者中中性/非经典单核细胞的重新出现以及全身性CCL3和CCL4水平的升高。我们的数据为对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染的早期炎症反应的动力学性质提供了新见解，并确定了持续的病理性先天免疫反应是严重COVID-19的可能关键机制，