The inflammatory response to SARS-coronavirus-2 (SARS-CoV-2) infection is thought to underpin COVID-19 pathogenesis. We conducted daily transcriptomic profiling of three COVID-19 cases and found that the early immune response in COVID-19 patients is highly dynamic. Patient throat swabs were tested daily for SARS-CoV-2, with the virus persisting for 3 to 4 weeks in all three patients. Cytokine analyses of whole blood revealed increased cytokine expression in the single most severe case. However, most inflammatory gene expression peaked after respiratory function nadir, except expression in the IL1 pathway. Parallel analyses of CD4 and CD8 expression suggested that the pro-inflammatory response may be intertwined with T cell activation that could exacerbate disease or prolong the infection. Collectively, these findings hint at the possibility that IL1 and related pro-inflammatory pathways may be prognostic and serve as therapeutic targets for COVID-19. This work may also guide future studies to illuminate COVID-19 pathogenesis and develop host-directed therapies.

对SARS冠状病毒2（SARS-CoV-2）感染的炎症反应被认为是COVID-19发病机理的基础。我们对3例COVID-19病例进行了每天的转录组分析，发现COVID-19患者的早期免疫反应是高度动态的。每天对患者的咽拭子进行SARS-CoV-2测试，病毒在所有三名患者中持续3-4周。全血细胞因子分析显示，在最严重的单个病例中，细胞因子表达增加。但是，除IL1途径中的表达外，大多数炎症基因表达在呼吸功能最低后达到峰值。对CD4和CD8表达的平行分析表明，促炎反应可能与T细胞活化缠绕在一起，从而加剧疾病或延长感染时间。总的来说，这些发现提示IL1和相关的促炎途径可能具有预后性，并可能成为COVID-19的治疗靶标。这项工作还可以指导未来的研究，以阐明COVID-19的发病机理并开发针对宿主的疗法。