Immunophenotyping of COVID-19 and influenza highlights the role of type I interferons in development of severe COVID-19
Immunophenotyping of COVID-19 and influenza highlights the role of type I interferons in development of severe COVID-19
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DOI：
10.1126/sciimmunol.abd1554
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发表时间：
2020-07-01
影响因子：
24.8
通讯作者：
Shin, Eui-Cheol
中科院分区：
文献类型：
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作者：
Lee, Jeong Seok;Park, Seongwan;Shin, Eui-Cheol
尽管大多数SARS-CoV-2感染者经历了轻度的2019冠状病毒病（COVID-19），但部分患者患有严重的COVID-19，并伴有急性呼吸窘迫综合征和全身炎症。为了确定导致COVID-19严重进展的因素，我们使用从健康供体、轻度或重度COVID-19患者以及重度流感患者中获得的外周血单核细胞（PBMC）进行了单细胞RNA-seq。与严重流感相比，COVID-19患者在PBMC中所有类型的细胞中都表现出高度炎症特征，特别是TNF/IL-1 β驱动的炎症反应的上调。在严重COVID-19患者的经典单核细胞中，I型IFN反应与TNF/IL-1 β驱动的炎症共存，而这在轻度COVID-19患者中未观察到。有趣的是，我们也记录了严重流感患者中I型IFN驱动的炎症特征。基于此，我们提出I型IFN反应在严重COVID-19的炎症加剧中起着关键作用。
Although most SARS-CoV-2-infected individuals experience mild coronavirus disease 2019 (COVID-19), some patients suffer from severe COVID-19, which is accompanied by acute respiratory distress syndrome and systemic inflammation. To identify factors driving severe progression of COVID-19, we performed single-cell RNA-seq using peripheral blood mononuclear cells (PBMCs) obtained from healthy donors, patients with mild or severe COVID-19, and patients with severe influenza. Patients with COVID-19 exhibited hyper-inflammatory signatures across all types of cells among PBMCs, particularly up-regulation of the TNF/IL-1 beta-driven inflammatory response as compared to severe influenza. In classical monocytes from patients with severe COVID-19, type I IFN response co-existed with the TNF/IL-1 beta-driven inflammation, and this was not seen in patients with milder COVID-19. Interestingly, we documented type I IFN-driven inflammatory features in patients with severe influenza as well. Based on this, we propose that the type I IFN response plays a pivotal role in exacerbating inflammation in severe COVID-19.