Severe coronavirus disease 2019 (COVID-19) is characterized by overproduction of immune mediators, but the role of interferons (IFNs) of the type I (IFN-I) or type III (IFN-III) families remains debated. We scrutinized the production of IFNs along the respiratory tract of COVID-19 patients and found that high levels of IFN-III, and to a lesser extent IFN-I, characterize the upper airways of patients with high viral burden but reduced disease risk or severity. Production of specific IFN-III, but not IFN-I, members denotes patients with a mild pathology and efficiently drives the transcription of genes that protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In contrast, compared to subjects with other infectious or noninfectious lung pathologies, IFNs are overrepresented in the lower airways of patients with severe COVID-19 that exhibit gene pathways associated with increased apoptosis and decreased proliferation. Our data demonstrate a dynamic production of IFNs in SARS-CoV-2-infected patients and show IFNs play opposing roles at distinct anatomical sites.

2019 年严重冠状病毒病 (COVID-19) 的特点是免疫介质过度产生，但 I 型 (IFN-I) 或 III 型 (IFN-III) 家族的干扰素 (IFN) 的作用仍存在争议。我们仔细检查了 COVID-19 患者呼吸道中 IFN 的产生，发现高水平的 IFN-III 和较低程度的 IFN-I 是病毒负荷高但疾病风险或严重程度降低的患者上气道的特征. 产生特定的 IFN-III 而不是 IFN-I 的成员表示具有轻度病理的患者，并有效地驱动保护免受严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的基因转录。相反，与具有其他感染性或非感染性肺部病变的受试者相比，IFN 在重症 COVID-19 患者的下呼吸道中过多，这些患者表现出与细胞凋亡增加和增殖减少相关的基因通路。我们的数据证明了 SARS-CoV-2 感染患者体内 IFN 的动态产生，并显示 IFN 在不同的解剖部位发挥相反的作用。