IFN-I and IFN-III immunity in the nasal mucosa is poorly characterized during SARS-CoV-2 infection. We analyze the nasal IFN-I/III signature, namely the expression of ISGF-3–dependent IFN-stimulated genes, in mildly symptomatic COVID-19 patients and show its correlation with serum IFN-α₂ levels, which peak at symptom onset and return to baseline from day 10 onward. Moreover, the nasal IFN-I/III signature correlates with the nasopharyngeal viral load and is associated with the presence of infectious viruses. By contrast, we observe low nasal IFN-I/III scores despite high nasal viral loads in a subset of critically ill COVID-19 patients, which correlates with the presence of autoantibodies (auto-Abs) against IFN-I in both blood and nasopharyngeal mucosa. In addition, functional assays in a reconstituted human airway epithelium model of SARS-CoV-2 infection confirm the role of such auto-Abs in abrogating the antiviral effects of IFN-I, but not those of IFN-III. Thus, IFN-I auto-Abs may compromise not only systemic but also local antiviral IFN-I immunity at the early stages of SARS-CoV-2 infection.

中文翻译：

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具有针对 I 型 IFN 的自身抗体的患者对 SARS-CoV-2 的早期鼻 I 型 IFN 免疫受到损害

在 SARS-CoV-2 感染期间，鼻粘膜中的 IFN-I 和 IFN-III 免疫特征很差。我们分析了轻度症状 COVID-19 患者的鼻 IFN-I/III 特征，即 ISGF-3 依赖性 IFN 刺激基因的表达，并显示其与血清 IFN-α2 的相关_性水平，在症状发作时达到峰值并从第 10 天开始恢复到基线。此外，鼻 IFN-I/III 特征与鼻咽病毒载量相关，并与传染性病毒的存在有关。相比之下，尽管在 COVID-19 重症患者中鼻病毒载量较高，但我们观察到鼻 IFN-I/III 评分较低，这与血液和鼻咽中存在针对 IFN-I 的自身抗体 (auto-Abs) 相关粘膜。此外，在重建的 SARS-CoV-2 感染人气道上皮模型中的功能测定证实了这种自身抗体在消除 IFN-I 的抗病毒作用中的作用，但不是 IFN-III 的抗病毒作用。因此，在 SARS-CoV-2 感染的早期阶段，IFN-I 自身抗体可能不仅会损害全身性而且会损害局部抗病毒性 IFN-I 免疫。