Preexisting anti–interferon-α (anti–IFN-α) autoantibodies in blood are associated with susceptibility to life-threatening COVID-19. However, it is unclear whether anti–IFN-α autoantibodies in the airways, the initial site of infection, can also determine disease outcomes. In this study, we developed a multiparameter technology, FlowBEAT, to quantify and profile the isotypes of anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and anti–IFN-α antibodies in longitudinal samples collected over 20 months from the airways and blood of 129 donors spanning mild to severe COVID-19. We found that nasal IgA1 anti–IFN-α autoantibodies were induced after infection onset in more than 70% of mild and moderate COVID-19 cases and were associated with robust anti–SARS-CoV-2 immunity, fewer symptoms, and efficient recovery. Nasal anti–IFN-α autoantibodies followed the peak of host IFN-α production and waned with disease recovery, revealing a regulated balance between IFN-α and anti–IFN-α response. In contrast, systemic IgG1 anti–IFN-α autoantibodies appeared later and were detected only in a subset of patients with elevated systemic inflammation and worsening symptoms. These data reveal a protective role for nasal anti–IFN-α in the immunopathology of COVID-19 and suggest that anti–IFN-α autoantibodies may serve a homeostatic function to regulate host IFN-α after viral infection in the respiratory mucosa.

中文翻译：

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气道中的瞬时抗干扰素自身抗体与 COVID-19 的恢复有关


血液中先前存在的抗干扰素α （抗 IFN-α） 自身抗体与对危及生命的 COVID-19 的易感性有关。然而，目前尚不清楚气道（感染的初始部位）中的抗 IFN-α 自身抗体是否也能决定疾病结局。在这项研究中，我们开发了一种多参数技术 FlowBEAT，用于量化和剖析 20 个月内从 129 名轻度至重度 COVID-19 供体的气道和血液中收集的纵向样本中抗严重急性呼吸系统综合症冠状病毒 2 （SARS-CoV-2） 和抗 IFN-α 抗体的同种型。我们发现，超过 70% 的轻度和中度 COVID-19 病例在感染发作后诱导了鼻腔 IgA1 抗 IFN-α 自身抗体，并且与强大的抗 SARS-CoV-2 免疫力、较少的症状和有效的恢复有关。鼻腔抗 IFN-α 自身抗体跟随宿主 IFN-α 产生的峰值，并随着疾病的恢复而减弱，揭示了 IFN-α 和抗 IFN-α 反应之间的调节平衡。相比之下，全身性 IgG1 抗 IFN-α 自身抗体出现较晚，并且仅在全身炎症升高和症状恶化的患者亚群中检测到。这些数据揭示了鼻腔抗 IFN-α 在 COVID-19 免疫病理学中的保护作用，并表明抗 IFN-α 自身抗体可能在呼吸道粘膜病毒感染后发挥稳态功能来调节宿主 IFN-α。