PDF(Pubmed)
Abstract：
OBJECTIVE: We sought to explore the prevalence of type I interferon-neutralizing antibodies in a Chinese cohort and its clinical implications during the Omicron variant wave of SARS-CoV-2.
METHODS: Type I interferon (IFN) autoantibodies possessing neutralizing capabilities were identified using luciferase assays. The capacity of the autoantibodies for in vitro interference with antiviral activity of IFN was assessed by using a SARS-CoV-2 replicon system. An analysis of the demographic and clinical profiles of patients exhibiting neutralizing antibodies was also conducted.
RESULTS: In this cohort, 11.8% of severe/critical cases exhibited the existence of type I IFN-neutralizing antibodies, specifically targeting IFN-α2, IFN-ω, or both, with an elderly male patient tendency. Notably, these antibodies exerted a pronounced inhibitory effect on the antiviral activity of IFN against SARS-CoV-2 under controlled in vitro conditions. Furthermore, a noteworthy correlation was discerned between the presence of these neutralizing antibodies and critical clinical parameters, including C-reactive protein (CRP) levels, D-dimer levels, and lymphocyte counts.
CONCLUSIONS: The presence of type I IFN-neutralizing antibodies is a pervasive risk factor for severe/critical COVID-19 in the Chinese population.
METHODS: Type I interferon (IFN) autoantibodies possessing neutralizing capabilities were identified using luciferase assays. The capacity of the autoantibodies for in vitro interference with antiviral activity of IFN was assessed by using a SARS-CoV-2 replicon system. An analysis of the demographic and clinical profiles of patients exhibiting neutralizing antibodies was also conducted.
RESULTS: In this cohort, 11.8% of severe/critical cases exhibited the existence of type I IFN-neutralizing antibodies, specifically targeting IFN-α2, IFN-ω, or both, with an elderly male patient tendency. Notably, these antibodies exerted a pronounced inhibitory effect on the antiviral activity of IFN against SARS-CoV-2 under controlled in vitro conditions. Furthermore, a noteworthy correlation was discerned between the presence of these neutralizing antibodies and critical clinical parameters, including C-reactive protein (CRP) levels, D-dimer levels, and lymphocyte counts.
CONCLUSIONS: The presence of type I IFN-neutralizing antibodies is a pervasive risk factor for severe/critical COVID-19 in the Chinese population.
摘要：
目的：我们试图探讨I型干扰素中和抗体在中国队列中的流行情况及其在SARS-CoV-2的Omicron变异波中的临床意义。
方法:使用荧光素酶测定法鉴定具有中和能力的I型干扰素(IFN)自身抗体。通过使用SARS-CoV-2复制子系统评估自身抗体体外干扰IFN抗病毒活性的能力。还对显示中和抗体的患者的人口统计学和临床特征进行了分析。
结果：在此队列中，11.8％的严重/危重病例表现出I型IFN中和抗体的存在，特异性靶向IFN-α2，IFN-ω，或者两者兼而有之,有老年男性病人的倾向。值得注意的是,这些抗体在受控的体外条件下对IFN对SARS-CoV-2的抗病毒活性具有明显的抑制作用。此外，这些中和抗体的存在与关键临床参数之间存在显著的相关性，包括C反应蛋白（CRP）水平，D-二聚体水平,和淋巴细胞计数。
结论：在中国人群中，I型IFN中和抗体的存在是严重/危重COVID-19的普遍危险因素。
方法:使用荧光素酶测定法鉴定具有中和能力的I型干扰素(IFN)自身抗体。通过使用SARS-CoV-2复制子系统评估自身抗体体外干扰IFN抗病毒活性的能力。还对显示中和抗体的患者的人口统计学和临床特征进行了分析。
结果：在此队列中，11.8％的严重/危重病例表现出I型IFN中和抗体的存在，特异性靶向IFN-α2，IFN-ω，或者两者兼而有之,有老年男性病人的倾向。值得注意的是,这些抗体在受控的体外条件下对IFN对SARS-CoV-2的抗病毒活性具有明显的抑制作用。此外，这些中和抗体的存在与关键临床参数之间存在显著的相关性，包括C反应蛋白（CRP）水平，D-二聚体水平,和淋巴细胞计数。
结论：在中国人群中，I型IFN中和抗体的存在是严重/危重COVID-19的普遍危险因素。
