Rapid and accurate diagnosis of COVID-19 plays an essential role in the current epidemic prevention and control. Despite the promise of nucleic acid and antibody tests, there is still a great challenge to reduce the misdiagnosis, especially for asymptomatic individuals. Here we report a generalizable method for highly specific and ultrasensitive detection of serum COVID-19-associated antigens based on an aptamer-assisted proximity ligation assay. The sensor is based on binding two aptamer probes to the same protein target that brings the ligation DNA region into close proximity, thereby initiating ligation-dependent qPCR amplification. Using this system, serum nucleocapsid protein has been detected quantitatively by converting protein recognition into a detectable qPCR signal using a simple, homogeneous and fast detection workflow in ∼2 hours. In addition, this system has also been transformed into a universal platform for measuring specific interactions between spike S1 and its receptor ACE2, and more importantly demonstrated the feasibility for screening and investigation of potential neutralizing aptamers. Since in vitro selection can obtain aptamers selective for many COVID-19-associated antigens, the method demonstrated here will serve as an important tool for the diagnosis and therapeutics of COVID-19.

中文翻译：

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血清学适体辅助邻近结扎法用于COVID-19诊断和寻找中和适体

快速准确地诊断COVID-19在当前的流行病预防和控制中起着至关重要的作用。尽管有可能进行核酸和抗体检测，但减少误诊仍然存在巨大挑战，尤其是对于无症状的个体。在这里，我们报告基于适体辅助邻近结扎测定的血清COVID-19相关抗原的高特异性和超灵敏检测的通用方法。该传感器基于将两个适体探针与同一蛋白靶标结合，从而使连接DNA区域紧密接近，从而启动依赖于连接的qPCR扩增。使用该系统，已通过在约2小时内使用简单，均一和快速的检测流程将蛋白质识别转换为可检测的qPCR信号，从而定量检测了血清核衣壳蛋白。另外，该系统也已转变成用于测量刺突S1及其受体ACE2之间特定相互作用的通用平台，更重要的是证明了筛选和研究潜在中和适体的可行性。以来体外选择可以获得对许多COVID-19相关抗原具有选择性的适体，此处证明的方法将作为诊断和治疗COVID-19的重要工具。