CRISPR diagnostics are powerful tools for detecting nucleic acids but are generally not deployable for the detection of clinically important proteins. Here, we report an ultrasensitive CRISPR-based antibody detection (UCAD) assay that translates the detection of anti-SARS-CoV-2 antibodies into CRISPR-based nucleic acid detection in a homogeneous solution and is 10,000 times more sensitive than the classic immunoassays. Clinical validation using serum samples collected from the general population (n = 197), demonstrates that UCAD has 100% sensitivity and 98.5% specificity. With ultrahigh sensitivity, UCAD enables the quantitative analysis of serum anti-SARS-CoV-2 levels in vaccinated kidney transplant recipients who are shown to produce “undetectable” anti-SARS-CoV-2 using standard immunoassay. Because of the high sensitivity and simplicity, we anticipate that, upon further clinical validation against large cohorts of clinical samples, UCAD will find wide applications for clinical uses in both centralized laboratories and point-of-care settings.

CRISPR 诊断是检测核酸的强大工具，但通常不能用于检测临床上重要的蛋白质。在这里，我们报告一个你超灵敏的基于 CRISPR 的抗体检测 (UCAD) 检测，可将抗 SARS-CoV-2 抗体的检测转化为均质溶液中的基于 CRISPR 的核酸检测，其灵敏度是经典免疫检测的 10,000 倍。使用从一般人群（n = 197）收集的血清样本进行的临床验证表明，UCAD 具有 100% 的敏感性和 98.5% 的特异性。UCAD 具有超高的灵敏度，能够定量分析接种过疫苗的肾移植受者的血清抗 SARS-CoV-2 水平，这些受者使用标准免疫分析显示产生“无法检测到的”抗 SARS-CoV-2。由于高灵敏度和简单性，我们预计，在对大量临床样本进行进一步临床验证后，