A CRISPR-based ultrasensitive assay detects attomolar concentrations of SARS-CoV-2 antibodies in clinical samples

Yanan Tang, Turun Song, Lu Gao, Saifu Yin, Ming Ma, Yun Tan, Lijuan Wu, Yang Yang, Yanqun Wang, Tao Lin () and Feng Li ()
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Yanan Tang: Sichuan University
Turun Song: Sichuan University
Lu Gao: Sichuan University
Saifu Yin: Sichuan University
Ming Ma: Sichuan University
Yun Tan: Sichuan University
Lijuan Wu: Sichuan University
Yang Yang: Second Hospital Affiliated to Southern University of Science and Technology
Yanqun Wang: the First Affiliated Hospital of Guangzhou Medical University
Tao Lin: Sichuan University
Feng Li: Sichuan University

Nature Communications, 2022, vol. 13, issue 1, 1-10

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-32371-4

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