An optimized stepwise algorithm combining rapid antigen and RT-qPCR for screening of COVID-19 patients

PLoS One. 2021 Sep 23;16(9):e0257817. doi: 10.1371/journal.pone.0257817. eCollection 2021.

Abstract

Background & aim: We investigated the combination of rapid antigen detection (RAD) and RT-qPCR assays in a stepwise procedure to optimize the detection of COVID-19.

Methods: From August 2020 to November 2020, 43,399 patients were screened in our laboratory for COVID-19 diagnostic by RT-qPCR using nasopharyngeal swab. Overall, 4,691 of the 43,399 were found to be positive, and 200 were retrieved for RAD testing allowing comparison of diagnostic accuracy between RAD and RT-qPCR. Cycle threshold (Ct) and time from symptoms onset (TSO) were included as covariates.

Results: The overall sensitivity, specificity, PPV, NPV, LR-, and LR+ of RAD compared with RT-qPCR were 72% (95%CI 62%-81%), 99% (95% CI95%-100%), 99% (95%CI 93%-100%), and 78% (95%CI 70%-85%), 0.28 (95%CI 0.21-0.39), and 72 (95%CI 10-208) respectively. Sensitivity was higher for patients with Ct ≤ 25 regardless of TSO: TSO ≤ 4 days 92% (95%CI 75%-99%), TSO > 4 days 100% (95%CI 54%-100%), and asymptomatic 100% (95%CI 78-100%). Overall, combining RAD and RT-qPCR would allow reducing from only 4% the number of RT-qPCR needed.

Conclusions: This study highlights the risk of misdiagnosing COVID-19 in 28% of patients if RAD is used alone. A stepwise analysis that combines RAD and RT-qPCR would be an efficient screening procedure for COVID-19 detection and may facilitate the control of the outbreak.

MeSH terms

  • Algorithms
  • Antigens, Viral / immunology
  • COVID-19 / diagnosis*
  • COVID-19 / immunology*
  • COVID-19 / virology
  • COVID-19 Nucleic Acid Testing / methods*
  • Female
  • Humans
  • Male
  • Mass Screening / methods
  • Middle Aged
  • Real-Time Polymerase Chain Reaction / methods
  • SARS-CoV-2 / genetics*
  • SARS-CoV-2 / immunology*
  • Sensitivity and Specificity

Substances

  • Antigens, Viral

Grants and funding

The authors received no specific funding for this work.