Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Oct 5:12:714242.
doi: 10.3389/fmicb.2021.714242. eCollection 2021.

Factors that Influence the Reported Sensitivity of Rapid Antigen Testing for SARS-CoV-2

Valentin Parvu  1 , Devin S Gary  1 , Joseph Mann  1 , Yu-Chih Lin  1 , Dorsey Mills  1 , Lauren Cooper  1 , Jeffrey C Andrews  1 , Yukari C Manabe  2   3 , Andrew Pekosz  2   4 , Charles K Cooper  1
Affiliations

Factors that Influence the Reported Sensitivity of Rapid Antigen Testing for SARS-CoV-2

Valentin Parvu et al. Front Microbiol. .

Abstract

Tests that detect the presence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antigen in clinical specimens from the upper respiratory tract can provide a rapid means of coronavirus disease 2019 (COVID-19) diagnosis and help identify individuals who may be infectious and should isolate to prevent SARS-CoV-2 transmission. This systematic review assesses the diagnostic accuracy of SARS-CoV-2 antigen detection in COVID-19 symptomatic and asymptomatic individuals compared to quantitative reverse transcription polymerase chain reaction (RT-qPCR) and summarizes antigen test sensitivity using meta-regression. In total, 83 studies were included that compared SARS-CoV-2 rapid antigen-based lateral flow testing (RALFT) to RT-qPCR for SARS-CoV-2. Generally, the quality of the evaluated studies was inconsistent; nevertheless, the overall sensitivity for RALFT was determined to be 75.0% (95% confidence interval: 71.0-78.0). Additionally, RALFT sensitivity was found to be higher for symptomatic vs. asymptomatic individuals and was higher for a symptomatic population within 7 days from symptom onset compared to a population with extended days of symptoms. Viral load was found to be the most important factor for determining SARS-CoV-2 antigen test sensitivity. Other design factors, such as specimen storage and anatomical collection type, also affect the performance of RALFT. RALFT and RT-qPCR testing both achieve high sensitivity when compared to SARS-CoV-2 viral culture.

Keywords: RT-PCR; SARS-CoV-2; diagnostic accuracy; meta-regression analysis; rapid antigen testing; systematic review and meta-analysis; test sensitivity; viral culture.

PubMed Disclaimer

Conflict of interest statement

VP, DG, Y-CL, DM, LC, JM, JA, and CC are employees of Becton, Dickinson and Company. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Mechanism of action for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antigen detection through lateral flow assay design. (1) The specimen analyte, containing SARS-CoV-2 antigen suspended in assay buffer, is deposited in the sample well (at 2). (3) The analyte (containing antigen; in green) is absorbed into the sample pad and begins to diffuse across the reaction chamber into the conjugate pad. (4) The analyte comes into proximity of a SARS-CoV-2-specific antigen antibody that is conjugated to a tag (usually consisting of gold, latex, or a fluorophore). (5) The antigen–antibody complex migrates via diffusion across the nitrocellulose membrane. (6) The SARS-CoV-2 antigen–antibody complex comes into proximity of a second SARS-CoV-2 antigen antibody (different epitope) that is covalently bound to the device pad, and an antibody–antigen–antibody complex forms, resulting in the test line. Further diffusion of excess SARS-CoV-2 antibodies (unbound to antigen) results in association of a second covalently bound antibody that is specific for the first SARS-CoV-2 antibody. (7) An antibody–antibody complex forms resulting in the control line.
FIGURE 2
FIGURE 2
Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) flow diagram for reconciliation of articles/sources included in this study.
FIGURE 3
FIGURE 3
Determination of bias associated with the source articles/documents included in this meta-analysis. (A) Scoring as Low, Moderate, and High was performed for Detection bias, Performance bias, and Spectrum bias associated with each data source included. The frequency of the scores is plotted along the Y-axis. (B,C) Funnel plots of logit-transformed sensitivity in a model without any moderators (B) and with moderators included (C).
FIGURE 4
FIGURE 4
Forest plots containing calculated sensitivity values for index [severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antigen test] testing compared to reference [SARS-CoV-2 quantitative reverse transcription polymerase chain reaction (RT-qPCR assay)] test. Data are stratified by days from symptom onset.
FIGURE 5
FIGURE 5
Forest plots containing calculated sensitivity values for index [severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antigen test] testing compared to reference [SARS-CoV-2 quantitative reverse transcription polymerase chain reaction (RT-qPCR assay)] test. Data are stratified by viral load [genomic copies/ml (cpm)] and by symptomatic or asymptomatic status.
FIGURE 6
FIGURE 6
Forest plots containing calculated sensitivity values for index [severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antigen test and SARS-CoV-2 quantitative reverse transcription polymerase chain reaction (RT-qPCR assay)] testing compared to reference (SARS-CoV-2 viral culture) test.
See this image and copyright information in PMC

References

    1. Abbott Diagnostics Scarborough Inc (2020a). BinaxNOWTM COVID-19 Ag CARD HOME TEST[package insert, EUA]. Scarborough, ME: Abbott Diagnostics Scarborough Inc.
    1. Abbott Diagnostics Scarborough Inc (2020b). BinaxNOWTM COVID-19 Ag CARD [package insert, EUA]. Scarborough, ME: Abbott Diagnostics Scarborough Inc.
    1. Abdelrazik A. M., Elshafie S. M., Abdelaziz H. M. (2020). Potential use of antigen-based rapid test for SARS-CoV-2 in respiratory specimens in low-resource settings in egypt for symptomatic patients and high-risk contacts. Lab. Med. 52 e46–e49. - PMC - PubMed
    1. Abdulrahman A., Mustafa F., Alawadhi A. I., Alansari Q., Alalawi B., Alqahtani M. (2020). Comparison of SARS-COV-2 nasal antigen test to nasopharyngeal RT-PCR in mildly symptomatic patients. medRxiv [Preprint] 10.1101/2020.11.10.20228973 - DOI
    1. Access Bio (2020). CareStartTM COVID-19 Atigen-Rapid Diagnostic Test for the Detection of SARS-CoV-2 Antigen [package insert, EUA]. Somerset, NJ: Access Bio, Inc.