Diagnostic performance and clinical implications of rapid SARS-CoV-2 antigen testing in Mexico using real-world nationwide COVID-19 registry data

  1. Omar Yaxmehen Bello-Chavolla
  2. Neftali Eduardo Antonio-Villa
  3. Luisa Fernández-Chirino
  4. Enrique C. Guerra
  5. Carlos A. Fermín-Martínez
  6. Alejandro Márquez-Salinas
  7. Arsenio Vargas-Vázquez
  8. Jessica Paola Bahena-López

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Abstract

SARS-CoV-2 testing capacity is important to monitor epidemic dynamics and as a mitigation strategy. Given difficulties of large-scale quantitative reverse transcription polymerase chain reaction (qRT-PCR) implementation, rapid antigen tests (Rapid Ag-T) have been proposed as alternatives in settings like Mexico. Here, we evaluated diagnostic performance of Rapid Ag-T for SARS-CoV-2 infection and its associated clinical implications compared to qRT-PCR testing in Mexico.

Methods

We analyzed data from the COVID-19 registry of the Mexican General Directorate of Epidemiology up to April 30th, 2021 (n = 6,632,938) and cases with both qRT-PCR and Rapid Ag-T (n = 216,388). We evaluated diagnostic performance using accuracy measures and assessed time-dependent changes in the Area Under the Receiver Operating Characteristic curve (AUROC). We also explored test discordances as predictors of hospitalization, intubation, severe COVID-19 and mortality.

Results

Rapid Ag-T is primarily used in Mexico City. Rapid Ag-T have low sensitivity 37.6% (95%CI 36.6–38.7), high specificity 95.5% (95%CI 95.1–95.8) and acceptable positive 86.1% (95%CI 85.0–86.6) and negative predictive values 67.2% (95%CI 66.2–69.2). Rapid Ag-T has optimal diagnostic performance up to days 3 after symptom onset, and its performance is modified by testing location, comorbidity, and age. qRT-PCR (-) / Rapid Ag-T (+) cases had higher risk of adverse COVID-19 outcomes (HR 1.54 95% CI 1.41–1.68) and were older, qRT-PCR (+)/ Rapid Ag-T(-) cases had slightly higher risk or adverse outcomes and ≥7 days from symptom onset (HR 1.53 95% CI 1.48–1.59). Cases detected with rapid Ag-T were younger, without comorbidities, and milder COVID-19 course.

Conclusions

Rapid Ag-T could be used as an alternative to qRT-PCR for large scale SARS-CoV-2 testing in Mexico. Interpretation of Rapid Ag-T results should be done with caution to minimize the risk associated with false negative results.

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  1. Version published to 10.1371/journal.pone.0256447
  2. ScreenIT

    SciScore for 10.1101/2021.01.02.21249141: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: Thank you for sharing your code and data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Unfortunately, POCTs have relevant limitations on its diagnostic performance which may question its widespread use to inform public policy or for clinical decision making. Particularly, Rapid Ag-T require an active and symptomatic infection and sampling must be done no later than 7 days after beginning of symptoms, while RT-PCR can be used to assess asymptomatic cases and requires less amount of sample to yield a positive result28. Our data similarly suggests that the time-varying diagnostic performance or Rapid Ag-T might have similar shortcomings to those observed in RT-PCR testing and which need to be considered when using the result of either method to inform decision-making29,30. Future studies should investigate the utility of Rapid Ag-T as triage for RT-PCR use in asymptomatic SARS-CoV-2 infection as well as the ideal time frames to reduce the likelihood of discordant results when implementing sequential testing. Our study had some strengths and limitations. We are using a large national registry of COVID-19 cases, many of whom were tested using both Rapid Ag-T and RT-PCR in a real-world setting which allowed us to reasonably assess diagnostic performance of Rapid Ag-T to detect SARS-CoV-2 infection. We were also able to assess the clinical impact of discordant results on COVID-19 outcomes as well as predictors which indicate settings where additional testing might be useful to reduce the externalities associated with false negative results. Regarding the limitations t...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

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  3. Version published to 10.1101/2021.01.02.21249141 on medRxiv