SARS-CoV-2 Diagnostic Tests: Algorithm and Field Evaluation From the Near Patient Testing to the Automated Diagnostic Platform.

Charlotte Martin,Nathalie De Vos,Fatima-Zohra Bouazza,Marc Decroly,Vincent Collot,Stefano Malinverni,Cecile Duterme,Cyril Debuysschere,Fanny Ponthieux,Frédéric Cotton,Magali Wautier,Marius Gilbert,Marie-Luce Delforge,Nicolas Yin,Hafid Dahma,Magali Bartiaux,Marie Hallin

doi:10.3389/fmed.2021.650581

Abstract

Introduction: Since the first wave of COVID-19 in Europe, new diagnostic tools using antigen detection and rapid molecular techniques have been developed. Our objective was to elaborate a diagnostic algorithm combining antigen rapid diagnostic tests, automated antigen dosing and rapid molecular tests and to assess its performance under routine conditions.Methods: An analytical performance evaluation of four antigen rapid tests, one automated antigen dosing and one molecular point-of-care test was performed on samples sent to our laboratory for a SARS-CoV-2 reverse transcription PCR. We then established a diagnostic algorithm by approaching median viral loads in target populations and evaluated the limit of detection of each test using the PCR cycle threshold values. A field performance evaluation including a clinical validation and a user-friendliness assessment was then conducted on the antigen rapid tests in point-of-care settings (general practitioners and emergency rooms) for outpatients who were symptomatic for <7 days. Automated antigen dosing was trialed for the screening of asymptomatic inpatients.Results: Our diagnostic algorithm proposed to test recently symptomatic patients using rapid antigen tests, asymptomatic patients using automated tests, and patients requiring immediate admission using molecular point-of-care tests. Accordingly, the conventional reverse transcription PCR was kept as a second line tool. In this setting, antigen rapid tests yielded an overall sensitivity of 83.3% (not significantly different between the four assays) while the use of automated antigen dosing would have spared 93.5% of asymptomatic inpatient screening PCRs.Conclusion: Using tests not considered the “gold standard” for COVID-19 diagnosis on well-defined target populations allowed for the optimization of their intrinsic performances, widening the scale of our testing arsenal while sparing molecular resources for more seriously ill patients.

Highlights

Since the first wave of COVID-19 in Europe, new diagnostic tools using antigen detection and rapid molecular techniques have been developed
In the second part of the evaluation, we evaluated the Lumipulse R performance on universal transport media (UTM) samples sent to our laboratory for SARS-CoV-2 real-time PCR (RT-PCR) for patients who required scheduled hospital admission, COVID-19 contacts, or for healthcare workers
Antigen rapid diagnostic test was considered for symptomatic outpatients, automated antigen dosing for screenings and molecular point-of-care tests for hospital admissions

Summary

Introduction

Since the first wave of COVID-19 in Europe, new diagnostic tools using antigen detection and rapid molecular techniques have been developed. These tools could allow diversification of testing strategies and decrease shortages and overflows Thanks to their high sensitivity, ranging from 73.9 to 89.5% for high viral load samples [105-107 RNA copies/swab [3]], and their overall specificity [4, 5], antigen-detection rapid diagnostic tests have been integrated in several countries’ testing strategies [6,7,8,9,10]1,2. Both Centers for Disease Control and Prevention (CDC) [11] WHO [12] and European Center for Disease Control and Prevention (ECDC) [13] have issued guidelines for their use. Several manufacturers have developed molecular point-of-care tests, most of which target influenza and/or RSV [14, 15] while others offer wider respiratory syndromic panel [16]

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Discussion

Conclusion