In France, the massive deployment of antigen tests has been organized by the government to complete the diagnostic arsenal. However, competent authorities did not factor in the doubts voiced by learned societies on the highly targeted specification of these tests. Indeed, a vast majority of biology laboratories alerted the authorities of the sensitivity and specificity flaws of these tests against RT-PCR, by relying on internal studies and studies executed in a hospital environment. A study on Antigen tests reality by Biogroup.

Context of the study

Massive use of these test by health professionals without a proper medical biology training, the lack of skills in pre-analytical phases (execution of swabbing, identity monitoring, etc), analytics (control of the execution conditions of the test according to strict recommendations from the supplier: temperature, playback time, etc) and post-analytical (results interpreted on a summary, document normally opposable) seem to be aggravating factors of bad performances obtained with these tests.

Objectives and Process

In order to obtain a reel vision over the antigenic test method’s impact in France, Biogroup laboratories (1st French private laboratory network) conducted the following study.

Since November 23rd, 2020, patients coming to a Biogroup test centre for a PCR SARS-Cov-2 are invited to answer the following question: “have you done an Ag test searching for SARS- Cov-2 and if so, what was the result?”. The answers are saved, then an extraction of databases allows us to compare the result obtained with the Ag test to the result obtained with the RT-PCR test, considered like the gold standard.

Result

Between November 23rd, 2020, and December 15th, 2020, over 300 laboratories in regions Ile de France and Provence Alpes Côte d’Azur participated in the study. 1,327 patients had realized an Ag test in the 24 hours before coming to the centre.

The data is shown in the table below: 

Week

# tests Ag Neg. < 24h

# PCR Pos. with test Ag Neg. <24h

# PCR Neg with test Ag Neg. < 24h

# tests Ag Pos. <24h

# PCR Pos. with test Ag Pos. <24h

# PCR Neg. with test Ag Pos. <24h 

Total

1,327 111 1,216 339 125 214
48 31 1 30 5 2 3
49 418 35 383 123 39 84
50 737 64 673 159 65 94
51 141 11 130 52 19 33
Antigen tests reality

Conclusion

Sensitivity

Ag tests give a vast quantity of false negatives. These last weeks, several tens of thousands of positives wrongfully came out as negative.

Specificity

The scale of the specificity flaw is more significant than we were expecting or than what we found in literature. Use and interpretation flaws of these Ag tests by staff that lacks the “medical biology culture” certainly explains these bad results.

Although resorting to Ag testing in a strict environment (executed in the right way and by qualified staff) can turn out to be useful when RT-PCR testing is not accessible in the next 24hours, the situation of the last few weeks during which the turnaround of PCR test improved greatly (100% of PCR test results provided in less than 24hours in the Biogroup network realizing 20% of all international PCR testing), does not justify the use of Ag tests in the way it is envisioned in France.

The reality of these antigen tests is that they were meant to be a complement for RT-PCR tests. The first indications of HAS were clear and well contextualized: the use of antigenic tests were supposed to be solely in the case of a RT-PCR test that could not come back on time. Indeed, the lack of reliability of these tests was then offset by the benefit of retrieving a result more quickly. Nevertheless, the expanding of these tests to all patients, including asymptomatic ones (people for whom the performance of these tests have been the worse) led the grand public to using them massively at the expense of RT-PCR reference tests.

In the end, through insufficient information from authorities to the public, and an insufficient training of the people executing the tests, the authorities substituted to a test with very good performances (RT-PCR), one of poor quality, leading to an important loss for the patients.

Discussion

The study of the Antigen tests reality presumably comprises a selection bias. Indeed, Why do patients with an Ag test come back for a RT-PCR test? Probably because their clinical state or the context were discordant with respect to the result. However, the interest of the study lies in the multiplicity of tests used and people tested. It represents a real picture of the field, of what is occurring during screening campaigns. Every other study focuses either on a unique reactant, or on a unique population (such as symptomatic people for instance). Moreover, our study takes into consideration every interpretation, reading and manipulation mistake that could occur with unqualified operators. Indeed, every study evaluating the performance of these tests is executed in strict conditions of control over the testing procedures: temperature, migration time, skilled readers, etc. This could explain the strong discrepancies observed between our results and the supplier files, which announce exceptional performances that not a single study has found.

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