More than 217,000 new cases on March 29, an average of 136,000 infections per day over the past week, an increasing incidence and positivity rate: the new wave of Covid-19 in France is growing. Faced with the resurgence of the virus, the French are again using the tests massively. But are they still as effective in detecting the sub-variants of Omicron, BA.1 and especially BA.2, which have become the majority in France?
The question arises, as biologists and patients regularly report cases of false negatives. “I had symptoms, but I had done a negative self-test. I still asked for a PCR test in the laboratory two days later, and it came back positive”, says for example Laurent, a 45-year-old Parisian. Have some tests become less sensitive to these new viruses?
Omicron does not multiply in the same places
“The main explanation is related to the change in tropism of the Omicron variants compared to the previous ones in our organism, i.e. the place where they multiply preferentially. For BA.1 – we are still awaiting confirmation for BA.2 – this is the oropharynx, the area at the back of the throat, just above the trachea, whereas previous viruses primarily targeted the nasopharynx, behind the nose”, explains Professor Jean -Michel Pawlotsky, head of the bacteriology virology department at the Henri-Mondor hospital in Créteil. With two notable consequences: painful angina for the patients, but also a small effect on the results of the tests, when they are carried out too early: “At the very beginning of the infection, the patient will have a lot of virus at the bottom of the throat, but not necessarily as much in the nasopharynx, even if it is symptomatic”, details this expert.
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As a result, nasopharyngeal swabs for antigen testing, or nasal swabs for self-testing, may not “harvest” enough virus, and come back negative. In this case, advises Professor Pawlotsky, the best solution is to wait a day or two, and to redo a test, “especially if you have been in contact with a patient, or that you have symptoms”. But for the professor of virology, this small difference remains marginal, and it does not justify calling into question the interest of antigenic tests or self-tests, even with nasopharyngeal or nasal samples.
The peak of positivity is “narrower”
Member of the collective On the side of science and researcher in immuno-oncology in Strasbourg, Eric Billy also insists on the importance of the moment when the test is carried out. “False negatives – especially for antigens – could be explained by the fact that they are carried out when people are not yet positive, he confirms. In order to reduce the risk of false negatives due to a sampling too early, you should isolate yourself as soon as symptoms appear and do a test two days later, i.e. at D+5 after infection. Indeed, several scientific studies suggest that with Omicron, the peak of positivity occurs on average between 4 and 8 days after an infection. “This peak is probably narrower than before – we are positive for less time – a phenomenon favored by the immunity acquired gradually through contamination or vaccination”, adds Maxime Sol, biologist in a laboratory private member of the INOVIE group. According to him, some weakly positive people become negative just two days later.
In France, there are two types of virological tests. RT-PCR consists of looking for the presence of the RNA of the virus and the analysis is carried out by a biologist in a medical biology laboratory. Antigenic tests aim to flush out the N protein (for nucleocapsid) of the virus and can be carried out by a health professional, for example a pharmacist, or at home, thanks to self-tests. A hypothesis often mentioned to explain the false negatives would be that the viruses of the Omicron family would have changed too much compared to the old strains of SARS-CoV-2 and that the tests would struggle to spot them. It turns out to be wrong.
Regarding RT-PCR tests, “it seems unlikely”, sweeps Eric Billy. Same thing for antigen tests: “We compared the performance of antigen tests compared to PCR for different variants, and apart from that possibly linked to the quantity of virus sampled, we did not note any loss of sensitivity between the variants. Alpha, Delta and Omicron”, explains Professor Pawlotsky. Nothing surprising according to this expert: “The protein N of the virus is a well-conserved structural protein, which means that it mutates little from one variant to another, unlike the surface protein, the spike (protein S or Spike, targeted by vaccines). It could happen, but it hasn’t yet, so antigen tests continue to recognize it.”
Poor quality samples
But other phenomena could be at play. “We sometimes have much less visible bands which appear at the end of the reading time, notes Maxime Sol. However, some do not wait until then and read the tests less attentively”, which could explain a part of the false negatives. But why are the bands less visible and later? “If infection with BA.2 produces a large quantity of virus – which a preliminary study which must be confirmed – suggests, this would mean that the variant ‘clings’ less to the antibodies of the antigen tests, continues the specialist. This could explained because the samples are less clean, with a predominance of rhinorrhea [des écoulements de nez, NDLR] abundant which interfere with the good recognition of the virus”. A solution would make it possible to avoid this pitfall: “to blow your nose thoroughly before the sample”, advises Maxime Sol. The quality of the sample remains, in any case, essential. If BA.2 is less recognized by the tests, it is then necessary to take a real nasopharyngeal and not nasal sample.And in case of doubt, it is better to go through an RT-PCR test, the reliability of which remains superior.
Especially since another problem, already pointed out with the previous variants, remains intact: the differences in reliability between the different brands of antigenic tests on the market today. “We studied 22 products, and some still produce too many false positives or false negatives”, notes Professor Pawlotsky. Only here, there are today more than 200 tests marketed in the world: “We had reported certain problems to the public authorities, which proceeded to withdrawals. But laboratories like ours do not have the means to evaluate them all “, he regrets. The only solution, according to this expert: that pharmacists look at the scientific literature and buy the products for which evaluations are available.
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Finally, another hypothesis could explain that symptomatic people test themselves and find a negative result: the flu. “There is a probable cognitive bias coming from the fact that this virus is circulating a lot at the moment. Thus, out of 100 suspected Covid cases, we have around 50 negatives, 40 to 45 positives and 5-10 flu”, underlines Maxime Sol. Which, in the end, makes little difference: whatever the virus, the main thing is to isolate yourself well, to avoid participating in the spread of the epidemic, and contaminating fragile people.
Stephanie Benz and Victor Garcia
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