Covid, the problem of rapid swabs that do not intercept variants of the N- time.news gene

by time news

Rapid antigenic tests to look for Sars-CoV-2 may not be able to intercept variants with some mutations of the N gene (nucleoprotein), what most rapid tests look for in order to make the diagnosis. The problem does not arise for the most widespread variants, the English and the Brazilian, which mutate in the Spike (S) protein involved in the entry of the virus into the host cells and the main target of vaccines, but which keep the N gene unaltered. . This was reported by a study published by researchers from the Department of Molecular Medicine of Padua recently published on the medRxiv platform. The problem is mostly diagnostic. Rapid tests have only one target and often the protein N. If mutated variants in the N gene circulate (harmless and irrelevant from the point of view of diffusion and pathogenicity) the test will not be able to detect the coronavirus.

I study

The researchers, led by Professor Andrea Crisanti, analyzed 1,441 swabs performed at the Padua hospital between 15 September and 16 October 2020, 44% of the total for that month. The antigen test failed to correctly identify the presence of Sars-Cov-2 in 19 of the 61 samples showing a clear positive molecular buffer signal. Some infected have escaped the antigenic despite a high viral load. The sequencing analysis of viruses that showed discordant results in molecular tests and antigenic tests revealed the presence of multiple destructive mutations in the structure of the N protein (the viral protein used as mentioned to detect the presence of the virus in antigenic tests) grouped by positions 229 to 374, a region known to contain the key regions that allow identification of the virus in these tests. According to the researchers, the study demonstrates how genetic variants of the N gene may impair the ability to use antigen tests for both diagnosis and mass testing to control virus transmission. The data are still limited but certainly need to be studied – he comments Pierangelo Clerici, president of the Italian Clinical Microbiologists Association – without forgetting that the diagnosis of choice is the molecular test and there are very precise guidelines on the use of rapid tests. In many contexts the antigenic is not enough and must be followed by the molecular. In any case, any problem or anomaly that emerges with the diagnostic tests reported with alerts that arrive in every hospital.


The spread of variants

Further laboratory tests have also shown that this problem is common to antigenic tests developed by various manufacturers – comments Professor Crisanti -. The sequences of viruses with these mutations are much more frequent in samples negative for antigen tests but with positive PCR and have progressively increased in frequency over time in Veneto, an Italian region that has significantly increased the use of antigenic tests reaching almost 68% of all swab tests for SARS -Cov-2. It is therefore hypothesized that the mass use of rapid antigen tests may unintentionallyand favor the spread of viral variants that are not detectable by these tests, thus contributing to their free circulation and the ineffectiveness of their containment.

Problem already reported

In light of the emergence of new variants, the problem of mutations in the N gene, target of antigenic drugs, had already been reported in mid-February by a circular from the Ministry of Health. It should be specified that the new variants, from the so-called UK variant to the Brazilian variant, which present different mutations in the spike (S) protein, should not in theory cause problems with antigen tests, as these detect the N protein. mutations are emerging for protein N which must be carefully monitored to assess the possible influence on antigen tests

And the materials?

Sequencing Sars-CoV-2 is therefore also useful for diagnostic reasons. If the tests no longer intercept the virus it is clear that they must be updated with new, unchanged loci to be detected. The problem emerged with the rapid swabs, but especially the molecular ones are to be kept an eye on. The analysis of the molecular buffer is in fact looking for three different target genes in the RNA of the virus named S, N and Orf (unlike the rapid which looks for only one, usually N). When all three sites are present we are faced with a variant fully recognized by our diagnostic system. With a 90% negative S it is an English variant, but genome sequencing is needed for further confirmation, he points out Nicola D’Alterio, general director of the Experimental Zooprophylactic Institute of Abruzzo and Molise (IZSAM). We have found it recently 20 N negative patients all in the province of Chieti: they were infected with a “daughter” of the Spanish variant (dominant in Europe in autumn) characterized by a new mutation in the N gene. This change could undermine the diagnosis with molecular swab since N is one of the three sites searched. as if the virus took off the hair band (N) and then also the shoes (S). The molecular swab that looks for those characteristics in the virus no longer finds them. But what if the virus also got rid of the glasses (Orf)? With three negative targets the result would be a negative swab even if the virus is still present, just different. We are not at this point – specifies the director – but these changes must be kept in mind with the genomic investigation, which tells us where the virus is changing, so that we can eventually redesign the molecular test.

March 29, 2021 (change March 29, 2021 | 17:21)

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