Screening for new mutations specific to Omicron

The Omicron variant has a significant number of mutations, but none of the three mutations included in the screening strategy deployed in France until December 20. This strategy was based on the detection of three mutations of interest (E484K, E484Q, and L452R). In a context where the Delta variant is overwhelmingly dominant, as observed in France since the summer, viruses lacking any of these three mutations are in the minority, allowing for the suspicion of a potential Omicron variant case by process of elimination. Following the WHO’s classification of Omicron as a variant of concern (VOC) on November 26, 2021, monitoring of screening results for viruses carrying none of these three mutations and an increase in sequencing activity through the EMERGEN* consortium for these triple-negative viruses made it possible to suspect and then confirm the first cases of Omicron in France. However, other variants also do not carry any of these three mutations, which is why the new, more specific screening strategy currently being rolled out will allow for more accurate identification of the Omicron variant.
Thus, since December 20, 2021, screening has been based on a strategy that incorporates a combination of mutations specific to Omicron (such as the 69/70 deletion and the K417N, S371L-S373P, and Q493R substitutions). The SI-DEP information system has been adapted to include a new code (D) alongside the three existing ones (A, B, and C), allowing clinical laboratories to enter the results of additional screenings targeting these mutations carried by Omicron.

These flags help identify suspicious samples for potential whole-genome sequencing of the virus, which is the only way to confirm the presence of this new variant.

The new screening strategy has been gradually adopted by laboratories since December 20, which affects how data is reported to the SI-DEP system. This impacts the screening indicators currently generated under the old nomenclature and published on the InfoCovidFrance dashboard, which should therefore be interpreted with caution.

Until the new indicators are published as open data in January, we are therefore in a transitional phase during which Santé publique France publishes, in its weekly epidemiological report, the screening data corresponding to each of the screening strategies (old and new nomenclature).

Before making the new screening indicators based on this new strategy available as open data, Santé publique France must ensure that they are adopted by as many laboratories as possible and verify the quality, reliability, and completeness of the reported data in order to make any necessary corrections.

Full viral genome sequencing to confirm the presence of the Omicron variant

Unlike screening, sequencing is a technique that takes more time (one week on average) and requires advanced bioinformatics tools to analyze the entire genome and definitively confirm the nature of the variant.
Coordinated by Santé publique France and the EMERGEN* consortium, the random sequencing strategy implemented in France aims to detect a variant whose frequency is low but sufficiently widespread in the country to have an impact on public health. To this end, weekly FLASH surveys analyze a representative random sample of positive tests received on a given day, enabling the determination of the level of variant circulation in France and the identification of new variants. These results are published in the national epidemiological bulletin as well as on the Agency’s website.

In addition, targeted sequencing strategies are implemented to meet specific objectives, such as cluster analysis or the study of severe cases.

Currently, nearly 12,000 samples are sequenced each week as part of the EMERGEN consortium and then deposited in the international GISAID database. These sequencing efforts are conducted both for surveillance and as part of research projects.

For more information:

• Coronavirus: Circulation of SARS-CoV-2 Variants

• InfoCovidFrance

• EMERGEN Consortium

• FLASH surveys