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Sequencing to detect coronavirus variants



What is sequencing

The SARS-CoV-2 genome is made up of approximately 30,000 nucleotides, organic molecules. Sequencing, “Is to read these 30,000 characters of the genome of the virus”, summarizes Vincent Maréchal, professor of virology at Sorbonne University.

To sequence, we start by taking a PCR sample; then the sequence of nucleotides is observed, corresponding to letters for ease of reading. Finally, this sequence is compared with the other genetic sequences already identified to see any differences. For example, in the case of the N501Y mutation, present in several variants and which seems to make them more contagious, it is an asparagine (abbreviated N) at position 501 of the genome which is replaced in the variant by a tyrosine (abbreviated Y ). Hence the name of the mutation. “A variant often contains several mutations, recalls Philippe Froguel, geneticist and professor at Imperial College, London. Recognizing just one is not enough to determine the variant, you have to read the whole sequence. “

What is the point of detecting variants?

Let’s start by recalling that all PCR tests detect the coronavirus well, regardless of the version. Getting tested is therefore enough to know if you are sick or not.

On a large scale, detecting variants first of all makes it possible to predict the evolution of the epidemic, the future saturation of hospitals and therefore the measures to be taken. In France, for the moment, the reproduction rate of the virus is around 1.1: ten infected people infect eleven others. However, the British variant, for example, increases this rate by 0.4: ten infected people cause fifteen new infections. The more this variant circulates, the more the epidemic gets carried away.

Sequencing is also used to try to link mutations in the genome to changes observed in the propagation or the dangerousness of the virus, to understand which part of the genome does what. “By reading the genome, we can assume what the observed mutations engender, even if this is never completely certain”, recognizes Philippe Froguel, who calls for intensifying sequencing in France.

Who performs the sequencing in France?

Originally, the burden fell on the national reference center (CNR) for respiratory diseases, which itself depends on the Institut Pasteur. This CNR covers two sequencing poles: a Parisian, which currently sequences a little more than 600 viruses per week, and a Lyonnais, which performs around 300 per week. In theory, it is therefore to these two structures that hospitals, nursing homes, and even city laboratories send positive samples for sequencing. In reality, with the arrival of new variants, the CNR found itself overwhelmed.

Another organization is therefore being set up, with a new agency dedicated to infectious diseases. “CNR’s capacities need to be strengthened in these times of crisis, acknowledged Bruno Coignard, of Public Health France. About fifty hospital laboratories within a coordinated network will provide support, and we are in discussions with private laboratories to establish common sequencing protocols. We will mobilize all available resources. “ In fact, some hospitals and research centers did not wait, such as the Marseille IHU. “From the moment the virus is inactivated, any equipped laboratory can do the sequencing”, points out Philippe Froguel.

For the whole of France, the various actors involved had sequenced and deposited a little more than 3,300 sequences of SARS-CoV-2 in the international Gisaid database last week. A participation rather in the European low average. At the head of the Lyon laboratory, Bruno Lina recognized “A delay that we are in the process of filling”. Champion in all categories, the United Kingdom has submitted more than 180,000 analyzes, or nearly a quarter of the sequences carried out worldwide.

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