Posted on Feb 23, 2019 2021 at 11:10Updated Feb 23, 2019 2021 at 11:31
Sequencing the coronavirus genome: the operation is crucial to controlling the Covid-19 epidemic, by spotting the appearance of new strains. Unlike several of its European neighbors, like the United Kingdom or Denmark, France does very little.
What does this technique consist of? What lessons can we learn from the epidemic? The explanations of CQFD.
1) What is coronavirus sequencing?
The SARS-CoV-2 genome, or all of its genetic information, is made up of nearly 30,000 nucleotides. Sequencing the virus is like reading these nucleotides, represented by letters for clarity. To sequence, a PCR test is necessary. In the laboratory, the genetic material is then recovered to observe the sequences of nucleotides. They can then be compared with the other sequences already listed.
This technique makes it possible to note any differences, to identify the variants and to analyze them. This relatively recent discipline is called phylodynamics. It had already been used by researchers to work on Zika, Ebola or even HIV. The Covid-19 epidemic once again proves the importance of discipline. “The idea of phylodynamics is that the way in which viruses are propagated leaves traces in their genome”, explains to the “World” Samuel Alizon, researcher at CNRS.
2) What is the interest?
The sequencing of the virus, and its analysis, allow a better understanding of the viral evolution. Concretely, phylodynamics makes it possible to date the appearance of a virus, to find its geographical origin, to understand how it was transmitted from animals to humans, then from humans to humans, and how it spread over the planet.
The phylodynamics also makes it possible to recover data on the duration of contagiousness, the speed of circulation of the virus or to determine the doubling time of the epidemic. Finally, this molecular biology technology is the only way to know if the virus has mutated. By analyzing variants, phylodynamicists are further able to determine whether mutations will make vaccines less effective.
In the case of the Covid-19 epidemic, the sequencing of the virus and the phylodynamics made it possible to infer a number of elements. First, the analysis of the first available sequences demonstrates a common origin of the virus. The latter would go back to around October 2019, in China. This allows us to affirm that there has “not been a circulation of this virus for years”, detailed on May 18 on France Culture Samuel Alizon.
By comparing this new coronavirus to others already identified, the phylodynamics have made it possible to raise the trace of transmission to humans via bats and pangolin. Researchers also extracted information from the sequencing regarding the speed of mutations, that is, the number of letter changes per year. They say the annual rate of change is 0.08% per year, slightly less than influenza or HIV.
The compilation of the different genomes, associated with algorithms to fill in the missing sequences, allows us to learn more about the spread of the virus. The Nextsrain site, collects the genomes of Gisaid, an open access platform, and presents them in the form of trees representing different mutations. It then appears that the contaminations in the United States have various origins.
More recently, sequencing has made it possible to identify the appearance of new strains, such as British variantsand South African. Therefore, “knowing which variant is circulating makes it possible to predict the evolution of the epidemic, the future saturation of hospitals and therefore the measures to be taken”, explains to “La Croix” Philippe Froguel, geneticist and professor at Imperial College, London.
3) Where is France at?
Researchers publish, on Gisaid, the sequences they see around the world. But France is accumulating delays. Of all the people tested positive for the coronavirus in France, around 0.15% have so far been the subject of sequencing.
Even though many other countries are lagging behind, such as Germany and Italy, this proportion contrasts with countries practicing more intensive sequencing such as Denmark – 20% – and the United Kingdom – 5%. And in recent days, several researchers, like Samuel Alizon, have accentuated their criticisms and give opponents to the government the opportunity for a new controversy after that on the supposed slowness of the French vaccination campaign.
Here is the new episode in the saga of government anticipation failures: […] once again, France is late, ”accused the right-wing member (LR) Emmanuelle Anthoine in the Assembly on Tuesday, calling on the Minister of Health, Olivier Véran. He defended himself from insufficient monitoring of the epidemic by stressing that operations to “screen” the coronavirus were already being carried out on a large scale.
4) What are the differences between screening and sequencing?
Screening is not sequencing. It is a much more partial operation, which only makes it possible to identify variants that are already known. The screening is not without interest. It made it possible to establish the significant presence of several new strains in Moselle and to take emergency measures, such as sending additional doses of vaccines. On the other hand, it does not make it possible to identify new variants.
“The completely new ones, you don’t see them and the variants of the variant, you don’t see them either”, underlines the geneticist Philippe Froguel to AFP. “If this variant mutates, you don’t see it: it’s the sequencing that will tell you,” he insists, further noting that the screening tends to give a distorted picture of reality by overestimating the presence of known variants. To avoid being caught off guard by the appearance of a more contagious or deadly strain in the individual, sequencing gives much more visibility.
To be effective, it is not necessary to sequence all the positive cases but only a representative sample. Philippe Froguel judges that 5% would be sufficient. We are far from it, a situation attributed by several researchers to a long-standing lack of public investment in this area, which is currently reflected in a lack of personnel and technical efficiency.