Covid-19: sequencing, this essential tool for tracking down the virus

To watch for changes in the coronavirus that could worsen the pandemic or make vaccines less effective, scientists must sequence its genome. But few countries carry out and share this laborious, complex and necessary surveillance.

Experts are therefore as concerned about risky mutations that pass under the radar as they are about those they can spot.

The publication of the first genomic sequence of SARS-CoV-2 in January 2020, at the very beginning of the pandemic, made it possible to identify it as a new coronavirus and to start developing diagnostic tests and vaccines.

Since then, tens of thousands of sequences have been uploaded to public databases, allowing mutations to be tracked with precision and speed never before seen.

The lion’s share of this information comes from one country: Great Britain.

By mid-January, GISAID – a major data sharing platform originally created to monitor influenza – had received 379,000 sequences. Of these, 166,000 came from Covid-19 Genomics UK (COG-UK), a partnership between health authorities and academic institutions.

“This is the first time that we see how a pathogen evolves on this scale,” notes Ewan Harrison, director of strategy and transformation at COG-UK and a member of the Wellcome Sanger Institute, where much of the sequencing is performed. “We are learning that these mutations are accumulating much faster than we thought.”

Currently, the program is sequencing 10,000 genomes per week (about 6% of known cases in Britain) and the goal is to double that number.

“The UK has crushed everyone,” says Emma Hodcroft, epidemiologist at the University of Bern and co-developer of the international virus monitoring project, Nextstrain. Denmark, she notes, also regularly sequences and shares data, but information from most other countries is sporadic at best.

– Sequencing, a priority –

Sequencing has identified variants of concern in Britain, South Africa and Brazil.

The new, rapidly spreading variant in the UK is “like a mini-pandemic within the pandemic,” Dr Harrison says. Without systematic monitoring, scientists might not yet have understood that it is “a game-changer.”

The early warning hasn’t stopped its spread – dozens of countries have detected it – but it has allowed others to prepare. Without the warning from British scientists, the world would sail blindly, adds Emma Hodcroft.

Other variants of the virus only became visible when they spread internationally from their point of origin.

This month, for example, a new strain, which carries a mutation called E484K, and which researchers fear may escape immunity, was identified in Japan in people arriving from Brazil.

For the World Health Organization (WHO), improved sequencing capacity is a priority.

Maria Van Kerkhove, WHO COVID-19 technical manager, recently called the number of sequences shared so far “incredible”, but lamented that they only came from a handful of countries.

“Improving the geographic coverage of sequencing is essential for the world to have eyes and ears (on) the changes in the virus,” she said in an online forum.

According to the WHO, a “revolution” in the genomic investigation of viruses has contributed to a better understanding of several diseases, from Ebola to influenza. “For the first time, genomic sequencing can help guide the public health response to a pandemic in near real time.”

When another coronavirus, SARS, began to spread in 2002, only three variants of the genome were shared publicly in the first month and 31 in the third month.

This time, six genomes were available to researchers around the world a few weeks after the virus appeared. In six months, 60,000 were published.

– A minibus ride –

Initially, the new coronavirus did not show much genetic diversity, says Emma Hodcroft, even though it “exploded across Europe”. “We could see that it really seemed to come from China, because all the sequences detected in the world were found in the various Chinese sequences,” she told AFP.

In the summer of 2020, new strains appeared, replacing previous versions of the virus. Mutations are part of viral evolution and occur when the virus replicates. This is “basically a typo,” says Dr. Hodcroft.

Most of the new strains do not confer any advantage on the virus, some even adversely affect it. But sometimes a mutation increases the infectiousness or causes more serious disease.

The more people a virus infects, the greater the possibility of mutation, and the likelihood increases in a person with a chronically weakened immune system. This may be how the new variant appeared in the UK, and researchers are now sequencing strains from immunocompromised patients, says Dr Harrison of COG-UK.

Systematic nationwide sequencing has given researchers new insights into viral transmission.

This made it possible, for example, to identify a trip by minibus (in which a group of people were transported) as the origin of an epidemic focus in a hospital.

The next step is to study how the different mutations affect the transmission of the virus, the severity of the disease and the efficacy of the vaccine, and to predict the behavior of a new variant as quickly as possible.

For WHO, global sequencing will help “better understand the world of emerging pathogens and their interactions with humans and animals in a variety of climates, ecosystems, cultures, lifestyles etc.”

But large-scale sequencing is logistically complex. The Wellcome Sanger Institute, south of Cambridge, England, stores the tens of thousands of samples it receives every day in huge freezers and has designed a whole robotic infrastructure to sort them and use them in his research. .

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