Covirus 19 coronavirus: how smart science can untangle New Zealand’s ‘spaghetti’

A new case of Covid-19 appears in a city in New Zealand.

Did it come from another group of infected, as happened when a case related to the group from Auckland Marist College in Christchurch arose, or was it transmitted by someone else at the local supermarket?

Scientists in New Zealand are working on a clever way to untangle the spaghetti dish that is the community spread of Covid-19, by decoding the genetic puzzles of each new case.

“We have just completed the analysis of two suspected cases of community spread for which, in both cases, genomics provided clues as to where the infection might have occurred,” said Dr. Joep De Ligt, ESR scientist.

“This will help inform new containment measures and contact tracing.”

In just 20 years, genome sequencing went from being a long, billion-dollar exercise to one where scientists can decode pathogens in near real time, at the cost of a few hundred dollars.

As expected, the particular pathogen behind the Covid-19 pandemic has been the subject of intense attention.

In positive virus samples sent to his laboratory, De Ligt has been carrying out what’s called complete genome sequencing, or determining the complete genetic sequence of SARS-CoV-2 at the same time.

First sequenced by Chinese researchers, the SARS-CoV-2 genome is a molecule made up of ribonucleic acid, or RNA.

It contains approximately 30,000 bases, or letters, that contain 15 specific genes, including the “S” gene that encodes a protein on the surface of its viral envelope.

Being an RNA molecule, the genome is single-stranded; The human genome, by comparison, is a double helix of DNA, or deoxyribonucleic acid, that contains about three billion bases and about 30,000 genes.

These SARS-CoV-2 genome sequences, often completed in less than 24 hours, have allowed scientists to obtain crucial information about the origin and spread of the virus, and have targeted vaccinologists at specific parts of its protein structure. to attack.

Amid cautious optimism that New Zealand may have acted in time to eliminate the virus, genome sequencing is also expected to play an important role in cleanup here, especially when it comes to evaluating suspected cases of community transmission.

“Community transmission means that traditional epidemiology and contact tracing have failed to identify how the patient became infected,” said De Ligt.

“Sequencing the genome and comparing it to other sequences in the sample genome both here and abroad can help us understand where it comes from.

“Questions like, have we missed it on the border? Did we lose close contact? Is it transmitting between or within cities? Should we block a certain area?

“Since we are seeing fewer cases during the level 4 block, identifying exactly how transmission occurs is crucial if we want to eliminate the disease.”

Rapid sequencing of each case could help identify whether it was linked to a certain group, to other nearby cases, or from another region.

“For example, if a Kiwi has recently returned home and tests positive, we can find out if they actually became infected abroad or if they actually became infected after they returned,” said De Ligt.

“This, in turn, enables political decisions to be made to better stop the spread. This will be a powerful tool to help shape how and when we reduce the alert level.”

As the number of cases in the country crossed the 1000 mark, scientists have been prioritizing the sequence of certain cases.

“The sequencing capacity across New Zealand at Crown research institutes and universities has been supported by initiatives like Genomics Aotearoa, and we have actively increased the number of Covid-19 cases that we can sequence every week,” said De Ligt.

“This involves an interaction of logistics, technical expertise, and having enough sequencing machines and reagents.”

In the early stages of the crisis, when there was robust data indicating links in New Zealand cases to overseas travel, scientists carried out sequencing of samples to confirm that they had been imported infections.

“With our increased sequencing capacity and decreased time between sample collection and sequencing, we can help with suspected cases of community transmission where epidemiological data is less conclusive,” said De Ligt.

“Genomics alone will never be able to identify exactly who infected whom, but it can improve our epidemiological response and is especially adept at saying whether or not a case is part of the groups currently circulating in New Zealand.”

‘We are learning all the time’

De Ligt and colleagues have been sharing their work with the global GISAID Initiative, which acts as a publicly available repository for virus sequence data.

Making the data available gave labs around the world new clues to how the virus, which likely came from an animal, managed to enter human cells.

And ESR’s own work had been impressively fast. According to the World Health Organization’s guidelines on initial case testing, his team generated a complete RNA sequence in two days.

This was done using protocols designed by the ARTIC network, another group focused on rapid processing of viral outbreak samples, and with data integrated through platforms such as Nextstrain.

Dr. James Hadfield, a Wanaka-based phylogeneticist with the Bedford Lab in Seattle, said the level of collaboration among scientists around the world was unprecedented.

“This has allowed efforts like Nextstrain.org to present a continuously updated view on the movements of the virus around the world, and it is a good example where the sum of data from around the world is more informative than any single source,” Hadfield said. .

Scientists had even launched a week-long “biohackathon” to work on different aspects of the virus and how to fight it.

Hadfield said the global sequencing effort had been best placed to deal with this year’s pandemic due to lessons learned from the Ebola outbreak in West Africa in 2013-16.

“Many projects and collaborations have been shaped by what was learned there, including the ARTIC network,” Hadfield said.

“These techniques have been used to combat many outbreaks since then, including the current Ebola outbreak in the Democratic Republic of the Congo, Lassa fever in Nigeria, Zika in the Americas, and Yellow fever, dengue, and other arboviruses in America. from the south”.

It also helped Chinese scientists publicly sequence and publish the SARS-CoV-2 genome a few weeks after the first reported cases.

“This was a great achievement and laid the foundation for the global data sharing effort that we are now seeing,” Hadfield said.

“This allowed us to identify early community transmission in Washington state, which changed the course of the national response.

“Publicly available ARTIC protocols and software are being used in dozens of countries right now, and in some cases genomes are being generated, shared, and analyzed via Nextstrain in less than 24 hours.”

But that didn’t mean there were no more lessons to learn.

“We are learning all the time and working to improve the different bottlenecks in the process,” said De Ligt.

“There are currently some delays in the samples being derived for whole genome sequencing, in part due to the increased burden of proof in testing laboratories.

“This hampers our ability to get an accurate picture of what is happening right now, which will be crucial as we work to eradicate Covid-19 from our shores.”

• Covid19.govt.nz – The official government Covid-19 advisory website