Covid-19

How genomics will help us track Covid-19

Director-General of Health Ashley Bloomfield says the Government will sequence the genomes of yesterday's four Covid-19 cases to help identify how the outbreak started. What does that mean?

New Zealand has found itself suddenly plunged into a dire situation: Four new cases of Covid-19 in the community with no obvious link to the border, managed isolation and quarantine facilities or overseas travel.

While contact tracing is underway to attempt to find out who infected yesterday's four cases and search for more links to the border, it could still come up blank. Contact tracing will never be perfect and the Government is even investigating the possibility that the virus came in a cooled shipping container from overseas, rather than via a person who crossed the border on an Air New Zealand flight.

Given this, the Government has turned to a new tool in its arsenal.

"I should add that we are also doing genome sequencing on all those who have tested positive and our recent cases and current cases in managed isolation and quarantine," Director-General of Health Ashley Bloomfield said on Wednesday.

"That will help us track where this virus may have arisen from and then gotten out into the community."

Viruses mutate

How will it do that? To begin with, we have to understand how virus mutations work. If you don't have the time to read this lengthy Newsroom investigation into the genomics of the SARS-CoV-2 virus, here are the basics.

The coronavirus started small, a 30,000-long string of the same four letters representing nucleotides (A for adenine, C for cytosine, G for guanine and U for uracil) endlessly replicating itself as it circulated through a colony of bats in central or southwestern China.

At some point, it made the leap from bats to humans, sickening tens of thousands of people in Wuhan in December and January - and likely infecting many more.

On December 26, as Chinese authorities told worried Wuhan residents there was nothing to fear, even as they locked up whistleblowing doctors and journalists, one Wuhan man got tested. The result came back positive - a swab from the back of his throat or the inside of his nose had detected the presence of the novel coronavirus.

Scientists at the Chinese Center for Disease Control sequenced the RNA of the virus and uploaded it to a global flu-tracking database called GISAID on January 12. This sample, 29,903 letters long, became the official genome for the virus.

As it circulated in Wuhan in the early days of the outbreak, the virus largely kept its form. Replicating thousands of times to seize control of the respiratory systems of hundreds of patients, inbuilt mechanisms ensured that the few times it made a typo in that sequence of 30,000 nucleotides, the error was corrected.

Then, finally, mistakes began slipping through the cracks. As the virus spread overseas, more typos occurred, until many countries and regions developed their own variants identifiable by certain mutations.

Nearly every country with a significant outbreak now has identifying mutations. Viruses where the 27,964th letter has changed from a C to a U are American. A mutation in Belgium in late January, in which the 28,881st and 28,882nd letters changed from G to A and the 28,883rd letter changed from G to C, has now spread throughout Europe.

Provincial strains also exist. Unique mutations associated with outbreaks in Washington and California have shown up in New York City - as have strains from Europe and Asia. 

It's important to note that, thus far, there's no reason to think any mutations have had an impact on the severity or transmissibility of the virus. Experts have urged the public to treat with caution reports of a particular mutation, the D614G strain, that has been linked to faster spread of SARS-CoV-2.

Tracing through genomes

So, how does this help contact tracers today? The Government will sequence the genomes of all four of yesterday's cases, as well as all recent and current cases in the managed isolation and quarantine system.

This will be able to tell us two things, Jemma Geoghegan, a senior lecturer in viral evolution with a focus on infectious diseases at the University of Otago, told Newsroom.

"It is vital that genomics is part of this response," she said.

First, it could point to the origin of the virus.

"Using the virus genomes from these cases, we can compare them to both the ones that we've sequenced from the quarantine facilities as well as the ones that have been sequenced from the global population and shared publicly," Geoghegan said.

In the ideal scenario, the genome of the virus that has infected the South Auckland family of four is identical or nearly identical to the genome of the virus that has infected one of the managed isolation patients. That would strongly indicate that the managed isolation case in question is the source of the outbreak.

Even if there were intermediaries, the contact tracing could begin to identify those missing links, but having the identities of individuals on both ends of the chain of transmission would be an immense aid.

In another scenario, the genome of the South Auckland four might not match with anyone in managed isolation but could have strong indicators that it came from a particular country or region. Officials could then see which recent arrivals travelled from that location and begin testing and contact tracing them where appropriate.

"Presumably the new cases came from managed isolation facilities and it hasn't been circulating in New Zealand. Genomics can determine which quarantine facility it came from, likely the source of that infection, when that transmission occurred and how long it's been circulating for," Geoghegan said.

The second thing that genomics could reveal is the extent of the outbreak.

"Genomics can tell us the likely size of the cluster - so how many people are actually infected that are represented by these genomes. At that works by looking at the genetic diversity between the genomes."

On average, the virus is thought to undergo about 23.92 mutations a year, or two every month. If the virus in the South Auckland four is one or two mutations away from that of a recent managed isolation case, that could indicate it has been making its way through the community for longer than we might like.

By contrast, if there are no mutations separating it from the index case, then it there are likely to have been few jumps between the managed isolation case and the South Auckland four. That would indicate the outbreak is smaller and will be easier to contact trace, isolate and contain.

The full extent of the usefulness of genomics will become apparent as the week progresses. Bloomfield said on Wednesday that the swabs needed to be sent to ESR, the country's national testing agency, but that sequencing could occur quickly.

"We're wanting to have those results to help inform a decision on Friday, so that will be a key part of our decision-making," he said.

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