25 Nov 2020

How Covid-19 genome sequencing maps the spread of the virus

From Checkpoint, 5:07 pm on 25 November 2020

Urgent genome sequencing in the case of an Air New Zealand crew member with Covid-19 could provide more clues to where they got infected.

The person tested positive during routine screening in China and was flown back to New Zealand yesterday on a freight flight to avoid contact with other passengers.

The crew member and seven of their close contacts are now in quarantine at Auckland Jet Park Hotel.

Health officials have been investigating and tracing the case as if it were a confirmed community case in New Zealand.

ESR is racing to complete the genome sequence for this case and will compare it to others on a database.

"We have an almost complete picture of everything that is around in the country. But there's still the very small possibility that it is something that we haven't picked up yet in the community," ESR scientist Dr Joep de Ligt told Checkpoint.

"As I say that is a small possibility, because there is good testing in New Zealand and we have a near complete picture, but it's something that we cannot exclude as a possibility.

"Of the complete overview of cases, there would be about an 80 percent coverage. And in terms of the last couple of months that is 90 percent complete.

"There's a couple of cases where we sometimes don't have enough RNA to actually get a complete genome out, but it is almost as complete as we can have it.

"That could be because the person was infected historically and doesn't have a lot of virus in their body anymore. That's what most typically happens, or for some reason there's just not a lot of RNA in the sample."

Dr de Ligt said ESR scientists were trying to keep coverage above 90 percent.

"We will try to sequence any sample just to be sure that we can get as close to that mark as possible. But if you have that sort of level of coverage, then you can start to make some conclusions about your missing data.

"What is promising is that if it is indeed those historic cases, it's also less likely that they will lead to onward spread, so it's not as bad of a problem if you miss them."

There is a global database of genome sequences of Covid-19 strands, where scientists can upload their information and download other sequences from other countries.

"So there's quite a good international effort where that sharing happens to help us with these types of investigations," Dr de Ligt said.

"In this case, if we were to find a link to one of our New Zealand genomes… that tells us with quite some certainty that they are part of a same transmission chain as we call it.

"That means that in terms of investigations, we can start to look at how those two people might have interacted, and that probably is through an additional person, but that we can start looking for the missing links.

"If we wouldn't find a link to a New Zealand genome, we can then look at those international genomes. If it is very close to one of those international genomes that makes it more likely that it is what we call a travel-related infection, where we might start to look more in detail at the airports, or the airlines involved with the movements of a certain person.

"Some genomes are quite unique. Some of the ones that we have in New Zealand, because we have a quarantine system, they have not spread to anywhere else in the world.

"So if we find a mutation that is like that, that hasn't been seen anywhere else, that is quite certain. But if it is a sequence that is widespread across the globe, then it becomes less certain. So it really depends on the individual genome that we find, how certain or uncertain we can be."

A genome sequence is 30,000 As, Ts, Cs and Gs in a row, Dr de Ligt said. "That is what the genome sequence looks like.

"If we want to abstract that even further, it's a bit like every virus carries a book of instructions. And those instructions, when it enters the human cells, they are used to make more copies of the virus.

"And that book of instructions, that's the genome.

"It's almost a recipe that defines how the virus is made. Sometimes in that recipe changes happen, just like if you get a recipe from the internet and you read that there's only one clove of garlic and you really love garlic, you might make two or three cloves of garlic.

"That is your version of that recipe, and if you then hand that recipe over to another person, they will have that starting version with more garlic in it."

Dr de Ligt said in the cluster of Covid-19 cases related to a Defence Force member, all but one of the genomes were identical.

"So they're the exact same recipe, so no changes are made. And that is increasing the confidence that they were recently related to each other."

The genome sequencing, however, did not explain how the virus gets passed from one person to another.

"That's where the epidemiological investigation that the public health units and our epidemiologists get into play," he said.

"It's about when does a person start showing symptoms, what was their movement what was their contacts - that will dictate the direction of that transmission chain.

"Every time the virus goes to a new person, there's that chance for a difference to occur. So the more people it goes through, the larger the chance that that happens.

"What we, for example, saw in August up in Auckland was that at some point we had cases that were four mutations or four changes away from the original outbreak.

"So as time progresses you expect those mutations to occur. If all of a sudden you would find someone that has two or three mutations away from what you knew previously, that's when you really start scratching your head about missing links and those types of things, because that must have passed through multiple people to accumulate that number of mutations."