Covid 19 coronavirus: What is genome sequencing and why is it so important?

With a fresh Covid-19 cluster in New Zealand - and a new mystery US link - we're hearing more about something called genomic sequencing. What is it, how can it help us get on top of the virus again, and why should we be trying to sequence every positive case? Science reporter Jamie Morton breaks it down.

First off, what exactly is genomics?

We can think of a whole genome as a complete box of genetic jigsaw pieces that make up any organism.

Our own genome - organised into 22 paired chromosomes, along with a 23rd that differentiate our sex – is formed as a double helix of DNA, or deoxyribonucleic acid, containing about three billion bases and around 30,000 genes.

The genome of the SARS-CoV-2 virus that causes Covid-19, however, is different in that the molecule is made up of ribonucleic acid, or RNA, so is single-stranded.

It packs only 30,000 bases, or letters, containing 15 specific genes – among them the "S" gene which codes for a protein on the surface of its viral "envelope" that it protects its genetic material when traveling between host cells.

By sequencing the virus' whole genome – or effectively decoding its genetic puzzle – scientists can visualise what makes it tick, and point vaccinologists to specific parts of its protein structure to target.

Just as importantly, whole-sequencing individual samples can untangle sources of outbreaks – or use a sample's specific RNA signature to directly link one positive case to an infection in another town or country.

The SARS-CoV-2 virus packs only 30,000 bases, or letters, containing 15 specific genes - among them the "S" gene which codes for a protein on the surface of its viral "envelope". Photo / Supplied

For officials trying to mount effective public health responses, the benefit of having that information at hand is obvious.

And whereas sequencing work used to cost billions of dollars and take months, scientists can now do the job in a matter of hours. Samples sent to ESR's labs, for instance, have routinely been turned around within 24 hours.

What has it already been able to tell us?

Before this latest outbreak, New Zealand had recorded around 1200 cases of Covid-19 - the vast majority of them being returned travellers from overseas.

After whole-sequencing about half of the total cases from our February to May crisis period, scientists were able to tease out 277 separate introductions of the virus.

Of those, about a quarter led to only one other secondary case – while just 19 per cent of those introduced cases led to a chain of transmission that could be observed as a lineage.

Most of those lineages could be traced back to North America, rather than to Asia where the virus first emerged – which reflected where it was most prevalent during the time of sampling.

The largest clusters in New Zealand were often associated with social gatherings such as weddings, hospitality and conferences.

The biggest of those - which comprised a lineage called B.1.26 and was linked to a "super-spreading" event at a Southland wedding - most likely originated in the United States.

The team also found no evidence the virus had been circulating before New Zealand's first case was reported on February 26 – and also that fewer cases were missed later in the country's epidemic than in early stages.

Moreover, they were able to use genomic data to help get a handle on how effective our first lockdown was.

For instance, they found the effective reproductive number of New Zealand's biggest cluster - or the average number of times it could spread from one person - was squashed from seven to just 0.2 in the first week of level 4.

The relatively small number of cases we did get also remarkably represented the virus' entire worldwide genetic diversity, reflecting how connected New Zealand was to the rest of the globe.

What has it already told us with this new cluster?

University of Otago and ESR evolutionary virologist Dr Jemma Geoghegan said the origin of the latest outbreak in South Auckland remained unclear - but it wasn't linked to any of New Zealand's previous cases.

"But it's clear that the genomes from this outbreak are all very closely related, because we've been dealing with one source," she said.

"So what we can do is confirm whether there is one outbreak going on - or just one cluster."

Having the genomic data has given officials more confidence in responding to the outbreak, as, together with contact tracing, it's allowed them to link the handful of cases outside Auckland back to the cluster.

But that picture became slightly more blurry today, with sequencing showing that one new Covid-19 case wasn't linked to the cluster, but to a maintenance worker at the Rydges Hotel managed isolation facility.

The sequencing showed a returnee from the US with the same sequence as the maintenance worker stayed at the hotel from July 28 to July 31 before they returned a positive test on day three of their stay.

While there was no obvious person-to-person connection between the worker and the returnee from the US, further investigation and more sequencing work was underway.

Professor Michael Plank, of Canterbury University and centre of research excellence Te Pūnaha Matatini, pointed to the possibility of transmission having come from a contaminated surface - or via another border worker not yet detected.

"This underscores the importance of regular testing of everyone working at the border or quarantine facilities," Plank said.

"If the worker is the index case for this outbreak, there is a good chance we have caught it before it can cause a major new cluster. But we won't know for sure until the contact tracing investigation is complete."

And the latest information again showed just how important genome sequencing could be in helping to identify potential sources of transmission in countries like New Zealand which were managing the pandemic well, University of Auckland microbiologist Associate Professor Siouxsie Wiles said.

"The case of the maintenance worker also shows how tricky this virus is, and highlights the importance of casting the net wide in terms of regular testing of those working in and around our managed isolation and quarantine facilities and airports and ports."

Geoghegan said she'd like to see every positive case in New Zealand sequenced.

"It's clear that if you do know the genomics, you can play an extremely important role when dealing with an unknown source of an outbreak."