The Delta variant is a highly contagious Sars-CoV-2 virus strain. Video / Paul Slater
Scientists have sequenced samples from hundreds of confirmed cases in this outbreak, to generate whole genomes that represent the virus' entire genetic make-up. It's made a crucial difference in managing the outbreak in real time, while also confirming a link with Australia's Delta outbreak. What other insights have we gleaned? Dr David Welch and Dr Jordan Douglas of the University of Auckland, Dr James Hadfield, a Wanaka-based phylogeneticist with Seattle's Bedford Lab, Otago University and ESR virologist Dr Jemma Geoghegan, and ESR's Dr Joep de Ligt discuss the results.
Why is genome sequencing an important tool in managing Covid-19 outbreaks?
First, it reassures us that the cases are indeed part of the current outbreak, as opposed to transmission from an unrelated border incursion, such as the Air New Zealand worker from earlier in August.
Second, as diversity appears within the genomes of the outbreak it allows contact tracers to focus on the locations of interest where the genomes match, and rule out those associated with a different sub-cluster.
Sequencing every positive case allows us to define cluster membership when epidemiological links are lacking or murky, which is particularly important during a large outbreak like this one.
The rapid pace at which genomes are generated in New Zealand - usually within less than 24 hours of a case being detected - means that they can assist public health investigations in real time, with sequence data often available at about the same time contact tracing interviews are completed.
From a research point of view, the data we are collecting is invaluable because we have a very complete sampling of genomes and very detailed epidemiological data associated with each case.
Having these sources together allows us to create an accurate transmission tree from which we can understand properties of the virus such as how fast it spreads within households and where super-spreading events have taken place, or how effective alert levels are at slowing the spread.
Finally, sequencing every case in MIQ tells us exactly which variants are coming into the country.
When variants of concern such as Alpha or Delta that need more stringent management are found, the public health response can change accordingly.
What has sequencing taught us in this latest episode?
In this outbreak, we found a genomic link to an MIQ case who tested positive eight days before the first community case was detected.
It is clear that this outbreak is linked to New South Wales as the genomes of the first local cases exactly match recent genomes from there.
Indeed, they exactly match the genome of a case in MIQ who come from New South Wales.
But we must be cautious when interpreting genomic data.
While genomic data can provide clues about the transmission chain, proving transmission is a lot more difficult even with infection from a genetically identical coronavirus – there are lots of genomes in New South Wales that are identical to the first case here and there were lots of people on those "red zone" flights.
So, although the genomics strongly supports a connection there are some missing pieces in the transmission puzzle.
Genomic evidence shows that there was, within MIQ, spread from the New South Wales traveller in question to their neighbours, which further bolsters the view that this MIQ case was the source; we just need to find those epidemiological links.
At this point we can't definitively rule out a separate introduction but that is not for lack of trying.
And what can we say about the evolution of this variant, and its path from its point of origin to New Zealand today?
The Delta lineage was first detected in late 2020 and caused an enormous second wave in India in early 2021.
The genetic make-up or "genome" of SARS-CoV-2 is much less complex than our own - and contains just 30,000 bases, making up 15 specific genes. Photo / USCDC
The variant began to rise in frequency across the world replacing many other variants, including Alpha, which was dominant at that time.
Public Health England declared it a "variant of concern" in May 2021 based on its increased transmissibility.
Delta continues to be the most dominant lineage sequenced worldwide and, in many countries, it's pretty much the only lineage found.
There are many millions of Delta chains of transmission globally and a large diversity of genomes within the Delta lineage, including "Delta+" variants that contain mutations associated with other variants of concern.
Looking at the positive MIQ cases we've sequenced in the past two months, all but one was Delta.
As this graph shows, the vast majority of all covid cases around the world are now Delta.
Within this outbreak itself, can we see any level of genomic diversity?
As with any large Covid-19 outbreak, there is a great deal of genomic diversity within the outbreak.
Of the 388 complete genomes we have so far, we can identify about 80 distinct genomes.
There are 56 so-called "single nucleotide variations" which are single letter changes within the genetic code of the 30,000-letter-long genome.
The remainder of the changes are "deletions", where a small number of letters are omitted from the sequence.
Results from genome sequencing are making a crucial difference to the management of New Zealand's Delta outbreak. Photo / Dom Thomas/RNZ
These mutations help to define sub-clusters and link cases together.
This information, combined with epidemiological data, can help contact tracers by linking cases to a potential source or even excluding them from a sub-cluster.
Having said this, 221 of the 388 genomes are genetically indistinguishable from each other, which is similar to what we have seen in other outbreaks.
Genomes are also being shared with global platforms. How do these work, and why are they important in managing the wider pandemic?
Researchers around the world, including us, share genomic data - without any personally identifiable information - to databases such as GenBank and GISAID.
This reciprocal sharing helps when trying to understand where a new case may have originated.
Check out each of the community outbreaks in Aotearoa in the year to June 2021 in the form of a @nextstrain narrative. Not only can you read how rapid sequencing helped contain each of these outbreaks, but you can explore the genomic data yourself.https://t.co/Q8ciONoTT4pic.twitter.com/bWJFZP9jG7
Platforms such as Nextstrain analyse global data and present a high-level view into Sars-CoV-2 spread and evolution.
Our understanding of the behaviour of variants such as Delta relies on this kind of global sharing.
How does the genomic profile of this outbreak differ from those of previous ones? Our main wave last year, for instance, carried much more genomic diversity and included 300 introductions from different parts of the world.
The genomic profile of this outbreak is very different to the first wave in 2020.
Not only because it is the Delta variant, but also because the outbreak's genomic diversity is much smaller, due to all cases sharing a single introduction.
This differs from our first wave where there were multiple introductions and genomic diversity that reflected the diversity seen across the world.
We are also testing and sequencing much more so will be picking up the large majority of cases involved in this outbreak.
In the first wave, particularly early on, there were significant gaps in testing so that the extent of the outbreak was not fully understood.
This outbreak, with over 550 cases, is by far the biggest single cluster we have seen in New Zealand.
Before this, the largest outbreak was the 2020 Auckland outbreak - with 179 cases followed by the Bluff Wedding cluster with 98 cases.
