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The technological revolutions and data-sharing that enabled an initial sequence of Covid-19 to be produced so quickly have defined an important role for genomics in the pandemic response.

It must be the most important scientific result ever communicated through a tweet. “An initial genome sequence of the coronavirus associated with the Wuhan outbreak is now available.”

Just days after the World Health Organisation notified the world, Professor Eddie Holmes, from the University of Sydney, was sharing the genome of the virus behind it all.

Now, more than five million genomes have been sequenced and shared. The technological revolutions that enabled an initial sequence to be produced so quickly, and the consequence of open data sharing, have defined an important role for genomics in the pandemic response.

Genomic data has been used to develop diagnostic tests and new vaccines and have been crucial in identifying new variants. In Aotearoa, genomics has entered the national lexicon through the regular press conferences.

Despite hearing “genome sequencing” regularly, many people may be generally unaware of quite how genomic technologies have changed the course of this pandemic, and how the lessons learned might help us prepare for future challenges.

What is a genome and what can it tell us?

The genome is the set of genetic instructions that enable any biological entity to function.

Our own genomes contain 3.5 billion letters, but the SARS-CoV-2 genome needs slightly fewer than 30,000 to hijack our biology, copy itself and cause Covid-19.

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Each time the virus makes a new copy there is a chance the genome will mutate, changing the letters it’s made up of. 

Taken together these mutations record the history of any given virus, allowing researchers to trace viral genomes to their origin.

Where did SARS-CoV-2 come from?

By reading virus genomes, researchers have discovered that at least nine different coronaviruses have made the leap from animals to humans, many of them starting out as bat viruses.

SARS-CoV-2 appears to be another gift from bats.

Although it is still unclear exactly how SARS-CoV-2 successfully infected humans, nothing in the genome supports the idea that the virus was engineered to infect us.

We need to keep a much closer eye on the viruses out there in nature, especially those in wildlife which we might come in contact with.

How do you go about sequencing a genome?

The first step in sequencing a SARS-CoV-2 genome is taking a sample (e.g. a nasal swab) and isolating RNA, the molecule that encodes coronavirus genomes.

The amount of SARS-CoV-2 RNA present in a sample will usually be swamped by RNA molecules produced by our own cells and other microbes.

To sequence only the SARS-CoV-2 genome, we employ a technique called PCR to make many duplicate copies of the SARS-CoV-2 sequences in the sample.

Once enough SARS-CoV-2 genome is ‘amplified’, scientists can read the genome sequence and draw conclusions from it.

It can go from swab to genomic report in less than a day – this is what we call ‘real-time’ genomics.

How is SARS-CoV-2 evolving?

As appears to have been the case for SARS-CoV-2, when a virus jumps from one host species to another, it usually will not be as good at infecting its new host.

As it spread around the world, however, genomic sequencing has shown repeated mutations that improve interactions with host cells.

New genetic variants with these mutations arise and steadily displace the ancestral virus – evolution in action.

Now, almost every new case is a result of the Delta variant, which is more than twice as infectious as the original one.

Already, sub-variants of Delta are spreading. And we might well expect mutations that evade our current vaccines to arise in future.

Ongoing genome sequencing will be crucial for tracking the emergence of new variants and guiding us through the race between vaccine and virus evolution.

How does real-time genomics assist in contact tracing?

The availability of real-time genomics added another tool to the public health response toolkit.

As SARS-CoV-2 passes from person to person it leaves a genomic trail. If there is no clear physical link, there may still be a genomic link.

If available in real time, a genomic link can identify who is likely to be the exact source, or at least narrow the field.

New Zealand’s researchers have rapidly developed this new capability to make a tangible difference in New Zealand’s pandemic response: linking cases from the border into the community; linking transmission networks within communities; and helping to identify super-spreader events.

How is SARS-CoV-2 transmitted?

You have likely heard debates about how significant aerosols, droplets, fomites and ventilation might be in SARS-CoV-2 transmission. Genomics can help provide answers.

For example, research has provided evidence of in-flight transmission, influencing decision-making on in-flight protocols and mask wearing.

Likewise, genomic proof of inter-MIQ transmissions between people staying in adjacent rooms provided the evidence needed to change how our MIQ facilities implemented infection prevention and control measures.

What can genomics offer moving forward?

Cutting-edge genomic sequencing technologies rapidly revealed that the cause of Covid-19 was a novel coronavirus – SARS-CoV-2. However, genomics has applications far beyond the pandemic.

It is a very powerful tool which can be used to address a variety of issues, from diagnosing early childhood genetic disorders to creating truly personalised cancer treatments.

As for infectious diseases, genomics has historically been used retrospectively. Now, genomics in real time has proven its worth, not only in supporting informed decision-making during outbreaks, but also as one of our best tools for diagnosing new infections.

Genomics has played a starring role in this pandemic. It may even help prevent the next one by highlighting high-risk practices in areas such as wildlife trading and farming.

The recent announcement of $36 million in funding for an infectious disease research platform will help to cement what we have learnt in this pandemic and help Aotearoa be better prepared for the next one.

Genomics has potential to help us identify and navigate a number of problems in health, disease and the environment. Not least because people now have a better idea of what genomics is and its value.

Dr Jemma Geoghegan is a Rutherford Discovery Fellow and Senior Lecturer at the University of Otago and the Institute of Environmental Science and Research. She is an evolutionary virologist with a research focus in emerging infectious disease.

Dr David Winter is the Technical Lead, Pathogen Genomics at ESR were he uses whole genome sequencing to track and trace the evolution of pathogens in New Zealand and support public health responses to them.

Dr. Joep de Ligt is the Lead Bioinformatics & Genomics at ESR where his work involves both Human and Infectious diseases. He was involved in the implementation of genomics techniques in both research and clinical settings.

Professor Mike Bunce is Principal Scientist (Genomics) at the Institute of Environmental Science and Research and works in the Ministry of Health’s COVID-19 Directorate. His research has spanned a diverse number of applications from virology to ancient and environmental DNA.

*The authors declare that they have no conflicts of interest.

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