Mon. Dec 6th, 2021


While the pandemic is heading for an enviable two-year milestone, the Otago Global Health Institute’s Covid-19 Masterclass Series brings together a network of experts to discuss key Covid-19 topics. We run a piece daily until December 5th.

The technological revolutions and data sharing that made it possible to produce an initial sequence of Covid-19 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 coronavirus genome sequencing associated with the Wuhan outbreak is now available.”

Just days after the World Health Organization announced the world was Professor Eddie Holmes of the University of Sydney divide the genome of the virus behind it all.

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

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

Despite regularly hearing “genome sequencing”, many people may generally be unaware of how genomic technologies have changed the course of this pandemic and how the experience gained can 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 a little less than 30,000 to hijack our biology, copy itself, and cause Covid-19.

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Every time the virus makes a new copy, there is a chance that the genome will mutate and change the letters it consists of.

Together, these mutations record the history of a given virus, enabling researchers to trace viral genomes to their origins.

Where did SARS-CoV-2 come from?

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

SARS-CoV-2 seems 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 viruses out there in the wild, especially those in the wild that we may come in contact with.

How do you proceed to sequence a genome?

The first step in sequencing a SARS-CoV-2 genome is to take a sample (eg, a nasal inoculum) and isolate RNA, the molecule that encodes coronavirus genomes.

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

To sequence only the SARS-CoV-2 genome, we use 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 does SARS-CoV-2 develop?

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

However, as it spread throughout the world, genomic sequencing has shown repeated mutations that enhance interactions with host cells.

New genetic variants with these mutations are constantly emerging and repressing the ancestral virus – evolution in action.

Now almost all new cases are a result of the Delta variant, which is more than twice as contagious as the original.

Already now sub-variants of Delta are spreading. And we can very well expect that mutations that evade our current vaccines will occur in the future.

Continuous genome sequencing will be crucial to track the emergence of new variants and guide us through the race between vaccine and virus development.

How do real-time genomics help with contact tracking?

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

When SARS-CoV-2 passes from person to person, it leaves a genomic trace. If there is no clear physical connection, there may still be a genomic connection.

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 researchers have rapidly developed this new ability to make a tangible difference in New Zealand’s pandemic response: connecting issues from the border to society; interconnection of transmission networks within communities; and helps identify super-spreader events.

How is SARS-CoV-2 transmitted?

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

For example, research has provided evidence of in-flight transmission, which has influenced flight logging and mask wearing.

Likewise, genomic evidence of inter-MIQ transmissions between persons residing in adjacent spaces provided the necessary evidence to change how our MIQ facilities implemented infection prevention and control measures.

What can genomics offer in the future?

Advanced genomic sequencing technologies quickly revealed that the cause of Covid-19 was a new coronavirus – SARS-CoV-2. But genomics has uses far beyond the pandemic.

It is a very powerful tool that can be used to solve a variety of problems, ranging from diagnosing genetic disorders in early childhood to creating truly customized cancer treatments.

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

Genomics has played a major role in this pandemic. It may even help prevent the next by highlighting high-risk practices in areas such as wildlife trade and agriculture.

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

Genomics has the potential to help us identify and navigate a range of health, disease and environmental issues. 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 new infectious diseases.

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

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

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

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

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