Doherty Institute calls for better approach to viral sequencing in pandemics like COVID-19

One of Australia’s principal infectious disease research agencies has called for a rethink on the way virus testing is handled during pandemics to prevent overwhelming health and viral surveillance systems.

Writing in PLOS Genetics, experts from the Doherty Institute – a specialist infectious disease research organisation based in Melbourne – are calling for a new approach to the collection and analysis of viral genomes, saying the way testing occurred through pandemic is unsustainable.

With the continued evolution of the SARS-COV-2 virus, which causes COVID-19, the Doherty Institute’s Dr Ash Porter says Australia’s high level of sequencing carried out during the national case peak at the at the beginning of the year has not continued.

That process was somewhat random – taking samples of individual tests and determining the genetic makeup of the virus prevalent in certain individuals.

They want to see that system changed.

“Doing lots and lots of sequencing is not really possible anymore,” Porter told Cosmos.

“We just have so many cases now that we can’t sequence the proportion that we used to, and having more and more genomes may not correlate to having better results.”

Sequencing: It’s Who Do you Think You Are? for viruses

Genome sequencing is widely used in several scientific disciplines to determine the genetic makeup of organisms. In the case of a virus like SARS-CoV-2, it allows researchers to connect a current sample to ancestral strains – effectively charting a viral family tree.

Take the currently circulating subvariant Omicron BA.5.

BA.5’s ‘family tree’ shows it’s a descendant of the BA.2 variant that prevailed at the beginning of 2022.

BA.2 is itself a descendent of the original Omicron variant, which mutated from the first SARS-CoV-2 strain. In effect, the relationship between Omicron BA.5 and the Delta variant that ran rampant in 2021, is akin to the relationship you have with your great-grand uncle or aunt – it’s still in the family, but we’re getting further and further away.

Sequencing has been used by authorities to guide their public health policy. Omicron was elevated to ‘Variant of Concern’ status because of more than 30 mutations detected in its genome, allowing it to evade immunity and reinfect those previously infected by Delta.

It’s also possible to trace the spread of variants geographically. For instance, testing a newly arrived international traveller could help chart the importation of a strain into a country.

Right now, fewer samples are being sequenced by professionals like Porter and their colleagues. Their proposal is for a new strategy that would provide those working in this field the best opportunity to analyse the evolution of viruses during a pandemic.

Their recommendation is a selective approach to testing and sequencing, rather than the randomised genomic profiling of samples acquired during the large-scale testing implemented during COVID-19’s big Australian bursts in 2020 and 2021.

This approach is broken into sequencing ‘streams’.

Stream and sequence

Under Porter’s approach, those who fit into specific groups such as cross-border travellers, those in living in vulnerable settings such as aged care or outbreak communities, or vaccinated people who have a breakthrough infection, would be prioritised.

Genomic sequencing of viruses among these groups would enable experts to track potentially high-impact variants and their movements.

The second stream involves ‘representative’ sampling – sequencing a proportion of positive cases to contextualise the background prevalence of viral lineages circulating within communities.

“To have a set of cases that are being sequenced from those specific areas of interest might help better, than broad, random sequencing,” Porter says.

A third stream would involve obtaining samples from wastewater and animal populations to identify possible variants that exist in the community and connecting them to source species in the event of zoonotic spillovers.

Overlayed with these samples, Porter says, should be the introduction of metadata collection – information that captures useful details about the person providing the sample for analysis.

Such information could include vaccine status, travel history, disease severity, previous or current medical treatments and demographic data. Combining this information with genomic sequencing could enable experts to determine the movement of viral lineages and diversity within groups, transmission networks and emerging variants of concern.

Metadata tagging could potentially transform global analysis of viral lineages.

“The metadata can prove really helpful in our analysis,” says Porter.

“It’s been collected at different points of the pandemic. At the very start of the pandemic they [authorities] did a really great job of collecting all the travel history of the positive cases and that led us to do some really interesting analyses with that information.

“Metadata is really, really important.

“I know that there’s a lot of privacy issues with sharing metadata that might be associated with an individual patient, but I think that’s something we could overcome and be able to share it within Australia and across the globe.”

A strategy for now and the future

Last month, the WHO boldly declared the end of the pandemic is in sight.

Even so, the ability to implement an effective, cross-jurisdictional system to track evolving pathogens is important, especially with the emergence of new zoonotic diseases in recent weeks including monkeypox and LayV. Even the return of vaccine-derived polio in the US shows the importance of pathogen sampling.

The methods used in viral genomics implemented for COVID-19 have been previously used in Ebola, influenza and some zoonotic diseases, but the current pandemic has seen the need to sustainability use them at scale.

Implementing a targeted, nationwide system for genomic services is something Porter hopes will be considered as pandemic management increasingly adjusts to a ‘living with the virus’ situation both in Australia and globally.

“These systems are definitely applicable to other pathogens out there and I think the way we deal with SARS-CoV-2 is going to be representative of how we deal with future pandemics,” Porter says.

“With climate change and urbanisation, we’re at more risk of zoonotic spillover and emerging infection disease. So, it’s not going to be problem that goes away.”