Published on MIT Technologie Review on February 23, 2022
Genomic surveillance of SARS-CoV-2 is helping us spot new variants and figure out how to respond. What else could it help us do? By Linda NORDLING
Tulio de Oliveira cuts a lonely figure as he paces across the parking lot of Stellenbosch University’s new $100 million biomedical research building. It’s early January, the height of summer in South Africa, and most students and staff are on holiday. But not de Oliveira. He’s on a conference call with the country’s president, Cyril Ramaphosa.
It’s the second time they’ve spoken in just over a month. The first was right after his genomic sequencing lab had discovered a new covid variant. Today, they’re talking about something else—de Oliveira doesn’t want to give specifics. The call has lasted for some time, and de Oliveira is pacing because he is, by his own admission, not a patient man. Still, his science is directly influencing policy—something he relishes.
“The pandemic has changed the way that science is done,” he tells me once he’s off his call. For one thing, science is happening faster. Six weeks earlier, his team had suddenly felt “a little weirded out” by a resurgence of covid cases in Gauteng, the country’s most populous province. This uneasy feeling prompted a flurry of sequencing activity. It took them only a day to identify the highly transmissible new variant now called omicron. They briefed the health minister and the president, and spent another day checking their work. Then, on November 25, de Oliveira announced the discovery to the world.
Omicron, which is better at evading the body’s immune defenses than its cousins, has since spread everywhere, fueling unprecedented waves of the pandemic. In early January, it was causing weekly infections to rise by 65% in Europe, 78% in Southeast Asia, and 100% in the Americas. Deaths were rising too, albeit more slowly.
Still, the team’s detection and identification of the new variant in November provided a crucial early warning to the rest of the world. In the weeks after the discovery, scientists subjected omicron to a battery of tests. Massive efforts quickly got underway to understand its sensitivity to existing covid vaccines and figure out just how infectious and lethal it was. Policy-wise, the discovery sparked an uptick in booster vaccinations, renewed restrictions, and travel bans.
Before covid, de Oliveira was sequencing scourges like Zika, chikungunya, and tuberculosis from his base in Durban. The pandemic injected unprecedented resources into his field and generated immense political interest in his work. The lab at his new Centre for Epidemic Response and Innovation is stocked with millions of dollars’ worth of equipment—much of it donated by wealthy labs, international health organizations, and manufacturers. Eventually, it’s expected to be the most powerful sequencing lab in Africa.
The spread of SARS-CoV-2 set off an avalanche of genomic sequencing all around the world. More than 7.5 million viral sequences have been uploaded to the global database GISAID, and scientists have sorted millions into tree diagrams tracking the virus’s evolution. That’s the most sequences generated and shared for any germ by far. Sequencing has also grown more common in parts of the world that didn’t have the technology before, which will be vital in spotting any new threats as they arise.
The glut of data on SARS-CoV-2 has allowed scientists to track, in close to real time, how the virus is evolving. And it’s transformed the way we use genomic sequencing to inform health policy, says Sharon Peacock, a microbiologist at the University of Cambridge who leads the UK’s covid genomics consortium. “If we look at previous threats, sequencing was used as a research tool, in a retrospective way,” Peacock says. “Now we have seen that sequencing can provide actionable information.”
With covid, scientists have tried to see if they can forecast how variations in a germ’s genetic sequence might influence how it behaves in people and even help predict its next move. While there remain gaps in the global sequencing effort, which might allow variants to circulate undetected, capacity on continents like Africa has increased dramatically. And de Oliveira and his colleagues want to go further.
While keeping an eye on covid, they want to use the momentum and funding they’ve amassed for genomic sequencing to tackle other diseases, like tuberculosis, HIV, and viral hepatitis. And they want to see if the technology can give us an edge in the ongoing and deadly fight against antimicrobial resistance.
Indeed, the full value of this work may not become clear until long after the pandemic recedes.
The science behind genomic tracking for viruses these days is relatively simple. To sequence a SARS-CoV-2 genome, scientists isolate the viral RNA from a patient sample such as a positive covid test swab. Then they process the RNA into a form that sequencing machines can read.
Twenty years ago, it cost $100 million to sequence one human genome. Today, it costs less than $1,000. However, it’s still not cost-effective to sequence every positive covid test to look for new mutations. So de Oliveira and his team prioritize samples from areas with unexpected upticks in infections reported by national laboratories or doctors in the field.
Using this targeted approach, which he calls “nonlinear sequencing,” they were able to raise the alarm about not one but two variants of concern discovered in South Africa: omicron in November 2021, and beta a year earlier in the Eastern Cape province.
While the rapid detection of new, more infectious versions of SARS-CoV-2 has certainly spurred governments and health systems to act, it has not stopped those variants from spreading. However, knowing about new variants does offer some time to prepare, Peacock says. Many countries rolled out booster vaccinations after scientists established that omicron was better at dodging our immune defenses. “There can’t be any doubt in anyone’s mind that real-time sequencing has had a real impact during the pandemic,” she says.
It’s difficult to quantify the exact impact sequencing has had on hospitalizations or deaths. As one measure, using data from South Africa and elsewhere on how omicron behaved, scientists in the US estimated in early January that doubling the number of boosters given could prevent 41,000 deaths and more than 400,000 hospitalizations by the end of April.
Emma Griffiths, a genomic data expert based at Simon Fraser University in Vancouver, Canada, says genomic surveillance has helped us understand why our diagnostics, vaccines, and therapeutics have become less effective over time, allowing us to update our arsenal of weapons. The pandemic has also built a backbone for sharing genome data across borders, she adds, which could be useful in future outbreaks. And just as important, the global SARS-CoV-2 sequencing boom helped establish sequencing technology in areas that did not have it, or had very little, before the pandemic.
In Peru, genomic sequencing was very “niche” before covid, says Pablo Tsukayama, a microbiologist at Universidad Peruana Cayetano Heredia in Lima. But since April 2020 his lab has received increased funding from the government, which allowed it to discover a new variant of concern, lambda, by the middle of 2021.
While this discovery came too late to prevent the huge wave of illness that lambda caused in Peru, which racked up some of the world’s highest excess mortality rates, he says Peru’s new sequencing capacity will help it track new pathogens coming out of the Amazon rainforest, an area rich in biodiversity where diseases are at high risk of spilling over from animals to humans.
“We need to be able to ring the alarm early,” he says. “That’s where my lab is going.”
Two thousand miles south of Lima, in Argentina’s capital city, Buenos Aires, Josefina Campos is also reaping the rewards of the pandemic’s sequencing boom. Before covid, her genomics lab didn’t actually do surveillance. Sequencing was a retrospective scientific pursuit rather than a tool to assist in public health. Now “everyone wants to sequence,” she says. 2022