Doctors and nurses at a South African hospital group noticed an odd spike in the number of Covid-19 patients in their wards in late October.
Their government had slackened its lockdown grip, and springtime had brought more parties. But the numbers were growing too quickly to easily explain, prompting a distressing question.
"Is this a different strain?" one hospital official asked in a group email in early November, raising the possibility that the virus had developed a dangerous mutation.
That question touched off a high-stakes genetic investigation that began in Durban on the Indian Ocean, tipped off researchers in Britain and is now taking place around the world.
Scientists have discovered worrisome new variants of the virus, leading to border closures, quarantines and lockdowns, and dousing some of the enthusiasm that arrived with the vaccines.
Britain has been particularly overwhelmed. Infections and hospitalisations have skyrocketed in recent weeks since that country discovered its own variant of the virus, which is more contagious than previous forms. By one estimate, the mutated virus is already responsible for more than 60 per cent of new infections in London and surrounding areas.
The coronavirus has evolved as it made its way across the world, as any virus is expected to do. But experts have been startled by the pace at which significant new variants have emerged, adding new urgency to the race between the world's best defences — vaccinations, lockdowns and social distancing — and an aggressive, ever-changing foe.
The new variant pummelling Britain has already been found in about 45 countries, from Singapore to Oman to Jamaica, but many countries are effectively flying blind, with little sense of how bad the problem may be.
Long before the pandemic emerged, public health officials were calling for routine genetic surveillance of outbreaks. But despite years of warnings, many countries — including the United States — are conducting only a fraction of the genomic studies needed to determine how prevalent mutations of the virus are.
Denmark, which has invested in genetic surveillance, discovered the variant afflicting Britain in multiple Danish regions and recently tightened restrictions. The health minister compared it to a storm surge, predicting that it would dominate other variants by mid-February.
And as countries go looking, they are discovering other variants, too.
With the world stumbling in its vaccination rollout and the number of cases steeply rising to peaks that exceed those seen last spring, scientists see a pressing need to immunise as many people as possible before the virus evolves enough to render the vaccines impotent.
"It's a race against time," said Marion Koopmans, a Dutch virologist and a member of a World Health Organisation working group on coronavirus adaptations.
The vaccine alone will not be enough to get ahead of the virus. It will take years to inoculate enough people to limit its evolution. In the meantime, social distancing, mask-wearing and hand-washing — coupled with aggressive testing, tracking and tracing — might buy some time and avert devastating spikes in hospitalisations and deaths along the way. These strategies could still turn the tide against the virus, experts said.
"We do know how to dial down the transmission of the virus by a lot with our behaviour," said Carl Bergstrom, an evolutionary biologist at the University of Washington in Seattle. "We've got a lot of agency there."
Yet, in the course of the pandemic, governments have often proved reluctant or unable to galvanise support for those basic defences. Many countries have all but given up on tracking and tracing. Mask-wearing remains politically charged in the US, despite clear evidence of its efficacy. Cities like Los Angeles have been gripped by a spike in cases linked to Christmas festivities, and national public health officials are bracing for surges elsewhere, driven by people who ignored advice and traveled during the holidays.
Much remains unknown about the new variants or even how many are sprouting worldwide. Scientists are racing to sequence enough of the virus to know, but only a handful of countries have the wherewithal or commitment to do so.
The variants' rapid spread is a reminder of the earlier failings and missteps of major countries in containing the virus. Just as China failed to stop travellers from spreading the virus before the Lunar New Year last year, Britain has failed to move fast enough ahead of the new variant's spread. Britain lowered its guard during the holidays, despite a rise in cases now known to be linked to a variant. And just as China became a pariah early on, Britain now has the unfortunate distinction of being called Plague Island.
The spread of the variant lashing Britain has left some countries vulnerable at a time when they seemed on the brink of scientific salvation. A case in point: Israel. The country, which had launched a remarkably successful vaccine rollout, tightened its lockdown on Saturday after having discovered cases of the variant.
About 8000 new infections a day have been detected in recent days, and the rate of spread in ultra-Orthodox communities has increased drastically.
Hodgepodge of restrictions
The variant discovered in Britain, known as B.1.1.7, has 23 mutations that differ from the earliest known version of the virus in Wuhan, China, including one or more that make it more contagious and at least one that slightly weakens the vaccines' potency.
Some experiments suggest that the variant spreads more easily because mutations enable it to latch more successfully onto a person's airway.
Bergstrom and other scientists were surprised to see this more transmissible variant emerge, given that the coronavirus was already quite adept at infecting people. But other experts had warned from the start that it would only be a matter of time before the virus became an even more formidable adversary.
"Every situation we have studied in depth where a virus has jumped into a new species, it has become more contagious over time," said Andrew Read, an evolutionary microbiologist at Penn State University. "It evolves because of natural selection to get better, and that's what's happening here."
Much of the global response has focused on shutting out Britain, with a hodgepodge of national restrictions that hark back to the early reactions to the epidemic.
Experts say that countries should focus instead on ramping up vaccinations, particularly among essential workers who face a high risk with few resources to protect themselves. The longer the virus spreads among the unvaccinated, the more mutations it might collect that can undercut the vaccines' effectiveness.
That is why, when the WHO working group saw the first data on the variant circulating in South Africa on December 4, everyone took notice.
"Your next question immediately is, can the vaccines still protect us if we get viruses with these mutations?" said Koopmans, who was in the meeting.
For now, the answer seems to be yes, said Jesse Bloom, an evolutionary biologist at the Fred Hutchinson Cancer Research Center in Seattle. Koopmans agrees.
The variants that have emerged in South Africa and Brazil are a particular threat to immunisation efforts because both contain a mutation associated with a drop in the efficacy of vaccines.
In one experiment, designed to identify the worst-case scenario, Bloom's team analysed 4000 mutations, looking for those that would render vaccines useless. The mutation in the variants from Brazil and South Africa had the biggest impact.
Still, every sample of serum in the study neutralised the virus, regardless of mutation, Bloom said, adding that it would be a few years before the vaccines need to be tweaked. "There should be plenty of time where we can be prospective, identify these mutations and probably update the vaccines in time," he said.
'These variants will spread'
That sort of surveillance is what led to the discovery of the new variants.
Liza Sitharam, a nurse and infectious disease specialist in coastal South Africa, was among those who first noticed a small cluster that was quickly bulging. "We'd have five cases, and then it'd double really quickly," she recalled. The raw numbers were not alarming, she said, but "there was something just not looking right".
Her boss at the Netcare hospital group, Dr Caroline Maslo, figured that with the country's borders open, business travellers from German auto companies had perhaps brought in a European variant. She sought help from Tulio de Oliveira, a professor and geneticist at the Nelson Mandela School of Medicine in Durban who had studied viral variants during the first Covid-19 wave.
Soon his lab was analysing swabs, shipped on ice by courier overnight. On December 1, he emailed a British scientist, Andrew Rambaut, and asked him to review some early findings: a series of strange mutations on the virus's outer surface.
De Oliveira shared his findings at a December 4 meeting of the WHO working group. All took notice because of the variants' potential to disrupt the vaccines' effectiveness.
Days later, he recalled, Rambaut emailed him with a discovery of his own: British scientists had scoured their databases and found a similar but unrelated mutation that appeared linked to a cluster of infections in the county of Kent.
It was two weeks before Christmas, and de Oliveira immediately thought of the Lunar New Year early in the pandemic, when millions of people in China travelled far and wide for the holiday, some carrying the virus. "It was crystal clear," de Oliveira said in an interview. "These variants will spread nationally, regionally and globally."
Rambaut and colleagues released a paper on the variant discovered in Britain on December 19 — the same day British officials announced new measures. The variant had apparently been circulating undetected as early as September. Rambaut has since credited the South Africa team with the tip that led to the discovery of the variant surging in Britain.
Public health officials have formally recommended that type of swift genetic surveillance and information-sharing as one of the keys to staying on top of the ever-changing virus. But they have been calling for such routine surveillance for years, with mixed results.
"The message was very clear that this is the way surveillance has to go," said Dr Josep Jansa, a senior public health researcher at the European Centre for Disease Prevention and Control. Just as Covid-19 exposed flaws in the world's pandemic plans a year ago, the hunt for new variants is exposing gaps in surveillance. "We're learning," he said. "Slowly."
Britain has one of the most aggressive surveillance regimens, analysing up to 10 per cent of samples that test positive for the virus. But few countries have such robust systems in place. The US sequences less than 1 per cent of its positive samples. And others cannot hope to afford the equipment or build such networks in time for this pandemic.
In Brazil, labs that had redirected their attention from Zika to the coronavirus had discovered a worrisome mutation there as early as this spring. But little is known about the variants circulating in the country or how quickly they are spreading. "We just don't know because no one is either sequencing or sharing the data," said Dr Nuno Faria of Imperial College and Oxford University, who co-ordinates genomic sequencing projects with colleagues in Brazil. "Genomic surveillance is expensive."
As the virus continues to mutate, other significant variants will almost certainly emerge. And those that make the virus hardier or more contagious will be more likely to spread, Read said. "The faster we can get the vaccines out, the faster we can get on top of these variants," he said. "There's no room for complacency here."
Written by: Matt Apuzzo, Selam Gebrekidan and Apoorva Mandavilli
Photographs by: Joao Silva, Alessandro Grassani, Andrew Testa, Samantha Reinders, Alex Welsh, Andrea Mantovani
© 2021 THE NEW YORK TIMES