By the time scientists in southern Africa discovered a new strain of the SARS-CoV-2 virus with an “unprecedented” 30-plus mutations in the crucial spike protein, the pathogen was already quietly circulating in Europe.
Researcher Sikhulile Moyo was stationed at the Botswana–Harvard AIDS Institute Partnership, just across the border from South Africa, when he scanned the institute’s weekly genome sequences of its coronavirus samples.
It was Friday, November 19.
To an untrained eye, the output looks like a Scrabble board that has been tipped over. But in the jumble of letters, the research associate noticed something new.
“This sequence really shocked us,” he told The Boston Globe this week. “When you see a constellation of mutations you begin to wonder what kind of virus this is and what kind of impact it might have.”
Within days, Moyo and his colleagues had their proof: this was an entirely new variant of the coronavirus that has swept the globe since late 2019. On November 23, the results were posted in an open international database and, hours later, scientists in South Africa revealed similar results.
Nobody knows for sure where this virus mutated, and in whom, but Botswana’s Ministry of Health and Wellness revealed in a statement on November 26 that these particular samples were taken from four foreign nationals who had entered the country on November 7 and tested positive for Covid-19 on November 11.
“Immediate results of the ongoing investigations show that the new virus has many mutations, some of which have previously been characterised,” Dr Christopher Nyanga said in a statement from the ministry.
“The ministry is conducting further investigations and sample analysis to gain more knowledge and understanding about the properties and behaviour of this virus.
“Contrary to speculations and in some cases insinuations by some that the variant was only detected in Botswana, the truth is that the variant has so far been detected in other countries in Africa and beyond.”
On the same day Botswana released this public statement, the World Health Organization’s Technical Advisory Group on SARS-CoV-2 Virus Evolution met to discuss the new virus lineage and determine whether it was a low-alarm “variant of interest” or more troubling “variant of concern” (VoC).
Their verdict was the latter and it came with a new name: Omicron.
“This variant has a large number of mutations, some of which are concerning,” the WHO statement said.
“Preliminary evidence suggests an increased risk of reinfection with this variant, as compared to other VoCs. The number of cases of this variant appears to be increasing in almost all provinces in South Africa.
“Current SARS-CoV-2 PCR diagnostics continue to detect this variant. Several labs have indicated that for one widely used PCR test, one of the three target genes is not detected (called S gene dropout or S gene target failure) and this test can therefore be used as marker for this variant, pending sequencing confirmation.
“Using this approach, this variant has been detected at faster rates than previous surges in infection, suggesting that this variant may have a growth advantage.”
In all, there are more than 50 mutations in the Omicron lineage with 30 of these in the spike protein that coats the viral surface. It is this protein that triggers entry of the virus into human cells and, crucially, is the lightning rod for the host immune response. Covid-19 vaccines all work by training the body to recognise and respond to these spike proteins before the real thing shows up, significantly boosting the ability to prevent infection entirely or lessen the severity of illness.
While many of the Omicron mutations are unique, some have been seen before in previous variants. Notably, it shares a few changes in the viral code with the Delta variant that was first found in India and swiftly became the dominant strain of Covid-19 this year.
There are caveats, of course. There is no understanding of Omicron that is currently set in stone. Some evidence suggests it may be at least as transmissible as the Delta variant. Early reports from South Africa indicate it may even be a milder version of the virus than what we currently see, but again this is in a small sample of early infections among young university students. There is some suggestion that the reconfigured Omicron may blunt the effectiveness of the current generation of coronavirus vaccines but, again, nobody actually knows.
In a technical brief for member states, WHO is upfront about these unknowns.
“Omicron is a highly divergent variant with a high number of mutations, including 26-32 in the spike, some of which are concerning and may be associated with immune escape potential and higher transmissibility,” it says.
“However, there are still considerable uncertainties. The main uncertainties are (1) how transmissible the variant is and whether any increases are related to immune escape, intrinsic increased transmissibility, or both; (2) how well vaccines protect against infection, transmission, clinical disease of different degrees of severity and death; and (3) does the variant present with a different severity profile.
“Public health advice is based on current information and will be tailored as more evidence emerges around those key questions.”
One element of the WHO advice is clear, however. Blanket travel bans have little evidence to support them and often cause more damage than they avert. Some countries closed their borders entirely while others, such as Australia, have closed them to select nations entirely based on an early response that has now been rendered moot by the presence of the Omicron variant in key locations around the world.
Botswana’s Minister of Health and Wellness Dr Edwin G. Dikoloti expressed his consternation at this approach in a November 30 address to the World Health Assembly, a decision-making arm of WHO.
“At the start of the pandemic, the country invested in building some capacity to be able to detect and respond, and contribute to the growing scientific knowledge on genomic sequencing and evolution of variants in Botswana,” he said.
“We have cumulatively sequenced over 2200 samples since September 2020. In this regard, we have been able to identify many virus lineages, some of which have been classified by the WHO as Variants of Concern and Variants of Interest.
“Contrary to our efforts, together with other neighbours in the region, we have recently experienced travel and flight restrictions that have been imposed on us, presumably due to our agility, transparency and timely reporting of the Covid-19 new variant. Botswana therefore wishes to categorically condemn this and calls for the lifting of these restrictions.”
Once the news of Omicron broke, other countries around the world began looking more closely at their existing viral samples and genome sequences.
As Sikhulile Moyo noticed the surprising mutations from his lab terminal in Botswana on November 19, samples were routinely taken from a person in the Netherlands who had tested positive for Covid-19. On November 22, another case was logged in Belgium.
In both matters, the tests were retrospectively checked by authorities after the new strain was announced on November 24. Both were a match for Omicron, shifting back the earliest possible dates for the strain’s entry into Europe.
Prior to this, authorities in the Netherlands believed the first cases of the variant had arrived in the country via flights from South Africa. They tested 624 people returning from the country on November 26, identifying 61 who were positive with Covid-19 and 14 with the distinct Omicron genome.
“Laboratory tests identified several different strains of the Omicron variant,” the Netherlands’ National Institute for Public Health said in a statement on Tuesday. “This means that the people were very probably infected independently from each other, from different sources and in different locations.”
But what of the revelations the virus had been there even earlier? So far, the Dutch authorities have been unable to explain this.
“It is not yet clear whether these people had also visited southern Africa,” the NIPH said in relation to the samples taken on November 19 and November 23.
“The spread of the Omicron variant is being monitored closely around the world. Experts are eager to learn more as soon as possible.
“How infectious and virulent is the variant? And how well do the existing vaccines work against this variant? All over the world, experts are in daily contact to answer these questions.”
Last Saturday, the Australian government shut its border to all people who are not citizens, permanent residents or their immediate family travelling from or through South Africa, Namibia, Zimbabwe, Botswana, Lesotho, Eswatini, Seychelles, Malawi and Mozambique. It also suspended flights from these nations for two weeks. For those who are permanent residents, the government reinstated 14-day quarantine arrangements.
By then, however, the variant had turned up in other places in Europe and in Hong Kong, but these were not subject to the revised travel restrictions.
On Tuesday, Health Minister Greg Hunt told reporters the national security committee of cabinet had resolved to “pause” the reopening of Australia’s borders to international students and working visa-holders, which was meant to begin on Wednesday. Now, the tentative schedule will have these arrangements reinstated on December 15. Travel bubbles for Australians with Japan and South Korea, which were due to open at the same time, have also been deferred for two weeks.
“We are doing this out of an abundance of caution but our overwhelming view is that whilst it is an emerging variant, it is a manageable variant,” Hunt said.
“Australia is as well prepared as any nation in the world to deal with emerging variants. We are now at 92.4 per cent first [vaccination] doses, 87 per cent second doses and 430,000 boosters.”
Hunt, who noted Australia’s delayed vaccine rollout now makes us one of the most “freshly” vaccinated countries in the world, said the two-week pause was granted at the request of advisers such as Chief Medical Officer Paul Kelly so that experts had time to work with the global community to fully understand what Omicron may mean.
The national cabinet met late on Tuesday and also resolved that there was “no immediate need” for further changes to pandemic settings.
“National cabinet agreed that the Commonwealth and state and territory governments will continue to pursue a suppression strategy, noting the objective is to limit the rate of Omicron incursions into Australia, rather than eliminate it at the border,” a statement issued by the prime minister said.
This week, there were eight recorded cases of the Omicron variant in Australia. This number will certainly rise. Most, but not all, were in quarantine with infections that were either mild or asymptomatic. One, identified by New South Wales authorities on Thursday, has been in health accommodation in Sydney since November 23.
Evolution is a game of chance and selection. Viruses, which move fast and replicate quickly, are prone to random copying “errors” at greater rates than more complex systems – say, a marmoset. Often these changes are useless. Sometimes they will prove harmful to the virus itself and its mission to spread. Equally, there are occasionally mutations that make the virus fitter in the Darwinian sense: more transmissible, greater survivability in certain environments or even more potent.
“There are 13 named variants of SARS-CoV-2,” the Australian Department of Health says. “Some previous variants of concern eventually turned out to be not as severe as feared, and so were no longer classified as a variant of concern. We are still learning about Omicron and do not yet know how it will affect the pandemic.”
Moderna’s chief executive, Stéphane Bancel, took a dim view of events when he told the Financial Times this week that “there is no world” in which vaccine effectiveness against Omicron “is at the same level we had with Delta”. Pfizer and Oxford University disagree. BioNTech co-founder and chief executive Uğur Şahin, whose German firm developed an mRNA vaccine with Pfizer, said: “We think it’s likely that people will have substantial protection against severe disease caused by Omicron.”
In a statement, Oxford University said: “Despite the appearance of new variants over the past year, vaccines have continued to provide very high levels of protection against severe disease and there is no evidence so far that Omicron is any different.”
In any case, mRNA vaccine platforms are revolutionary in the sense that they can be easily adapted. If a variant did escape vaccine-induced immunity, scientists need only swap out the activating viral sequence for a new one and go again. Pfizer and BioNTech said they could produce and ship an updated vaccine within 100 days. Moderna has already been working on higher-dose boosters and two “multivalent” boosters designed to anticipate Covid-19 variants. One of these includes several mutations present in Omicron.
For rich countries, the new variant is no cause for serious alarm. But the more countries fall behind in containment or vaccination, the more chances the Covid-19 virus has to spread and mutate. The evolutionary game of chance is played on raw numbers.
Vaccine inequality is a humanitarian issue first and foremost but reversing that gulf between nations that are able to vaccinate and those that are struggling is also key pandemic management.
New Covid-19 strains will continue to emerge. The question is, how many is the world willing to tolerate before offering more vaccine support to developing nations?
On Monday, WHO and Africa Centres for Disease Control and Prevention released a statement highlighting this exact issue. While some 90 million doses of vaccine have been delivered to the continent, “the majority of the donations to date have been ad hoc, provided with little notice and short shelf lives”.
“Countries need predictable and reliable supply. Having to plan at short notice and ensure uptake of doses with short shelf lives exponentially magnifies the logistical burden on health systems that are already stretched,” the joint statement says.
Remarkably, the bulk of vaccines donated to Africa so far have not included anything but the vials themselves. No syringes, no diluent, no freight costs. A vial is very hard to put into an arm without the ancillaries.
The world has at least a week to wait before solid evidence about the reality of the Omicron variant emerges, but it has a reminder of a wisdom known since the very beginning of the pandemic: this isn’t over until the whole world is vaccinated.
This article was first published in the print edition of The Saturday Paper on December 4, 2021 as "Omicron variant: What happens now".
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