It’s been just a year since the first anti-COVID-19 vaccine surfaced. And the virus has again turned up as a complicated avatar, its fifth since the original emerged from Wuhan in China two years ago. The World Health Organization (WHO) has christened it Omicron.
Since its emergence in South Africa on 24 November, cases have been identified in more than two dozen countries on every continent barring Antarctica. Omicron’s discovery has prompted considerable panic across the globe, with a number of countries banning flights from southern Africa, or — like Israel, Japan and Morocco — barring the entry of foreign travellers altogether.
Much remains unknown about Omicron, including whether it is more transmissible and capable of causing more serious illness. There is some evidence the variant can reinfect people more readily, according to the authoritative science.org (www.science.org/content/article/covid-19-reinfection-study-south-africa-yields-ominous-data-about-omicron?)
In South Africa, where Omicron is already the dominant form of the virus, scientists have reported a sudden, sharp rise last month in coronavirus cases among people who had already been infected, in a study that has not yet been reviewed and published by a scientific journal. The authors noted that there was no such upswing when the Beta and Delta variants emerged.
The finding hints that Omicron may be less vulnerable to the body’s immune defences. Researchers in South Africa also reported that the variant appears to be spreading more than twice as quickly as Delta. which had been considered the most contagious form of the virus so far.
There are some early signs that Omicron may cause only mild illness. But that observation was based mainly on South Africa’s cases among young people, who are less likely overall to become severely ill from Covid.
Researchers in South Africa sounded the alarm because they found more than 30 mutations in the spike protein, a component on the surface of the virus that allows it to bind to human cells and gain entry into the body. Some of the samples from Botswana shared about 50 mutations throughout the virus not previously found in combination. Having so many mutations raises concerns that Omicron’s spike might be able to somewhat evade antibodies produced by either previous infection or vaccination.
Still, it is worth remembering the fate of earlier variants that stirred concern: Beta and Mu, for example, evolved the ability to partially evade the body’s immune defences, but they never became a serious threat to the world because they proved to be poor at transmitting.
Citing the potential for waning immunity six months or more after vaccination, some health experts are promoting booster shots to increase antibody levels.
Moderna, Pfizer-BioNTech and Johnson & Johnson, makers of vaccines approved for use in the United States, and AstraZeneca, which is widely used in Europe, have all said they were studying Omicron, and they expressed confidence in their ability to tailor their formulations to target the variant. Also reassuring: Omicron’s distinctive mutations make it easy to quickly identify with a nasal swab and lab test.
A study published as a preprint suggests Omicron is causing more infections in people who have recovered from an earlier bout of the virus, one sign that the new variant is able to escape at least some of the immune system’s defences.
South Africa has seen three massive COVID-19 waves already: One with the original SARS-CoV-2, one with the Beta variant—which never made much headway outside the country and has now disappeared—and one with Delta. Studies found that a previous infection offered imperfect but significant protection against Beta and Delta, and many had hoped that the population immunity built up in South Africa so far would help dampen further spread of SARS-CoV-2. But scientists worry Omicron’s dozens of mutations might help it evade immunity.
An analysis of 35,670 reinfections among nearly 2.8 million positive tests carried out through late last week suggests their fears are warranted.
In genomic terms, Omicron is wildly different from any other variant seen to date. The nature of its differences suggested, in theory, that it might be better at getting into human cells than its relatives were. It might also be better at avoiding the attentions of antibodies from vaccination or an earlier infection. Virologists had long thought that a variant which combined both those advantages “would be a pretty dangerous thing”, according to Noubar Afeyan, a co-founder of Moderna, one of the manufacturers of mRNA vaccines against SARS-CoV-2. But they also thought it was unlikely. Now “Omicron is exactly that”, Afeyan says. Its mutations and its apparently rapid spread added up to something potentially scary.
The WHO has warned that the new strain carries a “very high” risk of causing surges in infection all around the world. As yet, though, such a surge has been seen only in South Africa, and things may stay that way. It is possible that the surge had other causes and that any variant around at the time would have spread. Or some factor which favours the variant in South Africa may be absent everywhere else.
There is precedent for this. Southern Africa suffered a wave of the Beta variant at the end of 2020, but it never became established elsewhere. Alpha swept across Europe but never became established in southern Africa. (www.science.org/content/article/where-did-weird-omicron-come?utm_campaign=news_daily_2021-12-02)
At the genetic level, Omicron differs from the original Wuhan version in more than 50 places. But it is also very different from other recent versions of the virus. Its closest relatives are versions of the virus first spotted at least a year ago and rarely sequenced since. There are three possible explanations for this.
One is that Omicron’s ancestor managed to circulate for almost a year without being detected by the genomic-surveillance apparatus, and while picking up many more mutations than any other variant has. This seems unlikely. Says Andrew Rambaut of the University of Edinburgh: “I’m not sure there’s really anywhere in the world that is isolated enough for this sort of virus to transmit for that length of time without it emerging in various places,” he says.
Another is that Omicron’s ancestor jumped into and out of an animal population over the past year, picking up its large number of mutations there. Many of the mutations are completely new, not seen before in any variant, lending some credence to this hypothesis. Some think the virus might have hidden in rodents or other animals, rather than people, and, therefore, experienced different evolutionary pressures that selected for novel mutations.
“It is interesting, just how crazily different it is,” says evolutionary biologist Mike Worobey of the University of Arizona, Tucson. Worobey notes that 80% of white-tailed deer sampled in Iowa between late November 2020 and early January 2021 carried SARS-CoV-2, according to a recent preprint.
But it is the third possibility which seems most likely, not least because similar things have been documented before. This is for the ancestral SARS-CoV-2 to have infected someone with a compromised immune system. Because such people are unable to get rid of it, the virus can evolve inside them for months, accumulating mutations as it does so. Rambaut and others propose the virus most likely developed in a chronically infected COVID-19 patient, likely someone whose immune response was impaired by another illness or a drug. When Alpha was first discovered in late 2020, that variant also appeared to have acquired numerous mutations all at once, leading researchers to postulate a chronic infection. The idea is bolstered by sequencing of SARS-CoV-2 samples from some chronically infected patients.
“I think the evidence supporting it is becoming stronger,” says Richard Lessells, an infectious disease researcher at the University of KwaZulu-Natal. In one case Lessells and his colleagues described in a preprint, a young woman in South Africa with an uncontrolled HIV infection carried SARS-CoV-2 for more than 6 months. The virus accumulated many of the same changes seen in variants of concern, a pattern also seen in another patient whose SARS-Cov-2 infection persisted even longer.
Ugur Sahin, the boss of BioNTech, one of the two companies that have developed mRNA vaccines against the virus, accepts that because the vaccines get cells to make spike proteins according to the recipe used in the earliest genomes to be sequenced, the neutralising effect of vaccine-elicited antibodies will be lower for Omicron.
Because 97% of Omicron sequences are identical to the original virus found in Wuhan, Dr Sahin says, these T-cell responses should still work. He expects that most fully vaccinated people with boosters should at worst fall only moderately ill if infected with Omicron.
Nonetheless, BioNTech is working on a vaccine using mRNA that describes the Omicron spike. So is Moderna. Both companies have been down this road before, developing tailored vaccines against Beta and Delta. They did not go into production because they did not, in the end, prove necessary; the original vaccines held up well. Whether the same looks likely to be true for Omicron should be known, the companies say, in a matter of weeks. Dr Sahin says that if a new vaccine does turn out to be needed, his firm could deliver it within 100 days–the estimate includes regulatory approval.
Lalita Panicker is Consulting Editor, Views, Hindustan Times, New Delhi