December 2: What we know about Omicron so far

On Wednesday, the Network for Genomic Surveillance in South Africa (NGS-SA) released new details about their surveillance of Sars-Cov-2 variants, including findings specific to Omicron that they first sequenced in a sample collected on November 8.

The big questions -- whether the newest variant of concern (VOC) is more transmissible, more resistant to vaccine or past infection immunity, or more virulent – are likely to take some time to be answered. To determine these, experts will need to wait for adequate epidemiological and clinical data. At the least, cases need to be watched for three weeks, the time by when infections usually completely resolve or take a turn for the worse.

Omicron is likely displacing Delta, the VOC that led to India’s devastating summer surge and is at present triggering hotspots of outbreak in much of Europe. (FILE)

For now, there are only two approximate knowns with the Omicron variant: first, it is almost certainly out-competing the Delta variant; and second, evolutionarily, it has taken a much farther leap than variants typically have.

Late on Wednesday, the Network for Genomic Surveillance in South Africa (NGS-SA) released new details about their surveillance of Sars-Cov-2 variants, including findings specific to Omicron that they first sequenced in a sample collected on November 8.

Much still remains unknown about the variant of concern (VOC), but the new report strengthens one of the earliest assumptions: Omicron is likely displacing Delta, the VOC that led to India’s devastating summer surge and is at present triggering hotspots of outbreak in much of Europe. From no sequences in October, Omicron accounted for 74% of the 249 genotyped samples by NGS-SA. In the same period, Delta prevalence plummeted from 83% to 22% of the samples.

The switch is almost identical to what happened in May and June, when the then prevalent variant, Beta, dropped from being found in 65% of the samples to 18% in a span of 30 days, while Delta accounted for 66%, after being found in 16% of samples in the month before.

Delta went on to displace Beta and trigger a new wave in South Africa, and it appears Omicron is on a similar course. Overall, South Africa’s case numbers doubled daily for the last two days.

Beyond that, scientists are reluctant to draw any conclusions – and with good reason: There has to be more evidence.

That brings is to the second known: there are 45-52 changes in the variant’s entire genome, with 26-32 in the Spike protein alone. In contrast, Delta has 15-17, and Alpha has 23 mutations. They each have unique combinations, but they share the characteristic of being significantly more transmissible (as opposed to being significantly more resistant like the Beta variant).

The number of mutations, then, is unlike any seen before, and scientists note that there are many changes that have not been observed in any other variant at all – one of them being the fact that there are two mutations surrounding what is known as the furin-cleavage site, the portion of the pathogen that essentially activates the spike to cleave into two and infect a human cell.

Answering the top three questions is crucial for what Omicron means for the pandemic in the immediate term. But what the VOC says about the future of the pandemic needs a different answer: How did Omicron arise?

In a Twitter thread on Wednesday, immunologist and Scripps Research professor Kristian G Andersen said there could be three main possibilities: the variant was in undetected circulation, quietly picking up mutations over a long period; it developed in a person with a chronic infection; and it came from an animal. Each of these possibilities will mean something else for the pandemic.

Andersen says he believes it is unlikely, and other scientists have separately made similar remarks. Even in low resource regions such as Africa, experts believe such a fast-spreading variant would have shown up in surveillance in other countries sooner. But if it did circulate in a region, likely with low testing and vaccination coverage, it spotlights a risk vaccine equity activists have been flagging for long: the world is setting up a catastrophe if it does not fix the imbalance in supplies.

Every time the virus replicates, it has some errors – or mutations. In a chronically infected person, this process is far long drawn than in regular cases; most people clear out the virus in 10-14 days. But when the pathogen is in a tug-of-war with the immunity, the copies that have the “fittest” mutations survive, likely being passed on to others. The Alpha variant, which has one of the largest numbers of mutations after Omicron, is believed to have formed in a chronically ill, immunocompromised person in the UK, who was also possibly exposed to convalescent plasma.

Experts have called on helping people with immune deficiencies secure antivirals and monoclonal antibody therapies.

Andersen, in his opinion, identifies this as having a high likelihood. “I slightly favour reverse zoonosis for a few reasons... SARS-CoV-2 is a generalist virus and we have seen human>animal>human transmission happen in e.g, mink... “Several of the mutations in Omicron have been observed in animals, including rodents,” he wrote. Essentially, Andersen argues that the fact that some of mutations seen when the virus multiplied in animals are also in Omicron, which could be the proverbial smoking gun in the mystery of Omicron’s origin.

If this is the case, the world will need to increase surveillance on animal-human transmission, and the threat of animal reservoirs could have distinct implications for future flare-ups.