Getting to grips with Omicron (Part One): What the data tells South Africa about how quickly the virus spreads

Figuring out how fast Omicron, the new SARS-CoV-2 variant that was discovered in November by South African and Botswana scientists, spreads and to what extent this form of the virus can outsmart our bodies’ ability to fight it has become a 24/7 job - and a race against time - for scientists around the world. 

Omicron, which has now overtaken its predecessor, the Delta variant, to become the most common form of the Covid virus circulating in South Africa, has the most mutations of SARS-CoV-2 (the virus which causes Covid-19) to date, many of them associated with increased transmissibility and immune escape. 

But what exactly does it take to establish, for certain, what characteristics this variant, which will shape so many of our experiences of this year’s December holidays, have? 

In Part One of a two-part series, we break down the process — and why getting answers is not as straightforward as you’d think. 

Step 1: Find the variant

To identify a variant, in other words, to establish if a virus has changed, scientists need to unravel the genetic code of the virus. That involves sequencing the genomes (in the case of SARS-CoV-2, a genome is made up of RNA) of the virus to see if mutations have occurred. 

Mutations occur when a virus is making copies of itself and small errors appear in its genetic code. Decoding the virus regularly helps to unveil these changes.

The process of decoding the genetic code is called genome sequencing, and the process of tracking how the virus evolves over time is called genomic surveillance.

South Africa has a leg-up in this field. There’s a group of labs across the country that make up the Network for Genomic Surveillance in South Africa, with teams who sequence SARS-CoV-2 samples ​​to track if there are any significant changes to the virus that might influence the epidemic and our response.

Over the past year, the Network has built up systems to prepare itself for the eventuality of a new variant, explains Richard Lessells, an expert on infectious diseases based at the University of KwaZulu-Natal. Lessells is part of the Network that identified both the Omicron and Beta variants (Beta dominated South Africa’s second Covid wave). 

Because of the structures the Network developed, they were able to spot Omicron at the early stage of its growth and to raise the alarm globally.

On average, the labs sequence about one sample for every 100 new Covid cases identified (so, one sample for every 100 positive Covid tests). In total, the seven labs in the Network can do up to 1,000 samples per week. In contrast, countries such as the United Kingdom do tens of thousands of sequences each week.

Since South Africa isn’t dealing with such a high volume of samples, it enables the labs to be “quite flexible and nimble”, says Lessells.

He recalls: “As soon as we got the first sample here in Durban off the sequencer and knew it was Omicron, that sample was sent straight up to the labs [that need to grow the virus to test how well our antibodies can stop it from replicating] within a few minutes. So, there’s no messing around here from that perspective. We know what the system is, we know we need to move at speed.”

But even when they’re fast, scientists are generally only able to detect a variant about two weeks after it’s already begun spreading in a country. This is because sequencing takes time - it takes up to 16 hours to run the required number of samples through a sequencing machine and then another 24 hours to analyse the data. Having enough genomes to sequence (each run needs 92 samples) means that the samples first must be collected and transported from the Covid diagnostic labs, which is time-consuming in itself.

South Africa’s sequencing network confirmed the new variant on 23 November, and reported it to the Department of Health and to the World Health Organization (WHO) immediately. Just three days later, it was designated a variant of concern by the WHO and given the name Omicron.

But because of the time that lapsed between identifying the variant and the collection and sequencing processes that preceded the identification of the variant, the samples that were analysed were from Covid tests conducted between 14 and 16 November. Further analysis revealed that the earliest positive Covid test result caused by Omicron was actually from 8 November.

When Omicron was discovered, it accounted for 78% of samples sequenced in South Africa, so almost eight out of 10 Covid cases were caused by the variant. Almost all of the samples scientists have managed to sequence in December (so far) have been confirmed as Omicron infections.

Step 2: Count the mutations and figure out their meaning

In total, Omicron has more than 50 changes to its genetic make-up - more than any other SARS-CoV-2 variant identified so far.

The number of mutations a virus has provides clues about how much to expect its behaviour to change — and because scientists have also identified other variants such as the Beta, Alpha, Gamma and Delta, and studied their mutations, they can use that knowledge to spot common traits across variants. 

For instance, both the Alpha and Delta variants (first identified in the United Kingdom and India, respectively) have changes that allow them to spread more efficiently from person to person. The Beta and Gamma variants (first identified in South Africa and Brazil, respectively), on the other hand, share mutations that help them to escape some of the body’s natural defences against the virus in people who had already been infected. 

The worrying part of Omicron is that it has changes in common with all four of these variants. 

The WHO calls Alpha, Beta, Delta, Gamma, and now also Omicron, variants of concern. The organisation classifies variants under this group when they’re associated with increased transmissibility, more severe disease or reducing the effectiveness of tests, treatments or vaccines.

Several of Omicron’s changes have been seen in the other variants of concern, but there are also new mutations that scientists haven’t come across before — so, there’s still a lot left to untangle when it comes to figuring out exactly what Omicron can do.

“When you’ve got as many mutations as this, it’s not just as if each mutation is acting independently,” cautions Lessells. “It’s likely that the structure [of the virus] has changed quite substantially from all the different mutations, so there are limitations to what you’re inferring, as you do that deep dive into individual mutations.” 

Step 3: Calculate how fast the variant spreads

Where mutations are located on a virus can also provide scientists with hints about the way a variant might behave.

Omicron’s changes are mostly in places that have already been seen - particularly at the points where the virus attaches to our human cells. These areas are the spike protein and particularly the receptor-binding domain. The spike protein sits on the surface of the SARS-CoV-2 virus and helps it enter your body’s cells so that it can replicate. The receptor-binding domain is the part of the spike protein that connects with the cells.

To help scientists figure out how different mutations could potentially change the behaviour of a variant, a group of United States researchers created a blueprint, based on lab experiments, for possible SARS-CoV-2 mutations.

Although the blueprint provides a rough outline of what to expect, what happens in real life might be different. That’s because knowing how individual mutations behave doesn’t necessarily tell you how they will interact with each other. To know that, more than lab work is required - we need real-world data, so we need to look at what happens when Omicron infects people in real life.

In South Africa, for instance, Omicron very quickly overtook the Delta variant, which drove the country’s third Covid wave. Up until Omicron’s arrival, Delta had been the most transmissible form of the virus the world had seen. During our third wave, the day with the highest number of new reported infections at the peak of the Delta wave was 3 July, with 26,485 cases.

But Omicron seems to be moving considerably faster than Delta.

South Africa’s Omicron wave is not yet near its peak, but on 15 December, just over a month after the first recorded Omicron case in the country on 8 November, the number of new daily cases - 26,976 - had already exceeded that of the day with the highest number of cases during the Delta wave’s peak.

That gives scientists an indication that Omicron could either be more transmissible than Delta, better at reinfecting people who already have immunity (so, people who have previously had Covid or who have been vaccinated), or both. 

Lessells explains: “We could see early on that this virus was clearly spreading very rapidly, in a population that we know has high levels of immunity - and that’s immunity from past infection, vaccination or both - so that already, just in the general sense, is telling you something about the properties of this variant.”

Moreover, the reproduction (R) number of SARS-CoV-2 - the effective R-value tells you, on average, how many other people one infected person will infect within a community - is now, with Omicron, the highest that it’s been since the start of the pandemic.

In November, South Africa’s R number was on par with previous waves. But by 2 December, it had increased to over 2.5, which means that, on average, an infected person will spread the virus to more than two other people. 

Data from the United Kingdom shows that Omicron is potentially twice as transmissible as Delta within a household.

But the situation is a lot more nuanced than that.

So, how do you figure out how quickly a virus is spreading?

“The bottom line is, it’s difficult,” says Lessells. “It’s not like a simple calculation and we will only really get a sense when we see data from different settings.”

Step 4: Wait for the data to come rolling in

You might be familiar with the phrase “it’s still too early to tell”, which most scientists have begun to tack on to the end of any explanations or assumptions about what Omicron means. That’s because it is.

Lessells says that allowing for more time to pass is the greatest challenge. “Researchers need it, but the public doesn’t have the patience to allow for it. Time is needed to not just get more data from various countries, but also to separate the possible factors driving the numbers.”

This includes the fact that South Africa currently has virtually no lockdown restrictions in place, which means the virus is able to spread more easily, or that the country was in between waves and not seeing a high caseload, which could have allowed the variant to become dominant more quickly.

When a virus spreads faster, it’s also not necessarily because it’s merely more transmissible. It could be because the virus is able to escape immunity, in other words, reinfect people who already have immunity.

In the case of Omicron, we don’t yet know what proportion of its seemingly faster spread is because it’s more transmissible or because it appears to be able to escape, to at least some extent, the protection that previous infection or vaccine-derived immunity offer us against contracting SARS-CoV-2. DM/MC

In Part Two of this series, we will look at what scientists need to take into consideration when they try to figure out if the Omicron variant is able to outsmart Covid antibodies and the cells that protect us against falling seriously ill.

This story was produced by the Bhekisisa Centre for Health Journalism. Sign up for the newsletter.