How the New Omicron Variant Was Found and What We Know So Far

Scientists find variants by sequencing samples from people who have tested positive for the virus.

Since the start of the COVID pandemic, the Network for Genomics Surveillance in South Africa has been monitoring changes in SARS-CoV-2. This was a valuable tool to better understand how the virus spread. In late 2020, the network discovered a new virus lineage, 501Y.V2, which later became known as the beta variant. Now a new SARS-CoV-2 variant has been identified – B.1.1.529. The World Health Organization has declared it a variant of concern and named it Omicron. To help us understand more, Ozayr Patel of The Conversation Africa asked scientists to share what they know.

What is the science behind the search?

The search for variants requires a concerted effort. South Africa and the UK were the first major countries to implement nationwide genomic surveillance efforts for SARS-CoV-2 as early as April 2020.

Hunting for variants, exciting as that sounds, is done through whole genome sequencing of samples that have tested positive for the virus. This process involves checking each set obtained for differences compared to what we know circulating in South Africa and the world. If we see multiple differences, a red flag will immediately go up and we’ll move on to confirm what we’ve noticed.

Fortunately, South Africa is well prepared for this. This is thanks to a central repository of public sector laboratory results at the National Health Laboratory Service (NGS-SA), close links with private labs, the Western Cape Province Provincial Health Data Center and state-of-the-art expertise in models.

In addition, South Africa has several labs that can grow and study the actual virus and discover the extent to which antibodies formed in response to vaccination or previous infection can neutralize the new virus. With this data we can characterize the new virus.

3D variants of the Covid-19 virus (Sars-COV-2). Alpha, Beta, Gamma, Delta on white background.

The beta variant spread much more efficiently between humans compared to the “wild-type” or “ancestral” SARS-CoV-2 and triggered the second wave of pandemic in South Africa. It was therefore classified as a variant of concern. In 2021, yet another variant of concern, called delta, spread across much of the world, including South Africa, where it sparked a third pandemic wave.

Very recently, routine sequencing by Network for Genomics Surveillance affiliated labs has discovered a new virus line called B.1.1.529 in South Africa. Seventy-seven samples collected in Gauteng province in mid-November 2021 showed this virus. It has also been reported in small numbers from neighboring Botswana and Hong Kong. The Hong Kong case is said to involve a traveler from South Africa.

The World Health Organization has named B.1.1.529 Omicron and classified it as a variant of concern, like beta and delta.

Why does South Africa present worrying variants?

We’re not sure. It certainly appears to be more than just the result of concerted efforts to keep an eye on the circulating virus. One theory is that people with severely compromised immune systems, and who experience a long-term active infection because they cannot clear the virus, could be the source of new viral variants.

The assumption is that a certain amount of “immune pressure” (meaning an immune response that is not strong enough to eliminate the virus, yet exerts a certain selection pressure that “forces” the virus to evolve) creates the conditions for its emergence ​of new variants.

Despite an advanced antiretroviral treatment program for people with HIV, many people in South Africa have advanced HIV disease and are not receiving effective treatment. Several clinical cases have been studied that support this hypothesis, but much remains to be learned.

Why is this variant of concern?

The short answer is: we don’t know. The long answer is that B.1.1.529 carries certain mutations that are worrisome. They have not been seen in this combination before and the spike protein alone has more than 30 mutations. This is important, as the spike protein makes up most vaccines.

We can also say that B.1.1.529 has a genetic profile very different from other interesting and worrisome circulating variants. It does not appear to be a “daughter of delta” or “grandson of beta”, but rather represents a new lineage of SARS-CoV-2.

Some of the genetic changes are known from other variants and we know they can affect transmissibility or allow immune evasion, but many are new and unexplored. While we can make some predictions, we are still studying to what extent the mutations will affect its behavior.

We want to know more about the transmissibility, the severity of the disease and the ability of the virus to “escape” the immune response in vaccinated or recovered people. We study this in two ways.

First, careful epidemiological studies try to find out whether the new lineage shows changes in transmissibility, the ability to infect vaccinated or previously infected individuals, and so on.

At the same time, laboratory studies are investigating the properties of the virus. The viral growth characteristics are compared with those of other virus variants and it is determined how well the virus can be neutralized by antibodies found in the blood of vaccinated or recovered individuals.

Ultimately, the full significance of the genetic changes observed in B.1.1.529 will become apparent when the results of all these different types of studies are considered. It is a complex, demanding and expensive undertaking, which will take months, but is indispensable to better understand the virus and devise the best strategies to fight it.

Do early indications indicate that this variant causes other symptoms or a more serious illness?

There is as yet no evidence for clinical differences. What is known is that the number of cases of B.1.1,529 infection has risen rapidly in Gauteng, where the country’s fourth wave of pandemic looks set to begin. This suggests easy transmissibility, albeit against a background of many relaxed non-pharmaceutical interventions and a low number of cases. So we can’t really say yet whether B.1.1.529 will be transferred more efficiently than the previously dominant care variant, delta.

COVID-19 is more likely to manifest itself as a serious, often life-threatening disease in the elderly and chronically ill. But the populations that are often first exposed to a new virus are younger, mobile and usually healthy people. If B.1.1.529 spreads further, it will take some time before the effects, in terms of disease severity, can be assessed.

Fortunately, it seems that all the diagnostic tests that have been checked so far can identify the new virus.

In fact, it seems that some commonly used commercial tests show a specific pattern: two of the three target genome sequences are positive, but the third is not. It’s as if the new variant consistently ticks two of the three boxes in the existing test. This can serve as a marker for B.1.1.529, meaning that we can quickly estimate the proportion of positive cases due to B.1.1.529 infection per day and per area. This is very useful to monitor the spread of the virus in near real time.

Are current vaccines likely to protect against the new variant?

Again, we don’t know. Known cases include individuals who had been vaccinated. However, we have learned that the immune protection afforded by vaccination diminishes over time and protects not so much against infection but rather against serious illness and death. One of the epidemiological analyzes that has been started is looking at how many vaccinated people become infected with B.1.1.529.

The possibility that B.1.1.529 can evade the immune response is troubling. The hopeful expectation is that the high seroprevalence rates, people already infected, found by several studies, would provide some measure of “natural immunity” for at least a period of time.

Everything known so far about B.1.1.529 shows that universal vaccination is still our best bet against severe COVID-19 and, along with non-pharmaceutical interventions, will go a long way in helping the healthcare system during the coming wave.

Written by:

Prof. dr. Wolfgang Preiser, Head: Department of Medical Virology, Stellenbosch University Cathrine Scheepers, Senior Medical Scientist, University of the Witwatersrand Jinal Bhiman, Chief Medical Scientist at National Institute of Communicable Diseases (NICD), National Institute of Communicable Diseases Marietjie Venter, Head: Zoonotic, Occupational Health and Respiratory Virus Program, Professor, Department of Medical Virology, University of Pretoria Tulio de Oliveira, Director: KRISP – KwaZulu-Natal Research and Innovation Sequencing Platform, University of KwaZulu-Natal

This article was first published in The Conversation.