Ask the Expert: Dr Mark Ali Explains What We Know So Far About Omicron

In this Q&A Blog, Private Harley Street Clinic's Founder and Medical Director Dr Mark Ali explains what we know so far about the new covid-19 variant Omicron. Dr Ali is a Consultant Cardiothoracic Surgeon with a degree in Immunology and Molecular Biology. You can learn more about him here.

What is the Omicron variant?

The Omicron variant is a newly emerging variant of SARS-Cov-2, the virus that causes covid-19. On 26th November the World Health Organisation designated the variant B.1.1.529 a variant of concern, named Omicron.

Experts in South Africa alerted the world to the newly detected variant on 25th November. Retrospectively, the earliest sample in which the variant was detected was collected on November 8th in Gauteng, South Africa’s most populous province, where Johannesburg and Pretoria are located. Omicron seems to be spreading quickly across South Africa, rapidly becoming the dominant variant.

There has been a sustained increase in cases in recent days in most provinces of South Africa, rising most rapidly in Gauteng where Omicron was first detected. The rise in cases is steeper than the Delta wave that hit South Africa during their winter.

The Delta variant swept across South Africa, infecting millions. Vaccination rates are estimated at around a quarter of the population but combined with prior infection levels, it would be expected that there was reasonable population immunity. If a virus were as transmissible as Delta, on a background of a high degree of population immunity, you would expect to see a much slower growth in infections. However, the steep rise in Omicron, on a background of high levels of immunity is a cause for concern.

Omicron has now been detected in at least 23 countries, including the UK, with the WHO expecting the number to rise.

Why is Omicron a variant of concern?

The WHO has designated Omicron a variant of concern because the virus has several mutations that may have a significant impact on how it behaves. The mutations suggest that Omicron may have a greater ability to escape prior immunity than previous variants. Furthermore, the mutations may render many of the currently available monoclonal antibodies used for treatment ineffective.

On a population level, there are concerning signs from South Africa, where the rates of infection have increased dramatically on a background of presumed high level of population immunity.

The genetic profile of Omicron is concerning. NERVTAG (new and emerging respiratory virus threats advisory group) held and extraordinary meeting on 25th November to discuss Omicron and they concluded that Omicron is a “fit” virus undergoing extensive community transmission in South Africa and possibly elsewhere.

The estimated R value of 1.9 is occurring against a background of high levels of immunity following a recent wave of Delta variant infections in South Africa and an active immunisation programme. When we study the genetics of Omicron, we can see why this might be happening - the multiple genetic mutations observed in the spike protein (the major target for antibodies) are highly likely to result in reduced neutralising ability of antibodies raised to earlier variants and vaccination: the concern is reduced protection from prior infection or vaccination.

Together, the genetic makeup of Omicron and the epidemiology in South Africa are highly suggestive that Omicron is a divergent variant that is able to successfully infect previously infected or vaccinated people.

NERVTAG concluded that, if introduced into the UK, it “would likely be capable of initiating a new wave of infections”. They “cannot exclude that this wave would be of a magnitude similar, or even larger, than previous waves”.

In conclusion, Omicron has significant genetic mutations that are concerning for immune escape. We are seeing epidemiologically that this is likely to be the case.

Outstanding questions about Omicron

It is unclear yet whether there is an impact on disease severity but the data should follow soon. Preliminary data suggest that there are increasing rates of hospitalisation in South Africa but this may be due to overall numbers of infected people rather than a result of infection specifically with Omicron.

We do not yet know whether the symptomatology of Omicron is different. As more data is collected, this will become more clear.

We also do not know whether existing treatments for covid-19 will be effective. Of particular concern are the monoclonal antibodies that have proved to be of great support. The multiple mutations observed in the spike glycoprotein are likely to render many of the currently available monoclonal antibodies ineffective.

How can we detect if a person with covid-19 has the Omicron variant?

The way to definitively show which variant of covid-19 someone carries is via a PCR test that then goes on to be fully-sequenced. The full genetic sequence can precisely show the genetic make-up of the covid-19 virus a person is carrying.

However, we can use a proxy to identify samples that are likely to carry the Omicron variant; this is known as S gene target failure (SGTF).

SGTF is used as a proxy for the Omicron variant; it is found in other SARS-Cov-2 lineages and lineage identity can only be confirmed by sequencing.

Some PCR tests are processed by laboratories that use commercial detection kits looking for three coronavirus gene targets: S, N and ORF1ab. With the Omicron variant, the spike (S) gene is mutated in a way that makes it undetectable by the kits. They still detect N and ORF1ab and so they can still pick up covid-19. But the lack of S gene detection, so-called S gene target failure (SGTF) can be a useful signal, highlighting samples for further investigation.

The alpha variant also had S mutations that caused SGTF but delta did not (the S gene is detected by the PCR test). Omicron, the latest variant of concern, also has SGTF and so can be distinguished from delta samples in a PCR test.

As mentioned, it is a proxy, some rare lineages will have SGTF without being a new variant and sometimes SGTF can occur because loads on samples are low. But SGTF does allow us to distinguish between Delta (dominant in the UK right now) and Omicron (newer variant of concern).

From 24-28th November, the level of SGTF in the UK has gone up from 0.1-0.3%, representing around 60 more cases of SGTF than would be expected. But the number will most likely go up and the “excess” SGTF cases are likely Omicron cases. The SGTF cases are concentrated in the same areas as Omicron cases so it would strongly suggest that SGTF is a proxy for Omicron.

The fact that alpha had SGTF but delta did not allowed us to detect rising delta cases. Similarly, the return of SGTF with Omicron, the new variant of concern allows us to detect these new cases.