#FEMSmicroBlog: Does the Omicron variant force us to start all over again?


As a new variant of concern, Omicron joins the already established group of Delta, Alpha, Beta and Gamma of SARS-CoV-2 mutants. These mutants – or variants – show increases in transmissibility or virulence, changes in epidemiology or decreases in the effectiveness of public health and social measures. Sarah Wettstadt explains what is currently known about the new variant and why experts push for booster vaccinations. #QuarantineDiary


Where does the Omicron variant come from?

As if the Covid-19 pandemic hasn’t been enough already and everyone was looking forward to the end of another pandemic-loaded year, a new player emerged, yet again, affecting our well-deserved holiday plans.

The newly identified Omicron variant is of major concern to scientists since it seems to be an escape variant that causes so-called breakthrough infections. As such, Omicron was first reported in South Africa where many people live with HIV and have thus highly compromised immune systems. This can already result in a longer SARS-CoV-2 infection time.

One hypothesis even states that the Omicron variant emerged here in an immunosuppressed patient suffering from chronic Covid-19 disease while being vaccinated. This scenario might have provided the virus with the ideal — but unfortunate — environment to evolve within the patient. The virus’ aim to evade the body’s immune response is what causes us trouble in the end.


How different is Omicron from previous SARS-CoV-2 variants?

As a reference to the original SARS-CoV-2 virus, Omicron carries about 50 mutations in its genome while several of them were already unique in the previous variants. So, due to the lack of complete overlap of any of these mutations, it seems that Omicron is no direct descendant of any of the already known variants.

Schematic of genetic mutations of different SARS-CoV-2 variants showing that the Omicron variant carries many mutations that were already present in previous mutants.
Gene mutations of SARS-CoV-2 variants. From the WHO.

Out of Omicron’s 30 mutations in the spike protein, about 15 are located in the receptor-binding domain. This region binds to the ACE2 receptor on the surface of human lung cells resulting in virus membrane fusion and entry into the cell.

Unfortunately, several of these mutations were already concerning in previous virus variants. For example, the N501Y mutation — also identified in Alpha, Beta and Gamma — allows the virus to bind tighter to ACE2. Hence, it is generally thought that lineages carrying this mutation are possibly more infectious.

Other mutations, such as K417N, T478K and Q498R, impact the interaction surface with ACE2 so that cells more easily take up the virus allowing it to escape the immune system. Similarly, the mutations N679K, P681H, N679K, and D614G have been related to increased transmissibility in previous variants. Yet, it is not completely clear how these mutations impact the transmissibility and infectivity of Omicron.


How does our immune system fight Omicron?

Since the receptor-binding domain is essential in recognising human cells, it is the goal of neutralising antibodies to block this interaction. These immune fighters recognise several parts — so-called epitopes — within this domain to trigger an immune response and neutralise the intruder. Hence, even if one portion of the spike protein changes, vaccines should still perform well.

However, Omicron’s spike mutations are of concern, since virtually all of them are located in the antibody-recognising regions. Thus, it seems that this changes Omicron’s epitopes sufficiently so that antibodies have trouble recognising the virus.

In practice, this was backed up by preliminary studies. One study analysed sera in vitro from patients previously double-vaccinated with either Astra Zeneca’s or Pfizer-BioNTech’s vaccines. These showed that the patient’s sera barely neutralised Omicron with some recipients not neutralising at all.

Another study used the sera from patients that were double-vaccinated and yet infected with the Delta variant or double or triple-vaccinated with various vaccines. They showed that Omicron is rather able to escape vaccine-induced antibody protection than other variants. Yet, a third heterologous vaccine shot increased neutralisation ability against Omicron. Hence, scientists highly recommend immune-strengthening booster shots.


Is COVID-19 caused by Omicron less severe than previous strains?

While we’re currently beginning to understand the new variant and its pathogenesis, preliminary data show that COVID-19 caused by Omicron is less severe than the disease caused by previous variants. Yet, more research is needed to corroborate this hypothesis.

For example, preliminary evidence from a non-peer-reviewed publication shows that, in South Africa, patients infected with Omicron had a lower risk of ending up hospitalised. Another study in South Africa looked at hospital admissions of sequenced infections in November and December 2021. While 90% of patients carried the Omicron variant, hospital admission among adults was 29% lower than in the first wave of the pandemic.

Lastly, modelling studies suggested that individuals who received at least two vaccine doses were mainly protected against hospitalisation. This was also the case for the Omicron variant, against which current vaccines elicited reduced protection.

Hence, preliminary studies underline the need for third booster shots or even a new vaccine to protect against Omicron. Until then, it will be our all responsibility to keep preventing Omicron from spreading further!


About the author of this blog

headshot of Dr Sarah Wettstadt: science writer and science communicator

Dr Sarah Wettstadt is a microbiologist-turned science writer and communicator working on various outreach projects and helping researchers talk and write about their scientific results. Her overall vision is to empower through learning: she shares scientific knowledge with both scientists and non-scientists and coaches scientists in writing about their research. Sarah is blog commissioner for the FEMSmicroBlog and was a social media editor for FEMS for 1.5 years. Previous to her science communication career, she worked as a postdoc in Marían Llamas’ lab on Pseudomonas aeruginosa’s ability to use heterologous iron sources and completed her PhD with Alain Filloux investigating the type 6 secretion system in Pseudomonas aeruginosa.

About this blog section

In the section #QuarantineDiary for the #FEMSmicroBlog, microbiologists tell us about the challenges and opportunities from a personal and professional (development) perspective during the current SARS-CoV-2 pandemic. These can range from a list of useful resources to keep learning, to how researchers can offer their help, to a personal view of current events.

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