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Omicron: The Story So Far (03/12/2021)

Posted on 3 December 2021

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It’s been a week now since the World Health Organisation (WHO) declared Sars-CoV-2 variant B.1.1.529, named Omicron, a variant of concern. This is a designation for variants with mutations in the spike protein that increase its binding affinity to the human ACEII receptor, which is the cell surface protein the virus uses to enter human cells. News of Omicron has been met mainly with panic, followed by a mix of reassurances or more panic from the experts. We probably won’t know for a while which of these reactions is more justified, but let’s take stock of the Omicron situation as it currently stands.

What is the Omicron variant?

The Omicron variant is a new variant of the Sars-CoV-2, with the first known sample having been collected on the 9th of November. It is not known where the variant originated, as it would have been spreading for some time before its initial detection.

The Omicron variant has a large number of mutations, 32 of which affect the spike protein, which is the main target of antibodies generated in response to infections and many vaccines. Of these mutations, 15 are located in the receptor binding domain of the spike protein, which is the part of the protein that interacts with the ACEII receptor on the surface of human cells. This is noteworthy because the receptor-binding domain is the main target of neutralising antibodies, which are antibodies that interfere with the virus’s ability to infect cells. The variant also has three mutations at the furin cleavage site, which is important for viral entry into the cell and has the ability to affect infectivity of the virus.

Note that the above figure shows only the proportion of sequenced viruses belonging to each variant, not the proportion of all cases in a country.

Is Omicron more contagious than previous variants?

The short answer is that we don’t really know. While Omicron appears to be ‘outcompeting’ the Delta variant in South Africa and appears to be spreading more rapidly across the country, the data remains limited and there are some confounding factors that may have caused the rate of spread to be overestimated. Most of the early data on transmissibility comes from an outbreak of cases at a university in Pretoria, which could have been due to a superspreading event. Only 25% of the population of South Africa are fully vaccinated, and some epidemiologists have also suggested that Omicron may have first appeared as early as late September, meaning it could have been spreading for quite some time before its detection. However, some of the mutations present in the Omicron variant do point towards increased infectiousness.

Is Omicron less deadly than previous variants?

There has been speculation that infections caused by the Omicron variant might be less severe and less likely to be deadly than previous variants. Unfortunately this is wishful thinking – we don’t yet have enough data to support the assertion that Omicron is any more or less deadly than other variants. Such speculation seems to have stemmed mainly from a quote by a South African doctor that was taken out of context. She reported only mild symptoms among patients, but was referring to a group of people who were young and in good health, and said she was still concerned about more at-risk groups.

Does Omicron bypass immunity (and should I still get my booster)?

We will need more data from countries with higher vaccination rates before we can say to what extent immune memory against other variants works against the Omicron variant. Unfortunately, scientists think that there is a good chance that the mutations in Omicron will allow it to bypass existing immunity (including from vaccination) to a much greater extent than other variants.

Plot of S1 spike protein mutations against time colour coded by variant. Omicron (red) has significantly more mutations than other variants, and appears to share its closest evolutionary connection with mid-2020 viruses. This suggests that what became the Omicron variant was either circulating undetected in a population with poor detection for a considerable period of time, or evolved in a single chronically infected individual.

The good news is that we are not ‘back to square 1’ – vaccination is still going to be protective against this variant, but potentially less so than against previous variants. Our immune systems have more than one weapon and more than one antibody for dealing with a given pathogen. Even if our neutralising antibodies are less effective against the virus, many more mutations would be required to completely escape existing immunity. Antibodies that recognise unchanged parts of the spike protein will still work and will still make the immune response more effective. We also have immunity mediated by T cells, which probably won’t be affected much by the new mutations, although we still aren’t sure how important this part of the immune system is when it comes to protection against infection and against severe disease.

The take-home message is that the immunity that we have built against other variants is far from useless and that vaccine boosters are still important. Due to a lack of neutralising antibodies right at the start of the infection, immune responses might be slower to get into gear against Omicron, but hopefully disease severity won’t be increased in comparison to other variants. As the situation unfolds and we get more data, what we really need to be paying attention to is not the number of cases but what proportion of these cases are ending up in hospital, and what proportion of those are occurring in vaccinated vs unvaccinated people. If we see a significant rise in hospitalisations among the vaccinated, then you have permission to panic.

Update as of 09/12/2021: Pfizer and BioNTech have announced results from a study into the effectiveness of their vaccine against the Omicron variant. The take-home is that in people who have had three doses, levels of neutralising antibodies against Omicron are lower than they are against other variants, but they are still 25 times higher than in people who have only had two doses. The preliminary data suggests that a third dose provides similar levels of neutralizing antibodies against Omicron as is observed after two doses against other pre-Omicron variants.

Do Travel Bans Help?

To put it bluntly, travel bans from countries with high infection rates do very little to slow the spread of a variant, and may actually make things worse in the long term. By the time a new variant is detected in a country, it will have already spread to many countries around the world. Once a new variant has reached a country, it is practically impossible to contain without the implementation of strict and total lockdowns, which most countries are not willing to implement. Many scientists warn that travel bans actually do more harm than good: they essentially punish countries for doing more sequencing and reporting of concerning variants, and also make it harder for said countries to import the reagents necessary for continued detection and monitoring of the variant as it spreads.

We are going to have to wait and see whether the initial panic over Omicron is justified. Omicron is almost certainly already in your country and is more widespread than the numbers suggest. There’s a good chance that it is more infectious and better at bypassing immunity than previous variants, but we aren’t going to be returning to a March 2020 situation. The most effective way of blunting Omicron’s impact will remain the same as it has for every previous variant: vaccinate as many people as possible.

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