Omicron: False alarm or new threat?

Each new ‘variant of concern’ is assigned a Greek letter in alphabetical order.
Not every mutation of the COVID-19 virus is designated as a ‘variant of concern.’
Why are the mutations of Omicron potentially dangerous?
Are vaccines effective against Omicron?

Looking for a silver lining, the COVID-19 pandemic is at least familiarising the global population with the Greek alphabet. Each new ‘variant of concern’ is assigned a Greek letter in alphabetical order. The first variant of concern was designated as ‘alpha’, followed by ‘beta’ and so on. We are now at ‘omicron’, the 15th letter in the Greek alphabet. So is this the 15th mutation of the original COVID-19 virus reported in November of 2019 in Wuhan? The answer is no.


Not every mutation of the COVID-19 virus is designated as a ‘variant of concern.’ In fact, there were 13 mutations designated as variants of concern at one point or another. This is not to say that the virus has had only 13 mutations though. In fact, the GISAID database reports some 5.6 million COVID-19 mutations. Only most concerning mutations get to have a Greek letter. You have heard of the first major mutation - the ‘alpha’ variant (first spotted in the UK), the fourth major mutation – the ‘delta’ variant (first detected in India). You have not heard however of the ‘epsilon’ variant (first detected in California), which later was no longer considered ‘of concern’ by the WHO.


But you may be less interested in viral nomenclature, and more concerned with the dangers that Omicron presents.


What makes Omicron a variant of concern?

The image below sourced from "The Economist" using Nextstrain.org data shows the degree of Omicron’s mutation (marked in blue) from its predecessors:



Omicron differs from the original Wuhan version in more than 50 ways and therefore, it is markedly different from other concerning mutations such as Beta, Alpha and Delta. Ten of Omicron’s mutations have never been seen before in any of the variants of concern. Because Omicron is so different, there are many unknowns, and this is what makes it a variant of concern.


Why are the mutations of Omicron potentially dangerous?

The most worrying of Omicron’s mutations is in the way that the virus binds to, and enters human cells, which makes it more infectious, or transmissible. Scientists are yet to determine if these new mutations make the virus more dangerous. But some information is already coming in.


When combined with the number of mutations, the locations of Omicron’s mutations reduce the neutralising effect of antibodies, potentially making it more dangerous than previous variants. This means that once your body is aware that it is infected, the antibodies it sends to fight the virus may be less effective on Omicron than on other variants.


If the virus fends off the antibodies and manages to enter the cell, it starts to replicate. Ravindra Gupta of Cambridge worries that three of Omicron’s mutations will give it an advantage in replication similar to that enjoyed by Delta. Therefore, the virus could potentially spread around your body at a faster rate.


There is also another mutation up Omicron’s sleeve that could allow it to confuse the way in which your body sends out messages to your immune system to send antibodies. Therefore, this means that your body is likely to be less aware of the presence of the virus, and therefore, late in fighting it.


To gather more information, scientists are using artificial intelligence to simulate how the virus operates. So far, early data shows that indeed, antibodies will fight Omicron at least a bit less well when compared with other variants.


Having said that, a large number of mutations does not necessarily imply that the virus is more dangerous. Some mutations may actually weaken parts of the virus, making it less dangerous.


So far, however, we have discussed one type of antibody cell versus one virus cell, when in reality, the types of antibodies outnumber viral cells. Experiments that pit a wide range of antibodies against the whole virus should provide a clearer idea of the dangers of Omicron. Such work is going on all over the world, especially in the labs of the various vaccine-developers.


Speaking of vaccines, how effective are they against Omicron?

BioNTech boss Ugur Sahin explains that antibodies created by vaccines follow the recipe (or pattern) as requested by the vaccine itself. Now, the vaccine has obviously been designed according to the mutations previous to Omicron. Therefore, when considering the 50 mutations, the neutralising effect of vaccine-elicited antibodies will obviously be lower for Omicron. Having said that, Dr Sahin adds that it is not clear how less effective vaccines are, and points out that immunological protection is not provided by antibodies alone.


On top of this, vaccines engage the immune system’s T-cells (another tool in the immune system’s arsenal). Despite the 50 mutations, Omicron is still 97% identical to the original virus found in Wuhan. In fact, immunologists at the La Jolla Institute have shown that T-cells preserve 93-97% of their targeting capacity when faced with a new variant. Therefore, Dr Sahin says, these T-cell responses should still work. On this basis, he expects that most fully vaccinated people with boosters should, at worst, fall only moderately ill if infected with Omicron.


Nonetheless, BioNTech and Moderna are both working on a vaccine specifically tailored to Omicron. Both companies have been through this process before when Beta and Delta emerged. These vaccines did not go into production in the end because the original vaccines held up well. Whether the same is true for Omicron should be known in the coming weeks.


Dr Sahin says that if a new vaccine does turn out to be needed, BioNTech could deliver it within 100 days. Substantial quantities of an Omicron-targeting vaccine could be produced after June 2022.


The WHO also stated on December 8 that vaccines should work against Omicron variant.


Will we see more social restrictions?

This is a delicate question to answer. First off, despite early evidence in South Africa suggesting that Omicron is spreading quickly, there are other factors beneath the surface. South Africa has very low levels of immunisation, which might have allowed Omicron to spread around, making it look like a super-spreader. Having said that, other variants, including Gamma and Lambda, looked dangerous for a while before they faded.


Being highly transmittable in one part of the world does not mean that a variant will spread fast around the entire globe. For example, southern Africa suffered a wave of the Beta variant in late 2020, but it never became established elsewhere. Conversely, Alpha was highly contagious in Europe alone, but never gained a foothold in southern Africa.


The reasons for these geographic differences are largely environmental. Immune systems are different all over the world. These differences are a result of the different population genes, historical endemic infections, general levels of health, and more.


Another question is whether Omicron causes severe disease. Early reports of mild cases in South Africa are not conclusive. They may have described symptoms in mostly young people, who are less vulnerable to all variants of covid-19. The sample needs to be widened to cover more groups of people. One thing to remember is that, if Omicron turns out to be less deadly than Delta but much more infectious, it could still lead to a rise in hospital admissions and deaths. Assessing Omicron’s severity could take one to two months.


In response, many countries have banned or restricted travel from southern Africa. Some, like Israel and Japan, have banned all foreigners from coming in. Even if cases are detected within a country’s borders, delaying the spread is still beneficial, because health systems still need to be able to cope with a large number of infections if it runs out of control. Slow growing numbers are better than sudden large increases. In Europe, hospitals are struggling with a winter wave of Delta cases, and in countries where vaccination rates are low, we are seeing increased social restrictions.


The European Commission is now pressing more on vaccine mandates, and with the current level of fear by health authorities, the prospect of renewed social distancing, working from home and even lockdowns is becoming more likely.


Western countries where double vaccination is common are now providing more booster shots, which makes sense even if it turns out that booster shots are not as effective against Omicron. The idea of a booster is not to improve the effectiveness of the vaccine-induced antibodies, but to help the immune system create more of them – overwhelm the virus with quantity rather than quality. In fact, studies have found that the quantity of antibodies against sars-cov-2 matters even if the antibodies are not specific to the variant.


A second task is for pharma companies to be able to make better vaccines. Jeremy Farrar, head of the Wellcome Trust, a medical charity, argues for a vaccine optimised against a range of existing variants. Specialising in an exotic one like Omicron may not be the best strategy.


Perhaps Omicron will never amount to much.


What (we think) the Maltese Government should do against Omicron

Malta boasts one of the highest vaccination rates in the world, and the booster programme is now also underway. This is an important advantage since as mentioned above, despite its heavy mutations, boosted-vaccines may in the end be enough to fend off Omicron. Also, preliminary evidence is suggesting that Omicron may not be as dangerous as we are fearing.


The need for social restrictions should therefore be low, since vaccines have substantially weakened the link between cases, hospital admissions and death. We are also seeing new antiviral pills from Merck and Pfizer which is another weapon against COVID-19.


People are realising that as vaccine-induced protection increases, the costs of social restrictions are ever more outweighing the benefits. The general public is also acknowledging that COVID-19 is becoming endemic, and targeting a zero COVID-19 policy is simply unrealistic. In America, for example, many state governors have promised never to implement lockdowns again. On November 30th, the British government resisted suggestions from their medical advisers that people should limit social contacts.


It also seems that people are less scared of the virus (or, at least, more resigned to their fate). The Netherlands and Austria are technically in lockdown, but according to Google mobility data, people are about twice as mobile as they were at the beginning of 2021. As we have shown in our Vaccines are working video, it is not lockdowns, social distancing, closure of schools or mask wearing that broke the link between infections and hospitalisations, but vaccines.


Having said this, we are yet to receive a clear and transparent target by the Maltese health authorities. The Ministry for Health should set a target threshold for the number of COVID-19 hospitalisations. This is easy as it depends on the number of beds the Government is willing to allocate specifically for COVID-19. Approaching that threshold should be a trigger point to start implementing restrictions.


All in all, lots about Omicron remains to be discovered. What is clear, however, is that the world is better placed to resist it.



Sources:

The Economist, BBC, Nextstrain.org