EXPERT REACTION: Omicron COVID variant - your questions answered

The emergence of yet another virus variant of concern causing COVID is a wake-up call for those of us who are remaining vaccine hesitant or opposed to vaccination. Herd immunity will ultimately shield us from variants penetrating our communities. However, we really need a variant proof vaccine that can protect us from different virus mutants of SARS-CoV2 and stimulate immunity with the production of broadly neutralising antibodies.

Coronaviruses share some regions of the spike protein (S2) that don’t mutate as much as the hypervariable S1 region, which has the receptor binding domain. Therefore, broadly neutralising antibodies made to the S2 region can block virus fusion to our cell membranes, preventing entry and thus replication of virus variants.  

• If it turns out that this is a less severe variant, and it takes over from delta, could it be a good thing for living with the virus? 

"Yes. A variant that causes less severe disease but is more transmissible from human to human would overtake Delta as the new dominant strain in circulation. However, other variants will continue to pop up amongst subpopulations of the unvaccinated and also in those who are immunosuppressed or immunocompromised with co-infections. It is vital that vaccination campaigns build momentum especially in places like Sub-Saharan Africa, where HIV and Hepatitis C are also widely prevalent."

• How will getting a booster shot mitigate the risk of infection and it’s causing severe disease from new SARS-CoV-2 variants, like omicron?

​"Theoretically, a booster aimed at the spike protein will allow the immune response to ramp up with memory B cells producing neutralising antibodies. However, with a highly mutated variant in the S1 region of the spike, the common regions of the S2, between the original vaccine strain and the new VOC omicron, will induce a broadly reactive immune response. Therefore, having any booster that sustains our protective antibody levels is wise at this stage." 

• Given the omicron genomic structure is known, can it be laboratory tested in real time now against available vaccines to assess whether those vaccines are effective against the new strain? Or are the only accurate tests those which assess efficacy in infected humans? 

"Although laboratory tests are limited they are predictive of both levels and types of antibody responses in humans. Antibodies can be assessed in microneutralisation assays in the laboratory for effectiveness against omicron. We should know these results from scientists around the world over the next few days."

The occurrence of a new and potentially disruptive variant has always been expected when the virus remains unchecked in millions of people. It will continue to mutate and that is why we need to remain vigilant and agile in our responses. This variant almost certainly emerged in an immunocompromised individual who could not clear the original infection. Most likely an unvaccinated HIV patient in South Africa where the virus can replicate and evolve.

Vaccinating more Africans (and people in developing countries in general) would help long term to try and reduce this reservoir of infection, but is not a quick fix. At some stage, the virus will mutate so much that it will be a strain not a variant and then we will have to call it SARS COV-3 - once this happens we would expect new biological properties to emerge of biomedical significance. We are not there yet but unfortunately, we are well on the way."

What's happening here on a planning level? Will new Doherty modelling be needed?

"New modelling will almost certainly be needed when we have new information on infectivity, incubation periods etc. This will be population dependent and will take weeks to gather. This variant only got its name a week or so ago and yet it is already in 12 countries so we can assume that it is highly infectious. It also has more mutations than any variant seen so far that combine infectivity and the possibility of vaccine evasion. All good reasons for caution."

If it turns out that this is a less severe variant, and it takes over from delta, could it be a good thing for living with the virus? 

"It is far too early to say whether this is less severe or not and again that will be population dependent. How can a new massively mutated variant with largely unknown properties be a good thing? Also if it is highly infectious more people will get it and it will continue to mutate in the general population. We have no idea whether or not this can give rise to Long Covid and Long Covid is not heavily dependent on early severity (except long term respiratory symptoms). It is not a good thing."

How will getting a booster shot mitigate the risk of infection and it’s causing severe disease from new SARS-CoV-2 variants, like omricon? 

"Most probably it will even if the effectiveness is dampened. It is an excellent reason to get a booster and Delta and Delta Plus variants are still rising."

• Given the omicron genomic structure is known, can we test the effectiveness of vaccines against it in the lab? Or are the only accurate tests those which assess efficacy in infected humans? 

"We can get an idea from in vitro testing and molecular modelling, but the only true test is in the population which will vary in any case according to genetic background.

What's happening here on a planning level? Will new Doherty modelling be needed?

Modelling requires data to be entered before a model can be created. Unfortunately, at this stage we don't have enough data on Omicron's infectivity (the R0) against different age groups and vulnerable populations, and the impact of vaccination against it. We will need that information before moving forward with a model. Those data should come soon. But if Omicron ends up being a transient variant, like a number of other COVID-19 variants, then we won't need modelling at all. Only time will tell.

If it turns out that this is a less severe variant, and it takes over from Delta, could it be a good thing for living with the virus?

If Omicron ends up being more infectious, but less severe in all age groups, vulnerable populations and vaccinated populations, then that wouldn't necessarily be a bad situation. It may not affect how well-vaccinated countries continue to open up. Of course, the risk again is that if it takes hold in unvaccinated regions around the world and generates lots of infections, including in immunosuppressed people in whom the virus can replicate for longer, then that would be a risk for a new, more dangerous variant to appear.

How will getting a booster shot mitigate the risk of infection and severe disease from new SARS-CoV-2 variants, like Omicron?

Boosters can improve immunity by increasing levels of certain types of antibodies that stop the virus from infecting a cell, so-called "neutralising antibodies". Data from Israel has shown the booster doses have had an impact on Delta there. So it is likely that a booster would improve immunity against Omicron; however, there are unknowns, such as by what degree a booster would protect against mild or severe disease.

Given the Omicron genomic structure is known, can it be laboratory tested in real time now against available vaccines to assess whether those vaccines are effective against the new strain? Or are the only accurate tests those which assess efficacy in infected humans?

There are different qualitative or quantitative tests where stored serum in vaccinated people can be tested against the virus to see how strong the neutralising antibody responses are. While it's not the same as seeing how vaccinated people respond to the variant in real life, it can give some idea if the vaccine will have some effect against Omicron.

​If this variant enters the community, will there be more lockdowns?

If Omicron is more infectious and displaces Delta, causes as much or more severe disease, and renders the vaccines ineffective, then yes, lockdowns may be back. But that's in a "perfect storm". If the vaccines prove effective, and Omicron causes mild disease despite being more infectious than Delta, then the chance of lockdowns are much less likely in a highly vaccinated country.

What's happening here on a planning level? Will new Doherty modelling be needed? 

We will require more information on the infectivity and disease severity caused by this variant, to determine if the modelling will require adjustment.

We still need to maintain the public health measures to restrict viral spread – hand hygiene, wearing a mask, getting a test if you have symptoms, quarantining active cases, vaccination.

If it turns out that this is a less severe variant, and it takes over from Delta, could it be a good thing for living with the virus?

Indeed, if this is less serious and becomes the dominant variant then it could be the next step in living with COVID-19.

How will getting a booster shot mitigate the risk of infection and severe disease from new SARS-CoV-2 variants, like Omicron?

The vaccines work on stimulating the immune system by exposure to a replicant of the viral spike protein. This immunity has been demonstrated to be strong against emerging variants to date. It is expected that the current vaccines will continue to provide immunity against the Omicron variant – the question is how strong this may be, which is unknown at this time.

Given the Omicron genomic structure is known, can it be laboratory tested in real time now against available vaccines to assess whether those vaccines are effective against the new strain? Or are the only accurate tests those which assess efficacy in infected humans?

It is possible to test the new variants against neutralising antibodies in the lab. This was done when the Delta variant emerged. These studies give an indication that the generated antibodies work against the virus, but we do require field experience before understanding the effectiveness of the vaccines.

If this variant enters the community, will there be more lockdowns?

This will only be able to be answered once we have a better understanding of how much of a concern the variant is. If it is more infectious, or more severe then we may need to use all the public health tools necessary to reduce the spread.

What's happening here on a planning level? Will new Doherty modelling be needed? 

Yes, more modelling is required especially regarding the replication number (R) value so we can get an understanding of how infective it is.

If it turns out that this is a less severe variant, and it takes over from Delta, could it be a good thing for living with the virus? 

This is a very good and interesting point. It really depends on the differences on the spike protein. In some ways, it is a similar question to whether the current vaccines will work. We also need to be reminded that there have been a huge number of variants. This is yet another one and has been labelled as a variant of concern by the WHO, so we need to get much information about this variant before we can make conclusive comments.

If this variant enters the community, will there be more lockdowns?

This is a very difficult question to answer until we understand the nature of the illness. So it is too early to make that call. However if the latest variant leads to severe disease, in high numbers, then understandably it is an option.

The emergence of a new variant, though unsettling, is far from unexpected. Viruses constantly mutate and take on new forms, and the level of existing immunity against a new variant is key in determining the impact an emerging strain will have. Scientists will now need to quickly use established laboratory methods to determine how much immunity blood from vaccinated people has against Omicron and we will then be able to use the established relationship between immunity and vaccine efficacy* to predict how existing vaccines will perform against Omicron, and therefore how much impact this new variant may have on the inroads we have made in the fight against COVID-19 disease. Closing borders may buy us some time to gather the data to answer these questions, however, as we have seen previously with both the original strain and with Delta, a virus will ultimately find its way past these barriers, and it will come down to how effective the immunity we have generated to date is against the new variant.

* Khoury, Cromer et. al. Nature Medicine (2021) and Cromer, Steain et. al. Lancet Microbe (2021)

If it turns out that this is a less severe variant, and it takes over from Delta, could it be a good thing for living with the virus?

Primarily what will be important for Australians in the short term is how well existing vaccines work against the new variant. If our vaccines are still able to protect against severe disease resulting from Omicron infection then we will be well placed from a public health perspective. In the longer term, and from a global health point of view, a more mild variant would be a positive for countries with low levels of vaccination and immunity.

How will getting a booster shot mitigate the risk of infection and severe disease from new SARS-CoV-2 variants, like Omicron? 

Booster shots increase immunity against the virus. What we have seen is that higher levels of immunity are required to combat new variants (both to protect against any infection and severe disease). Therefore, boosting immunity overall will help in combating disease from emerging variants.

Given the Omicron genomic structure is known, can we test the effectiveness of vaccines against it in the lab? Or are the only accurate tests those which assess efficacy in infected humans? 

Laboratory tests can be used to measure the level of immunity required for protection against omicron, but these tests will take a couple of weeks to yield results. Once the results of these laboratory tests become available we can use the established relationship between immunity and vaccine efficacy* to determine the efficacy of the existing vaccines against Omicron.

* Khoury, Cromer et. al. Nature Medicine (2021) and Cromer, Steain et. al. Lancet Microbe (2021)

• Given the Omicron genomic structure is known, can we test the effectiveness of vaccines against it in the lab? Or are the only accurate tests those which assess efficacy in infected humans? 
• What's the likelihood this variant is vaccine-resistant and if it is, what would we need to do to protect ourselves?

We do not have enough data to determine vaccine effectiveness against Omicron or disease severity, so any claims about either at this stage are not evidence-based.  The pathogen genomics show mutations that are associated with resistance to neutralising antibodies and immune evasion, suggesting some degree of vaccine escape is likely.  Vaccines will still likely provide protection against severe disease, but we do not yet have data to quantify this.

If it turns out that this is a less severe variant, and it takes over from Delta, could it be a good thing for living with the virus? 

So far the virus has not mutated to become less severe – in fact the opposite.  The WHO urges caution in interpreting preliminary reports from a South African doctor of mild symptoms in a small group of patients. Proper epidemiologic data are required to determine the relative severity of this variant.

• How will getting a booster shot mitigate the risk of infection and severe disease from new SARS-CoV-2 variants, like Omicron?
• What sort of revised timing for boosters should ATAGI be considering? Currently, it's six months after second dose, but what would be best?

For Australia, speeding up high 3rd dose coverage is important, because waning immunity after dose 2 starts 2-3 months after the second dose – the booster can be given any time from 2-6 months after the second dose, and we should be encouraging rapid, high 3rd dose uptake. We should also be ensuring supply of the paediatric vaccine formulations and a recommendation for kids 5-11 years asap.  And we should be talking to companies and making procurement plans for Omicron-matched boosters as well as the two new promising antivirals.

• What's happening here on a planning level? Will new Doherty modelling be needed? 
• Now that Omicron has reached Australia, what will we see now? Should international borders be closed immediately? What measures should be taken now?

Genetic mutations indicate the Omicron variant has enhanced transmissibility. Preliminary analysis of the genomic epidemiology suggests the R0 could be much higher than for Delta (so much more transmissible). This makes border control important in the short term to buy us time to get our 3rd dose coverage high, vaccinate kids and make procurement plans for vaccines and antivirals. We must also address safe indoor air, and keep using masks in indoor spaces. It is critical to maintain high testing and tracing rates in Australia. Moves to stop QR codes, or in the case of Victoria, to get infected patients to notify their own contacts, will make epidemic control impossible if this variant takes off.

Where was it discovered?

The B.1.1.529 variant was first reported to WHO from South Africa on 24 November 2021. The epidemiological situation in South Africa has been characterized by three distinct peaks in reported cases, the latest of which was predominantly the Delta variant. In recent weeks, infections have increased steeply, coinciding with the detection of B.1.1.529 variant. The first known confirmed B.1.1.529 infection was from a specimen collected on 9 November 2021. This variant has a large number of mutations, some of which are concerning. Preliminary evidence suggests an increased risk of reinfection with this variant, as compared to other variants of concern (VOCs). The number of cases of this variant appears to be increasing in almost all provinces in South Africa.

Current SARS-CoV-2 PCR diagnostics continue to detect this variant. Several labs have indicated that for one widely used PCR test, one of the three target genes is not detected (called S gene dropout or S gene target failure) and this test can therefore be used as a marker for this variant, pending sequencing confirmation. Using this approach, this variant has been detected at faster rates than previous surges in infection, suggesting that this variant may have a growth advantage.

Several variants have emerged since the coronavirus was discovered, what makes this one different? Why is it such a concern? 

This new variant descends from the B.1.1 lineage and is “unprecedented” and “very unusual” in the number of its mutations. B.1.1529 has 32 mutations located in its spike protein. These include E484A, K417N and N440K, which are associated with helping the virus to escape detection from antibodies. Another mutation, N501Y, appears to increase the ability of the virus to gain entry to our cells, making it more transmissible. Another important matter to note is that most of the major mutations are located at the receptor-binding domain of the spike protein, the exact location where antibodies from vaccines are binding/targeted. In other words, the 32 mutations detected in the new variant’s spike protein will change the shape of this structure, making it problematic for the immune response induced by the vaccines. These mutations can make the spike protein less recognisable to our antibodies. As a result, they won’t be as effective at neutralising the virus, which is then able to slip past immune defences and cause infection.

Should we be concerned?

While the 32 mutations in the spike proteins is a 'real concern', giving this variant a better way to evade antibodies from vaccines, this should not deter the current worldwide vaccination drive including booster doses together with the 'weapons' that we already have. We should not forget that already we have the ‘weapons’ (e.g., masks, social distancing, proper hand hygiene etc.) to reduce the risk of becoming infected. It should therefore be our main goal to slow down virus spread by adhering to the existing hygiene and speeding up the vaccination including the booster doses process (especially in vulnerable populations). Getting vaccinated against COVID-19 is the strongest form of protection.

How do new variants emerge? What can we do?

Every time the virus reproduces inside someone who is not vaccinated, there’s a chance of it mutating and a new variant emerging. This is a numbers game. It’s a random process, a bit like rolling dice. The more you roll, the greater the chance of new variants appearing. It’s basically a ticking timebomb. The main way to stop variants is EQUAL global vaccination. The emergence of Omicron reminds us of how important that goal remains. We must get vaccines to these people as quickly as possible (especially in countries that are behind in vaccination rate), both to help the people there who are vulnerable but also to stop new variants from emerging.

Let us not forget that in South Africa, where just 35 per cent of people are fully vaccinated, the variant has begun to spread rapidly. A number of factors could be contributing to the rising caseload, including the nation’s low vaccination rate.

Vaccine equity is a global problem! If we don’t address this quickly enough, our exit from the pandemic will be set back, possibly for months or years on end. The only way is to sprint towards the finish line to have any protection against these emerging variants. In the case of the Omicron variant, as explained before, it contains the recipe for disaster as an initial look at the viral genome suggests the possibility of immune evading capabilities is higher compared to other variants of concern. As we are currently looking in-depth at its pathogenicity, virulence and transmission, we will only get a clearer picture in the coming weeks. But countries cannot rest on their laurels and risk another variant wreaking havoc similar to what Delta is doing currently.

Can border closures fully prevent the virus from entering other countries?

If we look at it objectively, imposing travel bans/blanket border closure on certain countries would be doing more harm than good, noting that the variant was most likely 'already here'. We have to remember that you can’t stop a respiratory virus from coming in with travel bans because there are all sorts of other ways that it can be introduced into the country like through supply chains. Let’s not forget that the virus is already being discovered in other countries including Belgium, Hong Kong and Israel.

Let us also not forget that when the Delta strain was initially discovered/announced, it was found in 53 countries within 3 weeks, clearly indicating that blanket closure of borders is not the most sustainable way to counter this. I feel that it’s too late to impose a blanket closure of the border as it will do more harm than good in the long run as the variant has probably reached the borders of many countries. We must look at a more sustainable way to counter the threat of emerging variants.

For example, a more effective way to prevent the variant’s spread would be to increase vaccination rates in South African countries as opposed to locking them out from the rest of the world. Vaccine equity is a real problem and the major cause for these types of variants to emerge!!! We must think logically, the majority of the 'rich countries' have high rate of vaccination, and if the vaccines hold up against severity — what’s the end goal here? Are we shutting down southern Africa? As I have stressed before, if the virus really was that much more transmissible, it would more than likely take over all of Africa and spread throughout the world — even to the countries with significant travel restrictions. The long-term solution will be aiding these countries with extremely low vaccination rates with vaccine rollout and medical supplies instead of shutting them down.

Have we forgotten the news that not long ago, the US disposed of millions of doses of expired vaccines due to the selfish nature of vaccine hoarding!!! Imagine how many people in Africa needed those vaccines!!! This is just one example of many. The COVID-19 pandemic is a global problem and it needs a GLOBAL SOLUTION and not LOCKDOWNS.

There's a lot of discussion around the patenting of vaccines and a suggestion that if countries were able to produce vaccines in-house, outbreaks of new variants would be minimal. How true is that?

One of the biggest hurdles in getting vaccines in time all over the world is the logistics/transport involved. Another issue that proved to be a stumbling block in ensuring vaccines reach countries in time was “vaccine hoarding” by vaccine producing countries and rich countries to ensure the majority of doses reached their own population first. If countries are able to produce vaccines/vaccine technology “in-house” it will enable these vaccines to reach their populations much faster which is vital in providing protection and stopping newer variants from emerging.

China is one good example. All of their vaccines are produced in-house and they were one of the first to control the pandemic. The emergence of newer variants from China is almost non-existent as they were able to vaccinate the majority of their population at breath-taking speed.

It is reassuring to see that World leaders are acting fast to curb transmission of the new variant of SARS-CoV-2 named Omicron. But we must remember this is not the last mutation, viruses mutate all the time as this is an inherent property of all viruses. However, not all mutations are lethal, it's very early on to comment on the Omicron variant. We need to wait at least another 2-3 weeks to see data from other countries where Omicron has spread to, to understand the virulence, infectiousness and capacity of the variant to evade the immune response across different populations.

We know that selective border closures don’t work, the virus doesn’t understand borders. It's very likely what we are seeing with Omicron is just the tip of the iceberg and it has probably spread to many more countries than we currently know of.

New variants will continue to emerge but we can only live with an endemic level of transmission of SARS-CoV-2 when we have reached a very high level of vaccine coverage in the general population across the world. We need to put all our efforts into ensuring global vaccine equity specifically for people in low middle income countries where less than 10 per cent of the population has been vaccinated.