Credit: NIAID-RML

The rapid rise of Omicron – Expert Q&A

The WHO has warned the Omicron Covid-19 variant is spreading at an “unprecedented rate” after being reported in 77 countries.

Each day researchers are learning more about Omicron, with the WHO saying it is likely to outpace Delta. Early studies show vaccines may have reduced effectiveness against the variant, but there are some promising results around booster shots.

The SMC asked experts to explain the latest Omicron science. This Q&A has been updated with comments on the first Omicron case detected at the border on 16 Dec.

Dr David Welch, Senior Lecturer, Centre for Computational Evolution and School of Computer Science, University of Auckland, comments:

What does the Omicron case detected at the border mean for NZ?

“Given the high prevalence of Omicron in many countries, including across Europe, it is no surprise to see a case arrive here at the border. The fact it was detected shows the system is continuing to work as intended.”

How quickly is Omicron spreading?

“Omicron is globally the fastest spreading variant we have seen. Multiple countries – including those with very good surveillance such as South Africa, Denmark, UK, Australia – are seeing large and rapid outbreaks where the doubling time for daily cases is about 2-3 days which means that 10 daily cases can become 10,000 daily cases in less than a month. All these countries where we are seeing rapid spread have high levels of immunity already, either by vaccination or due to previous widespread outbreaks. Multiple lab studies also show that Omicron can evade immunity from previous infection or two doses of a vaccine. Lab studies also show that a third dose of a vaccine is effective in restoring much of our immune response against Omicron.”

What might this rate of spread mean for our public health response?

“Like all other variants, we can expect Omicron to arrive in Aotearoa and we need to quickly prepare for it. If it arrived undetected in the community now, we would expect to see our largest outbreak yet. It is thus important that we keep it out of the country while we prepare. Keeping it out requires ongoing maintenance of the MIQ system for all arrivals into the country, whether vaccinated or not. With rapid spread in Australia, the plan to allow NZ citizens to return with no MIQ from 15 January should be immediately postponed to provide certainty to those affected. The vaccination requirement for arrivals should be raised to 3 doses of the vaccine to reduce the risk of Omicron coming here.

“We need to maintain high levels of testing in the community and people need to follow the fundamental health advice of isolating and testing when symptomatic. Third doses need to be rapidly rolled out to the entire population, dropping the requirement to wait six months. A strong equity focus is needed in the booster programme to protect the most vulnerable communities. All border workers and MIQ staff should be triple dosed. We cannot rely on vaccination alone to protect us and need ongoing measures to reduce spread. COVID is an airborne disease so we need to upgrade ventilation in our schools, workplaces, and other indoor environments, and wear good quality masks in poorly ventilated environments.

“The traffic light system will likely need strengthening if an Omicron outbreak occurs before the population is more widely vaccinated. Assumptions around immunity of vaccinated people that underpin the traffic lights do not hold for Omicron. The testing and tracing systems also need to be boosted to prepare for a large outbreak. This includes making rapid antigen tests widely and freely available when we see hundreds of cases a day here.”

What are we still waiting to hear about Omicron before we can assess its threat level?

“The main thing we don’t yet know about is exactly how severe it is. Nearly all the infections we are seeing now are in people who have immunity to previous COVID variants and so have a good level of protection against severe disease, including from the Omicron variant.

“In Aotearoa, about 25% of the population (all those younger than 12 and 10% of the 12s and older) still has no immunity at all as they are unvaccinated and have never had COVID. This group is highly vulnerable and the working assumption of most specialists is that Omicron is as severe as previous variants. Breakthrough infections in vaccinated people can also cause severe disease, although at a lower rate than in unvaccinated people.

“Even if Omicron turns out to be less severe than other variants, and a reason to believe it may be is given in a new study, the fact it spreads so rapidly means hospitals and other health systems will quickly become overwhelmed without strong measures to contain it.”

No conflict of interest declared.

Professor Mike Bunce, Principal Scientist (Genomics), Institute of Environmental Science and Research (ESR), comments:

Do we know how Omicron evolved?  

“This is still uncertain and may continue to be. The evolution of Omicron is likely to be either (i) an immune-compromised individual or (ii) an animal reservoir. The former is the favoured hypothesis. The genomics of Omicron came as a surprise to many working in the field as it looks as if the Alpha variant went into hiding (for about 12 months) and then reappeared with a new game plan.

“To complicate matters further, and in an ongoing evolutionary twist, there are two distinct lineages of Omicron (called BA.1 and BA.2). Through the use of genomics researchers are tracking both lineages as they gain a foothold around the globe. The complication for BA.2 is that the ‘simple’ PCR test often used for rapid detection of Omicron (called SGTF) does not work, meaning BA.2 might be flying under the radar. Using genomics, there remains a lot of scrutiny of Omicron and Delta including the possibility of the variants ‘merging’ (in a process known recombination) which can occur if infected with both variants at the same time.”

Is Omicron more transmissible than Delta? 

“Both variants are highly infectious. Some preliminary studies (not peer reviewed) suggest that Omicron’s spike protein binds about four times as well to human cells (the ACE2 receptor) than the original ‘Wuhan’ variant and twice as well as Delta (study here). While it is still early days, and more experiments need to be run, the evidence to date suggest Omicron might have a more accurate key to our cells. This, coupled with its ability to dodge some antibodies, provides clues to why Omicron is causing a new wave of infection even in highly vaccinated countries like Denmark and the UK. Recent data (also not peer reviewed, reported here) suggests Omicron might be better at replicating in our upper airway (bronchus) than previous variants – this might aid in the spread of virus from person to person.”

How does Omicron evade the immune system and what are ‘breakthrough’ infections? 

“Mutations in the viral gene that encodes the spike protein of the virus sit at the heart of any discussion surrounding immune system ‘escape’. The spike protein of all coronavirus variants differ – these differences impact the ability of our immune system, ideally primed with vaccines (or prior infection), to rapidly respond to new challenges such as Omicron. The ‘kick in the guts’ with Omicron is that unlike previous variants, there is evidence that the antibodies repertoire we build up aren’t quite as effective (e.g. study here).

“The good news is that, while reduced, these early studies still indicate some antibody binding. In addition, antibodies are not the only game in town – there is our cell-mediated immunity (T-cells) which can protect us too. Finally, there is some evidence that third/booster doses confer an added level of protection. In response to Omicron outbreaks the UK, Denmark and Australia have all recently shortened booster dose intervals to between three and five months. Accordingly, the Ministry of Health’s expert advisors are examining the evidence, need and timing here in Aotearoa for maximum protection and effect.

“With Delta we have still observed ‘breakthrough’ infections where vaccinated individuals can contract and pass on the virus. Mounting evidence suggests that with Omicron we will see a higher number of breakthroughs. It is a salient reminder that vaccines are not the only tool in the pandemic toolkit and we need to continue other infection measures e.g., mask use (you should be thinking of the swiss-cheese model of disease protection right now). Modified vaccines to tackle Omicron are already being developed, with time these may slot into the toolkit.”

What is the risk of Omicron spreading to NZ?  

“Each of the existing coronavirus variants has found its way to the NZ border, it goes without saying that some have evaded our border defences. It seems it is only a matter of time before Omicron presents at the border – the hope is that it stays at the border. Every day ESR scientists are closely watching any border cases using genomic surveillance.

“Omicron data from highly vaccinated countries including UK, Denmark and Australia provides us, as a country, with the opportunity to evaluate infection data, hospitalisations and efficacy of interventions, and importantly make evidence-based decisions based on these data. The cautious ‘wait-and-see’ approach to COVID-19 has served us well throughout the pandemic and will likely be the case when grappling with Omicron.”

What about Omicron’s disease severity?

“I don’t see a lot of value in speculating about Omicron’s disease severity at this point in time. There are a lot of anecdotes and larger studies are just starting to appear (see here). Accurate commentary on disease severity requires a lot of carefully controlled data that take into account the many confounders that exist when trying to make direct comparisons of variants. For example; vaccine type/timing, boosters, previous infections, matched cohorts (e.g. age), better COVID-19 drugs, early diagnosis and season all impact on how the disease presents – it is not easy to disentangle all these factors.

“Even if Omicron (or another variant) result in half the hospitalisation rate, twice as many infections will place the same net demand on the hospital system. While the narrative that Omicron may be ‘less severe’ resonates with people it is worth remembering that the virus doesn’t care what makes us feel better. Assuming a lower disease severity may have poor public health outcomes if this proves not to be the case.”

No conflict of interest declared.

Dr Fran Priddy, Executive Director Vaccine Alliance Aotearoa New Zealand – Ohu Kaupare Huaketo, comments:

How is Omicron affecting our current vaccines?

“The Omicron variant is characterized by a markedly increased number of mutations, including approximately 30 in the spike protein which is a critical location for infectiousness and for neutralization by vaccine-induced antibodies.

“A small number of non-peer reviewed, preliminary studies from Europe and South Africa show that blood from vaccinees is 20-180 times less able in lab testing to neutralize Omicron than the early Wuhan strain, and at least 10 times less than is seen against Delta strain. This is concerning because lab-based neutralization correlates with protection from infection and suggests that current two-dose vaccine regimens will not protect against Omicron infection.

“Good news is that at least two studies so far show that a third booster dose of mRNA can improve neutralization titers against Omicron. However, this data does not tell us about current vaccine protection from disease​ due to Omicron. Early data on protection from symptomatic infection from the UK looked at 581 symptomatic Omicron cases and found that a third booster dose of Pfizer vaccine improved vaccine effectiveness to about 75%.

“We do not yet know whether Omicron is likely to cause significant hospitalization or mortality and whether current vaccine regimens can protect against those outcomes, which are not solely related to neutralization responses.

“New Zealand is in a good position to prepare for Omicron as we have access to an mRNA vaccine regimen, including availability of booster doses. Until we understand how pathogenic Omicron may be (ie how deadly) it is critical to complete 2-dose vaccinations, accelerate the booster campaign, and also to consider whether the 6 month booster interval should be shortened. If Omicron does cause high rates of hospitalization even with boosting using current vaccines, then an Omicron-specific vaccine may be necessary. Companies and research groups, like VAANZ, are already preparing Omicron-specific candidates should they be needed.”

Conflict of interest statement: Dr Priddy is Executive Director of the Government-funded Vaccine Alliance Aotearoa New Zealand – Ohu Kaupare Huaketo, a partnership between the Malaghan Institute, the University of Otago and Victoria University of Wellington. She is Clinical Evaluation Director at Malaghan Institute.

Dr Dianne Sika-Paotonu, Immunologist, Associate Dean (Pacific), Head of University of Otago Wellington Pacific Office, and Senior Lecturer, Pathology & Molecular Medicine, University of Otago Wellington, comments:

What does the Omicron case detected at the border mean for NZ?

“Sadly a case of Omicron has now been confirmed in Aotearoa New Zealand. The variant has been spreading rapidly across the globe and it will be critical to keep it from spreading further.

“Although vaccination levels have increased across the country which has been encouraging, vigilance is still needed. Areas remain in Aotearoa New Zealand where there is lower vaccine coverage and we are still dealing with a serious Delta outbreak, with COVID-19 continuing to spread across the country. With the recent shift into the COVID-19 Protection Framework/Traffic Light system, more people will be interacting and getting out and about coming into close contact with each other, increasing risk that this will promote and accelerate spread – especially for those who are vulnerable, including our children.

“Children, tamariki and tamaiki aged 5-11 years may not have access to a fully approved COVID-19 vaccine until January. In the meantime, we still need to keep them safe and protected from COVID-19. If fully approved, they will be the most recent cohort to be added to the COVID-19 vaccination programme. This means they will have had less time than others across Aotearoa New Zealand to get the COVID-19 vaccine  – an equity focus with appropriate prioritisation with the vaccination roll-out will be important and critical moving forward.

“Preliminary data from Pfizer/BioNTech relating to vaccine-induced protection against Omicron indicated that immunity was better with three doses of the Pfizer vaccine than with two doses. The third dose, also showed stronger T cell immune responses were still generated, which is important as T cells are considered to indicate protection against severe COVID-19 disease. This supports the need for a third dose of the Pfizer-BioNTech COVID-19 vaccine in the form of a vaccine booster after the initial two doses, in order to help protect against the OMICRON variant.”

No conflict of interest declared.