Fifth COVID-19 wave named Omicron to hit Hungary - Why should we be concerned?

Portfolio
Defence measures that might just be enough in the pandemic wave caused by the Delta coronavirus variant will be insufficient against Omicron, this is the main conclusion of a study that has been recently published in Hungary. Portfolio has spoken with its co-author, Gergely Röst, mathematician and Head of COVID-19 Epidemiological Analysis and Modelling Response Team, as well as with epidemiologist Beatrix Oroszi, who both analysed the latest developments of Omicron’s spread. They expect this new and highly contagious variant to become dominant in the EU/EEA by early January 2022. Consequently, Hungary cannot avoid a negative turn in the epidemiological situation and the start of the fifth wave in the coronavirus pandemic. They both argue that new defence measures need to be prepared because the super variant is spreading so fast that there will be simply no time to diagnose new cases.
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Omicron emerges

The Omicron variant of the coronavirus was first discovered in South Africa, and it is spreading around the globe at an alarming rate. At the end of November, the Delta variant accounted for 99% of COVID-19 new cases around the world, according to the World Health Organisation (WHO), but by 19 December Omicron sequences have been found already in 95 countries despite in spite of serious travel restrictions.

Several countries in Western Europe have already tightened restriction measures to stem the spread of the virus, while Hungary remains the second most relaxed country in the EU after Sweden in this respect. Bar a couple of countries in Africa, Hungary scores the lowest on the Stringency Index in the entire world.

In Europe, the sharp rise in infections by Omicron was detected first by countries where the conditions are given for variant-monitoring, such as the United Kingdom. Omicron is becoming the dominant strain there although 69% of the population are vaccinated with two doses of a COVID-19 vaccine.

The number of new cases share of SARS-CoV-2 sequences that are the Omicron variant is on the rise in France (72% of population vaccinated with two doses), Spain (81%), Denmark (78%), and Portugal (89%).

Epidemiologist Beatrix Oroszi pointed out that these figures suggest two doses might not be enough to fend off infection by Omicron, and a higher level of immunity requires three doses.

Many countries have come to the realisation that there is no other way to mitigate the damage of a new wave triggered by the Omicron variant than to increase the level of protection,

added the expert, who recommends that more people should be vaccinated against the coronavirus. She also called for more awareness and communication of individual protective measures to avoid people becoming infected and transmitting the virus.

Let’s model the new wave!

Gergely Röst et al. have assessed the potential consequences of the upcoming SARS-CoV-2 waves caused by the Omicron variant. The preprint (Gergely Röst is a mathematician and Department Chair, Applied and Numerical Mathematics, at the University of Szeged. He is also Head of COVID-19 Epidemiological Analysis and Modelling Response Team.)

“Our results suggest that even in those regions where the Delta variant is controlled at the moment by a combination of non-pharmaceutical interventions and population immunity, a significant Omicron wave can be expected.

“We stratify the population according to prior immunity status, and characterize the possible outbreaks depending on the population level of pre-existing immunity and the immune evasion capability of Omicron.”

They pointed out that two countries having similar effective reproduction numbers for the Delta variant can experience very different Omicron waves in terms of peak time, peak size, and total number of infections among the high-risk population.

The researchers pointed to accumulating evidence of high transmissibility and immune-evasion capability of the Omicron variant. They noted that ongoing neutralization studies indicate a significant drop in vaccine efficacy, and that increased frequency of reinfection has been reported in South Africa.

Röst revealed that the London School of Hygiene & Tropical Medicine Ethics Committee posted a modelling for the United Kingdom on 11 December, and then a Swiss group also calculated various possible scenarios. On 15 December, the European Centre for Disease Prevention and Control (ECDC) has published an updated Rapid Risk Assessment of the further emergence and potential impact of the Omicron variant in the context of ongoing transmission of the Delta variant. The release included various charts of the ECDC’s own modelling, adding that the Hungarian team’s model is “much simpler, but in turn it makes some important connections quite clear.”

When Omicron started to spread in South Africa, they estimated it had a four-fold transmission advantage over Delta, i.e. a single case of Omicron generates four times more new cases than a Delta case.

The World Health Organization (WHO) said that with Omicron the number of cases is doubling in 1.5 to 3 days in areas with community transmission. Imperial College London has published an updated analysis on Monday, showing a two-day doubling time.

In comparison, the Delta variant was spreading at its fastest rate in Hungary in the second half of October, when the number of new cases doubled in seven days, which later subsided to 10 to 14 days. “In the case of Omicron, we can expect an extremely rapid rise in the number of new cases,” said Oroszi.

As regards this transmission ‘advantage’ Röst highlighted that the rate at which the different variants spread is determined by the basic reproduction rate (R0), protective measures, and the general immunity of the population. The effective reproduction number corresponding to the Delta variant at a given time characterizes the current transmission of the infection in a population. It can be obtained by the correction of the basic reproduction number with the mitigating effect of the actual non-pharmaceutical interventions (NPI) and the population immunity level in reducing transmission.

As the measures are given, the four-fold transmission advantage could stem from a combination of the other two factors.

“Such a four-fold advantage of Omicron can emerge either from inherently higher transmissibility or a larger susceptible pool, when immunity obtained by vaccination or prior infection by other variants does not protect against the new variant as effectively.

“There is an obvious trade-off relationship between these two factors determining the transmission fitness: the higher the transmissibility, the lower the immune evasion must be to maintain the four-fold ratio of the effective reproduction numbers. Equally, if immune evasion is significant, then R0 must be more moderate.”

The main conclusion of the analysis is this:

"The Non-pharmaceutical interventions that are sufficient against Delta are not enough to stop the spread of Omicron,

for any considered combination of the population immunity level (p) and immune evasion (e). Since Omicron containment requires very stringent NPIs, the invasion of this variant is likely to result in widespread infection."

To estimate the severity of future Omicron waves in countries where Delta is under control, the researchers solved their transmission model for a range of parameters (p, e), and when population immunity is below the Delta herd immunity threshold, they employed the necessary NPIs (the red dashed curve in the graph below) to achieve .

211222rost01

The necessary level of non-pharmaceutical interventions (NPI) to control the Omicron and Delta (dashed) variants as a function of pre-existing immunity.

The heatmap below shows the fraction of the population infected during the Omicron wave with respect to the parameters (p, e) space.

211222heatmap

Heatmap of the total number of infections (as fraction of the population) during Omicron wave, depending on pre-existing immunity and Omicron’s immune evasion, assuming that no further mitigation measures will be implemented. We select examples from a feasible parameter region highlighted by a rectangle.

One can see that the only scenarios not to have a significant outbreak are the following:

  1. the population has extremely high immunity and Omicron is not very immune evasive (bottom right corner); or
  2. the competitive advantage of Omicron emanates from high immune evasion rather than inherent transmissibility and at the same lockdown-like NPIs are in place (top left corner).

None of these are plausible.

The researchers chose examples a, b, c, d from the highlighted rectangle of a feasible parameter region for more detailed investigation, but in their published code they provide an interactive tool that makes exploring other scenarios very easy for the reader.

The time course of the Omicron outbreak in the four selected scenarios are depicted in the graphs below. The dark red colour represents infected population without prior immunity, while the pink colour represents infected population having been vaccinated or previously infected.

In the insets, the cumulative infected fraction is shown, and the grey colour represents the population with prior immunity, while the lighter shade is the portion becoming available for Omicron-infections due to immune evasion.

211222ROSTbig

Epidemic curves of the Omicron wave under various assumptions on the pre-existing immunity and the variant’s immune evasion, without any additional measures.

Potential Omicron waves may have very different characteristics. In countries with very high population immunity, where Delta is contained with very mild or without NPIs, one can expect an extremely rapid increase of cases and a high peak in a matter of weeks, especially if Omicron is highly immune evasive (scenarios b and d in the chart above).

If population immunity is moderate and strong NPIs are being employed to contain Delta, then the Omicron wave is more flattened, as long as the NPIs remain in place (scenarios a and c in the chart above). In this case, as opposed to the high immunity scenarios, the peak is lower if immune evasion is higher.

The most important issue

The key issue, not just from the individuals’ but also from the policymakers’ perspective, is how severe the new wave can be. Röst said there are reassuring and not so promising developments in this regard, and that the overall picture is not yet clear.

Besides the sheer number of infections, to assess the severity of the outbreaks, it is very important to take into consideration the prior immune status of the population getting infected. For example, despite in b and d the peak is much higher than in a and c, if Omicron infections of those with prior immunity turn out to be overwhelmingly mild, than the severity is much better reflected by the number of infected without prior immunity, that is the red curves without the pink part in the graphs above). In this measure, the a and c are more severe.

For scenarios b and d, reintroducing measures with NPI = 0.4 can reduce the peak size roughly to half, and delaying the peak by a month, as shown in the graphs below).

fadf

Effect on the Omicron wave: introducing moderate NPIs in countries with high immunity against the Delta variant. Scenarios (3b) and (3d) from Fig.3).

The mathematician pointed out that even if a smaller share of people infected with the Omicron variant require hospitalisation, the health care system could still be facing serious problems due to a high peak in the wave. “A lot depends on the exact ratios but we do not know them yet,” he said.

Even if it’s just a football game you need to get well prepared, rather than just hoping the other team will be rubbish

, he stressed.

Based on the current epidemiological projections Oroszi has come to the conclusion that the combined impact of immune evasion and widespread transmission will have a much greater impact on the size of the fifth wave than the impact of a potential decline in the severity of cases.

She stressed that

even with a modest reduction in severity, a significant load on hospitals cannot be avoided with such a high transmission rate.

Röst said severity needs to be examined in every age group for those that had some previously gained immunity and for those that are extremely susceptible to the disease. This could take four to five weeks, he added, and by then we could be well into the Omicron wave.

Oroszi also noted that current data do not make it clear if the severity of the disease caused by Omicron is different than in the case of the Delta strain. At the same time, previous immunity is expected to reduce the risk of severe outcome. She also pointed out that it could take several weeks before this wave reaches high-risk elderly groups.

Also note that one of the symptoms of serious disease, difficult breathing, develops about ten days after infection and hospitalisation occurs generally around the 12th day.

This means we need to expect a delay between the rise in the number of cases and a rise in the number of severe cases requiring hospitalisation

, warned Oroszi.

South Africa vs. Europe

It is also reassuring that while the ratio of serious cases demanding hospital treatment is on the rise, but is well below what they recorded in the third wave. Only 1.7% of cases infected by the Omicron variant needed to be hospitalised, against 19% in the third wave. In the United Kingdom and Denmark, however, they found the same ratio as in the case of the Delta variant.

Oroszi pointed out that while South Africa’s readings are reassuring, we should not think the same will happen in Europe. South Africa’s vaccination rate is extremely low (26%), but most of the population had verifiably gained some degree of immunity via infection in the previous waves.

Also, the South African population is extremely young, the median age is slightly over 27 years. In other words, half of South Africa’s population is younger than 27, while the median age is 44 in the EU-27 and 43 in Hungary. This suggests that

as risks of severe disease of COVID-19 infection grow with age, the consequences in the EU-27 are expected to be more severe in the fifth wave than in South Africa.

The fifth wave will definitely hit, let's not delude ourselves!

Röst says the spread of Omicron is masked by the high number of cases caused by the Delta variant. Up to Monday evening, Hungarian authorities diagnosed only 15 people being infected with Omicron.

Oroszi projects a turnaround in the epidemiological statistics before the end of the fourth wave, just like as we witnessed a year ago in the case of the Alpha variant.

Only this time, the turnaround will be more abrupt, as Omicron spreads significantly faster.

Oroszi projects

young people to get infected first and when Omicron finds the elderly population the number of hospitalisations will also start to go up.

She and Röst stressed that there is an urgent need to estimate the potential impact of this variant. They urged continuous monitoring, lightning-fast decision making, and a transparent publication of up-to-date Covid statistics by the authorities. They warned that without these we will find Omicron is dominant only when the epidemiological curve shows that.

Hungary is characterised by a combination of high population immunity and feeble NPIs, and the model used by Röst et al. suggests that low immune evasion would be more fortunate. He noted that weak NPIs obviously help the spread of Omicron, but some other factors in Hungary are positive.

  1. We have just cleared the peak of a large Delta wave, and a lot of people have gained immunity (via infection) only recently.
  2. The winter break in schools comes at the right time.
  3. Hungary has made relatively good progress in the administration of third doses (some 32% of the population got their third jab). This is key because it is becoming clear that three doses of COVID-19 vaccines generate much greater immunity against Omicron than two.

In light of the above, we should not be shocked by the measures Austria, Germany, the Netherlands are putting in place and how Italy is managing the pandemic. These countries have all decided to err on the side of caution, and implement lockdown measures to stem the spread of the virus and thus buy time to rev up the administration of booster shots. Oroszi would deploy the same strategy but added that unfortunately you can’t have a third dose without getting two other shots first.

Some believe the spread of coronavirus can gather momentum during the holiday season when families get together. Others are of the view that the winter break in schools, people taking time off work, and production suspensions in plants will help mitigate the risks. You can help find out the truth by filling out the questionnaire on the contact tracing site of the University of Szeged here.

Consequences of the fifth wave in Hungary

Oroszi stressed that the large number of confirmed COVID-19 cases in the fifth wave of the pandemic could exert a serious impact not only on the health care system, but also on various other sectors. Businesses and schools will be faced with a shortage of staff unless people step up their defense game against the virus, she warns.

Oroszi, who is also a medical specialist, recommends doing everything to reduce transmission. The faster coronavirus spreads, the shorter time we have to implement effective protection measures, she warns.

With Omicron measures aimed exclusively at confirmed cases and their contacts will not be effective enough. There will simply be no time, as people become contagious before they are diagnosed.

As the Omicron variant can infect also those that are vaccinated and they can transmit the virus, they should also take the same precautions,

she stressed.

Most of those infected by Omicron are unvaccinated, but Oroszi warns that a lot of people already inoculated can get infected or re-infected, although their symptoms should be more moderate. As for those unvaccinated, severe disease cannot be excluded.

She noted that vaccines are likely to remain more effective against severe disease than against infection, highlighting that booster doses increase protection against infection. Studies have already shown that third shots can generate a strong immune response against Omicron as well.

Continuing and expanding the vaccination campaign in groups that have not been reached yet would be vital, so that they can get a three-dose protection as soon as possible, she said.

Hungary has a population of some 9.7 million people, 61% (cc. 5.7 mn) of which have received two doses of a COVID-19 vaccine. Only about 32% got three jabs so far, which implies that around 7 million Hungarians have a mid-level or low-level immunity. They are the ones that will be at the highest risk in the fifth wave, Oroszi warned.

She pointed out that many of those that have chosen not to get vaccinated now had received mandatory shots when they were children. These vaccines saved their lives and their children’s lives, protecting them from measles, diphteria, tetanus or polio.

It will be vaccines that could bring an end to the current pandemic if we can convince people to trust vaccines, because they have proven themselves many times,

she said.

The epidemiologist underlined that Omicron can be transmitted easily at superspreading events (where attendance is great), which points to the importance of wearing well-fitting face masks (FFP2 or FFP3), ventilating rooms well, preferring outdoor meetings, limiting attendance during indoor meetings, etc.

Another effective measure is to make attendance conditional to immunity certificates in public indoor spaces. Rapid testing before group events can also help mitigate risks,” she added.

Oroszi recommends vaccinating (with three doses) health care workers and high-risk vulnerable groups (e.g. patients in in-patient health care institutions and in long-term care facilities), and also “to reintroduce all infection prevention measures that were used in the second and third waves to protect people at high risk and contain the spread.”

These will buy time to administer more and more vaccine doses, thus lowering the load on the health care system, mitigating social burdens, saving lives and moderating the economic fallout in the fifth wave, she stressed.

Will this virus ever become more docile?

We asked Röst about such optimistic expectations and adages that during evolution viruses always became tame.

This is conventional wisdom, but it is not true. The evolution of pathogens is always in the direction of more efficient spread. Sometimes this coincides with a milder disease being more favourable for the virus, but not necessarily. There are various examples of a pathogen not becoming tame for millennia.

He also pointed out that with SARS-CoV-2 most infections occur around the time the first symptoms show, and severe disease comes only later when it matters very little from the perspective of the spread of the virus what happens to the host, explained Röst. Selection pressure towards becoming tamer is not substantial, he added.

So far the more virulent variants have been successful. The situation changed only as much as a large share of the population has some degree of immunity, either via infection or via inoculation.

"If Omicron turns out to be milder, it is more likely to be a collateral consequence of immune evasion,” concluded Röst.

Cover photo: MTI/ György Varga

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