With COVID-19, the next Variant of Concern (VOC) could be just around the corner. In the same way that the world was so focused on Delta that Omicron's emergence took us by surprise, similarly, we should be vigilant for another VOC that could surpass Omicron.

We always hoped that the next dominant VOC would be less virulent - just like Omicron - however, the reality is that we don't see many viruses that evolve into something less deadly. We could have just been lucky with Omicron and there is no guarantee that the next VOC won't be more deadly and perhaps just as infectious.

In that instance, our natural immunity to previous COVID-19 infections and our vaccine immunity might attenuate an illness with a new VOC, but one can't be sure. The likely sources of a new VOC are areas of the world where large populations are unvaccinated, or mutations within an animal, or even a single immunosuppressed person. In this last case, an immunosuppressed person might be well enough to not get too sick with the virus, but still allow it to replicate for weeks-months.

Global vaccine equity will reduce the likelihood and speed of a new VOC emerging, but there is a long way to go. While some wealthy countries are considering fourth doses of vaccines for their populations, a whole host of sub-Saharan African countries have less than 10 per cent of their population having received two doses: appalling.

In fact, the new "IHU" variant that caused cases in France may have come from Cameroon where only about three per cent of the population have been vaccinated.

But we also have to distribute vaccines properly to the developing world otherwise it's a waste of time and a snub in the face of impoverished nations. For example, Nigeria last month had to throw away 1 million doses of donated vaccines (via COVAX) because they had been delivered only within a few weeks of their expiration date, not giving the Nigerian government enough time to distribute it to the population. Why donate them at all?

In terms of a vaccine that can address multiple variants, the American military has developed a Spike Ferritin Nanoparticle COVID-19 vaccine. Basically, it is like a round protein with 24 faces, where a spike from different SARS-CoV-2 strains can be attached to each face, thereby giving broader immunity to various strains. They are about to start Phase 2 human trials.

It is quite likely that a new variant of concern will emerge in the future, likely from countries with low immunisation rates and where the virus is able to circulate widely and unabated.  

Even though a new variant of concern is likely to be more infectious and cause less severe disease, we shouldn't ignore the possibility that a more deadly variant could develop.

To prepare for the next variant of concern, we need to develop vaccines that have multiple targets on the virus, particularly enduring sites rather than those, like the spike protein, that regularly change. We need to continue to develop therapeutics to counter the virus and the effects of infection, and we also need to finesse our diagnostic pathways.

‍Is a new variant of concern (VOC) likely? How soon should we expect one to emerge?

"It would appear to be reasonable to expect that Omicron is not the last of the variants of concern that we will have to grapple with. Whilst we have significant transmission of the SARS-CoV-2 virus there is always the possibility, and in fact the likelihood, that new variants will emerge. Predicting when this will occur is difficult, but what we do know is that we can reduce the likelihood of this occurring by limiting the spread of COVID-19 globally."

Can we predict if it is likely to be more, or less transmissible and/or more, or less deadly?

"Predicting the attributes of any new variant of concern is difficult. What we can do, however, is use first principles to understand the drivers for selection that exist. It is clear that any variant that is more infectious will have a selective advantage and so you would expect that it is possible that a new variant will be more transmissible. Whether a new variant will cause more or less severe disease is more difficult to predict. Because severe illness follows infection by some time, whether the virus is more or less severe does not impact greatly on the ability of the virus to be spread, and so there isn’t the selective pressure particularly favouring either a virus that causes more mild or more severe disease. What is possible however, is that a new variant may have a greater ability to evade immunity. "

How should we prepare for the next variant of concern?

"The key is going to be making sure we reduce the likelihood for the emergence of a variant of concern. This involves making sure that we reduce transmission of the virus globally. We need to work harder to limit virus transmission in all countries of the world, and this primarily involves making sure we make vaccines available to all countries."

What scenarios should we be planning for?

"We should know by now to expect the unexpected and be prepared for all eventualities when it comes to VOC."

Is a universal COVID vaccine for all variants likely?

"There is absolutely no reason why a vaccine cannot be developed that is able to be effective against all variants. Although there are differences between variants of concern there are also likely to be antigens that can be targeted that are shared across all variants. It's not to say that this is going to be easy, but it is entirely possible.

‍Is a new variant of concern likely? How soon should we expect one to emerge?

"There have been hundreds of variants of the SARS-COV2 virus since it was first discovered. Some have been very short lived, others have become variants of concern. The WHO categorises these with labels such as variants under monitoring, variants of concern, variants of interest and variants of high consequence. It is highly likely a new variant will occur as is the case with other viruses. As can be seen on the WHO website, there are already variants of interest and variants under monitoring."

Can we predict if it is likely to be more, or less transmissible and/or more, or less deadly?

"This is impossible to predict, and as such we need to be prepared for all possible scenarios. It also needs to be remembered the SARS-COV2 virus is not the only virus in circulation. Influenza, HIV, Norovirus etc etc are still in circulation."

How should we prepare for the next VOC?

"One thing about viruses is that universal precautions work in regards to limiting the spread of a virus. Simple things such are social distancing, masks, hand sanitisation, isolating if symptomatic and most importantly vaccination are critical."

What scenarios should we be planning for?

"In my mind the biggest things we need to plan for are :

1. Increasing numbers of hospitalisations. The healthcare system needs to be expanded. We have a new disease that didn’t exist two years ago, and this one is significant and taking up significant resources from what was already an at-capacity system.
2. Forward-looking supply chains of vaccines, RAT, and new diagnostic technologies.
3. Sovereignty of medication supply.
4. Forward-looking plan for social distancing for new variants, especially variants of concern. Policy on the run has been demonstrated to not work. We are currently in a crisis situation and therefore we are managing that. However we have learnt so much over the past years that we now need to have developed forward-looking policies assuming that there will be further variants of concern that may be more severe than what we have currently."

Is a universal COVID vaccine for all variants likely?

"It is possible and a moonshot to aim for.

‍Is a new variant of concern likely? How soon should we expect one to emerge?

"Newer variants are inevitable when it involves RNA viruses. Generally, the RNA virus replication machinery is error-prone and each time the virus infection passes from person to person, given time, the possibility of newer variants is always high.

Why do we get variants? Every time the virus reproduces inside someone 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 their 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 close to 30 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/years on end.

Another problem we are facing is that currently available vaccines based on the ancestral strain are less effective with the current variant of concerns, especially the rapidly circulating Omicron variant. While booster doses seem to increase protection to a certain extent, it is not viable in the long run.

A variant specific vaccine (booster dose) is absolutely pertinent going forward in controlling transmission and the disease itself. While Pfizer and Moderna have indicated that we could be getting the variant-specific booster doses as early as March 2022, there is a huge problem in terms of logistics and procurements for many countries, especially among low-income nations."

Can we predict if it is likely to be more, or less transmissible and/or more, or less deadly?

"It is extremely hard to predict whether future variants of concern will be more or less likely to be deadly. The subject of mutation is always intriguing especially when it involves viruses. Generally, it all comes down to probability. Viruses are continuously changing as a result of genetic selection. They undergo subtle genetic changes through mutation and major genetic changes through recombination. Mutation occurs when an error is incorporated in the viral genome, and with error-prone replication machinery, the chances of it happening are extremely high especially when it goes from one host to another.

RNA viruses have much higher mutation rates, perhaps one mutation per virus genome copy. Mutations can be deleterious, neutral, or occasionally favourable. Another factor which drives mutations is selection pressure to adapt to the hosts, i.e., overcoming the host immune defence system. Only mutations that do not interfere with essential virus functions can persist in a virus population.

One thing for sure is that, with gross inequality in terms of vaccines between countries, chances of mutants arising in an unvaccinated population is much higher especially from immunocompromised individuals who don’t usually mount sufficient immune response against pathogens/infection. This needs to be seriously addressed by every country fighting the pandemic since it is a global problem."

How should we prepare for the next VOC? What scenarios should we be planning for?

"Despite the risks from Omicron and potentially the next Variant of Concern, the overall public health strategy used throughout the pandemic remains effective and is of utmost importance. We should not forget that already we have the ‘tools’ (e.g., masks, social distancing, 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 (which now has to include booster doses at all age groups) process. Current vaccines while shown to be less effective, have not been rendered completely ineffective. Until we have a variant-specific booster or a pan coronavirus vaccine, getting booster doses is the next best thing we can do.

Next, is disease surveillance. The first link in the disease surveillance chain is testing. Who is infected and where are they? Without accurate, timely testing, it can become impossible to curb the spread of a pathogen. We need to have a coordinated national testing plan in each country. We have learned from experience that countries without an efficient testing plan allowed the virus to spread, unseen and unchecked, increasing the burden on hospitals and making other mitigation measures more difficult. Without accessible testing, the strategy that helped other countries (successful ones) break the chain of transmission — swiftly identifying people with the virus, isolating them and tracing their contacts — stood little chance.

The next vital link in the surveillance chain is routine, widespread genomic sequencing. This kind of surveillance helps experts keep tabs on how a pathogen is mutating and how new variants are spreading. This requires coordinated efforts between the private and government sectors in each country so that it can be done in an accurate and timely manner since time is an essential factor in curbing transmission."

Is a universal COVID vaccine for all variants likely?

"A universal COVID-19 vaccine is definitely the way forward in the long run. To counter future coronavirus outbreaks, the global scientific and medical research community should focus a major effort now on three goals: characterising the range of coronavirus genetic diversity in multiple animal species; better understanding coronavirus disease pathogenesis in laboratory animal models and people; and applying this knowledge to the development of long-lasting, broadly protective coronavirus vaccines.

One such effort is the recent announcement from the US Army of the successful trials of a pan coronavirus vaccine, named SpFN, for Spike Ferritin Nanoparticle, which has shown promise in non-human primate trials. Early human trials are currently underway with results expected soon. The vaccine is designed on a new platform called "self-assembling protein nanoparticle." Unlike most currently available vaccines, which use mRNA to trigger the immune system, this shot would work by injecting a molecule that looks a little like a 24-faced football. Each face of the "ball" would carry a bit of the spike protein that can trigger the body to mount a protective immune response.

This allows scientists to attach the spikes of multiple coronavirus strains on different faces of the "ball," so the body could protect against several variants at once, instead of having to take a separate dose for each variant. According to a study published in the peer-reviewed journal Science Translational Medicine, SpFN protected non-human primates from disease caused by the original variant of the COVID-19 coronavirus. Two doses given 28 days apart also triggered strong immune responses against Alpha, Beta, Gamma, and Delta variants. This really looks promising!