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Future SARS-CoV-2 variants could be more or less infectious than the currently known variants. Paul Yeung/Bloomberg via Getty Images
  • The COVID-19 pandemic remains volatile and unpredictable, which makes it difficult to predict the features of the next variant after Omicron.
  • No evidence so far can say whether the next variant will be like Omicron; it may be more severe or vaccine-resistant.
  • Waning immunity, low vaccine uptake, and uneven global coverage heighten the risk of new variants, potentially spelling trouble for healthcare systems.
  • Scientists also believe that with many countries lifting all protective measures against SARS-CoV-2, increased spread and transmission could contribute to more mutations.

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It is unlikely that Omicron will end the pandemic as we know it or be the last SARS-CoV-2 variant that we encounter. We are already seeing that BA.2 — a sublineage of Omicron, or its sister variant — is outcompeting the BA.1 sublineage in parts of the world.

Although it is not a new or separate variant, the BA.2 subvariant has reignited discussions about how the next variant will look.

Based on projections so far, some scientists believe that the next variant after Omicron will likely attenuate. However, some argue that this is wishful thinking and the possibility of a strain that is both more transmissible and more deadly is very real.

All in all, they stress the need to consider all scenarios—best and worst.

Dr. Semih Tareen, Ph.D., a virologist and senior director of gene therapy at Sana Biotechnology, Seattle, told Medical News Today that it was natural for viruses to mutate and that it was a “normal and part of an evolutionary advantage for how they create diversity through quasispecies.”

He reiterated that Omicron came about as a result of one of the thousands of mutations and combinations of mutations that SARS-CoV-2 has undergone and continues to undergo throughout the pandemic.

Tareen said that authorities only designated Omicron as a variant of concern because of its increased infectivity and regional dominance, noting that there were many mutations before it.

“Omicron is certainly not the last variant. At this point, it would be hard to tell what the next variants will be like.”
– Semih Tareen, Ph.D.

“It is true that Omicron is not likely going to be the last variant we encounter, but there is no definitive way to predict what the next one be like. One would hope as we move into new normal that SARS-CoV-2 becomes an endemic virus like the flu that just circulates around worse in certain times of the year in places,” said Priya Luthra, a molecular virologist and scientific director who has just moved to the Infectious Diseases Research Unit at GlaxoSmithKline.

Not necessarily, say scientists.

A virus naturally mutates. SARS-CoV-2 has constantly evolved to become fitter, increasing its ability to infect more people, evade infection-acquired or vaccine-induced immunity, or both.

Scientists such as Peter V. Markov, Nikolaos I. Stilianakis, and Aris Katzourakis have argued that Omicron appearing less severe could be a lucky coincidence. They say the rapid emergence of new variants through antigenic evolution will likely “produce new variants that may escape immunity and be more severe.”

It is true that SARS-CoV-2 is not under pressure to evolve toward becoming less virulent, hence it is not possible to say whether the next strain’s mutations will make it so. As these mutations are random, such changes can go either way.

For example, the Alpha variant caused more severe disease than the original wild-type virus, and Delta was also more severe than Alpha.

Dr. John Roberts, lead of International Medical Corps’ U.S. Programs and Emergency Response, told MNT:

“It’s difficult to say what the next variant will look like. In general, these types of viruses become more contagious but less deadly over time. However, that is not always the case.”

Dr. Roberts said it was likely that both vaccination and previous infection would provide varying degrees of protection against infection and severe outcomes.

However, he stressed that it would depend on “a number of factors, including the mutation and the general health of the population.”

Scientists are waiting to see whether SARS-CoV-2 will start to evolve more predictably and become more like other respiratory viruses. One theory is that it could become similar to the common cold, while another is that it could evolve into something more dangerous, as other infectious diseases have done.

Dr. Roberts said the COVID-19 pandemic will probably “move to epidemic and then endemic stages, with likely seasonal fluctuations, similar to the flu.”

“These fluctuations may or may not be considered epidemics/pandemics, depending on how widely spread the disease is, how quickly it spreads, whether many people are infected at the same time, and other factors that will differ from year to year and that will depend on virus characteristics, as well as social factors,” he told MNT.

Researchers are currently working on a number of projections and models to predict future variants.

What we have seen so far is that Omicron is outcompeting previous variants. One of its newer subvariants, BA.2, also seems to be on course to outcompete BA.1 in countries such as Denmark and Nepal.

In comparison with its predecessors, Omicron is the most different variant and the one that is best at partially evading the current vaccines.

Prof. Mark Woolhouse, professor of infectious disease epidemiology at Edinburgh University, highlights that “the Omicron variant did not come from the Delta variant.”

“[Omicron] came from a completely different part of the virus’s family tree. And since we don’t know where in the virus’s family tree a new variant is going to come from, we cannot know how pathogenic it might be. It could be less pathogenic, but it could just as easily be more pathogenic,” he says.

As evident from Alpha, Delta, and Omicron, SARS-CoV-2 did not evolve in a linear manner. This means the next variant will likely not come from a lineage that is prevailing at the time.

Of all the variants so far, Dr. Tareen singled out Omicron and its recent BA.2 subvariant as representing “clusters that are unique and distant from the Alpha, Beta, Delta variant clusters.”

“What this means is that future variants could arise from an Omicron (also known as BA.1) cluster, from a BA.2 cluster, or from a Delta cluster (clusters here refer to subvariants that arise from these major variants). Only time will tell, but at the moment, these are the prominent variants in most parts of the globe,” he said.

Although a much less likely scenario, Dr. Tareen said that it was also “still plausible that new variants could arise from a reverse-zoonotic event.”

He gave examples of recent reports about scientists finding Omicron in non-human hosts, such as deers.

“[These] could generate new variants and represent a different lineage if they were to re-enter human circulation,” he said.

Many countries, including the U.K. and Denmark, among others, have started to scale back mitigation measures against COVID-19. However, lifting measures such as physical distancing and mask-wearing too early could give the virus more opportunity to circulate and mutate.

In an open letter criticizing Prime Minister Boris Johnson’s decision to end all protective measures against COVID-19, some of the U.K.’s leading scientists warned that increased and uncontrolled SARS-CoV-2 transmission would bring new risks. More than 3,700 other scientists have added their signatures.

“Every strain of SARS-CoV-2 to date has failed to reach population saturation. Instead, each has been replaced by a new variant that is more transmissible, more immunity-escaping, or both. This pattern will likely be repeated,” they wrote.

In that regard, for a better chance of fighting newer variants, scientists believe we need to reduce transmission through a “vaccines plus” approach, which includes mitigation measures such as mask-wearing.

Endemicity: Reaching an equilibrium

According to an early February statement from the regional director of the World Health Organization (WHO), Hans Kluge, it is “plausible that [Europe] is “moving toward a kind of pandemic endgame.” This is plausible due to the following factors: “a large capital of vaccine-derived and natural immunity to Omicron, a favorable seasonality pause, and a lower severity of the Omicron variant.”

This stance is based on the assumption that the pandemic will enter an endemic stage. However, not many scientists share Kluge’s optimism.

“This is very premature; we are still in a pandemic surge. There are different scenarios that the pandemic can play out, and we may get to endgame by reaching certain goals such as [vaccinating] 70% of the global population, including children and vulnerable populations, [and] improving testing and surveillance of [the] virus,” said Prof. Luthra.

Endemicity, scientists say, will happen when we can tolerate the burden the virus is placing on healthcare systems and societies. The current burden, for which measures include daily cases, hospitalizations, and deaths, is too high.

Reaching endemicity will likely not look the same for all countries. Some may still be going through an active phase in the pandemic, while others will have the virus under control.

“Till then, we need to disrupt the transmission of the virus by following good masking practice, avoiding crowds, and [incorporating] good ventilation, as we have learned in this pandemic that these interventions work,” Prof. Luthra stressed.

She said that having regular revaccination via boosters and getting kids vaccinated would play a pivotal role in reaching endemicity.

Low levels of vaccination, waning immunity, and vaccine inequity in a globalized world could increase transmission and aid viral mutations.

Dr. Tareen said one of the biggest challenges right now is vaccine inequity.

“We are lucky that there are vaccines and that there are parts of the world where vaccination campaigns and willingness to be vaccinated have resulted in high vaccination rates with boosters. But we do not live in a world of closed borders,” he said.

Prof. Luthra said that COVID-19 vaccines had provided significant protection against the Delta and Omicron variants with boosters.

“One would hope that if the vast majority of the population is vaccinated, even with a more virulent variant in the future, we don’t get nearly as sick,” she said.

Dr. Tareen also touched on how vaccination- and infection-acquired immunity could affect the next variant.

“It is theoretically possible that a more virulent strain may come along, but with the ongoing increase of immunity, both from vaccinations and infections, the chances of a more virulent strain wreaking havoc is decreasing,” Dr. Tareen told MNT.

However, with more widespread immunity and the number of susceptible individuals dwindling, some scientists argue that the next variant may be more virulent with a better ability to reinfect.

“Once Omicron infects the majority of individuals, the next variant will need to be as antigenically different from Omicron and previous VOCs as possible to overcome immunity against them,” say Prof. Markov and his colleagues.

Vaccines vs. newer variants

“We know so far that vaccination has protected people from severe disease and deaths. Even if [a] more virulent variant comes along, we would hope that vaccines continue to provide protection,” said Prof. Luthra.

High vaccination rates should also keep death and hospitalization rates down.

“The good news is that so far, approved vaccines, with the appropriate boosters, have demonstrated efficacy to all variants so far, including Omicron,” said Dr. Tareen.

“We should remind ourselves that the main goal of these vaccines is to decrease the risk of serious illness. As long as this is the case, we should continue to see declining hospitalizations in regions where fully vaccinated/boosted rates are high,” he added.

Dr. Roberts said that any changes in the current vaccines’ effectiveness will depend on the set of mutations the new variant undergoes.

He said that these mutations may or may not affect the effectiveness of vaccines. However, assuming that a new mutation does affect the protection that vaccines provide, it is likely that companies will elect to update the formula.

“The advantage of newer mRNA technology is that these changes will likely be able to be made more quickly,” Dr. Roberts said.

Bringing vaccines up to date

Updating vaccines has been something that scientists have been working on since earlier variants of SARS-CoV-2 emerged.

Researchers have conducted trials to assess the effectiveness of tweaked formulas for the Delta variant, for example. These demonstrated to scientists that variant-specific boosters were unnecessary. However, research is underway for Omicron-specific boosters.

Dr. Tareen said that many biotech companies had revisited the concept of updated vaccines with Omicron, but he pointed out the following caveat:

“Recent data with the Omicron-updated vaccines in animal models have shown that it can be effective against Omicron but not so much against past variants. As long as past variants exist, such as Delta still being prominent in parts of the globe, it is important to remind ourselves that an Omicron-updated vaccine would not be sufficient on its own but could be an option in combination, or as a booster, with existing vaccines.”

One question that may arise is regarding the necessity of an Omicron-specific vaccine if scientists do not know what comes next.

For that reason, recent studies have focused on a pan-coronavirus or “universal” vaccine that targets the whole virus and not just the ever-mutating spike protein.

***Semih Tareen is a virologist, and any opinions expressed are solely his own and do not express the views or opinions of his employer.

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