After Omicron, when will the next mutant emerge?

Originally written by Heidi Ledford

Scientists believe that it is only a matter of time before new variants appear.

What's next?

Just after the coronavirus (SARS-CoV-2) variant, Omicron, set off another round of infections and concerns in early 2022, confirmed cases of COVID-19 in some countries have shown a downward trend. But after more than two years of back-and-forth, even citizens of these countries can't help but ask: When is the next outbreak? And in what form?

Viral particles of the new coronavirus variant strain Omicron (orange, artificially colored) sprout from cells | Steve Gschmeissner/SPL

"I think there will definitely be new strains with different levels of immune escape," said Andrew Rambaut, a researcher in viral evolution at the University of Edinburgh in the United Kingdom. ”

While waiting for the next variant to appear, scientists study the current epidemic of Omicron, hoping to predict the next situation on this basis. Here are three key questions that scientists hope this type of research will answer.

When will the next mutant appear?

We have no way of knowing which variant will become popular and when, or whether it will become a "mutant to watch out for" — i.e., there are signs that it has new characteristics to be wary of, such as faster transmission, greater pathogenicity, or immune escape.

The public is most familiar with the earliest dominant sub-variants of Omicron and Delta. But the researchers are also monitoring various related sub-variants vying for this position. For example, at the end of 2021, Delta's AY.4 sub-variant is about to be replaced by AY.4.2. "Then, the menacing Omicron came on." Andrew Page, a bioinformatician at the Quadram Institute in the UK, said.

The history of these viral dynamics tells us that every few months a new variant emerges, "and they seem to be popping up on a regular basis," Page says. ”

However, whether this mutant strain will become a mutant strain that needs to be paid attention to is still an unsolved question. Currently, Omicron's original lineage, BA.1, is being replaced by BA.2. Although IT is likely that BA.2 will be more promissive than BA.1, the BA.2 lineage does not seem to have changed much compared to the original lineage that swept through many countries at the beginning of this year.

This kinetics can be common in viral pathogens. But we've never been so closely watched by an infection with a virus before, Page said, and as a result, scientists haven't been aware of any clues in it in the past. But that close monitoring has eased — he said the UK's COVID-19 detection rate has begun to decline, in part because of Omicron's weak pathogenicity. If the symptoms of infection are mild, people are less likely to go to testing, and the government's incentive to test is not high.

In the end, this will be detrimental to the monitoring of the COVID-19 genome. Page said that when Omicron was discovered, the alarm was sounded very quickly, but it may be several weeks ahead to spot the new type of attention-sensitive variant that is already spreading. "We certainly can't maintain the current rate of surveillance," he said, "but if it doesn't cause severe illness, is it necessary to carry out such rigorous surveillance?" ”

Will the next variant cause severe illness?

Compared to previous strains of concern, Omicron's ability to cause severe illness seems to have declined considerably – a feature that has more or less mitigated the impact of this wave.

Although some people speculate that the new crown virus will evolve in the direction of weakening pathogenicity, the evolution path of the new crown virus is still not clear enough, Rambaut said. At present, it seems that the new mutant strains that need attention have not evolved from the popular strain in front of it, but from other lineages. There is no guarantee that the next popular strain will definitely come from the "mild" Omicron branch of the COVID-19 genealogy tree. "The next mutant strain may also return to the Delta or Alpha lineage, and may have a strong immune escape ability, enough to drive Omicron off the stage." Rambaut said.

Researchers still don't know to what extent Omicron's relative virulence is due to the broader immunity the population has built up against the coronavirus, rather than because of its inherent properties. As more and more people are vaccinated, infected, and infected around the world, the immune barrier may be strengthened and the resistance to severe COVID-19 will naturally increase.

But Omicron did behave somewhat differently from previous variants, says Wendy Burgers, an immunologist at the University of Cape Town in South Africa. For example, several animal studies have found that Omicron is less likely to invade the lungs than previous variants [1]. "Will the next mutant strain have different properties?" She said, "I don't think we can guarantee that those inherent differences in the virus won't get worse." ”

"We know a lot about the human body, but viruses are unpredictable," she said, "and it scares me a little bit." ”

Are vaccines still effective against new variants?

Omicron's genome has 54 mutations, 34 of which are clustered on the spike proteins that are essential for the virus, and these mutations can severely weaken the anti-infection ability of the new crown vaccine. However, the vaccine's protective effect on severe diseases still appears to be high, which may also be one reason why Omicron does not appear to be very pathogenic.

This is good news, Burgers said, that vaccine-activated immunity remains effective for future strains of concern. While Omicron's mutation in the spike protein appears to weaken the antibody defense line, the scientists found that the ability of immune T cells to recognize viruses was only slightly reduced. These T cells are thought to be important in limiting the scope of the virus infection, killing infected cells, and controlling the spread of the virus. "I was really relieved when Omicron came along," Burgers said, "and I believe that even with a new mutant, the T cell response will still be strong." ”

But Burgers also pointed out that when antibodies become less important in immunity to the new crown virus, the importance of T cells begins to increase, and a strain that can evade T cell monitoring is tantamount to mastering the survival code. "The role of the T cell response is getting bigger and bigger," she said, "and we may see T cells escape next." ”

For other viruses, such as influenza viruses, the ability to escape T-cell immunity takes years to evolve. But it's hard to predict how long this will take in a pandemic that never ends.

As for how population immunity will determine the direction of the epidemic, immunologists have become more difficult to predict, because the factors that determine population immunity are becoming more and more complex. Some people may have been vaccinated with one or more vaccines and have been infected with one or more variants — whether or not.

In general, cumulative exposure to the NEWCC variant can boost immunity, said Santiago vila Ríos, an infectious disease specialist at Mexico's National Institute of Respiratory Diseases. In a preprint paper, Ríos and his team noted that repeated exposure to the new coronavirus, whether through vaccines or infections, enhances antibody responses, as well as immune cell B cells [2]. "So as long as more people complete covid-19 exposure in different ways, the emerging variant of concern may reduce the burden of disease," he said. ”

But in terms of training the body's ability to deal with new mutant strains, how to expose it is also exquisite. A peer-reviewed study[3] found that people who were re-infected with Omicron had a sharp increase in antibodies, said Penny Moore, a virologist at the University of the Witwatersrand in South Africa. These antibodies can also bind to a variety of coronavirus variants other than Omicron, reducing their destructive power, a property also known as cross-reactivity.

People infected with Omicron but never had previous exposure to the coronavirus (through vaccines or infections), who produced antibodies that blocked other variants were slightly weaker. "We cannot assume that these people will also be well protected when they encounter future strains that require attention."

At the end of the day, the importance of vaccinations can still be seen in the data, Burgers said. "We know that vaccines strengthen our immunity, and T-cell immunity also has the property of cross-reacting with another variant," she said. ”

bibliography

[1] Diamond, M. et al. Preprint at Research Square https://doi.org/10.21203/rs.3.rs-1211792/v1 (2021).

[2] Bednarski, E. et al. Preprint at medRxiv https://www.medrxiv.org/content/10.1101/2022.02.07.22270626v1 (2022).

[3] Richardson, S.I. et al. Preprint at medRxiv https://www.medrxiv.org/content/10.1101/2022.02.10.22270789v1 (2022).

The original article was published in the News Explainer section of Nature on February 28, 2022, titled The Next Variant: Three Key Questions About What's after Omicron

This article is reproduced from Nature Portfolio (ID:nature-portfolio) with permission, please contact the original author for secondary reprinting.