Has the coronavirus settled into a pattern?
“There seem to be two to three waves a year, each one caused by new variants,” says Atsushi Sakuraba, professor of medicine at the University of Chicago, US. “Given the nature of SARS-CoV-2, which is an RNA virus that mutates over time, this pattern is likely to persist.” The dominance of each new variant—usually from increased transmissibility or from mutations that help it partially evade immunity and allow re-infection—comes from the predominance of existing variants and brings a wave of infections, aided by the relaxation of restrictions and the reduction of vaccine immunity (fig. 1). Fig. 1 Waves of infection Credit: Our World in Data Laurence Young, a virologist at the University of Warwick in the UK, says: “We have plateaued [peaks in case numbers] between waves of infection, and the set point for these plateaus a little higher each time as the virus changes. “What we’re seeing right now is essentially the evolution of this virus in real time. We’re seeing these waves of infection with the different variants just outgrowing their predecessors.”
Are there local standards?
Some countries, such as New Zealand and Japan, have seen extremely steep increases followed by steep declines, compared to other countries. These countries maintained comparatively very low infection numbers thanks to a combination of strong policies such as border closures and high public adherence to measures for more than a year before restrictions were eased. What matters for these countries, says Joël Mossong, an epidemiologist at the Luxembourg Health Directorate, is not the transmissibility of the new variants as such, but the state of the population’s immunity. “The reason they scan is that they can actually find people who haven’t been infected yet or who have been infected for a long time,” he explains. “And they are able to evade or avoid pre-existing immunity, either from a vaccine or from a previous infection, that was based on a previous variant.” All existing Covid-19 vaccines are based on the original “wild-type” strain.
Will these patterns continue?
Young says, “As long as these variants continue to be selected for increased transmissibility and immune evasion, particularly for current vaccine protection, then we will continue to see this type of pattern around the world. But it depends on the variations and where you are.” We can expect the wave pattern to continue in the coming years, he adds, unless we become more proactive about mitigations or our vaccines adapt. Mossong says, “It seems that there are [new] variations that scan every three months. . . but it also seems that each successive wave will be smaller. It really seems to me that the virus is cleaning up any pockets of sensitivity that are still there in the population.” There is a lot of immunity in the population now, he says, since most people have been vaccinated, but also as a result of “natural” exposure to the virus, since most people have also been infected in the past. “Infectious diseases are a lot like wildfires,” he says. “People are like trees that haven’t burned yet.”
What happened to the previous variants — and could they return?
Sakuraba explains, “The old variants are still detected in small numbers, but they probably won’t become dominant, as the majority of the world is now vaccinated with vaccines that are effective against them.” With the dominance of the small family (fig. 2), it is unlikely that any previously dominant variant will be able to re-enter the ring. Mossong says that any previous variation would have struggled to regain dominance or even gain a foothold. “Vaccines, really, are what killed them,” he says. “That really created a lot of immunity against them. I think it’s unlikely that one of them will come back.” Fig. 2 Share of SARS-CoV-2 sequences that are the Omicron variant (dark shaded areas), 15 August 2022 Credit: Our World in Data Eleanor Riley, professor of immunology and infectious diseases at the University of Edinburgh in the UK, says that in retrospect “the alpha and beta variants weren’t really that infectious—although they looked like a lot of infections at the time—compared to how easily the micron, and the delta before it, spread.” At that time there were no vaccines or waning immunity. “For them to come back and take over from omicron, they would have to be really completely different immunologically,” he tells the BMJ. “And I’m not sure that would be enough, immunologically, to offset the fact that they’re actually not as infectious compared to the two in front.” An exception could be people who are immunocompromised or immunocompromised, who could harbor multiple infections from different variants or subtypes, Young and Mossong say. This could be an evolutionary opportunity for gene sharing – for example, there were fears in the media about “deltacron” in March 2022.1 A preliminary paper published on July 2 by researchers at Yale University in the US described a 60-year-old immunocompromised patient harboring an earlier variant, B.1.517, from November 2020.2 The researchers say it evolved at twice the rate of wild-type SARS-CoV -2, thanks to the patient’s lack of immunity. Lead author Nathan Grubaugh told the journal Science that some of the viruses circulating in the patient today could be classified as new variants if found in the community.
Will all future variants come from omicron?
At the time of writing, omicron is the only variant on the World Health Organization’s list of “variants of concern”3, although it is further divided into seven omicron “subvariants under surveillance”: BA.4, BA.5, BA.2.12 . 1, BA.2.9.1, BA.2.11, BA.2.13 and BA.2.75. “BA.5 is probably the worst version of the virus we’ve seen so far in terms of its infectivity and its ability to evade the immune system,” Young says, though he believes it will likely peak “very soon . . . Then I expect we’ll have a plateau, and then there will be another variant—omicron or not, we don’t know—that will appear in the September-October period. “The biggest fear is that something will come out of left field [as the existing variants and subvariants look to outcompete each other]: another non-small variant that is even better adapted to infection and immune evasion.” This will depend on where a new variant appears and what evolutionary advantages it has, in terms of transmission speed and immune escape, as well as the immune status of the immediate population in which it is found. To cite some earlier examples, a study this year suggested that in New York the gamma variant spread better in certain areas—some of which had been hit hard in the first wave of the pandemic—with higher levels of preexisting immunity.4 And BA.5 led hospital admissions in Portugal (which has high levels of vaccination but also a large number of elderly people) but not in South Africa. This may be due to a younger demographic as well as prior immunity from high exposure to SARS-CoV-2 early in the pandemic.5 Have a ‘Covid Answered Question’? Email [email protected] and we’ll try to cover it in a future installment of this series.
Footnotes
Competing interests: None. Provenance and Peer Review: Commissioned, not externally peer reviewed.
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