- Mun-Keat Looi, International Features Editor
- The BMJ
- mlooi{at}bmj.com
SARS-CoV-2 is here to stay, with a growing number of questions for science and medicine. In the first of a new series on Covid’s Unanswered Questions, the BMJ asks about our current understanding of waves and variants, and what they might mean for ‘living with the virus’.
Is covid settling into a pattern?
“There seem to be two or three waves a year, each one caused by new variants,” says Atsushi Sakuraba, a professor of medicine at the University of Chicago in the 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 by increased transmissibility or by mutations that help it partially evade immunity and allow reinfection, comes from overcoming existing variants and causes an increase in infections, aided by the reduction of restrictions and decreased vaccine immunity (Figure 1).
Fig 1
Waves of infection
Credit: Our World in Data
Lawrence Young, a virologist at the University of Warwick, UK, says: “We are reaching plateaus [peaks in case numbers] between waves of infection, and the benchmark for these plateaus is a little higher each time, as the virus is changing.
“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 outpacing their predecessors.”
Are there regional patterns?
Some countries, such as New Zealand and Japan, have experienced extremely sharp increases followed by sharp declines, compared to other countries. These countries maintained comparatively very low numbers of infections thanks to a combination of strong policies, such as border closures, and high public adherence to the measures for more than a year before restrictions were eased.
What mattered 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 sweep is that they can really find people who haven’t been infected yet or who have been infected for a long time,” he explains. “And they are able to avoid or evade pre-existing immunity, either from the vaccine or from a previous infection, which 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, especially for current vaccine protection, we will continue to see this type of pattern around the world. But it depends on the variants and where meet you”.
We can expect the wave pattern to continue for years to come, he adds, unless we are more proactive about mitigations or our vaccines adapt.
Mossong says, “It looks like there is [new] sweeping variants every three months. . . but it also seems that each successive wave will be smaller. It really seems to me that the virus is wiping out all the pockets of susceptibility that are still there in the population.”
There’s a lot of immunity in the population now, he says, as most people have been vaccinated, but it’s also the result of “natural” exposure to the virus, as most people have also been infected previously . “Infectious diseases are a lot like wildfires,” he says. “People are the equivalent of trees that haven’t burned down yet.”
What happened to the previous variants and could they return?
Sakuraba explains: “The old variants are still detected in small numbers, but probably do not become dominant, as most of the world is now vaccinated with vaccines that are effective against them.”
With the supremacy of the omicron family (Figure 2), it is unlikely that any previously dominant variant can re-enter the ring. Mossong says any earlier variant would struggle to re-establish dominance or even gain a foothold. “It’s the vaccines, really, that killed them,” he says. “That really built up a lot of immunity against them. I think it’s unlikely that one of these will come back.”
Fig 2
Proportion 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, UK, says that in retrospect, “the alpha and beta variants really weren’t that infectious, although they seemed like a lot of infections at the time, in comparison with ease omicron, and delta before it, spread.” At that time there were no vaccines or waning immunity.
“To come back and take over from omicron, they would have to be really totally different immunologically,” he tells The BMJ. “And I’m not sure that’s enough, immunologically, to counter the fact that they’re actually not that infectious compared to the two in front of them.”
An exception might be immunocompromised or immunosuppressed people, who might have multiple infections of different variants or sublineages, Young and Mossong say. This could be an evolutionary opportunity to exchange genes; for example, there were fears in the media about the “deltacron” in March 2022.1
A preprint published on July 2 by researchers at Yale University, US, described a 60-year-old immunocompromised patient harboring an earlier variant, B.1.517, since November 2020.2 The researchers say it evolved twice as 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 qualify 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 stratified into seven “omicron subvariants under control”: 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 infectivity and immune escape,” says Young, though he believes it will likely peak “very soon. .. Then I anticipate that we will have a plateau, and then there will be another variant—omicron or not, we don’t know—that will appear during the September-October period.
“The biggest fear is that something will come from left field [as the existing variants and subvariants look to outcompete each other]: another non-omicron variant that is even better suited to infection and immune evasion.”
This will depend on where a new variant arises and what evolutionary advantages it has, in terms of speed of transmission and immune evasion, as well as the immune situation of the immediate population in which it is found.
To cite some earlier examples, a study this year suggested that in New York City the gamma variant spread better in some areas, some of which had been hit hard in the first wave of the pandemic, with levels higher pre-existing immunity.4 And BA.5 increased 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 group, but also to prior immunity due to high exposure to SARS-CoV-2 at the beginning of the pandemic.5
Got an “Unanswered Question About Covid”? Email mlooi@bmj.com and we’ll try to cover it in a future installment of this series.
Footnotes
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Competing interests: none.
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Provenance and Peer Review: commissioned, not externally peer reviewed.
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References
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Chaguza C, Hahn AM, Petrone ME, et al. Accelerated intrahost evolution of SARS-CoV-2 leading to distinct genotypes during chronic infection. medRxiv 2022 [preprint]. doi:10.1101/2022.06.29.22276868
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Vasylyeva TI, Fang CE, Su M, et al. Introduction and establishment of gamma variant SARS-CoV-2 in New York City in early 2021. medRxiv 2022 [preprint]. doi:10.1101/2022.04.15.22273909
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