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Where did the new Covid-19 variants come from, and what do they mean?
Twice a year, in February and September, a group of experts representing over 100 countries meets to discuss influenza. The purpose of their meeting is not simply to discuss the latest research. The experts are there to analyse data collected by the World Health Organisation and use that data to predict which strains of the virus are likely to be the most common in the coming winters. From their predictions, they recommend which strains should be used to make the flu vaccine for the next season.
With the flu, we face an arms race against a virus that is constantly changing. Last year’s vaccine may not work to stop this year’s outbreak. But it’s not just about making the most effective vaccine. Some years, strains emerge that are particularly infectious, or particularly deadly. Flu experts are always looking out for the next pandemic.
To understand why this happens with the flu and not, for example, measles, we need to understand more about the virus, or, more correctly, the virus group, since “the flu” is not a single disease caused by a single type of virus. There’s a whole world of influenza viruses out there, infecting people, cats, chickens, pigs, ducks, bats and even seals and whales.
There are four main types of influenza virus, usually known simply as influenza A, B, C and D. Of these, three are known to infect people, although only two, A and B, cause significant human disease. Although both A and B contribute to “seasonal flu”, it is influenza A which is the most diverse, which infects the greatest number of different animals, and which causes periodic pandemics.
Influenza viruses look similar to coronaviruses – they are both round viruses with protruding spikes made from protein. Inside, they both also carry their genetic code as RNA – a similar molecule to the DNA which carries the genetic code in human cells. When DNA and RNA are being copied, to make new cells or new viruses, there are sometimes errors in the copying process. These errors are known as mutations. However RNA is much more prone to error than DNA. Viruses with RNA, such as influenza, therefore have a higher mutation rate than viruses with DNA, or human cells.
But even among the RNA viruses, mutation rates vary. Influenza viruses have a particularly high rate of mutation, which explains, at least in part, why they are constantly evolving. Mutations are the raw material for evolution. Many mutations are harmful, and viruses with these mutations don’t survive. But some mutations are beneficial to the virus, and so viruses with these mutations are more successful. Over time, viruses with the beneficial mutations come to dominate, and the new variant replaces the previous one.
Coronaviruses, on the other hand, belong to a small group of RNA viruses that have a slightly different copying process for their RNA. Their copying process includes a “proofreading” step, where errors in the RNA are detected and fixed. As a result, coronaviruses have a much lower mutation rate than influenza.
The high mutation rate of most RNA viruses is one reason why influenza is constantly changing, but it’s only one part of the explanation. It’s not enough to explain why we sometimes see the dramatic changes in influenza strains that result in periodic global pandemics. The last time that happened was 2009, but there were also pandemics in 1968, 1957 and, of course, 1918. All of these pandemics resulted from the same type of influenza – influenza A. When two different strains, or variants, of influenza A infect the same cell, they can recombine their RNA to produce new variants of the virus. New variants resulting from this recombination process are more different from the old variants than the variants that result from mere mutation.
The final factor that explains why influenza, and especially influenza A, changes so much is the wide range of animals it infects. When a virus shifts from species to species, such as bird to human, the new host may not have any suitable antibodies to that new virus. We see this with avian influenza, or bird flu, which mostly infects birds but does occasionally cross into people. One particular type of bird flu, known as H5N1, can be very dangerous when it infects humans. Fortunately, it is seldom transmitted from one person to another.
But there’s another important factor in how rapidly a virus, or for that matter a fungus, ant or mammal, evolves new forms. That factor is the generation time – the time it takes for something to reproduce itself. For humans, that time is usually estimated as around 20 years. For a fast-breeding mammal like a rat, that time is about six weeks. For a virus, the time can be measured in hours or, at most, a few days.
Generation time matters, because evolution is a numbers game. With each new generation of viruses, some individuals will have mutations which are more beneficial to survival and, more importantly, reproduction. Those viruses will reproduce more effectively, meaning that there are more of them in the next generation. In the next generation, there will be even more, and so on, until the viruses are different enough to be called a new strain or variant. The faster the generation time, the faster this process happens. In a single year, a virus can have as many generations as humans have had since we started sowing crops and domesticating animals.
There’s another factor in the numbers game as well. Last year, about 130 people caught the Ebola virus. That didn’t give it many opportunities to become better adapted to humans. But at least 100 million caught Covid-19. Even with a much lower mutation rate than influenza, the virus causing Covid-19 has had no shortage of opportunities to become better adapted. And that’s exactly what it has done.
In September last year, a variant of the virus, given the catchy name of B.1.1.7, was detected in Britain. That, in itself, wasn’t remarkable. There’s also a B.1.1.6 and a B.1.1.8, and many others, all entered into a database that allows scientists to keep track of the changes in the virus’s genes. But by December, B.1.1.7 was becoming more common, and scientists were starting to suspect that something important was happening. The variant had a number of different mutations that changed the spike of protein on the outside of the virus. Since the spike of protein affects the way the virus attaches to cells, changes in that spike can affect transmission of Covid-19. Perhaps the variant would turn out to be more transmissible.
By January, that suspicion was confirmed. The figure varies depending which source you look at, but B.1.1.7, by now usually known as the “UK variant”, was estimated to be somewhere from 30%-70% more transmissible. If the lower figure is correct, it means that instead of each person infecting an average of 3 other people, they would infect 4. If the higher figure is correct, then the average number rises to 5.
Britain wasn’t the only country to report variants that were spreading faster. Another variant, with the equally catchy name of B.1.351, was reported in South Africa. Again, the mutations carried by the variant affected the spike of protein on the outside of the virus. And again, the variant was reported to be more transmissible, by around 50%. There has also been a variant with similar mutations reported in Brazil. While it’s still too soon to tell whether that variant is more transmissible, it has been associated with a serious outbreak in Manaus.
The Manaus variant is probably more frightening than either the UK or the South African variant. Manaus was hit hard by Covid-19 early in the pandemic, and it was estimated that up to three quarters of the population of that city had caught Covid-19. With so many people infected, the city should have been getting close to herd immunity. But the new variant has caused another devastating outbreak there. At this stage, we don’t know why, but there are several theories. Among them is the alarming possibility that this variant can defeat any natural immunity people have from having been infected by the original variant of the virus.
There’s something else that we don’t yet know about the variants. All of our current crop of vaccines have been made to help the body fight off the original Covid-19. In particular, the vaccines are designed to teach our bodies to recognise Covid-19's spike proteins. If those spike proteins change, will the vaccines work against the new variants?
So far, the answer isn’t clear. There are signs that three important vaccines (Pfizer/ BioNTech, Moderna and Oxford/ AstraZeneca) don’t work so well against the South African variant, which has now been reported from 45 countries. In particular, the Oxford/ AstraZeneca vaccine was largely ineffective at preventing mild-moderate disease.
The signs are more hopeful with the UK variant, which is now in at least 70 countries. Both the Pfizer/ BioNTech and the Moderna vaccines still seem to work. And with the Brazilian variant, we just don’t have any data.
One question being asked about vaccines is whether Covid-19 will become like influenza, where we need an updated vaccine every year. Covid-19 doesn’t have the mutation rate of influenza, so it may not. But the problem is that there’s just so much of it around. The comparatively lower mutation rate is outweighed by the massive number of cases out there. Unless the countries with severe outbreaks can get the disease under control, there will continue to be new variants emerging which make the battle harder and harder.
Back in May 2020, when Covid-19 had infected 3 million people and killed around 220,000, the UN Secretary General, António Guterres gave the world a warning about the importance of getting the virus under control. “In an interconnected world”, he said, “none of us is safe until all of us are safe.” With Covid-19, that’s proving to be very true indeed.
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