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A number of mutations in the UK variant took scientists by surprise. Now they think its origins may lie in one person, chronically infected with the virus
In each warm body it infects, the virus behind Covid-19 has the potential to change. It can become more deadly, more transmissible or more resistant to the vaccines on which we are all pinning so much hope. Mercifully, the biology of Sars-CoV-2 means that such changes happen slowly and almost always fail to catch on.
But mutations, like pandemics, are a numbers game. Every new person infected provides another opportunity for the virus to adopt a new form. So far, Sars-CoV-2 has infected at least 106 million people worldwide and taken on many thousands of mutations. Most of those changes are slow and inconsequential – evolutionary dead ends that nobody will ever realise existed. But, in some people, the virus hits the jackpot.
That is seemingly what happened in Kent in September 2020. Usually Sars-CoV-2 mutates slowly. We can watch this happen, with single letters changing one at a time in a viral genome that contains almost 30,000 letters. But, in one great leap, the UK variant picked up 17 of those changes. Eight of them happened in the gene that encodes the spike protein – the hook the virus uses to latch on to and enter human cells. If the genome of Sars-CoV-2 was a 30,000-character-long poem then the UK variant re-wrote its first line, drastically changing its meaning in the process.
The emergence of the UK variant presented scientists with an urgent question: how did the virus make this genetic leap, seemingly out of nowhere? The leading hypothesis is that the new variant evolved within just one person, infected with Sars-CoV-2 virus for so long that the virus was able to evolve into a new, more infectious, form. Out of this human pressure cooker, a new variant burst onto the scene and sent the world scrambling to react. Borders closed, countries locked down once more, vaccines were re-tested.
None of this was enough to halt the spread of B.1.1.7 – the scientific name given to the UK variant. The new variant has now been found in 75 countries and is spreading locally in Brazil, Canada, China, the United States and most of Europe. Up to 70 per cent more transmissible than other coronavirus variants, B.1.1.7 is now responsible for the vast majority of new cases in England. On January 22, the UK’s chief scientific officer, Patrick Vallance, added another worry to the list: preliminary data suggests that the new variant may be 30 per cent more deadly than others.
Chronic infections are rare events, but give a virus enough hosts to infect, and these rare events are almost certain to happen. Now, as worrying new variants spread in other parts of the world, scientists are racing to understand the role that chronic infections might play in the emergence of new variants, and how to stop the next one before it takes hold.
We asked coronavirus experts what summer 2021 will be like
Sars-CoV-2 may be the most surveilled virus in history. In the 13 months since virologists Zhang Yongzhen and Edward Holmes published the entire genome of the virus, more than 360,000 Sars-Cov-2 genomes have been sequenced and uploaded to GISAID – a platform for sharing viral genomes. Almost half of those genomes came from the UK, which sequences roughly ten per cent of all its positive Covid-19 tests, making the country a canary in the coal mine for detecting new variants.
As B.1.1.7 has shown, the speed at which variants are detected will be key in the next phase of the pandemic, but genomic surveillance only gives us a partial picture of how a virus is changing. The first example of the UK variant was found on September 20 in Kent and then another one day later, in a sample from Greater London. On its own, the appearance of a new variant in genomic databases doesn’t tell us much about where the virus is heading. “That’s just one genome amongst thousands every week. It wouldn’t necessarily stick out,” says Oliver Pybus, a professor of evolution and infectious disease at the University of Oxford. New variants of Sars-CoV-2 are being created all the time but the vast majority of them go absolutely nowhere.
It was only when it became obvious that lockdown measures in Kent were failing that Public Health England (PHE) realised the outbreak was being driven by a new variant. By the first week of December, it was clear that the new variant was rapidly becoming the dominant variant in certain parts of the UK. Of the 915 cases of the new variant identified in Public Health England’s initial report on the outbreak, four dated from September and 79 were recorded in October. In November there were 828. Data from positive cases gave health authorities an important clue about the new variant’s behaviour: it seemed to be transmitting more readily than existing variants. But the data couldn’t explain where the new variant had come from. The emergence of the UK variant, with its 17 significant genetic changes, seemed to defy the logic of what we know about how coronaviruses evolve.
In evolutionary terms, Sars-CoV-2 is a genetic slowpoke. Viruses mutate as they pick up tiny errors in their genetic code when they make copies of themselves, but coronaviruses have evolved an extra trick that makes this copying process more accurate. Coronaviruses have proteins that spot and correct mistakes in their RNA, which slows down the number of errors that accumulate in their genome. Sars-CoV-2 tends to pick up one or two mutations per month – slower than flu or polio but faster than measles. “It was unusual in September to all of a sudden see [a variant] pop up that had 17 [changes],” says Adam Lauring, an associate professor at University of Michigan Medical School who studies the evolution of RNA viruses like Sars-CoV-2. “It suggested that something unusual happened.”
The odds are stacked against any one mutation taking hold and becoming the dominant strain in an outbreak. Although the Sars-CoV-2 virus starts replicating within days of infecting a person, producing lots of genetically distinct viruses as it does so, most of these mutants never grow to make up a significant share of all the Sars-CoV-2 viruses within a host. “Most of them are dead-enders,” says Lauring. “They go nowhere. They die within a person and we never find out about them.”
When viruses do mutate, they tend to pick up changes slowly enough that genetic epidemiologists can see the emergence of a new strain in real-time. The distinctiveness of the UK variant pointed to two likely origin stories: either the virus had mutated abroad and only been detected once it entered the UK, or many of the changes had happened within one person. Since most countries don’t have high levels of genomic surveillance like in the UK, it’s impossible to know conclusively whether the variant originated in Kent, or was just detected there for the first time. But most countries affected by the new variant have strong travel links with the UK, suggesting that it is the country of origin, says Pybus.
A third possibility is that the variant emerged through something called recombination. Viruses can sometimes swap parts of their genome with other viruses from similar strains, bringing in a set of mutations all in one go. But, again, evolutionary biologists haven’t seen any evidence of ancestor strains in the UK that may have blended together to create the UK variant. This leaves one remaining likely hypothesis: the UK variant emerged from just one person.
For most people who get infected, Covid-19 lasts two weeks. People with mild cases usually test negative for the virus ten days after first showing symptoms. In more severe cases, people can continue to spread the virus for up to 20 days after their first symptoms. For an unlucky subset of patients Covid-19 infections last much, much longer.
In each warm body it infects, the virus behind Covid-19 has the potential to change. It can become more deadly, more transmissible or more resistant to the vaccines on which we are all pinning so much hope. Mercifully, the biology of Sars-CoV-2 means that such changes happen slowly and almost always fail to catch on.
But mutations, like pandemics, are a numbers game. Every new person infected provides another opportunity for the virus to adopt a new form. So far, Sars-CoV-2 has infected at least 106 million people worldwide and taken on many thousands of mutations. Most of those changes are slow and inconsequential – evolutionary dead ends that nobody will ever realise existed. But, in some people, the virus hits the jackpot.
That is seemingly what happened in Kent in September 2020. Usually Sars-CoV-2 mutates slowly. We can watch this happen, with single letters changing one at a time in a viral genome that contains almost 30,000 letters. But, in one great leap, the UK variant picked up 17 of those changes. Eight of them happened in the gene that encodes the spike protein – the hook the virus uses to latch on to and enter human cells. If the genome of Sars-CoV-2 was a 30,000-character-long poem then the UK variant re-wrote its first line, drastically changing its meaning in the process.
The emergence of the UK variant presented scientists with an urgent question: how did the virus make this genetic leap, seemingly out of nowhere? The leading hypothesis is that the new variant evolved within just one person, infected with Sars-CoV-2 virus for so long that the virus was able to evolve into a new, more infectious, form. Out of this human pressure cooker, a new variant burst onto the scene and sent the world scrambling to react. Borders closed, countries locked down once more, vaccines were re-tested.
None of this was enough to halt the spread of B.1.1.7 – the scientific name given to the UK variant. The new variant has now been found in 75 countries and is spreading locally in Brazil, Canada, China, the United States and most of Europe. Up to 70 per cent more transmissible than other coronavirus variants, B.1.1.7 is now responsible for the vast majority of new cases in England. On January 22, the UK’s chief scientific officer, Patrick Vallance, added another worry to the list: preliminary data suggests that the new variant may be 30 per cent more deadly than others.
Chronic infections are rare events, but give a virus enough hosts to infect, and these rare events are almost certain to happen. Now, as worrying new variants spread in other parts of the world, scientists are racing to understand the role that chronic infections might play in the emergence of new variants, and how to stop the next one before it takes hold.
We asked coronavirus experts what summer 2021 will be like
Sars-CoV-2 may be the most surveilled virus in history. In the 13 months since virologists Zhang Yongzhen and Edward Holmes published the entire genome of the virus, more than 360,000 Sars-Cov-2 genomes have been sequenced and uploaded to GISAID – a platform for sharing viral genomes. Almost half of those genomes came from the UK, which sequences roughly ten per cent of all its positive Covid-19 tests, making the country a canary in the coal mine for detecting new variants.
As B.1.1.7 has shown, the speed at which variants are detected will be key in the next phase of the pandemic, but genomic surveillance only gives us a partial picture of how a virus is changing. The first example of the UK variant was found on September 20 in Kent and then another one day later, in a sample from Greater London. On its own, the appearance of a new variant in genomic databases doesn’t tell us much about where the virus is heading. “That’s just one genome amongst thousands every week. It wouldn’t necessarily stick out,” says Oliver Pybus, a professor of evolution and infectious disease at the University of Oxford. New variants of Sars-CoV-2 are being created all the time but the vast majority of them go absolutely nowhere.
It was only when it became obvious that lockdown measures in Kent were failing that Public Health England (PHE) realised the outbreak was being driven by a new variant. By the first week of December, it was clear that the new variant was rapidly becoming the dominant variant in certain parts of the UK. Of the 915 cases of the new variant identified in Public Health England’s initial report on the outbreak, four dated from September and 79 were recorded in October. In November there were 828. Data from positive cases gave health authorities an important clue about the new variant’s behaviour: it seemed to be transmitting more readily than existing variants. But the data couldn’t explain where the new variant had come from. The emergence of the UK variant, with its 17 significant genetic changes, seemed to defy the logic of what we know about how coronaviruses evolve.
In evolutionary terms, Sars-CoV-2 is a genetic slowpoke. Viruses mutate as they pick up tiny errors in their genetic code when they make copies of themselves, but coronaviruses have evolved an extra trick that makes this copying process more accurate. Coronaviruses have proteins that spot and correct mistakes in their RNA, which slows down the number of errors that accumulate in their genome. Sars-CoV-2 tends to pick up one or two mutations per month – slower than flu or polio but faster than measles. “It was unusual in September to all of a sudden see [a variant] pop up that had 17 [changes],” says Adam Lauring, an associate professor at University of Michigan Medical School who studies the evolution of RNA viruses like Sars-CoV-2. “It suggested that something unusual happened.”
The odds are stacked against any one mutation taking hold and becoming the dominant strain in an outbreak. Although the Sars-CoV-2 virus starts replicating within days of infecting a person, producing lots of genetically distinct viruses as it does so, most of these mutants never grow to make up a significant share of all the Sars-CoV-2 viruses within a host. “Most of them are dead-enders,” says Lauring. “They go nowhere. They die within a person and we never find out about them.”
When viruses do mutate, they tend to pick up changes slowly enough that genetic epidemiologists can see the emergence of a new strain in real-time. The distinctiveness of the UK variant pointed to two likely origin stories: either the virus had mutated abroad and only been detected once it entered the UK, or many of the changes had happened within one person. Since most countries don’t have high levels of genomic surveillance like in the UK, it’s impossible to know conclusively whether the variant originated in Kent, or was just detected there for the first time. But most countries affected by the new variant have strong travel links with the UK, suggesting that it is the country of origin, says Pybus.
A third possibility is that the variant emerged through something called recombination. Viruses can sometimes swap parts of their genome with other viruses from similar strains, bringing in a set of mutations all in one go. But, again, evolutionary biologists haven’t seen any evidence of ancestor strains in the UK that may have blended together to create the UK variant. This leaves one remaining likely hypothesis: the UK variant emerged from just one person.
For most people who get infected, Covid-19 lasts two weeks. People with mild cases usually test negative for the virus ten days after first showing symptoms. In more severe cases, people can continue to spread the virus for up to 20 days after their first symptoms. For an unlucky subset of patients Covid-19 infections last much, much longer.
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