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Why is omicron more infectious but less severe? What we know so far
The omicron variant infects cells in a different way, is present in higher levels in saliva and seems more likely to cause asymptomatic infections - all findings that could help explain why omicron is spreading so rapidly but resulting in a lower proportion of hospitalisations and deaths
HEALTH 6 January 2022
By Michael Le Page
Testing for covid-19 in Lisbon, Portugal, in December 2021
PATRICIA DE MELO MOREIRA/AFP via Getty Images
Scientific studies are beginning to shed light on why omicron behaves so differently from other coronavirus variants. Its reduced severity could be due to a change in how it fuses with our cells, while higher levels of the virus and an increased proportion of asymptomatic cases may help explain how it spreads so quickly.
The global number of confirmed covid-19 cases is currently hitting record levels as omicron spreads. But while this variant – which has around 50 mutations compared with the original SARS-CoV-2 virus – is much more infectious than previous ones, there is growing evidence that it is less likely to cause severe disease in those it infects. For instance, in South Africa, the first nation to have an omicron wave, reported cases peaked at 117 per cent of the level of the country’s delta wave, whereas hospitalisations peaked at 63 per cent and deaths at 16 per cent.
One factor in why omicron seems to be sending a lower proportion of cases to hospital could be that more people are now protected against severe disease, due to previous infections and vaccination. However, animal studies suggest that omicron is also inherently less likely to cause severe symptoms.
How the variant infects cells
For instance, a team led by James Stewart at the University of Liverpool, UK, has found that mice become less ill and recover faster with omicron compared with other variants.
“Ours is one of a number of animal studies now,” says Stewart. “They do point to very much the same thing.”
Work by Joe Grove at the University of Glasgow, UK, and his colleagues suggests that the reason omicron is less severe is that it infects cells in a slightly different way. The process begins when the spike protein of the virus binds to a protein called ACE2 that protrudes from the surface of most human cells.
The second step occurs when the spike protein is cut by another protein in our bodies, causing the virus to release its contents inside a cell. With other SARS-CoV-2 viruses, this cutting is done by a protein called TMPRSS2 found on the outside of cells, and it enables the viruses to then fuse with our cells.
With omicron, the spike protein doesn’t seem to be cut while it is still outside our cells. Instead, the virus seems first to become enveloped by the membrane of a cell and pinched off into a small sac within that cell. Only then is the spike protein cut by proteins called cathepsins. This process is slower.
Read more: How did the omicron coronavirus variant evolve to be so dangerous?
Put together with results from other teams, this finding suggests that omicron infects cells differently, making it more likely to infect the nose than the lungs. “The emerging picture is that this is probably the mechanism that underlies this switch from a lower respiratory tract infection to an upper respiratory tract infection,” says Grove.
Why this has happened isn’t known, he says, and there is no guarantee that future variants will remain less severe. The 2006 SARS virus infected cells in the same way as omicron, yet oddly was far more deadly, says Grove.
“That said, as we all get immunity from vaccines and natural infection, our antibody and importantly our T-cell responses are being strengthened,” he says. “So the ability of the virus to cause severe disease will be diminished.”
More prevalent in saliva
However, the impact of a virus depends on how many people it infects as well as on how severe it is, which is why flu kills far more people than Ebola. In countries such as Australia that had previously succeeded in preventing large outbreaks, omicron is already having a much greater effect than other variants.
“This variant is much more infectious and spreading very rapidly,” says Stewart. “It’s already putting pressures on healthcare systems worldwide.”
A big part of why omicron is so infectious is undoubtedly its ability to evade antibodies and infect a far greater proportion of people who have been vaccinated or infected by other variants. But this can’t be the whole story.
One possibility is that it is related to the observed higher levels of the virus in saliva, meaning the variant is more likely to spread when people talk, shout, cough or sing.
“I think the higher levels of virus in saliva relative to previous variants must correlate in some way with the increased infectivity,” says Diana Hardie at the University of Cape Town in South Africa. “I don’t have proof of it, but it makes sense.”
Her team has compared the results of PCR tests done using nasal and saliva swabs from the same individuals. The mouth swabs involved people coughing and then swabbing the inside of both cheeks, above and below the tongue, on the gums and on the hard palate for at least 30 seconds.
With the delta variant, only 70 per cent of saliva swabs were positive when the nasal swabs were all positive. But with omicron, it was the other way round. Only 86 per cent of nasal swabs were positive when all the saliva swabs were positive.
In other words, saliva swabs may be a more reliable way of detecting omicron infections with PCR tests. Hardie thinks this applies to lateral flow tests, too, and plans to investigate this. There are already anecdotal reports that mouth or throat swabs are better than nasal swabs for detecting omicron.
Asymptomatic infections
Another reason why omicron is so infectious might be that a much higher proportion of people are asymptomatic and spread the virus without ever realising they are doing so. Lawrence Corey at the Fred Hutchinson Cancer Research Center in Seattle, Washington, and his colleagues have been analysing data from ongoing studies in South Africa where people have been tested regardless of symptoms.
Their results suggest that the rate of asymptomatic infections is around eight times higher with omicron than with other variants, says Corey. The researchers think this could be a major factor in explaining why this variant is spreading so fast.
“It’s plausible,” says Stewart. But all these early findings are preliminary and need to be confirmed, he says. “I think it’s very early days. Tread cautiously, I would say, in interpretations of everything.”
It makes sense that there would be more asymptomatic cases with omicron, says Grove. “That data is completely consistent with the idea that this virus is, on a person-by-person basis, less severe.”
Read more: Covid-19: What can we expect from the pandemic in 2022?
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Why is omicron more infectious but less severe? What we know so far
The omicron variant infects cells in a different way, is present in higher levels in saliva and seems more likely to cause asymptomatic infections - all findings that could help explain why omicron is spreading so rapidly but resulting in a lower proportion of hospitalisations and deaths
HEALTH 6 January 2022
By Michael Le Page
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Testing for covid-19 in Lisbon, Portugal, in December 2021
PATRICIA DE MELO MOREIRA/AFP via Getty Images
Scientific studies are beginning to shed light on why omicron behaves so differently from other coronavirus variants. Its reduced severity could be due to a change in how it fuses with our cells, while higher levels of the virus and an increased proportion of asymptomatic cases may help explain how it spreads so quickly.
The global number of confirmed covid-19 cases is currently hitting record levels as omicron spreads. But while this variant – which has around 50 mutations compared with the original SARS-CoV-2 virus – is much more infectious than previous ones, there is growing evidence that it is less likely to cause severe disease in those it infects. For instance, in South Africa, the first nation to have an omicron wave, reported cases peaked at 117 per cent of the level of the country’s delta wave, whereas hospitalisations peaked at 63 per cent and deaths at 16 per cent.
One factor in why omicron seems to be sending a lower proportion of cases to hospital could be that more people are now protected against severe disease, due to previous infections and vaccination. However, animal studies suggest that omicron is also inherently less likely to cause severe symptoms.
How the variant infects cells
For instance, a team led by James Stewart at the University of Liverpool, UK, has found that mice become less ill and recover faster with omicron compared with other variants.
“Ours is one of a number of animal studies now,” says Stewart. “They do point to very much the same thing.”
Work by Joe Grove at the University of Glasgow, UK, and his colleagues suggests that the reason omicron is less severe is that it infects cells in a slightly different way. The process begins when the spike protein of the virus binds to a protein called ACE2 that protrudes from the surface of most human cells.
The second step occurs when the spike protein is cut by another protein in our bodies, causing the virus to release its contents inside a cell. With other SARS-CoV-2 viruses, this cutting is done by a protein called TMPRSS2 found on the outside of cells, and it enables the viruses to then fuse with our cells.
With omicron, the spike protein doesn’t seem to be cut while it is still outside our cells. Instead, the virus seems first to become enveloped by the membrane of a cell and pinched off into a small sac within that cell. Only then is the spike protein cut by proteins called cathepsins. This process is slower.
Read more: How did the omicron coronavirus variant evolve to be so dangerous?
Put together with results from other teams, this finding suggests that omicron infects cells differently, making it more likely to infect the nose than the lungs. “The emerging picture is that this is probably the mechanism that underlies this switch from a lower respiratory tract infection to an upper respiratory tract infection,” says Grove.
Why this has happened isn’t known, he says, and there is no guarantee that future variants will remain less severe. The 2006 SARS virus infected cells in the same way as omicron, yet oddly was far more deadly, says Grove.
“That said, as we all get immunity from vaccines and natural infection, our antibody and importantly our T-cell responses are being strengthened,” he says. “So the ability of the virus to cause severe disease will be diminished.”
More prevalent in saliva
However, the impact of a virus depends on how many people it infects as well as on how severe it is, which is why flu kills far more people than Ebola. In countries such as Australia that had previously succeeded in preventing large outbreaks, omicron is already having a much greater effect than other variants.
“This variant is much more infectious and spreading very rapidly,” says Stewart. “It’s already putting pressures on healthcare systems worldwide.”
A big part of why omicron is so infectious is undoubtedly its ability to evade antibodies and infect a far greater proportion of people who have been vaccinated or infected by other variants. But this can’t be the whole story.
One possibility is that it is related to the observed higher levels of the virus in saliva, meaning the variant is more likely to spread when people talk, shout, cough or sing.
“I think the higher levels of virus in saliva relative to previous variants must correlate in some way with the increased infectivity,” says Diana Hardie at the University of Cape Town in South Africa. “I don’t have proof of it, but it makes sense.”
Her team has compared the results of PCR tests done using nasal and saliva swabs from the same individuals. The mouth swabs involved people coughing and then swabbing the inside of both cheeks, above and below the tongue, on the gums and on the hard palate for at least 30 seconds.
With the delta variant, only 70 per cent of saliva swabs were positive when the nasal swabs were all positive. But with omicron, it was the other way round. Only 86 per cent of nasal swabs were positive when all the saliva swabs were positive.
In other words, saliva swabs may be a more reliable way of detecting omicron infections with PCR tests. Hardie thinks this applies to lateral flow tests, too, and plans to investigate this. There are already anecdotal reports that mouth or throat swabs are better than nasal swabs for detecting omicron.
Asymptomatic infections
Another reason why omicron is so infectious might be that a much higher proportion of people are asymptomatic and spread the virus without ever realising they are doing so. Lawrence Corey at the Fred Hutchinson Cancer Research Center in Seattle, Washington, and his colleagues have been analysing data from ongoing studies in South Africa where people have been tested regardless of symptoms.
Their results suggest that the rate of asymptomatic infections is around eight times higher with omicron than with other variants, says Corey. The researchers think this could be a major factor in explaining why this variant is spreading so fast.
“It’s plausible,” says Stewart. But all these early findings are preliminary and need to be confirmed, he says. “I think it’s very early days. Tread cautiously, I would say, in interpretations of everything.”
It makes sense that there would be more asymptomatic cases with omicron, says Grove. “That data is completely consistent with the idea that this virus is, on a person-by-person basis, less severe.”
Read more: Covid-19: What can we expect from the pandemic in 2022?
Sign up to our free Health Check newsletter for a round-up of all the health and fitness news you need to know, every Saturday
