OPINION: Another major hurdle

COVID-19 testing continues ... SARS-CoV-2 mutates regularly, acquiring about one new mutation in its genome every two weeks, the Centers for Disease Control and Prevention says. Picture: https://www.azcentral.com

As countries around the world grapple with the challenges of rolling out urgently needed COVID-19 vaccines, health authorities are now facing another major hurdle: a more contagious form of coronavirus.

The newly-identified variant, first recognised in England in late September, has spread to 45 countries and prompted lockdowns and new restrictions across Australia.

Initially, it was unclear whether the high number of cases of the variant in the UK were because it was more transmissible or because it emerged in an area where there was a high spread of COVID- 19. But evidence of the variant being more contagious is mounting, with the UK’s Office for National Statistics reporting that it now accounts for more than 60 per cent of positive tests in England — where case numbers have hit record highs — and more than 80 per cent in London.

“The really compelling thing for me is that it’s not just spreading really rapidly, but it’s replacing all the other variants in the population, and that suggests it’s got some advantages,” Prof Eddie Holmes, an evolutionary virologist at the University of Sydney, told Coronacast. The variant — officially known at VUI- 202012/01 or lineage B117 — is not thought to be more deadly or cause more severe illness.

But over time, a variant that infects more people will inevitably drive up rates of infection, hospitalisations and death, potentially posing a signifi cant threat to countries already struggling to contain COVID-19. So just how much more contagious is the B117 variant — and what makes it so?

Is it really 70 per cent more transmissible?

 In December, when it was fi rst revealed the new variant was circulating in southeast England, UK authorities said it could be up to 70 per cent more transmissible than previously circulating SARSCoV- 2. But it’s very diffi cult to work out exactly how much more contagious the new variant is, said medical microbiologist and genomics specialist Norelle Sherry.

“The problem with trying to estimate the transmission value is that we can’t do controlled lab studies to work out how much the increase in transmission is due to the virus, versus how much it’s due to social factors … things like the mobility of people, how well they’re adhering to lockdowns, whether schools are open,” said Dr Sherry from The Doherty Institute.

“We have to rely on our observations of what’s happening in the UK.” In recent weeks, a handful of preliminary reports and epidemiological observations have helped to pinpoint the effect of the new variant, with several suggesting an increase in transmissibility of around 50 per cent.

Researchers at the London School of Hygiene and Tropical Medicine tested different mathematical models to work out which one best predicted the number of new confi rmed cases seen in the UK.

Their study, which has not yet undergone peer review, estimated the new strain was 56 per cent more contagious. A separate preprint study from researchers at Imperial College London found the new variant increased the virus’s reproduction or R number — the average number of people an infected person infects — by between 0.4 and 0.7, said Prof Holmes.

“It doesn’t sound like very much, but in fact, in terms of transmissibility, it’s a lot.”

To keep an epidemic from growing, the reproductive number must remain below 1. If the reproductive number is 1 or more, it means each infected person on average passes the virus on to one or more other people.

The researchers estimated that during England’s November lockdown, previously circulating coronaviruses had a reproductive number of 0.92, while the B117 variant had a reproductive number of 1.45. Dr Sherry said more research was needed to tease out how much of that increase was a result of mutations (in the variant) versus social or population factors.

But she agreed the study provided evidence the new variant was “quite a lot more transmissible”. Similarly, a recent analysis by Public Health England (PHE) found the B117 variant had a higher secondary attack rate — meaning the number of people subsequently infected from a known case.

Using contact tracing data, PHE showed about 15 per cent of the contacts of people infected with the B117 variant subsequently tested positive for COVID- 19, compared with 10 per cent of contacts of those infected with previous circulating SARS-CoV-2.


What makes it more contagious? 

The speed at which B117 is spreading suggests the variant carries certain biological features — or mutations in its genome — that make it more contagious.

While genetic mutation is a normal and expected part of viral evolution (most of these changes don’t make a big difference to the way the virus behaves), sometimes viruses acquire advantageous mutations that enable them to out compete other circulating variants, Prof Holmes said.

“The virus has been mutating since day one, and that’s to be expected. RNA viruses like coronavirus mutate all the time.” The B117 variant, however, is defined by a unique number and combination of mutations, he said.

The variant has 23 mutations compared with the original virus discovered in Wuhan, 17 of which have appeared since the virus diverged from its most recent ancestor.

While it’s unclear which mutation or combination of mutations are responsible for the variant’s increased transmissibility, Dr Sherry said there are a few key suspects. One is a mutation called N501Y, located in the spike protein on the surface of SARS-CoV-2, through which the virus binds to and enters human cells.

“The N501Y mutation actually means the virus binds more tightly to the ACE2 receptor, so it might mean it would contribute to transmission,” she said. Other mutations may help the virus to evade our immune responses or better replicate once the virus infects us.

“Some of these mutations are in other strains throughout the world, arising independently,” she said. “It seems to be the combination of mutations here that has led to a more significant increase in transmission, as far as we can tell with the information we currently have.”

There is also preliminary evidence the B117 variant generates a higher viral load, which means when an infected person sneezes or coughs, they are likely to spread more of the virus.


What does this variant mean for vaccines? 

Research is now underway to better understand the B117 variant and whether it is likely to impact the effectiveness of vaccines.

Preliminary data, yet to be peer reviewed, suggests the variant is unlikely to evade immune responses generated by vaccines or previous COVID-19 infection.

Researchers found COVID-19 antibodies (designed to neutralise the virus) very rarely targeted parts of the virus that were mutated in the new variant.

The B117 strain is just one of a handful of new variants of COVID-19 that appear to be more transmissible, including B1351, a variant detected in South Africa that also carries the N501Y mutation.

Professor Holmes said it was increasingly important to understand what was driving the evolution of SARS-CoV-2.

“Is it just chance that we now have so many people infected, there are more mutations circulating?” he said. “Or is because those mutations are being … favoured by the virus?”

Unlike countries currently overwhelmed by new infections, Dr Sherry said Australia was well placed to monitor for the presence of the B117 variant and act accordingly.

“We’ve got strong border controls, we’ve got hotel quarantine programs, we’ve got coordinated national genomic surveillance efforts, and highly effective public health intervention,” she said.

“I think that puts us in a very good position.”

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