New Zealand: Covid-19: New variants could push level 3 to its limit
16 February, 2020
ANALYSIS: The emergence of new, more transmissible variants of Covid-19 and their arrival in New Zealand has experts reconsidering the efficacy of level 3, Marc Daalder reports.
As winter descended on the United Kingdom and Covid-19 case numbers ticked upwards, the country plunged into lockdown. The strict new measures, applied nationwide for the first time since June, were temporarily effective in crushing the case curve almost everywhere – except for Kent.
The county southeast of London was experiencing a surge of cases despite the harsh lockdown restrictions. When the genome of the virus that was spreading so successfully was sequenced, it bewildered scientists – it had more than a dozen mutations separating it from the next closest variant, indicating that it had spread undetected in the community for months (unlikely, as the UK sequences a high proportion of its cases) or something strange had happened.
Now, experts say, the latter seems most likely.
For months, a person in Kent battled Covid-19. The person had what doctors call a chronic infection – unlike those with so-called long Covid, people with chronic Covid-19 are not just continuously symptomatic for a long period of time but also continuously infectious.
While the virus that causes the Covid-19 disease, SARS-CoV-2, does mutate, it does so at a much slower rate than other viruses like influenza. On average, it experiences a mutation once every other week. In a line of transmission, that means it mutates once every two to four cases. The vast majority of these are random and have no effect on the function of the virus.
The virus transmitted by the chronic case in Kent, however, had more than a dozen mutations separating it from the likely variant they were infected with. These mutations were not just random, but came about as the result of a prolonged battle. Many chronic cases are immunocompromised, meaning they are unable to completely fight off the virus on their own and can spend weeks or even months wracked with the illness.
For the virus, rapidly replicating and infecting cells inside a chronic, immunocompromised person, the weakened immune system provides the perfect training ground for effective evolution. Over the course of the months-long game of cat and mouse with the Kent case's immune system, mutations which aided the virus in infecting cells faster or evading immune response accrued rapidly.
By the time it re-emerged in September, the new variant of SARS-CoV-2 was honed for defeating the human immune system. Scientists, placing it into a phylogenetic tree of other variants, have labelled it B.1.1.7. Although it was first identified in the UK, it has since made appearances in the communities of most other countries – including, as of Sunday, New Zealand.
What does the emergence of B.1.1.7 mean for New Zealand? How does its presence in the community change our response, compared to previous versions of the virus? And how worried should we be?
The variants
The new variant has been the focus of a significant amount of research since it was first identified in December. Scientists have identified a mutation labelled N501Y as making it easier for the virus to bind with human ACE2 receptors – its primary entrance into cells. The variant also has a number of other mutations clustered around the spike protein which is used to enter cells, with researchers still teasing out which of these might have functional impacts.
Since B.1.1.7 was found, a number of other variants have also emerged with the same N501Y mutation. In South Africa, variant B.1.351 was blamed for a sudden surge in cases and the near collapse of a regional health system. That variant was later identified in the Northland community case found in late January.
B.1.351 also has another mutation, E484K, which researchers say makes the virus harder to neutralise with antibodies, one of the building blocks of our immune system.
More recently, a third variant with N501Y and E484K was identified in Brazil. Labelled P.1, this variant has managed to wreak havoc in the city of Manaus and pushed its health system to the brink of collapse, despite the fact that up to three quarters of the population had been infected during earlier waves of the pandemic.
All three variants are considered to have emerged independently via a chronic infection in immunocompromised individuals. It's no coincidence that the virus, in separate locations around the world, is converging on beneficial mutations – it's evolution in action.
“The fact that all these mutations are around the spike protein which seems to be the main place that the immune system is recognising the virus, it shows that there's some immune escape going on by the virus,” David Welch, a computational biologist and expert on bioinformatics at the University of Auckland who has worked on the genome sequencing effort in New Zealand, told Newsroom.
In early February, a new version of B.1.1.7 was sequenced in the UK and found to have the E484K mutation as well.
In addition to easier binding to the ACE2 receptor, some of the new variants have been linked to a higher viral load in the upper respiratory tract. In other words, there are more virus particles in the throat, nose and mouth of a person infected with one of the new variants, and therefore a greater chance of transmitting the virus via droplets or aerosol (airborne) transmission.
Reproduction numbers
At scale, the effect of higher viral loads and easier binding to human ACE2 receptors is to increase the reproduction number by about 50 per cent. The reproduction number, also called the R0 or R value, is an epidemiological average of the number of people a given case will go on to infect.
In a society with no restrictions, the R0 for SARS-CoV-2 is around two or 2.5 – meaning that any given two people with Covid-19 will give the virus to four to five more. As long as the R0 is above one, case numbers will grow, because each person with the virus will infect (on average) more than one other person.
Public health restrictions are designed to lower the R0 by reducing opportunities for transmission. That could come through hand washing or wearing masks, or through keeping people away from another with social distancing requirements or stay-at-home orders.
Michael Plank, one of the members of the Te Pūnaha Matatini team tasked with modelling the spread of Covid-19 in New Zealand, said that the R0 of the virus would increase with the new variants.
“It is more dangerous with these new variants. What we know about the new variants is that the R value – the number of people that an infected person passes the virus onto – is anywhere between 30 and 70 per cent larger. What that means is that there's a higher chance that a single case can spark an outbreak and that if it does spark an outbreak it will grow faster,” he told Newsroom.
Welch agreed, saying the issue “is just around increased transmission. Now there's a lot of evidence that increased transmission is a real thing. The number that people seem to be settling on is a 50 per cent increase. Nearly all of those studies are in places which have quite strong controls so they expect a reproduction number of about one, but they're seeing it spread at an R number of about 1.5. In a New Zealand context where we guess there's a background rate of about two, that would mean that it might be as high as an R number of three.”
Take Denmark as an example. The Scandinavian country sequences a significant number of its cases, giving researchers a better understanding of how different variants might spread differently. From early December, Denmark has imposed a series of escalating restrictions in an effort to get a winter wave of Covid-19 under control.
Those efforts appear to have worked so far, with case numbers declining into the new year. Take a closer look however, and it becomes apparent that the overall Covid-19 epidemic is subsiding while the B.1.1.7 outbreak is just beginning. The R0 for B.1.1.7, in the midst of a lockdown about as strict as level 3 in New Zealand, has ranged from 1.14 to 0.99 in recent weeks.
Level 4?
What does that mean for level 3 in New Zealand? The increased transmissibility of B.1.1.7 may mean level 3 wouldn't be able to contain an outbreak larger than a handful of cases, experts told Newsroom.
Welch said B.1.1.7 would push level 3 restrictions to the limits of their efficacy.
“It's quite possible, if for example in this case we do discover new chains of transmission out there that could have been spreading for a few weeks, then it's quite possible that we would need to go to a level 4 lockdown,” he said.
“We saw in the August outbreak that level 3 was successful. It's quite possible that it wouldn't be successful this time. I think the estimated R number was about 0.6 at level 3, so we might just squeeze in at a 0.9.”
Plank also said that level 3 might not cut it.
“It's possible that it may not. We estimated that the R value in August under level 3 was about 0.7. If you do basic maths and multiply that by 50 per cent, you get something that's sort of close to 1. Maybe slightly above 1, but hovering about that threshold,” he said.
“If we're on the lower end of the scale, you get sort of get lucky in the early stages and don't get too many cases, level 3 may be enough to contain it. But if we're at the higher end of that transmissibility scale or you get a couple of super-spreading events early on in the outbreak, it is possible with an R value of above 1 that it wouldn't be enough to stop an outbreak. You might need additional measures, you might need to go to level 4.”
Even with an R0 of 0.9, level 3 could take weeks or months to extinguish an outbreak of any significant size.
“It depends a little bit on how many cases we've got out there that we don't know about. If there are only a handful of cases, then having an R0 of 0.9 or 0.95 is probably OK because there's only a small number of transmission chains that need to be extinguished,” Plank said.
“But if there are more cases out there, if we're in a comparable situation to the August outbreak, then an R0 of 0.9 would take a long time to get that outbreak down to a level where you think it can be eliminated.”
Jacinda Ardern, when asked about the efficacy of level 3 in response to the new variants, said she was confident the system would hold up.
But Michael Baker, an epidemiologist at the University of Otago, agreed that level 4 restrictions would likely be needed in the event of a more widespread outbreak.
“You'd probably need a level 4 alert level. It's partly because you want to actually contain it as fast as you can. While level 3 is obviously less restrictive, it just means you're going to be under that alert level for a lot longer, is what the modelling says,” he said.
“I think the philosophy of short, sharp lockdowns is probably more sustainable in the long run.”
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