A variant of the pandemic coronavirus, SARS-CoV-2, now dominates the headlines and inspires preventive travel bans around the world. But scientists are still trying to understand what the different variant can actually do and what it could mean for the pandemic of almost a year.
Researchers in the UK – where the variant has been identified and are now circulating rapidly – have suggested it may be up to 70 per cent more transmissible than other SARS-CoV-2 strains, causing fears of disease outbreaks on the eve of the year – end holidays. But other researchers are now working quickly to collect data on the variant’s interactions with human cells and immune responses to see if these interactions differ from those seen in other SARS-CoV-2 strains.
What do we know
Although much remains to be known about the variant, called B.1.1.7, there are some reassuring aspects. First, it is normal for viruses to accumulate small genetic changes, such as those that created the new variant in the UK (more on this below). Many other variants have been identified during the pandemic and none have generated any nightmare scenarios.
So far, there is no reason to believe that things will change much with the new. There is no evidence to date that B.1.1.7 causes different or more severe COVID-19 diseases; nor does it appear to make COVID-19 treatments less effective. British officials also suspect that the newly authorized vaccines will work just as well against the new variant, although researchers are working hard to confirm this.
Together, the available information suggests that B.1.1.7 should change little in terms of recommended strategies to try to eliminate the pandemic, regardless of the population-wide variant. “The bottom line is that we need to suppress the transmission of all SARS-CoV-2 viruses as soon as we can,” World Health Organization Director-General Tedros Adhanom Ghebreyesus said on Monday.
It is also important to put forward the increase in transmissibility. While the figure “up to 70%” seems really alarming, the actual increase in the transmission rate is modest. In the UK, the presence of B.1.1.7 has hit the virus’s reproduction number by just 0.4 – from 1.1 to 1.5, according to Maria Van Kerkhove, WHO’s technical lead on the COVID-19 pandemic. This small increase means that the number of people infected by each infected person has gone from an average of just over one person to 1.5 people. It is unclear whether this increase is due to something inherent in the virus, the behavior of infected people or a combination of both.
An increase of 0.4 is not good news, but neither is it dramatically bad, said Dr Mike Ryan, executive director of the WHO emergency program. A reproduction number of 1.5 can be controlled, he said, and the reproduction number of the virus during this pandemic was much higher at other times.
“[This] just put the bar a little, “Ryan said.” We are not talking about a reproductive number, such as measles, which is somewhere between 12 and 18, or mumps and chickenpox, from 10 to 12. We are talking about 1.5. The virus may have become a little more effective at transmission – which can have a big impact on the number when we have so many people infected. But it means that the virus can be contained, the virus can be suppressed [using] exactly the same interventions, exactly the same behaviors “as before.
Underlining the last point, Van Kerkhove explained that there is no reason to believe that the slight increase in transmission is due to the fact that the virus has changed the way it spreads from one person to another – such movement further in the air or easier spread on surfaces. “It’s a respiratory pathogen, so it spreads between you and me through these airborne particles,” Van Kerkhove explained. “Mainly, what happens is that the virus spreads between people who are in close contact with each other. That’s still the same.”
While the WHO pointed out the similarity between B.1.1.7 and other strains of SARS-CoV-2, the British government focused on the news. This is where the strain was first identified, and most people infected with it are in the UK.
Details about the new strain have become apparent due to ongoing surveillance in the UK, where researchers randomly sequence the genomes of dozens of virus samples each month. During the pandemic, circulating SARS-CoV-2 strains typically recorded an average of one or two mutations per month, so this level of surveillance was sufficient to track the origin and spread of new strains. But B.1.1.7, first identified in samples obtained at the end of September, had nothing in common with the cumulative gradual accumulation of changes we saw earlier. There were 17 differences between this and the nearest known strain, providing B.1.1.7 a branch of its own on the coronavirus family tree.
That “alone” is a curiosity rather than a concern. What caught people’s attention was a correlation. In response to the wave of winter infections across Europe, the UK has restarted a set of social restrictions aimed at reducing the level of infections. And in most parts of the country, these restrictions worked as intended. But not in the south-east and east of Great Britain. And precisely that region in which the levels of strain B.1.1.7 were the highest. In one county, B.1.1.7 accounted for over 20% of all new infections by mid-December, and this number has increased since then.
This is not conclusive evidence that strain B.1.1.7 has any advantage. The COVID-19 pandemic has been marked by numerous “over-spreading” events and social groups that run counter to public health measures. This combination can cause the rapid expansion of the stems that happen to circulate in these groups at the right times. But by the end of the week, B.1.1.7 accounted for about 60% of new cases in London, leading government officials there to say the strain could spread faster.
To know this for sure, however, we will need to design the mutations found in B.1.1.7 in a laboratory strain and then test its infectivity. Meanwhile, the scientists looked at the mutations in the new viral strain and speculated which of them could give it increased infectivity or change the course of the infections.
Old, but in a new combination
While B.1.1.7 is a new strain of coronavirus, we know quite a bit about the biology of coronavirus, allowing us to determine when mutations alter a critical region. And, in some cases, the mutations were found individually in different strains that we previously characterized. So it is possible to deduce some things about the behavior of B.1.1.7.
Several of them appear in the spike protein that is on the surface of coronaviruses and helps them cling to a protein on the surface of cells. One of the mutations found in B.1.1.7 specifically modifies a part of a peak that participates in this process and has been shown to increase the affinity between viral and human proteins. Another mutation removes two amino acids from the spike protein; this has been associated with a reduced immune response, but is usually found only in combination with other mutations (as here).
Finally, another mutation is near a site where the spike protein is cut into two smaller fragments, something essential for its functioning. Although the mutation was not characterized, its location is suggestive.
Another mutation found in B.1.1.7 completely eliminates a viral protein (called ORF8). A different mutation that harms this gene was found in Singapore earlier this year and appears to cause less severe symptoms among those infected. But thanks to Singapore’s successful control of the pandemic, there are no more active infections with this strain, so we have no other data there.
There is also some suggestive information that can be collected from the collection of mutations found in B.1.1.7 as a whole. Of the 17 mutations that characterize it, 14 modify the proteins encoded by the virus; only three do not produce changes. This is a very high percentage and is often an indication of evolutionary selection for some of the changes.
The high rate of mutation required to produce B.1.1.7 in a relatively short time has been observed before in immunocompromised individuals with infections. In these people, the infection can take more than a month to resolve and they are often given treatments that directly target the virus, such as convalescent plasma and remdesivir. Thus, it is possible that at least some of the changes observed here were due to the selective evolutionary pressure exerted by these treatments. (The researchers behind this analysis note that this is a hypothesis, rather than anything we have come to.)
Although all these differences are suggestive, it is important to point out that we have no definitive evidence that any of them change the behavior of the virus. So while the data on their spread is dramatic, we are not even sure that this is a product of these mutations, and their impact on the evolution of viral infections is largely a matter of speculation. While we wait for biologists to cope with the changes found in B.1.1.7, the WHO’s advice remains simple: be very sure that you will take the measures that public health experts have been advising for months.