We knew it was going to be a long, dark winter. But unfortunately it looks even grimmer now. Just as the first coronavirus vaccines were rolled out around the world in December – and the end of the Covid-19 pandemic seemed to be ushering in – two rapidly spreading variants of the SARS-CoV-2 virus were discovered: the UK and the South African. In the meantime we are on four mutations that are being closely monitored. What things should we be concerned about with the new Covid variants (and which not)?
Within weeks, the new variants replaced other versions of the virus in some regions. Scientists say these variants help explain the recent spike in cases that have led to new and harsh measures in nearly 60 countries. The five mutations that worry scientists are the British, the South African and the two Brazilian. The Japanese variety is actually one of two Brazilian varieties, which is now increasing there now.
The variant known as the British corona variant, also referred to as the B.1.1.7, appears to be more contagious and may eventually overgrow the other dominant variant, D614G. The D614G mutation is the most dominant mutant, pushing out the original virus from China. This variant is still most common in Europe.
Initially, the British mutant was said to spread 40 to 70 percent faster than the coronavirus we know so far. But in the meantime, British and Danish studies show that it may be 30 percent more contagious. The most research has been done on the British variant, because the genetic code of many samples is determined in the United Kingdom, and there is a lot of researchers and money available to study the distribution of this variant. These studies are somewhat less advanced in Brazil and South Africa.
The South African variant is the most feared variant, as experts are not sure whether the South African variant is susceptible to the vaccines that are currently being made. The South African and Brazilian variants have a spike protein mutation that may affect the efficiency of immune responses. That mutation is called E484K, and it is also in the South African and in both Brazilian variants.
All viruses mutate as they move through populations, and until recently the mutations in SARS-CoV-2 were not much of concern. By the way: a mutation is a change in the genetic makeup of a virus, while a variant is a virus with a series of mutations that change behavior.
B.1.1.7 in the UK and 501Y.V2 in South Africa each have a surprising number of changes in the virus’s spike protein, the part that fits into the receptor in human cells, allowing it to infect humans – and this one changes explain why the new variants are seemingly more contagious than previous versions of the already contagious virus. While there is no evidence that they cause a more serious clinical picture, more cases mean even more stress for hospitals and, subsequently, a rising death rate.
Scientists have warned that it was always possible the coronavirus could evolve to bypass the Covid-19 vaccines that have been approved to date. The arrival of the variants could be a step in that direction, increasing the chance that the vaccines will become less effective over time.
In SARS-CoV-2, the mutations that scientists consider important are located on the virus’ spike protein – the part of the virus that allows it to enter human cells. This is also the protein that Covid-19 vaccines currently available (from Moderna and Pfizer / BioNTech) are designed to mimic. About 4,000 mutations in the SARS CoV-2 spike protein have been detected at various points in the pandemic. Most have not changed the function of the virus. But in rare cases, one mutation, or several at once, leads to changes that give the virus a greater advantage. And that seems to be what is happening with the mutation in the UK, South Africa and Brazil.
The UK variant, B.1.1.7, contains 23 mutations in the virus genome, while the South African variant, 501Y.V2, has at least 21 mutations, with some overlap between the two. In either case, the changes appear to have increased the virus’ fitness or reproductive capacity. And while vaccine manufacturers like Pfizer and BioNTech say their technologies can easily adapt to changes in the virus, we have yet to learn how the vaccines will work in this new context – and give birth to the mutations in 501Y.V2 in South Africa in that context special concerns.
For example, with the South African variant, one such change is the E484K mutation in the receptor binding domain of the virus, where it attaches to human cells. Experiments have already shown that the E484K mutation decreases antibody recognition. This means it can help the virus bypass the immune protection provided by previous infection or vaccination.
In one such experiment, several generations of SARS-CoV-2 were spiked on antibody-rich plasma from a Covid-19 recovering patient. At first, the antibodies seemed to hit back the virus. But when the virus mutated and eventually made the E484K substitution, it started multiplying despite the presence of the antibodies.
In another study, researchers tracked how mutations changed the effectiveness of the antibody response in people who had the virus. They also found that E484K has antibody evasion capabilities. A third study using plasma from donors in South Africa showed that antibodies from a previous infection were totally ineffective against the new variant in about half of the donors.
A side note and something of concern from Brazil
A side note here: These studies were in vitro, involving the samples from Covid-19 survivors, rather than antibodies from someone who received a vaccine. So we don’t yet know how people in clinical trials who have received a vaccine will respond to the new variants.
Still, the findings are alarming. Another preprint study conducted by researchers in Brazil recently provided an alarming example of this. The paper documents the case of a 45-year-old Covid-19 patient with no co-morbidities: months after her first attack with the disease, she was reinfected with a version of SARS-CoV-2 that had the E484K mutation – and experienced the second times a more serious illness.
The evidence is limited, but it suggests that survival from a previous SARS-CoV-2 infection does not guarantee protection against variants with this mutation. “The discovery of the E484K, in an episode of SARS-CoV-2 re-infection, could have major implications for public health policy, surveillance and immunization strategies,” the authors wrote.
So what does this mean for vaccine rollout? Will pharmaceutical companies have to adapt their existing vaccines to combat the new variants? For one thing, as we write this, but that could change quickly, there is no evidence yet that the variants can outsmart the immune response triggered by vaccines. But scientists say in unison: we must be prepared for this to happen at some point in the future.
Currently available vaccines from Pfizer / BioNTech and Moderna help the immune system to target multiple areas of the spike protein, so the virus would have to change drastically to completely escape the immune response generated by the vaccines. The chance that this would happen is unlikely, but not impossible. Our immune system has also evolved to deal with antigenic drift – or the selection of different variants of circulating viruses.
And if the vaccines do prove to be less effective against the new variants, the developers say they can meet the challenge of adapting them. That’s because the new platforms they use can be easily adapted to counter new threats.
The Pfizer / BioNTech vaccine and the Moderna vaccine both use a molecule called mRNA as their platform to provide instructions for making the SARS-CoV-2 spike protein. The vaccine developed by the University of Oxford and AstraZeneca uses a reprogrammed version of another virus, an adenovirus, to transport DNA encoding the SARS-CoV-2 spike protein.
Human cells read that DNA or mRNA genetic information and manufacture the spike protein themselves, allowing the immune system to use it for target practice. An advantage of using this approach is that vaccine developers only need to modify DNA or mRNA to modify the vaccine, something they can do quickly and easily if necessary.
BioNTech and Pfizer have already found that the British variant may not pose such a major threat to their vaccine: antibodies in blood samples from people who received the injection were found to work against the mutations of B.1.1.7, making it unlikely that the variant can escape the vaccine. If a stronger viral enemy emerges, BioNTech CEO Ugur Sahin said, “we could produce a new vaccine within six weeks.”
Scientists at the University of Oxford are also working hard to develop new versions of the AstraZeneca vaccine that are effective against the corona variants from South Africa, Brazil and the United Kingdom. According to a university spokesperson, it is “known that viruses are constantly changing due to mutation” and we can expect that many new variants will be identified by 2021. “These changes are being closely monitored by scientists, and it is important that we remain alert to changes in the future.”
These new vaccines don’t necessarily require developers to overcome every regulatory hurdle again. Instead, new versions of Covid-19 vaccines could eventually go through an approval process similar to seasonal influenza vaccines – with some initial tests, but without massive clinical trials. That means revised Covid-19 vaccines can potentially be rolled out quickly.
What to do now
But while it may be possible to adapt the vaccine to new mutations, it is not ideal: it would require costly changes in the vaccine manufacturing process and time that could be used to inoculate more people during the pandemic. That is why researchers and health officials hope to reduce the number of cases and quickly build herd immunity with the existing vaccines, while also preparing for changes in the virus that are on the way.
To track mutations and understand how they affect vaccine effectiveness, governments must also invest more in genomic sequencing. Inadequate sequencing of SARS-CoV-2 genomes can create blind spots where new mutations may lurk.
There is, of course, another way to prevent dangerous mutations from developing: preventing cases by wearing a mask, social distancing, rapid testing, and treating and isolating infected people. After all, the virus cannot mutate if it does not multiply within many people.