While much is still unknown, what we do know about this new variant tells us important things about the virus: it can adapt to become more easily transmissible and may be able to become more difficult to neutralize and may possibly be able to outsmart the vaccine to a small extent.
To date, SARS-CoV-2 has mutated at a fairly steady rate, with just one or two variations per month. Some variations have given scientists pause, at times mutating to become more transmissible and at other times mutating to become more effective at avoiding detection by our immune systems. But with this new variant, called B.1.1.7, the virus has acquired 17 mutations all at once that change the virus’ proteins, according to the Centers for Disease Control and Prevention, which affect four different viral proteins: the spike protein, ORF1ab, Orf8 and the N protein, the major nucleocapsid.
While the sheer number of mutations in one variant is worrying, what is perhaps more worrisome is how the mutations, taken together, could change how the virus operates. One of the mutations, N501Y, increases how tightly the spike protein binds to the human ACE2 receptor, which may make it easier for the virus to take root in those infected. This mutation is likely why this new variant, first isolated in the UK in late September, now accounts for more than 60% of new infections in and around London.
A second mutation to the spike protein, 69-70del, deletes two amino acids, the removal of which may allow the virus to evade some immune responses and, combined with another mutation, may make it more transmissible. The 69-70del mutation has been found in other variant strains — including the strain in minks in Denmark — and seems to occur when patients carry the virus for several months under immune pressure, not necessarily from the patient’s own immune system but from treatments like convalescent plasma that pump antibodies into the patient’s system.
A third mutation, P681H, occurs in what’s called the cleavage site of the spike protein, which is an area known to affect how readily the virus can enter and kill cells. Changes to this part of the virus could potentially increase its ability to cause disease — and its lethality — though there is not yet any evidence that shows this new variant is more dangerous to humans. This mutation alone is enough to be disquieting. The fact that it is combined in this variant strain with another mutation to the Orf8 protein which may also increase pathogenicity, is cause for alarm indeed.
The mutations that affect the two other proteins — ORF1ab and the N protein — are also suspected of allowing the virus to replicate more rapidly and evade the immune system, though much more research is needed to see how each of these 17 mutations affects how the virus works. Still, we know enough to make a few assumptions.
First, SARS-CoV-2 knows how to adapt and adapt quickly, much like the flu virus. We must therefore be prepared for the possibility that the virus will be with us for the long haul. Like a flu vaccine, a Covid-19 vaccine might not be a one and done affair. We already know from a recent study published in the New England Journal of Medicine that the half-life of the neutralizing antibodies of at least one of the vaccines, the Moderna vaccine, decreases relatively rapidly over a period of three months in those who respond most vigorously and shorter in those who mount a less vigorous response. Though the study was small, it calls into question whether a vaccine taken today would remain effective 12 months, 18 months, or longer into the future. B.1.1.7 tells us something new — not only might immunity fade, but the potency of the vaccine itself may shift if the virus changes. This is not to say that modern medicine can’t keep up with an evolving Covid-19 virus, as it does with the flu. But it may not be as simple or as easy as many have hoped.
Second, with the 69-70del mutation we may be facing a medical paradox. In an effort to save the lives of the immunocompromised who were infected with the virus, providers sometimes administered multiple rounds of antibody treatments to their patients. In some cases, patients would recover after one round of treatment only to fall ill again and require another dose. Even in a single patient, immune suppression over a period of weeks and sometimes months gives the virus a multitude of opportunities to learn our best defenses and to mutate to become more effective at evading our immune system. While administering antibody treatments may save one human life, a UK study hypothesized that it could also facilitate the creation of new strains of the virus.
Finally, the variant suggests that we must immediately begin to plan for the next generation of Covid vaccines to respond more effectively to a changing virus. It should provide some hope that the authorized vaccines are already being tested against the new variant. The companies have expressed confidence that their vaccine could protect against it, with BioNTech noting that its vaccine could be altered to fight the new variant.
Still, it is worth further studying alternative vaccine targets that could prove more effective at protecting the population against virus variants. Right now, the majority of vaccines under development target the spike protein. This includes the Moderna, Novovax, and Johnson & Johnson vaccines as well as adenovirus-based vaccines like AstraZeneca’s. These vaccines may work against today’s version of the virus, but if we want to stay ahead of the spread of disease, we need to expand the targets for vaccines to include other proteins like the ORF1ab, Orf8 and N proteins or the ORF3b protein, which others have studied. Other countries have developed vaccines with more traditional methods, using inactivated whole virus. This type of vaccine, or other vaccines that target multiple proteins at the same time, may be the best approach moving forward.
I often liken viruses to code-cracking machines, continuously running the numbers until they find a new way to exploit whichever ecological niche they inhabit — trillions of copies of a single virus each changing and adapting to every new challenge. Sometimes, we run up against a virus that learns how to crack our defenses faster than we can rebuild them. I fear SARS-CoV-2 may be one of them.
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