“Right now, this variant in the UK is getting on a plane and flying to JFK”
Gov Andrew Cuomo is alarmed about this ‘new variant’ discovered in England. It’s spread through the UK very quickly, it’s carrying multiple mutations, and it probably flew out of London-Heathrow weeks ago. This is leading many to speculate that:
We’re going to see a surge in infections, hospitalizations, and possibly deaths
Our highly anticipated vaccines might not work against them.
Before we break the glass and pull an alarm, I want to try to review what we know - or at least, what I’ve been able to learn!
Greed might not be good
I hope the Infectious Disease specialists reading this will forgive my existential description of viruses… Simply put, a virus is programmed to follow a basic protocol: gain entry into a host cell, evade host defenses, replicate, and repeat that process for as long as it can. Anything that speeds up this process or makes it less prone to error is good for business. Following that logic, the more ‘successful’ viruses are the ones that mutate as fast as they can until one of them achieves a breakthrough. Once they acquire that game-changing mutation(s), our enterprising virus just needs to remain stable and pass the mutation(s) to the next generation.
No part of this ‘business model’ suggests the virus is destined to become more fatal. If your goal is to hijack a factory and repurpose it, you’re not doing yourself any favors by burning the building to the ground before you ship your product. Overwhelming the bat, pig, human you infected and killing them before you can replicate isn’t good for your bottom line: survival and self-replication!
So now we see why scientists expected SARS-CoV2 mutations and have already seen them. Until recently, it had been mutating slowly, with a limited number of mutations occurring at any time (~1-2 genetic changes per month). But B.1.1.7, a.k.a the British variant, has been acquiring mutations more frequently. And because it’s being seen in more and more cases, we fear this could mean another surge in hospitalizations and COVID deaths. Or, that it might mutate far enough away from the reach of our current arsenal of vaccines!
Keep calm and carry on
So what are these mutations and what do we know about them? The COVID-19 Genomics Consortium of the UK (COG-UK) has been studying SARS-CoV2 genomes since the beginning of the pandemic. Here are key points from their preliminary analysis of B.1.1.7:
“Mutation N501Y is one of six key contact residues within the receptor-binding domain (RBD) and has been identified as increasing binding affinity to human and murine ACE2.”
ACE2 is believed to be the key entry point into human cells. Increased “binding affinity” means the virus is more likely to successfully dock at ACE2 and gain entry into human cells. It’s not great that this new strain can more easily enter our cells.
“The spike deletion 69-70del has been described in the context of evasion to the human immune response but has also occurred a number of times in association with other RBD changes.”
The SARS-CoV2 spike protein interacts with the human ACE2 receptor, leading to viral uptake by human cells. The spike protein is the target of our current generation of vaccines, so a mutation here could have real consequences. From my reading, it appears that we’re not surprised to see this mutation, because the spike protein is an area of the viral genome that can mutate relatively rapidly. However, we’re not yet sure what the 69-70del mutation means. This mutation might make the spike protein unrecognizable to our B- and T-cells. Or it might not. We just don’t know yet.
“Mutation P681H is immediately adjacent to the furin cleavage site, a known location of biological significance.”
Okay, so here’s what this means to me: the “furin cleavage site” represents a key part of the SARS-CoV2 viral assembly line (P. Zhou et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin Nature . 2020). Certain mutations at this location could it easier for the hijacked human cell to reproduce the virus and ship it out.
So what?
Yes, daily infection rates and hospitalization rates in London have doubled in the past 3-4 weeks. But it’s unclear what proportion of new infections and hospitalizations can be blamed on this new strain. What we do know, thanks to the Johns Hopkins 2019 Novel Coronavirus Visual Dashboard, is that the death rate from COVID in the U.K. has been relatively stable over the past 30 days. These are interesting findings when you consider that COG-UK reports first seeing B.1.1.7 in mid-September. So, even as this new mutant strain has become more popular, we can’t say that it’s killing more people - or at least not more than other SARS-CoV2 strains. Let’s hope it stays that way…
What about the fate of our vaccines? Yes, it’s certainly possible that the mutations described above or other still-to-be-discovered mutations may make Pfizer, Moderna, and others’ vaccines less effective - or even obsolete. But, let’s remind ourselves that the virus was first described in December, 2019; one month later the viral genome was published, and by late March, the first mRNA vaccine had already been designed. When it comes to mutations, the main advantage of this new mRNA vaccine platform is that it’s theoretically straightforward to modify an existing product. If the viral genome and its corresponding spike proteins change, new mRNA vaccines could be prototyped quickly - within a matter of weeks if not days. With good computational modeling tools, we might even be able to predict likely future mutations and design new versions of vaccines preemptively. I haven’t found anything to suggest that such an effort is on-going, but I just have to believe it is. There’s too much social and business incentive to ignore that problem.
Hot Take
Viruses always mutate, and SARS-CoV2 will continue mutating
A rapidly evolving virus isn’t necessarily a deadlier virus. I’m hoping groups like COG-UK, the CDC, academic medical centers etc will release more genomic data from new cases so we can figure that out.
Even as SARS-CoV2 evolves, we now have technology that could model the evolution and allow us to create newer, better versions of a vaccine in a matter of days to weeks.
In the meanwhile, please don’t go to bars, restaurants, or large social gatherings. Masks and prevention are still the best tools and strategies we have against SARS-CoV2.
Someone asked me if we know what sorts of conditions allow the virus to mutate faster than usual. While I think that's still a very active area of research, a couple of factors likely play a big role: 1) the amount of time someone is infected with live virus, and 2) that person's ability to recognize and mount a response against the virus. There's sparse case report evidence (as opposed to studies of groups of people) that supports the notion that the longer the virus is able to replicate in your body, the greater the chance it's going to pick up some beneficial mutations.
https://www.nejm.org/doi/full/10.1056/NEJMc2031364