expert explainer

What to Know About Coronavirus Mutations

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By studying the SARS-CoV-2 genome, researchers have been able to map the coronavirus’s spread around the world from its emergence in China late in 2019. A recent analysis done in China estimates there are now more than 30 strains of the virus spread out across the globe; in New York, a team of researchers at Mount Sinai traced the strain responsible for most of the city’s infections to Europe. Intelligencer spoke with Dr. Harm van Bakel, one of the Mount Sinai study’s authors and a geneticist at the Icahn School of Medicine, to learn more about how the virus has mutated, whether any of those mutations are cause for concern, and what they might mean for vaccine development.

Can you walk me through the basics of virus mutation and what you’ve seen since this new coronavirus emerged late last year? 
As a virus spreads across the world during a pandemic, with every copy of the viral genome and every transmission, it slowly accumulates mutations. The reason for that is that the copy machinery — the proteins that essentially make copies of the viral genome — is not perfect. The virus is essentially a short story with 30,000 characters, and when that short story is copied from generation to generation, small mistakes are made. Once in a while, a letter will change here and a word will change there.

The pattern of those changes tells us something about the lineage of the virus. If a mistake is made early, it will be seen in all of the progeny. If a mistake is made later, it will only show up in some of it. By looking at the rate of the change of the virus, we can time some of those changes during the spread of the virus across the world.

Do you have any sense of how frequently this virus mutates? 
This is still subject to study, but roughly there is one letter change every two weeks.

What is the significance of those changes? 
Most of the changes will be neutral. They won’t really change anything in the function of the virus, its virulence, or its transmissibility. You can compare it to having a scratch on a car. It doesn’t change the way the car operates, but it does allow you to differentiate one particular car from the same model owned by somebody else.

So we’ve yet to see a significant mutation? 
There’s more study needed to determine that. There are definitely changes that have appeared in the virus — whether they lead to functional effects remains to be determined. What’s needed are large numbers of cases, where some of them have a particular mutation and others don’t. Then we could do comparisons between disease progression and outcome between those groups, taking into account other variables such as age, comorbidities, and underlying health conditions.

I know there’s at least one study, which hasn’t been peer reviewed, suggesting that virulence may vary between strains.
My personal opinion is that it’s probably still early to make any solid determinations on that. I think multiple independent studies are needed to get more certainty.

What’s the relationship between your work and the work being done by researchers who are trying to develop a vaccine? 
The genome sequence of a virus informs vaccine development. The virus was sequenced very early on in the outbreak, and knowing the genome sequence allows vaccine development to start. It means that you know the protein structure and you can start making constructs to build vaccines off.

Wouldn’t more strains of the virus make it harder to develop a vaccine that catches all of them? 
It depends on the level of chains. In theory, it’s possible that there could be a mutation that makes the particular strain less susceptible to a vaccine. Right now, there is no evidence of that.

Much has been made recently of different theories about the virus’s origin. It seems that the science is pretty clear that this didn’t originate in a lab in Wuhan, but is there any way for you to determine whether it passed through a lab? 
Based on this phylogenetic analysis, it’s difficult to make that determination.

Is there any way that your work or someone else’s work could contribute to that understanding? 
Our work has really been focused on the strains here in New York and how the virus got to the city. We haven’t really looked at the origins. There are other groups who have done surveillance in animal populations, bat populations, pangolin populations, who are going to be more suited to make determinations on that.

You’ve determined New York was hit hardest by a strain coming from Europe. What are you trying to learn now? 
We’re trying to answer some of the questions as to whether certain mutations have had any impact in the functioning of the virus. We’re also very interested in tracking spread across the community. As we follow the family tree of the virus, we want to see which branches are extinguished as a result of intervention methods, which branches continue, and how that helps inform what measures have been effective in controlling the spread of the virus. We’re also trying to understand more about how and when the virus entered the city and to see how the virus impacted health-care workers in the system.

Do you use contact tracing or is it entirely based on the study of the specimens? 
It is entirely based on the specimens we have available.

What have these past few months been like for you personally?
It’s very busy. We have a pathogen surveillance program here in our health system, and typically what we do is look at seasonal influenza, endemic nosocomial infections such as MRSA. That’s usually what we work on. As we realized it was inevitable that the SARS-CoV-2 virus would come to New York, we switched gears and applied our sequencing methodologies and analysis to study the coronavirus. I don’t know if you saw the figure in the study, but within a matter of two weeks, from mid-March until the end of March, we saw as many cases with coronavirus as we normally see during the entire influenza season. It’s really a massive influx. It’s a difficult situation because, of course, a lot of non-coronavirus research has been halted. It has made access to resources more difficult. Then, at the same time, you’re faced with a huge influx of new samples that have to be sampled very rapidly. It’s been very busy. I’m very thankful to the frontline health-care providers who have been treating patients and the clinical lab for processing samples and determining positivity. We are really at the end of a long line of people who have handled patients and samples as they come in.

The scientific community has really come together across the world to study the spread of this virus. The infrastructure that is in place now wasn’t in place during the first SARS outbreak years ago. The extent of the involvement with hundreds of research groups in different countries around the world, each investigating cases locally, really allows us to have a richness of data to put the puzzle together. A study like ours, looking at the introduction of the virus into New York City, would be very difficult to do if it weren’t for the background context of sequences generated all across the world.

Expert Explainer: What to Know About Coronavirus Mutations