Patrick Ayscue, PhD, on Whole Genome Sequencing and COVID-19

In this podcast, Patrick Ayscue, PhD, answers our questions about the role that whole genome sequencing has had on the COVID-19 pandemic and how this laboratory procedure can be used against variant strains.

Patrick Ayscue, PhD, is an epidemiologist and senior biosecurity fellow at Chan Zuckerberg Biohub. 

Additional Resources:

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To learn more about Chan Zuckerberg Biohub's whole genome sequencing initiative, visit www.czbiohub.org.

TRANSCRIPTION:

Leigh Precopio:  Hello everyone and welcome to another installment of Podcasts360, your go‑to resource for medical news and clinical updates. I'm your moderator, Leigh Precopio, with Consultant360 Specialty Network.

Whole genome sequencing has been a critically important tool in the development of our understanding of COVID‑19. The knowledge that genome sequencing has provided scientists and healthcare professionals over the course of the pandemic has been invaluable to the success of treatment of this virus.

To learn more about the role that whole genome sequencing has played throughout the pandemic, and how this process may aid us as variants become an increasingly major obstacle, Consultant360 reached out to Patrick Ayscue, PhD, who is an epidemiologist and a senior biosecurity fellow at Chan Zuckerberg Biohub.

Thank you for joining me today, Patrick. To begin, how has whole genome sequencing impacted the course of the COVID‑19 pandemic?

Patrick Ayscue:  Whole genome sequencing has been a nice tool that we've been able to use in the pandemic thus far. It's relatively new technology in the context of outbreaks. It's enabled a few things for us as the pandemic has unfolded.

Certainly, extremely critically early on some of those initial whole genome sequences that got posted publicly are what the mRNA vaccines are based off of. Those were critical to getting us to the record time of return for having vaccines available for the general population. Beyond that more broadly, I think about two buckets that we use whole genome sequencing for with COVID and the public health space.

One is that longitudinal surveillance piece, giving us a broad view of what's circulating within different communities, and potentially using that information to try and identify emerging variants that may be of more concern that can help us direct public health intervention as well as clinical guidance down the line as well if we start to see phenotypic differentiation there.

The other big bucket is in outbreak response and cluster investigation. One of the nice things about whole genome sequencing, it allows us to track every mutation in the virus when we're able to get those samples for sequencing. The virus will accumulate mutations on about 1 mutation every 1 to 2 weeks or 1 to 2 transmission events on average. Essentially, what that does is it leaves little breadcrumbs that can help us track how transmission chains have moved through the population. It gives us the ability to better understand where transmission is actually occurring, where and how people are getting infected, and guiding within the context of outbreaks in congregate settings ‑‑ places like jails, schools, workplaces ‑‑ help public health target interventions to help disrupt those transmission chains. That'll be particularly critical as we move forward as case numbers start to come down as well.

Leigh Precopio:  Is there any evidence we'll need a booster dose for the COVID‑19 vaccines?

Patrick Ayscue:  The booster dose question is certainly an interesting one. There is a possibility that that will be a recommendation. One of the questions in my mind is what conditions we'll have in front of us moving forward that would warrant a recommendation for a booster vaccination and in what populations. As we start to see the virus mutating and some of the new variants coming out, there is interest in having a booster vaccine against some of those specific variants.

However, what we've also seen is that the vaccination and to a lesser extent, natural infection may be quite protective even if not perfectly against infection, still quite efficacious at preventing severe disease or illness and death within that as well. Obviously, those are the outcomes we're most interested in. I can see a world on the order of a year or two where there may be recommendations for a booster vaccine for high‑risk individuals and different populations. It's an open‑ended question if that'll be a recommendation for everyone.

Leigh Precopio:  What is currently known about the level of protection that both doses of the virus provide against the variants? Is it a possibility that someone who is fully vaccinated may become ill if infected with a variant?

Patrick Ayscue:  A lot of data has started to become available very recently on the effectiveness of both the Pfizer and Moderna mRNA vaccines in the face of some of these new variants. Generally, what we see is that for a subset of these variants, there is a slight reduction in the efficacy at preventing an infection or a re‑infection but still extremely effective at preventing severe outcomes.

Earlier this week, a study out of Qatar looking at the Pfizer vaccine and implementation in a real‑world setting there was evaluating it against B.1.17, which was the variant first identified in the UK, as well as B.1.351, which was the variant first identified in South Africa. The latter in particular has been a concern as there've been indications that it may be leading disproportionately to re‑infections, but the data out of there are incredibly promising, showing 75% efficacy preventing infection for the B.1.351, and over 90% efficacy for B.1.17, and over 98% preventative against severe outcomes. So a lot of optimism that the mRNA vaccines will be able to handle those even in their current state.

The one other comment I'll make there is that the mRNA vaccine technology platform is really remarkable. One of the features of it is that it lends itself to a lot of flexibility and the ability to incorporate some of those genetic changes very rapidly. As these variants emerge, these companies are looking closely at the genomic surveillance data to identify any variants that may be emerging. Then they're very quickly able to turn around and incorporate that into an updated booster vaccine.

Leigh Precopio:  How do you expect the variants to change the course of the pandemic in the United States from here on out? Do you expect the United States to be hit as hard by variant chains as in other places where variants emerged, such as the United Kingdom or India?

Patrick Ayscue:  I am optimistic that within the United States, we may have gotten incredibly lucky and dodged a bullet with some of these more transmissible variants not getting here even just a few months sooner. Essentially, I think of it as we're in a race against some of the more transmissible variants and our ability to vaccinate the population widely. I think we've gotten just ahead of it even by just a few weeks or a month or 2, to where more effectively seeing case numbers go down. Hopefully, that's a trend that will continue and one that I would expect to continue as well.

What we're seeing more broadly, globally what's going on in India, I do worry that that may be some foreshadowing of what we can see in other locations as well. When these more transmissible variants can emerge in largely immunologically naive populations, certainly can have some pretty horrendous outcomes if that's the case.

Leigh Precopio:  Why is it important to sequence the viral variants in both the United States and around the world?

Patrick Ayscue:  I think of that sequencing as serving a couple of different functions. Returning to those two buckets I mentioned for that broad surveillance and understanding what's circulating generally, that's great for being able to detect new variants that are emerging, which may have phenotypic outcomes that will want us to get those variants into a vaccine pipeline or into a   medical countermeasures or therapeutic development pipeline more rapidly. That gives us the capability to parse some of that or potentially update clinical or public health guidance based on that as well.

It also helps public health direct their resources. If we're seeing a more transmissible variants start to pop up in certain populations or certain geographies, we may want to devote more testing, contact‑tracing resources into that region and help bolster support against those.

The other big bucket is for outbreak response. That's something that I think will become more prominent as we move forward as well. That gives public health departments in particular the opportunity to take those data, turn around and understand how people are getting infected.

A common scenario we've seen is in the context of, let's say a skilled nursing facility where they had some cases in their patient population. They've seen nothing for a few weeks, and then they start seeing some additional cases again. A natural question there is, "OK, is this a new introduction into the facility, or are we looking at cryptic transmission that we just hadn't identified for weeks at a time?" The genomic data are great at being able to parse questions like that and determine if something is coming in from the community or circulating within that facility itself. That can help public health officials, facility administrators, whoever that may be that's making those policies and decisions, ensuring that they're targeting where those sources of infection are occurring. We've seen instances of that where we've identified that those introductions were actually happening because facilities were sharing staff. They were getting introduced through that. That gives the public health officials the capability to go back to those facility managers and say, "Hey, this is a risk to your population here. This is something that we can take corrective action on." I don't think the genomic sequencing or genomic epidemiology piece is going to go away. If anything, it's only going to get more prominent as we move forward there.

Our work at the Chan Zuckerberg Biohub for the last year has been largely focused on supporting genomic epidemiology within departments of public health and delivering a lot of these data to them. As we're moving into 2021, we're focused on building that capacity within the public health system and enabling public health departments to generate these data on their own and analyze them, interpret them, and then turn around and use them in their own investigations. A lot of public health response, most of it in the United States, happens at the local level. There's a critical opportunity there for us to enable that capacity on the front lines of the pandemic moving forward.

Leigh Precopio:  Great. Thank you for taking the time to speak with me today.

Patrick Ayscue:  Thanks, Leigh. Thanks so much for having me.