Interviewers: Lydia Morrison, Marketing Communications Writer & Podcast Host, New England Biolabs, Inc.
Interviewees: Bas Oude Munnink, Principal Investigator, Erasmus MC; Bjoern Textor, Senior Application Specialist, NEB Germany
Lydia Morrison:
Welcome to the COVID-19 Researcher Spotlight series. Today I'm joined by Senior Application Scientist, Bjoern Textor of NEB Germany, and we interview Bas Oude Munnink of Erasmus MC in the Netherlands about the impact of multiple circulating strains of SARS-CoV-2. Bas shares with us what he has learned from his work sequencing the Coronavirus that could aid in identifying and stopping outbreaks of COVID-19 or other pathogens in the future.
Lydia Morrison:
Bas and Bjoern, thanks so much for joining me this morning.
Bas Oude Munnink:
Thank you. It's a pleasure being here.
Bjoern Textor:
Likewise, Lydia and Bas, it's great to be here and I'm looking forward to a great discussion.
Lydia Morrison:
Yes, me as well. Bas, could you tell us about your recent publication?
Bas Oude Munnink:
Yeah, so recently we published an article in Nature Medicine and in this manuscript we tried to describe what was happening in the Netherlands. So how SARS-Coronavirus-2 has entered the country, and how it subsequently spread throughout the country. And for that we used near to real-time whole genome sequencing. And we combined this with epidemiological data to try to facilitate early decision making, to control the local transmission of SARS-Coronavirus-2 in the Netherlands. Or at least to have an idea in how the virus has spread throughout the country.
Lydia Morrison:
Can you tell us a little bit about the findings of that? Do you believe that the different strains of the virus were introduced from different countries and that that has an impact on the severity of the infection?
Bas Oude Munnink:
Yeah. So in the beginning, it was very difficult because this all started off with one single virus which has spread, first in China, and then throughout the rest of the world. But we could see already in the Netherlands, that was in the beginning of March, that there were several strains circulating. So there were already some mutations occurring in the different viruses. So in the beginning we could see already after the first two cases of SARS-Coronavirus-2 in the Netherlands, we could see that they were not related to each other and they both represented the separate introductions.
Bas Oude Munnink:
And also later on, we could see that several different strains started to appear in the Netherlands. So most probably we had multiple introductions from abroad, mainly from Austria and Italy. And then we got subsequent local amplification of the virus. And that we could really see using whole genome sequencing, we could not really see a difference in the clinic. So it seems to be just one virus spreading throughout the country. Although there were several different introductions, there's not really a difference which we observed in the clinic. So it seems to be causing similar problems.
Bjoern Textor:
Bas, maybe one question from my end here. So when you think about the current spread, would sequencing be helpful in that scattered population screenings?
Bas Oude Munnink:
We use sequencing on mainly to see if some cases are related to each other. So for instance, in a hospital outbreak, we sequenced a lot of different hospital samples. I'm excited to see if there's a transmission within the hospital, or perhaps it reflects several introductions from the community. So I work in a very big hospital where we have around 5000 people working, and we got quite some coronavirus infections. But what we could see is that was mainly a representation of what's happening in populations rather than really outbreaks at specific departments.
Bas Oude Munnink:
So we want to try to use whole genome sequencing to try to see if the control measurements really help, and if there's hospital transmission or not. And the second thing we do in nursing homes and all kinds of other different settings. So also for instance, in the meat producing factories, we also sequenced a lot of viruses from that. And then we could see that there was really transmission on the workfloor, most probably. Because they all contain the same virus and in smaller instances we could see that the control measurements were really accurate, but people just got infected outside the work situation.
Bjoern Textor:
If you could comment on the community participations, when you think about academia or industry and happened to speed up pathologies and sharing data during the pandemic, would be difficult there.
Bas Oude Munnink:
Yeah, the difficulty is now actually not against the whole genome sequences. So we managed to sequence, I think, around 4,000 samples by now. So we are really up to speeds with producing sequences. But it's very difficult to get traveler meta-data for instance, travel history and these kind of things.
Bjoern Textor:
Mm-hmm (affirmative) .
Bas Oude Munnink:
So that's why I'm after every encounter now. It's very difficult to keep track of which inputs coming from where, and also to do the contact tracing. That's something we are not really up to speed here in the Netherlands. So it's not possible anymore with 8,000 cases a day at the moment. To perform really detailed contact tracing, and trying to find out where the people went to, if they went on holiday or not, or what's the likely mode of transmission, how they got infected. That's something, that's not very difficult to do, but it seems to be proven to be fairly difficult to do within, in a precise way, and to get all the data from one place.
Bjoern Textor:
Yeah, I believe also contact tracing is a quite an issue, at the time, having the second wave here in Europe. In terms of processes, maybe an additional question, as you have an NGS based approach sequencing all these samples. Can you share some insights, for example, how you automated your downstream bioinformatic pipelines, downstream of the NGS approach?
Bas Oude Munnink:
So after the sequencing we have implemented nanopore sequencing, amplicon-based nanopore sequencing. We have generated an automatic pipeline, which just starts immediately after you start the sequence run. And it will process the data in real time. So in the end you will get out a consensus sequence, which you can use for further analysis. So that bug's automated. We are also trying to set up some sort of database because at the moment it's still...Before this, we used to sequence around 200 samples a year and now we sequence 200 samples a week. So that's not really automated yet, but we're trying also to make some sort of a structured database. So also upload your sequences to a central database, and then you can select certain sequences for further analysis.
Bjoern Textor:
That's awesome. Maybe final question from my end here. So if you think about companies or different groups, I know you have a huge number of collaborators in the Netherlands. What can help you right now? What would you ask for to drive your research or COVID testing further?
Bas Oude Munnink:
So at the moment we are multiplexing 48 samples per sequence run because it still requires quite some network, also because there's a lack of reagents and consumables. So we now move towards a more simple RNA extraction protocol, but we still do a lot of things by hand. So it would be beneficial to just have some sort of pipeline or robot where you just insert your sample and everything's being done. At this moment, that's not really possible yet for the NGS approaches. There are some machines available, but they're also quite expensive. So at the moment I think it's around 100 to 200,000 euros to do that, to produce these kinds of robots. And then you still have to do some steps by hand. So that's something we could really use, I guess, in the future. So, automation of the library preparation.
Lydia Morrison:
Yeah. It seems like that would certainly help speed up the number of samples that could be sequenced in a single time. What have you learned from your work on COVID-19 that could aid in quickly identifying and stopping outbreaks of the disease or other pathogens in the future?
Bas Oude Munnink:
I think what we could now nicely see is that, we also, for instance, went to Suriname to do some sequencing there in the field. And we also saw there that after the implementation of certain restrictions or certain protective equipment that we could see that some interventions work better than others. So we could see that in general and hospital settings that people are adequately protected. But we also encountered some difficulties, for instance, in the department where people had dementia, that it's very difficult for them to report complaints, for instance.
Lydia Morrison:
Mm-hmm (affirmative).
Bas Oude Munnink:
Quite specific, but in these type of situations, you cannot really rely on what the people say. So perhaps you have to just have to do some routine screening to see what's going on rather than waiting until people develop complaints, because they just might not recognize it or might not remember it in these kind of settings.
Lydia Morrison:
Right. And that might make it more prevalent in like an assisted living type of facility.
Bas Oude Munnink:
Yeah, indeed.
Lydia Morrison:
Well, thank you so much for your work in sequencing the viral genomes in the Netherlands and helping inform the community there about the origins of COVID-19 in your country and the spread. And thank you for all your efforts in working to increase the speed of the number of genomes that are being sequenced. I think it's really important information for the community to have, as we all sort of wade into this pool of unknown with the pandemic and continue to try to be vigilant and really use the information that science is giving us to inform our choices and practices so that we can stop the spread of the virus.
Bas Oude Munnink:
Yeah, it's really now the next level in using next generation sequencing or whole genome sequencing to try to see how the virus is spreading. But it also has some upsides of course because we now have around, I think 150,000 whole genome sequences. And we never really used to work with these kind of amount of sequences. So we used to work with 100 to 200 sequences and then we could do our analysis, but now its really starting to get, its getting a lot to analyze the data. So we also need to think about how to efficiently downsample also the amount of data that we have. So that's also a new challenge in this growing pandemic.
Lydia Morrison:
Certainly I imagine there's some unidentified indicators potentially in the genomes yet that have yet to be discovered, but with that kind of a sample pool, it certainly seems like it would lead to more learning about the disease.
Bas Oude Munnink:
Yeah. By having this kind of very big data set, we're also trying to look at specific signatures of the virus, which we see occurring during time, for instance. And then we want to try to translate this into a certain phenotype as well. So really try to do a genotype to phenotype prediction and then also do some experiments in the lab to try to see it holds up.
Lydia Morrison:
That's great. I'm sure that would have implications on specific treatment plans as well for individuals carrying a certain phenotype with sort of the matching genomic footprint.
Bas Oude Munnink:
Yeah. That's really something we want to look into further.
Lydia Morrison:
Yeah. For some really targeted and individualized treatments.
Bas Oude Munnink:
Yeah.
Lydia Morrison:
That's interesting.
Bjoern Textor:
Bas, with building the data sets for the Netherlands, is there also any directions that you take in terms of the European Union to drive these data sets across different countries?
Bas Oude Munnink:
Yeah, so we work closely in a European consortium and we also work closely with GISAID and other partners. So now because we have a quite dense data set now of SARS-Coronavirus-2, we also try to facilitate sequencing for instance, in Iran and in Sudan. So we receive samples also from Cyprus, so we also try to help them out to also try to see what's going on in these countries, because we do see that the majority of the sequences are now derived from Europe and from the Americas, but it would be nice to have a global view. And we also try to assist there also at WHO reference center, we offer the countries which are not able to sequence themselves, to optimize and to do the sequencing for them.
Bjoern Textor:
That's fantastic.
Lydia Morrison:
Yeah. That's really nice to hear. I'm sure people really appreciate having access to those resources.
Bas Oude Munnink:
Yeah. It's getting relatively cheap and easy these days to perform the sequencing, but it still requires quite some knowledge as well. And also you just need the machines-
Lydia Morrison:
And some equipment.
Bas Oude Munnink:
Yes. And experience because it's for most people a new technique as well. So that also brings some challenges.
Lydia Morrison:
Absolutely. Well, thank you so much for being a resource to the greater European community. And thank you so much for joining us today and telling us about your research.
Bas Oude Munnink:
Thank you for inviting me.
Lydia Morrison:
And thanks to Bjoern for co-hosting with me.
Bjoern Textor:
Thanks for being with you and together with Bas, I really enjoyed here our conversation and I'm looking forward to see how the research around COVID-19 is moving forward.
Lydia Morrison:
I agree. I think the whole world is. Thanks for joining us for this episode of the COVID-19 Researcher Spotlight series. Join us next time when I interview 2014 Passion and Science Award winner and now frequent guest of CNN and NBC networks, vaccine expert, Dr. Peter Hotez, who is Dean of the National School of Tropical Medicine and Professor of Pediatrics and Molecular Virology and Microbiology at Baylor College of Medicine, where he's also the co-director of the Texas Children's Center for Vaccine Development. Join us to hear discussion of Dr. Hotez's, new book entitled, "Preventing the next pandemic, vaccine diplomacy in a time of anti-science," and his thoughts on the current COVID-19 pandemic, vaccine development and manufacturing, as well as democratizing vaccine distribution.
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