 I'm my uncle months, I'm head of the virus science lab and I will talk about our work, trying to understand aspects of forest transmission using genomic epidemiology. This is part of a series of key focus areas of our lab. First category is understanding infection pathways of emerging viruses. The second is a whole series of studies trying to understand pathogenesis. And what I want to talk about today is this work trying to gain an understanding of patterns of spread and virus evolution. A lot of that really being used to support public health and clinical decision making. Now, there is, of course, some very important questions that are our key knowledge gaps at present and for which genomic epidemiology can at least be used as part of the toolbox to try and address them. One of them is what is or are the reservoirs of SARS-CoV-2. What's the role of environmental transmission in different phases of the pandemic? What drives the pandemic? Can we understand that and what are sources and modes of transmission in outbreaks and of course there's many more. So when I talk about genomic epidemiology, I talk about the use of virus genomics in combination with epidemiological data to try and infer transmission pathways to try and find sources of infection. And to try and understand some of the drivers of the pandemic at a more population level. And this is work that we have been doing from the start with a setup that allows real time and 24 hour turnaround genomic sequencing of viruses directly from patients. And I'm going to walk you through some of the applications that where we think this is this is really important added technology and also the types of questions that we have come across. So this started right at the start of the first introduction of SARS-CoV-2 in our country. The week after the first cases were confirmed, there was concern given the talk about the mild clinical presentation and therefore concern how easily this virus might fly under the radar. So over the course of a single weekend in collaboration with the 10 hospitals, we looked at mild cold cases, mild common cold cases and found that 45% of them already were infected and were actually carrying a diverse array of viruses already. This was diversity that at the micro scale but already visible as early as March, but here the central Wuhan virus and that had been tapering out already. Now, this whole, so using whole genome sequencing, we're trying to address some of the questions on how is this virus transmitted during outbreaks. Of course, this requires a lot of other information. It is important to know and understand the infection biology in the infected host and in the recipient. Their behavior is critical determinant of what can happen. The importance of droplets of different sizes in relation to ventilation and behavior is important. Various properties come in and the role of animals comes in and I'm showing here an example of an outbreak investigation with the title not all that seems an outbreak is an outbreak and it is a word of caution. So this was an outbreak in a nursing home where the initial event was a church service with several people attending and then followed by a large scale outbreak with considerable mortality among the elderly patients of the nursing home. But when we then included the genome sequencing that that what seemed to be a single outbreak fell apart into different pieces. What we saw is so what you should look at is in black sequences from cases in the country and in blue sequences from patients in this outbreak. So you see that there were lots of sporadic cases, sporadic cases intermingled with cases in the community reflecting widespread community circulation and also a handful of truly clustered cases. So this was a mixture of many introductions with limited local amplification a very different pattern than what the initial epidemiology suggested. Here's a second example where we've looked at viruses viral sequences from patients involved in a slaughterhouse outbreak and in the initial working diagnosis was this is related to the housing quarters of the mostly migrant worker population in these facilities. And shown here and right again is the background diversity of Dutch patients here in red a large cluster of cases that were indeed migrant workers but they had separate employers and were brought to the facility through separate transporters and lived in separate quarters. So here that clearly showed that the linking pin where the transmission must has happened is in the facility itself, not the migrant worker homes. Same was the explanation for this small cluster. But here's an example where there was a cluster in the workplace, but these people were working in different parts of the facility, but shared the same household. So same environment, but two different very different explanations for the transmission and the mixture is really what we typically see. Then looking at a situation that is that has evolved and is, I think, an area of concern. And that is that we've seen since April, introduction of the virus from humans into mink, which are farmed in our country, but also reports now of mink farm outbreaks in Denmark, Sweden, Spain and the US, and from there back into people. So what you look at now is a circular reflection of the diversity of SARS-CoV-2 sequences in our country. And these five clusters, which are five independent introductions of the virus into mink farms. And here's a zoom in on one of those clusters with, again, background sequences here. Introduction onto farms here in red. And then from their farm to farm transmission in the different colors and then back animal to human transmission in orange. So we do see human to animal to animal to human transmission occurring in this farming environment. Now that's because it's proven to be difficult to control a spread among the farms. We are seeing an evolving situation here. These five clusters now shown again with alignments of the viruses. And what you can see is that each cluster now has a number of cluster defining mutations. And then over time we see accumulation of mutations. And that's of course not something you would want to see. We don't really know whether this is some form of host adaptation. But these viruses do still make it back into people. So it is a situation that we think needs looking at also another for producing regions like in China. So that's a very brief overview and some key points that I wanted to bring to this panel discussion is that we have to be careful to jump to conclusions too fast unraveling the modes of transmission of this virus is quite complex. And understanding the contribution of these different ways of transmission is a key knowledge gap. Not all that seems obvious is obvious and we need detailed studies that are embedded in outbreak investigations to get a better handle on this and essential to be able to do that is data sharing infrastructure. So what has been established from the start of this outbreak is the SARS CoV gizade sharing platform and there's also a European open data portal that has been launched to help the scientific community work on this virus together. So with that I just want to briefly acknowledge the many people that that contribute to this work as well as the funders.