 this evening by asking some of the basic questions. So what is Omicron? How do we identify it? And why does everyone seem so worried? But let's start at the beginning. What is a variant of concern anyway? We've heard so much about them, but what are they? So when a virus starts transmitting through a population, it moves from person to person and will sometimes acquire mutations, shown here as these colored diamonds. Now importantly, most of these mutations don't change how the virus works, but of course, as we've learned, some do. When we get genetic sequences from samples of people who've been infected, we can actually see these mutations and we can use them to look at which samples are more closely or more distantly related. And this lets us create a graph we call a phylogeny. It's essentially a virus family tree that shows us how different sequences are related, how the virus has moved around the world over time and perhaps most importantly, how the virus has changed and acquired new mutations. When we talk about a variant of concern, we mean a cluster of these sequences close together in the family tree that have mutations that we're concerned about. For example, mutations that could impact transmissibility, immune evasion and clinical outcome. Now each of these variants of concern has these specific mutations and this is what allows us to track and identify them. We can look for that unique pattern of mutations and be very confident when we get a new sequence, whether it falls into one of the existing variants of concern or a new one like Omicron when we identify it. But we've of course had many other variants of concern. So why does everyone seem so worried about Omicron this time? Well, with Omicron, it has a very worrying set of mutations and quite a few of them and a lot of them are in concerning positions. So in particular, we see a lot of mutations in the spike protein. Many of you will have heard of this. It's really critical for the virus to actually attach to cells and infect them. And also it's what our body uses to recognize SARS-CoV-2. So after a vaccine or after an infection, this is how your body knows to see SARS-CoV-2 again and to start fighting it off. And in particular, the top part of spike called S1 is really important for both of these functions. And if we look at Omicron, it has more mutations in this top S1 part of spike than we've seen in any other variant of concern. And we know they're in positions that can influence those critical things of transmissibility, clinical outcome, or immunovasion. We can take another look at how different Omicron is by looking at this graphic that shows the changes in spike as these colored dots and a list of the mutations in alpha, beta, gamma and delta, the other variants of concern. And then Omicron. It's really striking the number of mutations that we see and shows us that Omicron has a lot of mutations and many in places that we're concerned about. So where are we seeing Omicron in the world right now? And how do we find it? Well, as many of you will already know, Omicron is being detected right now in an increasing number of countries and it's essentially been found globally including right here in Switzerland. It's important to remember that Omicron was first picked up in South Africa but we don't know if that's where it started. We do think it probably expanded in Southern Africa originally but it could have been in another country and simply not been picked up until it moved to South Africa where they have good genomic surveillance. We can also look at where sequences for Omicron are coming in. So this is one of those phylogenies or viral family trees of Omicron and it's colored by the countries that have deposited or generated these sequences. And the size of the circle here is the number of sequences we have. So for example, we see a large number of sequences from South Africa and from the UK. Now something that's really critical to keep in mind here is that a country's ability to detect Omicron and its ability to sequence Omicron is determined by how many resources it has to do this. So countries with fewer tests might be less able to find it and countries that can't sequence as much won't be turning in as many samples. A good example of this is Denmark which has detect hundreds of cases of Omicron because they have a wonderful surveillance system but there's no real reason to think that Denmark has a particularly high number of Omicron compared to other European countries. It's very possible that we have a similar number here in Switzerland. We just haven't been able to find them yet and we aren't seeing them but we should use this information to prepare for the fact we may have more cases than we know about today. How do we know when we find Omicron? There's been some discussion about this. Some of you may have heard of something like SgDropout or Sgtf. This means that Omicron has a very small part of its spike protein missing and this makes a very particular signal on some PCR tests. So for example, with most of the other variants when we do a PCR test we get three signals that show up from different parts of the virus and this shows us that you're positive for SARS-CoV-2. With Omicron, because of this small deletion one of these signals doesn't show up. Because the other two are still there we still can diagnose you with SARS-CoV-2 but we also have a bit of a shortcut that you may have Omicron and this we can use to then sequence those samples and find out for sure whether they are Omicron. One question that's been hotly debated right now is where Omicron came from. The reason that scientists are really interested in this is because Omicron sits on what we call a long branch. This is a picture again of that viral family tree but it's in a kind of exploded view. So you can see the length of the branch is a little more easily and I've included some of the other variants of concern and interest here. And you can see quite clearly that Omicron is much further away from the middle than other variants of concern and variants of interest we've seen before. What this means is that it doesn't have many relatives and it's acquired a lot of mutations. This makes it harder for us to tell so clearly how it's evolved and where it might have been before we detected it. There have been some theories circulating about how Omicron may have come about with so many mutations. One is that it may have been an immunocompromised individual. This means when the virus gets into someone whose immune system doesn't work as well that person can't get rid of the virus as quickly and what we've seen in the past is that in this case SARS-CoV-2 sometimes develops a lot of mutations. Another idea is that Omicron may have been circulating undetected. I talked about this a little before. This means it may have been around for a while somewhere where they have much less surveillance which means we wouldn't have seen these ancestors, these close relatives as they popped up. Another thing you might have heard scientists discussing is that Omicron may have gone into an animal reservoir and then come back out and infected humans. One thing that's important to keep in mind here is that when we've seen these animal reservoir jumps in the past, for example, with the mink in Denmark, they actually haven't resulted in viruses that have done very well in humans. They really adapt to the animal that they're in. Of course, this doesn't rule out that this is possible but certainly I think it reminds us that we have seen circumstances where immunocompromised individuals have led to many mutations and we know that we don't have surveillance all over the world. It's also important to remember that it could be a combination of two or more of these that could lead to this long branch effect. So finally, in the last day or so, we've heard about a new Omicron, sometimes called the stealth Omicron. What's happened is that Omicron has been split into two lineages. These are called VA1 and VA2. Now, VA1 is the sequences that we identified originally. The ones that you've been hearing about for a couple of weeks now. VA2 is more like those VA1s and more like Omicron than anything else but it is a little different. So on this graph, I'm showing again this exploded family tree but I've zoomed in to help us see a little bit more detail of Omicron. So the rest of SARS-CoV-2 is over here and you can see that VA2 is definitely closer to VA1 than anything else and they share a lot of mutations but it's also very distinct. Importantly, we don't yet know if VA1 will behave the same, have the same phenotype as VA1, VA2 and VA1 will have the same phenotype but with more data, we'll be able to carry this out. Another thing you may have heard about VA2 is that it doesn't work as well for PCRs. Really critically, we can still detect VA2 with PCR tests. It will still come up positive. However, VA2 doesn't have that little signature that we can use with VA1 to give us a hint that it may be Omicron. We would have to sequence VA2 or use other testing methods to determine that it was Omicron. So to finish, the key points of what we can see right now is that Omicron has many more mutations that we've seen in other variants and they could impact how the variant spreads, the clinical outcome and how much it can get around our immunity. It's found worldwide and it's already spreading locally here in Europe so we need to start preparing for what impact this might have. We don't yet know much about its history or where it came from but hopefully we'll be able to see more as more data comes in. And finally, Omicron is divided into two lineages now but it's too early to know if they might behave differently. And with that, I'm happy to turn over to the other speakers this evening to talk more about what these things mean for the pandemic. Thank you. That's absolutely brilliant, Emma. A really, really wonderful and clear introduction to Omicron, where it might have come from and where it has spread to already. I want to welcome all of the listeners and watchers who've come to join us on YouTube and apologize for them for the slightly delayed start because we had some technical issues which have now been sorted out so we're all on Zoom and YouTube going forwards together. So what we will do next is move on to our second speaker who is Professor Volker Thiel and Volker is going to talk to us about how is Omicron different from other variants. Professor Volker Thiel is an expert in coronaviruses as many of you will know. He is professor of virology at the Wetzwitz faculty at the University of Bern and he is also the director of the Multidisciplinary Center for Infectious Diseases. Volker's special interests are in analyzing the replication of coronaviruses and in the host immune response using techniques of reverse genetics. He is a member of several international advisory bodies on SARS-CoV-2 virus evolution and characterization and he is a member of the Swiss National COVID-19 science task force. So welcome Volker and over to you. So thanks a lot Nicola for this nice introduction and thanks Emma for this great talk. So I want to continue now with essentially all what we don't know. So there are only a few things we know so far and I wanna go more into the virology but also tell a little bit of what we can expect in terms of data, in terms of new information in the next days or weeks. But Emma already explains why Omicron is probably much different than the previous variants of concerns. And I wanna also point out this issue because it just appeared Omicron and we don't know actually as Emma said where it did come from. And I wanna compare that with Delta which is shown here. So you see here the timeline from the beginning of the outbreak at the Wuhan seafood market at the end of 2019. And then until we knew from the WHO when the WHO declared the pandemic which was in March and what you see here is all and essentially every mutation that we know is specific for Delta for the variant of concern Delta with the date of appearance in the database. So essentially whenever we see full-length sequences we can now go back and really see the collection dates the submission date and then see when those mutations were detected for the first time. And before even there was the first Delta virus which combined all these mutations on one genome all the individual mutations were seen before. And you see here the genome entries of the Delta variant that came quite late. And you may remember at the end of 2020 we had the rise of Delta in mainly in India. So that is very much different if we compare that to Omicron. So the Delta specific mutations have been there and in the sequencing databases before actually the real Delta variant was present. And this shows a comparison. So all the orange peaks show the percentage of the Omicron mutations in the Omicron sequences we have so far and the blue one shows where those mutations have been detected before and according to percentage in all the other viruses in the database. So this already tells you that many of the mutations of Omicron have not been seen before. So that's clearly a difference and shows essentially what Emma said that we have this long or this large phylogenetic distance and maybe a period where the virus or the progenitors were not detected in our system. And this also shows here again what already Emma said these number high number of mutations that we have in the Omicron genome. So you see here the entire genome and a little bit enlarged is the spike and you see immediately that most of the mutations are in the spike gene. And we have here for comparison the number of mutations that are found in Delta. So really not as much as we see in Omicron. And that essentially raised concerns. Again, here you see this comparison on more a structural level. So how the spike protein is folded and we have essentially many mutations in what we call the receptor binding parts or the receptor binding domain and motif which is over here. So here at this surface there will be the human ACE2 receptor docking onto the spike. And you see already here there is a huge number of mutations. Another part is the so-called N or amino terminal domain where we have seen before in other variants that here are important epitopes where antibodies can bind to and also neutralizing antibodies. And also here we see an accumulation of mutations. And finally, the famous cleavage sites here are three mutations in the Omicron spike gene that are close or at this cleavage site. So there is also suspicion that here there are probably some functions affected that may also enhance probably the ability of the spike to enter cells. Also some very special things like a short insertion has been seen in certain regions here, for example in the N terminal domain. And this is also in a region that has been known before. So why is this new or concerning? Why is it a variant of concern? So the WHO declared B1, 1, 5, 2, 1 as variant of concern and named it Omicron and on Friday, November 26th in 2021. And because, as we already said, there are many mutations in the spike gene, some of them have been seen before and many of them are unknown. And one important thing was that there was reported a rapid spread in some regions of South Africa and that appears to continue at the moment. And also in other countries, the virus arrived and seems to be spreading very fast. And another issue was that the colleagues in South Africa reported an increased frequency of reinfections with Omicron compared to previous VOCs. So that means people that have been infected before and recovered obviously got frequently reinfected with Omicron to an extent that is higher if we compare that to other variants that appeared in South Africa before. So now what do we need to know? And what is happening right now? So of course, after declaring that a variant of concern, we need to know now, will Omicron replace Delta? So Delta is prevalent in most countries or in essentially all countries at the moment. Then according to the high number of mutations in the spike, is there immune evasion? So will antibodies still be functional against the Omicron spike? Then will severity of disease change? Is there mild or severe disease or is there no change? Will vaccines still protect? So that is clearly linked to the question of immune evasion and then finally will antivirus or therapeutic antibodies still work? So what is happening right now? So in essence, will Omicron replace Delta? So the image of epidemiology will tell us very soon whether that is the case. And we already have a clear evidence that it's spreading very well in South Africa but also where it arrives in other countries. Of course, the formal proof, let's say whether the virus is more fitter than Delta. That requires lab experiments which will take time. The second question is the immune evasion. So neutralization data are expected soon but actually that was a slide I prepared yesterday. And as you know, overnight we've seen at least part of the answer to this question is their immune evasion. And this is from Alex Siegel from South Africa, the first data on neutralization. And what they do here, essentially you take a certain amount of virus and you bring it together with antibodies that are for instance in the blood of somebody that has been vaccinated or somebody who recovered. So somebody who should have antibodies and then you see to which extent can those antibodies block virus infection. So that's what we call neutralization. And you see here two cases. So they took serum with the antibodies from twice vaccinated or fully vaccinated and they compared that the power of this antibody in blocking infection with what is here written as D6-4 in G. So that's the parental or the wild type virus. And you see here that there is a decent activity or neutralizing activity. So the higher this is, the better neutralizing are the antibody. And with Omicron, so if you want to neutralize the virus Omicron, then you see that there is much lower potency of those antibodies. That already indicates that we lose some of the power of our antibodies against Omicron. The second case is here, double vaccinated and infected. So these are people that have seen an infection but are also vaccinated. And you see immediately that the antibody levels are much higher in those people. And even if they lose the same order of magnitude, which is roughly 40 times, they end up in a level that is comparable to those who are twice vaccinated. So that means the higher your antibody levels are in the beginning when you probably get infected, the more likely is it that the level that is actually neutralizing Omicron is sufficient. A similar set of data and more elaborated concerning the different scenarios of vaccinations, different vaccine types is shown or has been tweeted by the lab from Sandra Cissek in Frankfurt. I don't want to go into that, but essentially we see the same kind of data. So we also have here 37 times reduction, for instance, in double vaccinated and boosted. And they start also with a high level and there is still something left to neutralize. So this is, I would say, worrisome, but also to some extent promising because we still have the benefit if we are boosted. So there is some immunity left. And we should not forget that we also have, besides the neutralizing antibodies, we have T-cell responses. So the immune system is not only dependent on neutralizing antibodies. So is there immunization? Yes, first data are now available since yesterday and T-cell data, which are more difficult to assess in the lab will take time. So is there increased severity of disease? I think that's too early to tell. We just need to wait until there are enough cases reported until these patients are really infected since a longer time so that they are really in the timeframe where they usually are expected to appear in the hospital if there is severe disease. So we are still too early to answer this question. Will vaccines still protect? I think we will soon know from the epidemiology so whether vaccinated people in real life are to which extent they are still protected against Omicron. So this will take time and also lab experiments will take time. But just from the neutralization data, I would not go as far as already predicting to which extent the vaccines are effective. Antivirals and therapeutic antibodies, will they still work? For sure some antibodies that target those regions that are mutated in Omicron will probably lose their efficacy, but there will be surely some antibodies left that could be used as therapeutic antibodies. And for sure, antivirals that are currently the licensed ones are targeting polymerase and protease. This is another target than the spike and we don't see any mutations that would indicate any resistance to those antibodies. So most likely they will continue to work. So finally, a word on travel bands. We have heard that South Africa in particular suffered a lot from being cut off from the rest of the world after they declared that they found this virus. And as Emma said, that's maybe not fair because they do a great job in surveillance and telling us that those viruses are around. So I want to thank here the colleagues in South Africa for their great and important work. But another thing that is also affecting the work of the scientific work and our work to find out the characteristics of this Omicron variant is that essentially the virus isolates that are in South Africa, that they have isolated in the lab, it would be so important to distribute them and share them with other labs so that we can do our analyses. But many flights, if not all flights are canceled and so far I'm not aware of any isolate that has been shipped so far. So we could have been two weeks ahead. So we lost, I would say at least two weeks if those shipments would have been possible. And with this, I stop here and hand over to Nicola. Thanks a lot. Thank you, Volker, for telling us what we don't know. But I think what you have already, what I think what you have actually shown us is that we have learned an enormous amount in an incredibly short amount of time based on the knowledge and the incredible research that has already been done over the past couple of years. We do have a couple of minutes all to spare because we're actually ahead of time here as well. And I wanted to ask pose a question to you, Volker, which is from Will Stokes. And this is, is there any indication that mutations in the spike that you just described have affected binding affinity to ACE2? And if so, what impact will these have on the severity of infections? I didn't get the middle parts on ACE2 binding. Yeah, you described, you showed the stereographic pictures and showed that there were mutations in the spike and including those that are in the ACE2. And are those affecting, do you have any information about whether those are affecting affinity? Affinity, it's too early to tell, but what the colleagues in South Africa also reported is that ACE2 is still the receptor. So that's another important message from their work, not only the neutralization data, but also that they had cells that do not express the receptor that could not be infected. And if they bring in the receptor, they can be infected. So despite all these changes, particularly in the receptor binding domain, this spike protein of Omicron can still bind and obviously provide immediate entry of the virus into ACE2 expressing cells. Okay. And if so, would that have any impact on severity? That's much too early to tell. So we have no idea at the moment. And the first data that will appear in that direction will be essentially what we observe, mainly or firstly in South Africa where the number of cases is higher at the moment and they are already let's say two or three weeks into this state of having higher numbers of infections. And whether they will turn up to a higher or lower degree at the hospitals, we have to wait for those data. Okay. Thanks very much for that. In that case, I'm going to, we asked still a little bit ahead with our time, but I'm going to move on to Christian Althaus, who's going to give us the next presentation. So Christian Althaus is Privat Dotsend at the University of Bern. He's a computational epidemiologist and an expert on emerging infectious diseases. Christian is head of the Interfaculty Platform for Data and Computational Science, known as input. And he uses mathematical and computational modeling to investigate the population biology of infectious diseases and their effects on the effects of environmental change, host immunity and public health interventions. The emerging diseases that Christian works on include Ebola, MERS and COVID now. In 2020, he was a member of the Swiss National COVID-19 Science Task Force. And Christian is also very active on Twitter and in the Swiss and international media. So thank you, Christian, for agreeing to give us a talk on how well does Omicron spread compared with other variants? Over to you. Thank you, Nikola, so much for the kind introduction and thanks a lot to Emma and Falko for this great introduction into the topic and the overview. I would like to go a bit a step beyond that and look at the question of how well does Omicron spread compared to other variants and what we can tell about that so far. So let's look at the growth of Omicron in South Africa and maybe more specifically in the province of Khauteng in South Africa. Two weeks ago, Tulio Dioliveira and colleagues from South African researchers gave a public online event where they informed the world about the appearance of this new SARS-CoV-2 variant in South Africa and neighboring countries. They showed this graph here on the top left that shows the proportion of different variants among the genomes they sampled in South Africa. So there was the original lineage here and then in green there was a big beta wave in South Africa followed by a delta wave this year. And now we see here in blue this spike, this rapid increase of this new variant which gave rise of concern. At the same time, we also saw here on the bottom right after a decline of the epidemic caused by delta in South Africa, a rapid increase again in cases here shown on the top and that translates then to an effective reproduction number that used to be below the critical threshold of one. So the epidemic was declining but then was rapidly increasing to very high levels also indicating that this new variant indeed might spread better in South Africa and elsewhere. So let's look a bit in more detail at this competition between these two variants, Omicron and Delta in the province of Khatang in South Africa. We made a preliminary analysis of this replacement and competition of the variants by looking at these eight sequences from this area and that allows us to estimate the growth of one which of these new variant Omicron compared to the previously circulating variant Delta and we found that it has a growth of one which of 0.3 per day. So each day and then subsequently every week it can spread considerably more than the previously circulating variant Delta. You have to be very careful with these analysis especially when we look at sequence data caused to a targeted sequencing as effort as soon as you find cases you try to go after them that can lead to a bias and sometimes an overestimation of this rate. There also so-called stochastic effects South Africa in the region of Khatang was a low incident setting because the epidemic was declining there were not so many cases around and then chance events like a series of subsequent super spreading events can suddenly change the proportion of the different variants. So we have to keep that in mind but let's take it from here. And it's also important to remember that these estimated growth advantage of Omicron is consistent with the difference in the rate of epidemic decline and growth. So the epidemic was indeed declining and growing again and that's quite strong evidence that Omicron is associated with a transmission advantage. Now this transmission advantage can happen either by an increased intrinsic transmissibility meaning that people can really infect more secondary cases or immunational both. So what does that exactly mean? Here you see a population on the left in gray that's the part of the population that is immune against infection and transmission with earlier variants. So it's that part of the population is immune against infection by Delta and earlier variants and on the right-hand side in black that's the remaining part of the population that is susceptible to infection and transmission with all variants. So when Delta spreads in such a population it can only spread on the right-hand side because the left side of the population is immune and like a transmission chain would look at something like that. If there is a new variant introduced like Omicron and if this variant would be associated with a higher transmissibility then we would see a pattern like that. So it also can only infect the susceptible part of the population but it can transmit much more efficiently because it has an increased transmissibility. A new variant like Omicron can also be associated with immuneration that means in the susceptible part of the population it can transmit as well as an earlier variant like Delta but it can also infect partly the other part of the population that is immune against infection and thereby generate more infections and over time replace the previously circulating variant Delta. And of course it can also be associated with both so it can have a higher increased transmissibility but it can also be associated with immuneration. So in both populations the susceptible part of the population and the part of the population that is immune it can spread much more efficiently. This of course depends very much on the level or the proportion of the population that is indeed susceptible and there's some information about that in South Africa. These graphs are coming from a study that had been published in the Emerging Infectious Diseases by Klinons and colleagues and show zero prevalence studies that have been conducted until March 2021. On the left hand side you see zero prevalence studies in rural communities and on the right panel you see the zero prevalence studies in an urban community and you see that it varies across age groups but with subsequent waves the zero prevalence has really increased up until March 21 to levels up to 40, 50 or 60%. Now today zero prevalence and thereby the potential level of protective immunity against infection subsequent transmission is arguably much higher because there was in addition the Delta wave in South Africa where a lot of people got infected and on top of that almost 30% of the population in South Africa has also been vaccinated. So the overall level of immunity against previously circulating variant is arguably quite high in South Africa. Now let's look at the relationship between a potential increase in transmissibility and univation for this new variant Omicron in Khao Tang in South Africa. So these results are based on a mathematical model informed by this growth advantage of Omicron from the province of Khao Tang in South Africa. You see on the horrid sunglasses the potential increase in transmissibility and on the vertical axis the potential for univation and the lines basically depict different scenarios for different levels of immunity in the population from 10 to 90%. So Omicron corresponds to the level of immunity in the population to previously circulating variants including Delta. Now we can sort of identify three potential scenarios where Omicron might actually lie. So we have this first scenario with the assumption that there is no univation at all. In this case, the transmissibility would be increased by 200% for Omicron that means Omicron is three times as transmissible as Delta. Delta is already quite transmissible. It's not impossible that a new variant would have such a high transmissibility that is three times higher as Delta. It's probably a bit unlikely. And as Foko has shown there is already quite some evidence for univation of Omicron. So a scenario with partly univation is probably more likely. So let's look at the second scenario where we account for sort of medium univation that's a level of 50% in that case. And here we see that for very high levels of immunity in the populations as it is the case in South Africa the transmissibility of Delta could actually, excuse me, the transmissibility of Omicron could actually quite similar to Delta. If there is medium univation meaning that the new variant Omicron can evade the immune response in 50% of previously infected individuals. Finally, we also have the third scenario. In the case when the level of immunity in the population is very high like 70, 80 or 90%, which is not unlikely maybe in some regions of South Africa. In this case, almost completely univation would actually be consistent with the reduced transmissibility of Omicron compared to Delta. So Omicron could actually be a bit less transmissible than Delta, but because it's so efficient and evading the immune response of previously infected individuals and possibly vaccinated individuals it can still spread better than the Delta variant. So far we cannot identify these three scenarios and the next days and weeks we will certainly shed more light on that. It's also important that there is still considerable uncertainty around these estimates when we try to estimate and scroll through the language of Omicron in the province of Khaldain in other provinces in South Africa and now in countries outside of South Africa. That's illustrated here. These are basically the same graphs as before for the three different scenarios of a level of immunity of 40, 60 and 80% in the population and that clearly shows that of course these results are still associated with a bit uncertainty but with time and time in the next days and weeks we will certainly start to learn more about the potential increase in transmissibility and the univation of Omicron. Volker already highlighted lab studies that sort of give indirect evidence for the univation of Omicron. He also mentioned the increased reinfection that is now being observed in South Africa. That's actually a figure coming from a recent preprint from Juliet Pulliam and colleagues in South Africa where they indeed investigated that over the course of the whole pandemic in South Africa. So you see here in the bottom panel in B that shows the hazard ratio for previously infected people to get reinfected with SARS-CoV-2. Of course, there is a lower likelihood to get reinfected than the rest of the population. And we see here that this hazard ratio has been sort of fluctuating varying between 0.1 and 0.2 so that's significantly lower than one. But now very recently in October and November we see this rapid increase in this hazard ratio means that people that have been previously infected in South Africa are now much more likely to be newly infected with this Omicron variant and that's quite strongly of any evidence for increased reinfection and unification of Omicron. So with that I'd like to summarize for what I've shown in the last few slides. There is this early evidence that the SARS-CoV-2 variant Omicron has a considerable growth advantage compared to Delta. There's still uncertainty around these estimates but many estimates also from other colleagues come at about 0.3 per day. There is partial unification of protective immunity against infection and subsequent transmission with previous variants can explain the observed dynamics particularly when population in the unit is high and that is the case in many areas in South Africa and other areas of the world. But an increase or decrease of the intrinsic transmissibility of Omicron compared to Delta can still not be excluded either. And for the future, we need close monitoring of the spread of Omicron in countries outside South Africa as well to better understand the potential of this variant to evade the naturally acquired immunity and vaccine elicited immunity. And to finish, I quickly like to thanks my colleagues in my team, especially Emma Hodcroft and Martina Reichmuth who work on these issues and also our colleagues in South Africa just a few who are technically Richard Lessels and studio de Oliveira with whom we are very happy to collaborate and who have done really very important work to present these early analysis and inform the world about the appearance of this new variant also Richard Nair from the University of Basel and next train and of course, he said initiative that basically collects these different sequences globally. Thank you very much. Thank you very much, Christian. That was extremely clear and worked through a lot of the questions that people have. We've got a kind of natural break between the first three speakers and the next two speakers who are going to talk more about public health and economic issues. And so I'd like to take a brief opportunity to ask the first three speakers to answer some what I hope are pretty quick questions that are coming from the Q&A. So this one is for Volker. Is anything known about Omicron spike glycosylation? Is that one that you can deal with? Oh, I could, but I... That's a long question. I haven't looked at that. So spike glycosylation, of course it's known that it's glycosylated but I didn't specifically look at the mutations that are seen in Omicron whether those effects glycosylation. Okay, not to worry. There was also, I believe, there was a question that was... Now I'm sorry, I've lost the question, the other question that I was going to ask you. This one is for Christian. This is really a point of information. You showed a graph about the growth of advantage of Omicron. Can you give that a source? Is that already published from another group or from your work? Yes, thanks. This has not been published. That's very preliminary, of course. And yeah, basically we will continue to work on that to better identify the real growth advantage of Omicron. And there was a question for Emma that I will paraphrase because I can't quite find it now. It was about the distance of the Omicron variant from all other known ones. And then you gave three potential explanations for that. And the question really is about the relative plausibility of those three explanations, given what we know about what goes on. A, with sequencing in other countries and B, about the presence of an infection in a chronically infected person. Yeah, so sorry, Nika, that was probably me. I think I just answered it in the text. So it probably made it disappear. But to just give a brief overview of what I said, the question was asking if this was circulating undetected somewhere else to get this many mutations at a normal rate would still take some time. So do we think that it really has been circulating that long? I think that this is a possibility we have to explore because we know that some countries really aren't able to do much genetic surveillance. But it is part of the reason why I think that perhaps a combination of undetected circulation and being in an immunocompromised person might be quite a scenario that's really worth considering because in immunocompromised people, the virus can actually acquire mutations a little bit faster. So it would mean that perhaps it didn't have to circulate undetected quite as long. But the bottom line here is we don't have a lot of data to tell these scenarios apart. And hopefully as we get more data in the future, we'll be able to narrow this down a little more. Okay, thanks very much. And last one for Volker. Having shown all of those mutations and the large number in addition to those that we already know for Delta, for you personally, are there any particular ones or a set of mutations that make you particularly concerned about the potential for Omicron and its spread? Yeah, so partially I already answered that in the talk. So there are these three regions that we know that are important concerning antibody binding like the receptor binding domain or the N-terminal domain. And here we see really a number of mutations. And the third region is this cleavage sites that may facilitate virus entry and therefore maybe could help the virus in spreading better. And in all, in these three regions, we see more mutations than in other variants of concerns. And those are the functional maybe equivalent, let's say, or the functional, these are maybe, this is maybe the functional impact of those mutations on the receptor binding domain. The function is the ACE2 binding, but also target for neutralizing antibodies. The N-terminal domain is target for neutralizing antibodies. And the cleavage site is important for virus entry. Okay, that's great. So we'll watch out for the research upcoming on those. Now we've caught up with our timetable. We're going to move to our next two speakers. The first speaker is Professor Dr. Annalise Wildersmith. Annalise is a medical doctor and she's an expert in travel medicine and emerging viral diseases. She's an adjunct professor here at the Institute of Social and Preventive Medicine and professor of emerging infectious diseases at the London School of Hygiene and Tropical Medicine. Her special interests are in the viral infections such as Zika, Dengue, Chikungunya, SARS influenza and now COVID. She's led and co-led several clinical vaccine trials and international project consortia about emerging viral diseases. But the reason that we asked her to talk about her expert area in travel restrictions is absolutely because of the issue that Volker raised very clearly about the fact that we have received very, very quick and timely information from amazing bunch of scientists in South Africa and yet they had travel restrictions imposed on them immediately. So let's move over to Annalise and please give us your take on what's happened. Thank you, Nicola. Can you just confirm that you can see the slides? See your slides. Please go ahead. Fantastic. Closed. The world has come to a global standstill because of a virus, flights canceled, travel bans, vaccine passports, quarantine, testing and this now almost for two years. Travel restrictions cause more public outcry than social distancing or masking. And with increasing vaccination coverage we saw an easing of travel restrictions and travel was just about to cover but then Omicron arrives. Countries have acted swiftly with travel restrictions and Christmas is now up in the air. Omicron was first reported from South Africa hence the immediate association that it also originated there. And so countries called for travel bans against South Africa. I must admit, I do not envy governments. If you wait for the evidence to accrue over time then you are too late and the virus will be imported and spread. If you don't wait for the evidence and all that just becomes a big bluff then you will be accused of overreacting. Whatever you do, you always receive criticism. That's the tragedy of politicians. And just to remind you, Europe was severely criticized for reacting too late to Delta at the time and for not closing airports. So many countries announced then total bans for South Africa as you know, and as expected this led to anger in South Africa with some calling it travel apartheid. Scientists say they are being punished for their hard work and scientific acumen. Shower bans should not become deterrents. We want countries to report new bans of concerns without being punished. So some, also we know that, so now by now as you've already seen Omicron is in more than 45 countries in all six double-edged regions. In fact, countries are now reporting cases Omicron even before South Africa reported it. So, and there's already community transmission so there's no more travel direct travel links anymore which means travel bans will now not have anymore. And what we need to do is to focus on containment. Just to give you a little bit of a background this map shows how many countries have resorted to travel bans and travel restrictions in the past two years. I think the most famous total closures were from Australia and New Zealand and we must acknowledge that these countries were spared from major damaging outbreaks and had the necessary time to roll out vaccines before now reopening to the world. But now we are almost two years into the pandemic and our policy decisions must evolve because we do not have a zero COVID policy anymore. So do travel restrictions still make sense? Let's look at this algorithm. We need to know the EPI situation in the departure and the arrival countries. If there's no difference between departure and arrival countries then travel restrictions make no sense. And this was a rationale for the travel hubs and the travel bubbles and also Europe opened up within itself. If you bring one case in and bring one case out it doesn't matter. However, if a country has indeed a much lower incidence or has a zero COVID policy then travel restrictions and in fact very stringent and strict travel restrictions do make sense. I just want to give you a feel of the risk of importation. So we looked at numbers in April, 2020. That was when we were at the height really of the outbreak in Europe where we did not do massive testing at the time. And several studies were published which showed that about one to 5% of air passengers were positive for SARS-CoV-2. That means out of 100,000 air passengers, 1,000 will be positive. This is a sizable number. And remember our annual air passenger volume before COVID was about 2 billion. So you have to calculate the risk ratio of imported cases to the local incidents. If it's high then travel restrictions make sense and will have a substantial impact. Another factor is that we have to take into account is actually are not in the country of arrival. If the extent of public health and social measures and the ongoing reproductive number is low even if you import case by definition it cannot really result in more than one secondary cases and so there also travel restrictions play less of a role. But there's more to travel restrictions and travel restrictions and travel bans are not everything. So what can be done in terms of border measures? And these include quarantine, pre-testing, post-arrival testing and such measures. China did the extreme. So China still today you have to do three weeks of screening in combined with serial testing. And with that you actually do get the zero COVID policy because really there's basically no case of conversion after three weeks especially if you combine it with testing. So however, if COVID is already endemic in a country and if you do not have a zero COVID policy and all of us don't have a zero COVID policy we need to strike a balance, a reasonable balance between the extent of importations that you allow to come in and that your system can cope with and the damaging effect of quarantine and other measures at borders. In this study, my research team looked at the differential reductions in importations compared to not doing anything. So not doing anything is called counterfactual. We studied five possibilities against the counterfactual and counterfactual it's here number one. So we tested, so we looked at models, testing means screening, so doing PCR testing. So testing everyone and the seven day quarantine versus testing everyone and the 14 day quarantine. Another option, no testing, just mandatory seven day quarantine, another one, no testing and 14 day quarantine and the last one screening everyone but no quarantine. So on the right, you will see the reduction in comparison to your counterfactual. At the highest reduction with this would be a combination of testing and seven day quarantine and even better would be a 14 day quarantine and you see here the incremental benefit of a 14 day quarantine versus a seven day quarantine is so little that it would not warrant. So long quarantines are not necessary and we already, as you know, worldwide have moved away from long quarantines. But yes, with these measures, it's not perfect. You still, so if you choose quarantine or seven days and testing, you still have, you still miss about 10% of importations. What does WHO say about travel bans and travel restrictions? Unlike what many think, actually WHO advises against travel bans and travel restrictions. In fact, from the very beginning, from day one, the advice against it and also the reason is is that the WHO is bound to the IHR and the International Health Regulations and the International Health Regulations have a mandate to have a reasonable, to keep trade and travel. And WHO was severely criticized in last year for not being more proactive in advising for travel bans and travel restrictions. And just as a proof, here is the IHR. So they meet very regularly, you know, to continue, you know, declaring the current epidemic a public health emergency of international concern. And here you see at the right, they say to, they advise against travel bans but use, but advise for risk-based approach without travel bans. Also, and many people don't know that, actually WHO advises against COVID-19 vaccine certificates the reason for that is not that they are against it but the reason is, is as long as we do not have equitable distribution to COVID-19 vaccines around the world, that means everyone has equal access to vaccines, WHO has no way of advising for vaccine passports to allow travel unless there is until there's equitable distribution. So in summary, what does Omicron mean for international travel? I do think that quarantine is disproportionate, clearly no travel bans, but in light of the potential danger that or setback that this vaccine could do in terms of vaccine effectiveness, I do think that we, that pre-departure testing and possibly even post-revival testing at day two to three for all travelers, including vaccinated travelers may be warranted because we know that vaccinated travelers with Omicron will have less, less impact against mild infection. And so you may still carry even if you are vaccinated until we have more evidence on the vaccine impact of this vaccine. So this is my last slide and it's very important to end. Why is it really essential that not every country goes out its own way but that we coordinate these COVID-19 measures? Well, we need to ensure freedom of movement. It's our human right to move. We have to increase transparency for citizens and businesses. We need to avoid fragmentation and disruption of services. So we really need to look at all these travel related restrictions from screening to quarantine, to travel restriction and make sure that they're not discriminatory, that they're proportionate to the problem, that they respect certain issues of cross-border regions and geographically isolated areas. Make sure that, for example, science can continue as Volker just alluded to and that specimens can be sent around and that personnel and experts can be flying around. And really, we need to lift any travel restriction as soon as the EPI situation allows it. Thank you for your attention. Thank you very much, Annalise. That was excellent because you linked together what the issues with travel are with questions about vaccine effectiveness and also with vaccine equity. And those are issues that I hope that we will be able to come back to in the panel discussion and that others will be able to contribute to. But what I would like to do now is to move on to introduce our last speaker, who is going to talk about why and how does Omicron cause an international economic shock? And our speaker is Professor Dr. Joseph Francis. He is Managing Director and Professor of Economics at the World Trade Institute at the University of Bern. His other positions include being a fellow of the Center for Economic Policy Research in London and Director of the European Trade Study Group and the Institute for International and Development Economics. Joseph has many current research interests and these include some of which he'll be talking about today, cross-border production chains and employment, globalization and inequality, modeling of economic policy, linkages between trade policy and sustainability and estimation and inference within large non-linear systems like economic systems. So thank you very much Joseph for joining us and giving us our last presentation of the evening. Thank you, thanks for the opportunity to talk. I guess now we move from science to pseudoscience in a sense. So I can wave my hands a bit. The previous presentations were really informative. What I'm gonna focus on is largely the impact that we've seen in shocks in terms of the global economy. This follows on the previous discussion about travel restrictions. It's related to the movement of people and also the movement of goods. How this is manifested at the moment, the big thing is supply chain chaos. Okay, so what I'll do is I'm gonna talk a bit about an earlier pre-COVID episode of seeing major disruption to supply chains. What we saw when COVID was first unveiled in early 2020 in terms of the economic shock there. What looks like the impact that we're having now from both from Delta and then the news on Omicron. And then finally, some points that essentially we're still seeing the entire shock from COVID work its way through the system. Okay, and so a lot of what's happening is not specific to any new varieties, but it does come from firms having kind of changed their game in terms of what they're doing. Okay, so the great recession, if we go back to 2008 and 2009, it was another driven by a different thing. It was actually a massive shock. It was a massive shock to the global economy. Supply chains there proved really good at spreading bad economic shocks, right? In terms of demand shocks hitting some economies and then that fed through to other ones as demand dropped for intermediate inputs. And the result is that the volume of world trade dropped tremendously, about 20% globally. If you look at manufactured goods trade for parts and components, it's even more. And supply chains were clearly a connection that caused basically the shock to spread faster. But it also was the mechanism by which things sort of self-repair more quickly, right? Because then as demand picked up in one country, then started buying things from other countries. And so we've been here before in the sense of seeing trade crash and seeing specifically trade in parts and components crash. There was a dramatic movement in this period in shipping prices, which we measure, for example, by the spot price for containers. So you want to move something from point A to point B. We then look at the current shock. And so here what I've got, this is from the IMF and this index on the right is basically, it's a measure of how quick you're able to move things from point A to point B in the global transport network. And as the index drops, it's a bad thing. It'd be just taking a lot longer and there are more delays in the system. And you can also see that largely where this shock occurred was as the epidemic first unrolled and we saw the first types of responses. We had borders being closed, also the goods and so on. So the U.S. Canada border, for example, is just recently reopened. There's a big integrated motor vehicle industry that operates in North America. And it's hard to move parts and components back and forth when you can't move your trucks because the borders were closed. Ports were closed, factories were shut down for critical components. We also then had delays in delivery time per that picture on the right there. And those delays in turn have translated into a lot of disruption in distribution networks. Okay, so currently in the headlines, you can read about the global supply chains being delayed, things taking a long time. I think I think actually, so what that has meant is, yeah, things sit in port. They sit in port for weeks and weeks, time is money. Also with things sitting in port, it means that there are containers in the wrong places because they're not unloaded. So there's a shortage of containers in China because the containers that left China never came back. Okay. And firms have been responding to this even before we talk about Delta or Omicron. What I've got then here is a survey looking at, in particular with the blue numbers, what firms had planned to do pre-epidemic? Okay, pre-epidemic. So in terms of outsourcing a bit more, adjusting the regulatory stocks, maybe try to relocalize production and so on. What they've done since is they've decided that given that there's uncertainty and when they can move stuff, how long it's gonna be stuck, which suppliers are gonna be shut down, is they're trying to build up inventories, right? That's a cheap way to relative to building new factories, to build a buffer, to handle the uncertainties that the system currently faces. So this has been a way that firms have been adjusting what they do, even before the new variant has come along, and even before we maybe have more information on what that variant means. So firms have adjusted what they're doing, and it's given expectations on what's likely to be happening moving forward. What that means though, is that in a sense the disruption to the supply chains is gonna continue regardless of what happens with Omicron. We're still seeing, I think I had some pictures here. I'll go back to this. I'll just take a picture here for a second. This is a port of Savannah, that's about a month ago. And there is a delay of perhaps a month to get a container processed over normal time. These things are stacked five and six containers high, waiting to be processed, so high in fact that some of the cranes are unable to properly position themselves to move the containers off and put them on trains. Okay, and in the ideal world, many of these containers would have gone back to where they came from to load more stuff up. Okay, in the port of Los Angeles, there are lines of ships waiting to get in, again, because of the backup. And with firms then ordering more parts and so on to put into warehouses, that means that this disruption will continue. Indeed, it doesn't look like it's gonna clear up anytime soon. So how does this shock compare to the first shock about COVID? Okay, so these headlines are similar to both in the Straits Times, both of them are, have pictures of traders looking sort of panicked because the market is crashing because of news about COVID, one being from March with the big crash that we had there, the other one from just a month ago. The headlines are similar, but if you look at the relative drops in the stock markets, okay, the one in March was pretty massive compared to what we had late November, early December, was about a 2.5% drop compared to, you know, say a 30% drop. Okay, so the first shock, when we first heard about likely lockdowns, canceling all flights, Chinese economy, shutting down factories and so on, was a massive drop in the stock markets. But this time, man, I mean, in a sense, firms know what's going on, they know there's gonna be uncertainty. They've been adjusting how they handle this, right? Again, by carrying inventories of costs or higher, but it means that the market still had a relatively big drop, the biggest one of the year, but it doesn't compare all to what happened in early 2020. Okay, so again, both of them are news, both of them were, you know, well, the first one was just that there's COVID-19 at all. The second one is then that there's a new variant. But, you know, the last uncertainty about how to deal with the uncertainty, I guess I'll put it that way, that the firms are adjusting how they're handling this. Nothing's the uncertainty is good, just the firms are managing with it. Another way to look at this, so this drop, okay, the chart on the left is the U.S. unemployment rate, where you see that shock again in March of 2020, where we end up going up to about 15% from below four. So it's a massive increase, and then on the right is non-farm employment. And again, you see the big drop that occurred initially, but then you can see that recovery has been happening, even despite, for example, Delta coming along, right? So firms are adjusting to how they do things. We're not back to where we were, but, you know, the economy does seem, and this is mirrored in other statistics in Europe and elsewhere is that it's, we don't like being here. We don't like what we went through in 2020, but firms have been adjusting. And I think they're, the surprise of the new variant is not really surprised in the sense that we now know that more of these things are gonna come along, and firms are adjusting accordingly. So in essence, I would say first off, that the big disruption occurred with the fact that we have COVID at all, okay, in terms of what's happened in supply chains. And it's still working its way through the system. It's the world economy is a mess in terms of being able to move things around. I spoke, there's a maker of eBuy, a Swiss maker of eBikes who told me that they had a wait list of about three weeks. It's now about a year because they can't get the parts that they need to put these things together. And that's even before we have a new variety or a new variant again. Certainly then we're gonna continue to see, as we heard with the previous presentation, travel disruption, governments unsure if they should go ahead and put measures in or not, firms are then unsure if the government's are sure what they're gonna do. So all this translates into sort of not knowing what's gonna happen, right? So in Switzerland, we had not, just a few weeks ago, that basically people from the UK would not be able to come to Switzerland to ski for Christmas unless they were gonna spend 10 days in quarantine. Then that was lifted with a requirement instead for testing, right? So that's in a short period of time where you've got people that are running hotels and resorts not knowing what's happening in terms of how the science that we heard earlier translated into policy impacts people moving around. What will impact things more, I think is if we get shocks that are way bigger than what we anticipated. Okay, so if some variety comes along that the science hasn't indicated, but also if there's a lack of clarity on what all the policy will be. And again, this gets back to the previous discussion about travel locked in pounds is people can adjust. We've seen the firms are adjusting how they do things given that there's uncertainty along the supply chains. But if you pile more uncertainty on top, if it's not clear what governments are doing, if they keep changing their minds, if they say one thing, not to worry people within suddenly do what they really meant to do all along, that doesn't help, right? So lack of clarity in terms of what the policy measures will be, that does add more costs. And that's regardless of whether we have on the front or not. The other thing is we have other shocks that are happening. And my sense is that these are interacting. We've been following in the UK where with Brexit, they have ejected people who drive trucks, right? People who are picking fruits and vegetables. They discovered that borders when you're not in a customs union involve paperwork, right? That's on top of the shocks that the supply chain management from COVID, right? And so those delightful pictures, if you Google them about cardboard cutouts of vegetables on store shelves in the UK. We don't have asparagus, but we have pictures of asparagus, right? And some of that is related to other things like Brexit. But some of that, you know, maybe not asparagus, but other stuff is related to the supply chains being disrupted. You know, it's harder for UK producers to get access to intermediates because there are no containers because of them in the wrong places. Okay, so that basically magnifies problems that we might have had anyway. And so, yeah, essentially, I guess on the economic side, I think firms already, they expect that there will be unexpected things, right? They didn't expect, they didn't see this in March last year. Then there was a big shock in March of last year. I think now, as long as policy is relatively clear and as long as we are pretty transparent in terms of what the risks are moving forward, firms can adjust. It doesn't mean it's good, but, you know, that's okay, I'll stop with that. Thanks very much for that comprehensive overview of the economic situation and miserable Christmas that we have to look forward to. What I would like to do is to take this opportunity to firstly thank our interpreters for the fantastic job that they've done for the speakers that we've had so far. I'm going to move us straight on into the panel discussion, partly because Annalise is not going to be able to join us for very long and we have some important questions to deal with about the travel related. So what I'll do straight away is to introduce to our other two panel members. We have with us, first of all, PD Dr. Manuela Funke-Shamboa. She's a medical doctor and expert in respiratory diseases, deputy chief physician and deputy director of the pulmonary department at Burn University Hospital. Manuela leads a pulmonary research group at the department of biomedical research and she also leads the Swiss COVID lung study group. And one of her special interests is in long-term pulmonary effects of SARS-CoV-2 infection. So welcome Manuela. And lastly, I'd like to introduce to you Professor Klaus Beisbart, who's an expert in ethics and philosophy. Klaus is professor of the philosophy of science at the Institute of Philosophy and his researching interests are in the epistemology, not the epidemiology of models and simulations, artificial intelligence and ethics. So welcome to you as well. Annalise, I'd like you to, if you have time, please be the first person to answer the first question that I'm going to ask, which is travel related. And this is a question about calculating risks of travel in the countries of departure and arrival, as you mentioned, and how one really gets realistic estimates. So for example, in South Africa, there are 3 million declared cases out of 60 million people. While in the previous talk, we heard about 50% zero prevalence or more in South Africa. So how do we reconcile those kinds of discrepancies and really weigh up what the risks are? So indeed the assumption or the prerequisite for travel bubbles, so where you share and without screening or testing, et cetera, is that you know the surveillance system of the countries that you have a travel bubble with and that you trust the surveillance. So in most countries, they now use the number, for example, 50 out of 100,000 over the past rolling seven days, as a measure. And then you have the red, green and so you have the light thing. So indeed, you need to know that you're using the same surveillance to make sure that apples, that you compare apples with apples, if you really want to make sure that there's no differential between the departure country and the arrival country. Thanks. Klaus, did you want to say something there? No, okay. We may come back to that question about actually estimating what risk is in particular countries. But I'm going to move you on to this next question, also Annalise. And this is a question about containment measures. And the question is, if you identified containment measures, which would be the ones more in line with the international legal framework, in particular, the right to leave a country in which there's a travel ban in place, how to prevent the adoption of measures that may be, oh, hang on, that question's disappeared. Maybe you can take the first part of it. So the WHO and the IHR, they will always emphasize containment within the country, rather than border measures. And indeed, high vaccine coverage is number one as a priority intervention that we all have to do. And then in addition, of course, the public health and social measures. Okay. How to prevent adoption of measures that maybe the risk would be then too restrictive? How do stock countries from essentially doing what they want to do when it's out of proportion? That's a very good question. And so the WHO cannot police. WHO can only provide guidance. So countries are sovereign countries and make their own decisions. And a lot of countries went disproportionate to the actual need, but different countries also had different policies. China continues with the zero COVID policy. So of course, they have to go into the extreme. But New Zealand did the same for many months, right? So countries are sovereign and there's no policing of IHR and that's the weakness of WHO. But that's what countries have signed up to. That's how they want WHO to function. Is there anything we can do about it? I don't think you will get an international agreement for WHO or any UN agency to become a policing force. So they have no, they cannot legislate. They cannot enforce their guidance. Maybe Joseph, would you have an opinion on any economic measures or economic pressures that would show that in fact, it is more viable and a better thing to do economically to have less restrictive travel measures? That gets into the math, which was heard by the real science earlier in the presentations in terms of what the implications are of the neologically, I guess, of whether you had tied to travel restrictions or not. There are costs certainly of, like I mentioned in tourism industry, a number of countries are reliant on this. In addition, there are sectors that need to be able to move people around. It's part of how the global economy works. So those are costs. And to the extent that we can get by without having to go through with that. Yeah, there are benefits from that, having less restriction. On the other hand, this venue that we're talking here, right, so now we're on Zoom. I guess we all hate Zoom at this point. We're all tired of looking at people on tiny screens, but there have been some workarounds, right? So the restrictions that seemed pretty horrific a year and a half ago are somewhat less horrible now, right? And we are able to accommodate some of those. And on balance, we're not the politicians that I don't pity their problem, right? In terms of listening to all the different parts of the decision calculus that they have to put together. I think that in terms of the socioeconomic dimensions, in Europe, there have been very vocal protests and they're getting broader, I think, as people are just tired. They want the whole thing to go away somehow. And it's not just sort of economic costs. It's social and mental costs as well. And again, that calculus is not easy. The best we can do is provide numbers on what the dollar cost would be or what the impact is on the spread of the disease and the pressure on the health system. But again, those decisions are not, those are not ones that any of us, I think want to be the ones making. Okay, I'll stop. Okay, okay, thank you very much. So maybe just a final one on travel, Annalise. Based on the question about lifting travel restrictions, would that have made an impact by today and given us more space in hospitals and lower case numbers? That's turning the question a little bit back on people who say that there should not be low travel restrictions. Does anyone want to take that? Maybe Annalise has gone. Okay, I think we'll move on in that case. There was one question which came up about children. And this is really a question that is about the very early data that came out from South Africa about potentially that more children were going into hospital. And what I would like to take that in two parts. One would be about the early emergence of information. I'm going to ask Emma and then I'm going to come on and ask Manuela perhaps if she has anything to add clinically to that. So Emma, can I ask you to come in on that specific question? Yeah, so this is something that is certainly understandably alarmed parents. This means that maybe children are being hospitalized more in South Africa. But I really want to emphasize that the data coming in right now is so early. We have to be very careful how we interpret it. For example, if you have room in hospitals, you might be hospitalizing people that you wouldn't otherwise as a precautionary measure. Another thing that we've seen is that in South Africa, fully vaccinated levels are only about 25% of the population. But as in many other countries, they've prioritized the elderly. This is fantastic because it means we're seeing less hospitalizations in those age groups. But it can mean that relatively, you might then think that there's more hospitalizations in younger age groups, even though the numbers might be the same, the proportions will shift because of that relative change. But I think the bottom line here really is we have to be very careful with this early data, not overinterpret it and wait a little while to see if this really is what we're seeing or if it could be impacted by some of these confounding factors and more. Okay, thanks Emma. And Manuela, from a clinical point of view, is there any plausibility that children would be more severely affected than adults, which would be a reverse of the situation that we've seen for all other, the wild type and for other variants? Yes, thank you. I would like to first start to underline what Emma said that we need to be very careful with the early data. We have seen this in clinics with the treatments. There was every week another treatment and in the end it turned out that the studies didn't show any effect. So instead of panicking, we should formulate good questions which needs to be answered scientifically. So we have to ask those questions. Is there any difference? And then Emma also said that there's the shift of patients affected as the elderly are more vaccinated. Clinically, we see that most of the patients who have a severe disease cause are elderly, are male, do have comorbidities, do have obesity. Whether this is the same for Omicron, I cannot say because the data are not there. It would be plausible because it's a coronavirus still. So, and then we need also to see what happens to those children who are hospitalized. It might still be a mild disease. So we need data to know and we should not panic but formulate good questions. Okay. Perhaps may I also add that we should also reflect on something one of the speaker has said about perhaps expanding the vaccination frame and also vaccinate younger persons as they do in the US now this is also something which needs to be discussed. Sure. And about boosters. Maybe we'll come on to that. Well, this is a question also that does come on to vaccination and it's a question from Uwe Vediga, concerning future mutations in the spike protein. Should one expect immune-escape variants necessary to make new vaccines on a yearly or regular basis in the future? Or under what circumstances could SARS-CoV-2 with the mutations go towards SARS-CoV-2's endemicity rather than pandemicity? I think I'll ask Falka to take that one first. Yeah, thanks, Nicola. I think, I mean, the questions, are we now pandemic or endemic? I mean, we are probably both at the moment. And the question is, do we expect that, you know, other mutations may pop up like we've seen now with Omicron? I think, yes, we will continue to see new variants. And if you look at other coronaviruses, so the maybe best example is infectious bronchitis virus in birds and chicken. There are huge, there's a huge number of different strains. So here they are called strains. So the difference between the individual viruses is so different that they call them strains and they also have another or a slightly other anti-immune response, similar as we know it from influenza virus. And SARS-CoV-2 is now diversifying during the pandemic. We will probably in the future have strains. We will see so far they are not so far apart, but the future can be seen as, yeah, SARS-CoV-2 has different strains. And then of course we need to monitor and probably adapt the vaccine maybe yearly like we do for influenza. But for now, I would say Omicron would be the first example where we now really have to thoroughly assess if we need to update the vaccine and we know that this takes time. So it will not be ready an updated vaccine during this current wave. So that's more the perspective for the next winter. So we should monitor and watch what is out there. And then at the right time modify the vaccine if needed so that it's available in late fall next year. Looking forward to that. I'm going to ask a question now which I'm gonna ask you, Volker, to deal with it again quickly from your point of view, but then going to ask Christian's point of view. And this is questions that arise in many, many countries where the country's population or epidemiological studies say that there is a large proportion of the population that is already immune. So that when we have a variant like Omicron that is coming along, this is then becomes a debate about whether, do you think this is about mutations? Are they going to go for vaccine escape that's going to escape both the vaccine induced immunity or natural immunity that's already gained or is the level of immunity so high already that one could expect populations to be protected from large outbreaks? That question came from India but there was a similar question from Bulgaria which has a very low vaccination rate as well. It's hard to tell us. So what we can expect, let's say in countries like Switzerland where we have around 60 to 70% fully vaccinated, the remaining 30% may have a high chance to get, as you call it, to get natural immunity by infection with all the costs that this has. And by the end of this winter, we may not have that many people anymore that are immunological naive. And then we will see how there is the balance between virus infections, numbers of virus infections but also the balance between severe disease and mild disease. So whether the broad immunity in the population may lower severity of disease, not because the virus changed but because we changed. And then we will get to know once SARS-CoV-2 virus is further evolving, how this plays into this game. Do we, are we still protected enough? Which I think most likely yes because we will always, once a new variant arises, the population will also adapt to this one. So there will be a balance at some points as we see for other virus. Thank you. Christian, is there anything that you can help us with about how we work out what this balance is gonna be? Mathematic. I can only second what Volker just said and of course now it will be really interesting to follow the trajectory of a variant like Omicron in different countries that have varying degrees of naturally acquired and vaccine visited immunity and maybe by different vaccines. So we learned to understand whether escape is about antibodies in general or it also involves T cell immunity, whether the escape is focused on unification from infection and transmission or whether it also affects disease severity. And I think really the comparison between countries will tell us more in the future. If this pattern that we have seen in South Africa now is being repeated in different European countries then probably we could argue that the unification is quite similar from the vaccines and natural immunity. Okay, very clear. Thank you. I think we're gonna move on to into a completely different tack. And this is really a question that should affect a lot of the panelists but I'm going to ask Klaus to deal with it from an ethical philosophical point of view. This is about anti science critics about COVID and where we are now. How do you deal with the problem that anti science critics don't have to wait on scientific data and make up their own narratives that come out and move ahead of where the science has got to and then overtake the part of society that is susceptible to those views. Yeah, thank you. This is a big problem. I agree with that. A couple of remarks. I think we first have to distinguish between people who push their own interests for instance in industry or some of the countries and then I mean that there's a broader public and that doesn't trust science. And I mean, there have been nice and interesting studies in the history of science about tobacco industry, for instance. There's a nice book Merchants of Doward and they explain how certain pressure groups or interest groups have to try to make if science less trustworthy than it is. But then we have to talk about the broader public and what is their perception and how can they come up and understand science. And I think, I mean, there are a couple of measures that one could take. I think events like this one are great because I mean, this is an opportunity to talk to the broader public and the broader public can participate and ask questions. And I think we need events like that one. Then I think what's also important is something that scientists can sometimes do. I think scientists shouldn't be too quick to give political recommendations because the effect is that they are very early tied to political parties or certain political directions and that's not good. I think science is neutral and can stay neutral. I mean, we should very, very clearly make our case and say, what would happen if we do that and that? But in the end, I think we have to respect the politicians, what they decide and it's their decision and the broader public should decide. And then I think to some extent it's also something about the new media and I think we have to learn to cope with the problems that the new media pose for us. I mean, I think it's a new situation. I mean, publicity and the broader public is constituted in no new way and we have to find measures to deal with that. And that's more technical. I think that that is related to certain measures that Facebook and other platforms can take. But I'm curious to see what other people think about this. Okay, thanks very much Klaus. I'm gonna ask Emma to come in because I think it's something that she faces a lot or that is faced a lot in those who are involved in science communication because you get it from all sides. So what would be your take on that, Emma? I mean, I completely agree. I think this is something we have to take really seriously and I do think that this is something we want to also consider, in future times where we're drawing a lot on science how are we gonna do better here? One of the main things I come up against when it comes to misinformation is that people who, as you say they don't have to wait for the science. They don't have to rely on the science. They aren't constrained by the science. They have a lot more time to put this out than I have in trying to combat this with science on social media in between everything else we're trying to do in this pandemic. But I do think one thing that can be effective here is to almost vaccinate people with good science first. One of the reasons people can be drawn to misinformation is that it's more approachable. It's often written in very lay language with pretty pictures, very understandable. It makes sense when people read it. In science, we sometimes have a problem that we don't make sense if you read it and you don't have a science background. So making steps to make sure that we get there first with the real science in a way that's understandable and approachable and that people can read and go, oh yeah, I get it. That can be really powerful that then people aren't drawn in by attractive claims of misinformation. Okay, we need to help with our science communication. What I would like, I think we're going to have to wrap up soon because I know we've actually gone over the end of when we had planned our time and there are so many questions left. But I think that it would be nice to finish up with looking at how we've have been dealing with Delta and now that Omicron is coming along and we are going to have to deal with it. I think that the scientific consensus is that this is something that we're going to need to take extremely seriously. So the question is about, are the measures that are in place, is it okay to keep on doing the same thing? How are we going to, do we need to keep on trying to reduce transmission? What is the role for vaccines and getting vaccination to as many people as possible? And maybe Manu Rala could come in here. Yes, thank you again. So we need to be prepared for Omicron but we also need to think that we are in a Delta situation right now. The hospitals are stretched. We have a lot of patients that have a severe disease that are not vaccinated. They are young. We have pregnant women. They are dramatic situations. Those are the patients we have on intensive care. Since two years, the nurses are working frontline. Many leave their job understandable. They are tired, the staff is tired. So we really need the effort of the population to get vaccinated. We have the tools and even if we have a lower response, we still have a response and we do not know those in vitro study, how are they going to work in the human body? I believe that there will be some immunity after vaccination and in any way it will help against the current Delta variant. And it's great that we have scientists as you are to prepare and not be so much in a healthcare stretch as we are right now internationally. And so we need now at this time use the tools we have and get prepared for the new variants. But right now we need to take measures, get vaccinated, keep distance, wear mask that we do not have to add additional measures to this. So that would be highly appreciated from the clinical side. And I speak in terms of in the words of everyone at the hospital. So we are motivated, but we need help. Thank you very much, Manuela. And I think it's a really, really good point that shows that for the people at the frontline of medical care that they are having to deal with the people who continue to come in and seriously ill and that the measures that we can take are public health measures that the whole population can take part in and can do so that what we do helps other people. What other people do helps us. I take that privilege of giving that message of what public health science tries to achieve. And with that, I would like to finish my part. I would like to thank all of our speakers and all of our panelists for having done a fantastic job for giving such informative and clear presentations and to the audience from whom we've had some absolutely amazing questions and the pace at which they're coming in we could carry on all night, but I know that you don't want to do that. So I'm going to hand back to Carmen, please. Can you take over and lead us out? Yes, thank you, Nicola. And thanks to all for an incredibly informative session that I think has been enjoyed by many, many people online on Zoom, on YouTube Live. We did have a couple of technical hiccups right at the beginning with our live streaming, but we did manage to catch up just in time for Emma's talk to begin. So we're glad that at least our audience managed to listen to our incredible lineup tonight from the very beginning. Thank you all for joining us. It's been a pleasure. We're looking forward to organizing other outreach events on behalf of the MCID, of the Multidisciplinary Center for Infectious Diseases at the University of Burns. So please stay tuned, check out our website, keep an eye on what's happening on our Twitter channel and look forward to more information and to more sessions, which will be at least as excellent as this one. It will be hard to trump, but I think we're starting off on the right foot. Thank you everybody and have a nice evening. Thank you. Bye-bye. Thank you.