Health and Healthcare Systems

Does Omicron mean the end for COVID-19? Anthony Fauci and other experts on Radio Davos

Omicron COVID-19 end - Dr Fauci

Anthony Fauci and other global experts discuss Omicron COVID-19 variant at the Davos Agenda Image: WEF

Robin Pomeroy
Podcast Editor, World Economic Forum
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This article is part of: The Davos Agenda
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  • Omicron is sweeping the world - but can it help make the pandemic end?
  • Experts at The Davos Agenda 2022 were cautiously optimistic.
  • The key is the virus becoming endemic: experts explain what that means.

"It is an open question as to whether or not Omicron is going to be the live virus vaccination that everyone is hoping for."

That was the cautious assessment from Anthony Fauci, who advises the US president on COVID-19. He joined three other global experts at The Davos Agenda to discuss what we might expect from the pandemic in the coming weeks and months.

Radio Davos has the full audio, and you can watch the discussion here.

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Omicron and COVID-19: What’s Next?

Francine Lacqua: Hi, everyone, I'm Francine Lacqua from Bloomberg, and we have the next 45 minutes to talk about that pandemic and, of course, what comes next. We'd love all participants to join the conversation on social media using the hashtag #DavosAgenda.

I'm delighted to be joined by Anthony Fauci, chief medical adviser to the president of the United States, Stéphane Bancel, Chief Executive Officer of Moderna, Annelies Wilder-Smith, Professor of Emerging Infectious Diseases, London School of Hygiene and Tropical Medicine, and Richard Hatchett, Chief Executive Officer, Coalition for Epidemic Preparedness and Innovations (CEPI). Dr Fauci, let me start off with you, we have many questions to get through. Is 2020 to actually the year that we go from pandemic to endemic and on the current speed up the process given its ability to spread and offer immunity through infection?

Anthony Fauci: Well, the answer is we do not know that, and I think we have to be openly honest about that. And when the word 'endemic' is used in different contexts.

Control means you have it present, but it is present at a level that does not disrupt society. And I think that's what most people see when they talk about endemicity.

When I talk about the pandemic, I put it into five phases: the truly pandemic phase where the whole world is really very negatively impacted as we are right now. Then there's that deceleration of the pandemic. Then there's control. There's elimination and eradication. I think if you look at the history of infectious diseases, we've only eradicated one infectious disease in man, that's smallpox. That's not going to happen with this virus.

Then there's elimination. Elimination means when you get rid of it in your own country, but it's somewhere, not in your country, but it's there. For example, polio has been eliminated in the United States and many developing nations. So what's the next one up the ladder? It's control. Control means you have it present, but it is present at a level that does not disrupt society. And I think that's what most people see when they talk about endemicity, where it is integrated into the broad range of infectious diseases that we experience. For example: the cold weather upper-respiratory infections, the para-influenzas, the respiratory syncytial viruses, the rhinoviruses. You want to get it at a level that doesn't disrupt society. That's the answer to your first question. That's my definition of what endemicity would mean: a non-disruptive presence without elimination.

When you talk about whether or not Omicron, because it's a highly transmissible but apparently not as pathogenic, for example, as Delta, I would hope that that's the case. But that would only be the case if we don't get another variant that eludes the immune response to the prior variant . For example, we were fortunate that Omicron, although it is highly transmissible, nonetheless is not as pathogenic. But the sheer volume of people who are getting infected overrides that rather less level of pathogenicity. So I really do think, Francine, that it is an open question as to whether or not Omicron is going to be the live virus vaccination that everyone is hoping for because you have such a great deal of variability with new variants emerging.

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Francine Lacqua: Thank you Dr. Fauci. Annelies, what does do you think actually Omicron means for new variants? And are we focused too much on calling it endemic? Of course it makes things easier and people see it as light at the end of a difficult tunnel.

Annelies Wilder-Smith: It is indeed too early to call it endemic, and I totally agree with Dr. Fauci that what people want to hear is when can we resume our normal activities. And Omicron will not be the last variant. Clearly, with such high viral circulation as we are seeing now, there's a high probability that we will have another variant coming up. The question is: where and when? And will it be more dangerous or less dangerous than the current variants of concerns. Where and when? I do think, you know, if you have high virus circulation that drives the risk of emergence - you've seen that for Alpha that emerged in the UK, we've seen that for Delta in India. Maybe less so for Omicron. Will it be more dangerous? Of course, we all hope it won't. And and based on the evolutionary advantage to a virus, it is more likely it will attenuate. That means will further be associated with less severe disease. Just based on the mere fact that a virus has as an advantage, you have high transmissibility but you don't also kill your host at the same time. So we're all hoping for that for the best case scenario so that the next one will be even further attenuated. That said, I think the world needs to be prepared for the worst case scenario. And the worst case scenario would be that, indeed, there could be another bi- recombination that would combine maybe the capacity to have high transmissibility and high mortality. That's the worst case, and I still think it is not so likely, but we have to consider all case scenarios.

Francine Lacqua: Thank you so much, Annelies. Stéphane, where do you think we are in the pandemic?

Stéphane Bancel: I don't think I have anything to add to those two infectious disease experts. What I can tell you from the the vaccine makers standpoint, we are, first, very happy that with such a change with Omicron that the vaccines holding very well and the third doses are proving to be very important. What we are doing right now is to prepare for what should the vaccine be in the Fall of 2022 and what should it contain? And our experts are working with public health experts like Dr. Fauci's team to figure this out because soon we're going have to decide what goes into a vaccine for the Fall of 2022.

The other piece we are doing, of course, is around manufacturing capacity. You know, in 2021 we shipped 807 million doses. We're very proud that around 25% went to middle income and low income countries, and we're continuing to ramp up. We have a lot of capacity coming online in Q1, this quarter, we will go to be able to make 2-3 billion doses for this year. And the other piece we are working on is for 2023 is how do we make it possible from a societal standpoint that people want to be vaccinated. We're trying to do this by preparing combinations, we're working on the flu vaccine, we're working on the RS vaccine and our goal is to be able to have a single annual booster so that we don't have compliance issues, where people don't want to get two to three shots at winter, but they get one dose where they get a booster for corona and a booster for flu and RSV.

Francine Lacqua: So Stéphane, how close are we to that, actually - one single shot for various protection against COVID-19, but also the flu?

Stéphane Bancel: So, the RSV programme is now in phase three, the flu programme is in phase two. and soon in phase three, I hope, as soon as the second quarter of this year. So a best-case scenario will be the Fall of 2023 as a best case scenario. I don't think it would happen in every country, but we believe it's possible to happen in some countries next year.

Unpredictably, the virus appears to have the capacity to become, essentially, a pandemic at any time

Francine Lacqua: Richard, what do you see as the shape of this future endemic phase?

Richard Hatchett: I certainly don't disagree with anything that Annelies and Tony have said, and Stéphane's new reporting on moving towards the combined shot is certainly encouraging. I would say that when most people talk about a disease becoming endemic, what they really mean or what they're anticipating is a disease in equilibrium with the human population. Flu is endemic and we've had annual epidemics as the virus evolved over time. And I if I would hazard a guess in terms of the near-term dynamics of our interactions with COVID over the next few months, Omicron will sweep the world, it may hopefully sweep out other variants, you know, eliminate Delta, ideally - that that wouldn't be completely unanticipated. And I do think that we will get to a point this year where populations around the world either have been infected or had the benefits of vaccination, and we will get closer to that equilibrium with COVID. And we're likely, probably post-Omicron, many countries will have, absent a new variant emerging, which it can do at any moment unpredictably, we will have a quieter period with the virus. But I think the long-term view on COVID, we have to anticipate that COVID is going to behave more like flu, in terms of it will continue to circulate, it will be around, people will get sick and there will be continual evolution of the virus and, unpredictably, the virus appears to have the capacity to become, essentially, a pandemic at any time. Omicron has moved very, very rapidly, and is behaving exactly like an acute pandemic, as Tony, I think, was describing, and the virus is going to retain that capability in the future, and that's something that I think should be quite concerning to all of us.

Francine Lacqua: Thank you so much. I'm getting a lot of great questions from everyone listening, so thank you for those. Dr. Fauci, this is basically a person writing and saying what is the best case scenario as per the data prediction to achieve herd immunity combining the vaccine administration and COVID infections. How difficult is it to actually calibrate something like that?

We're dealing with a very complicated situation here that makes our classic definition of herd immunity very elusive.

Anthony Fauci: Well, certainly the experience that we've had right now with COVID 19, with SARS-CoV-2, is that that is going to be a very difficult calculation because when you talk about herd immunity and you talk about the protection in the community, where you combine those who've been vaccinated with durable protection and those who've been infected-recovered with durable protection. However, when you have a virus in which the infection causes immunity that seems to wane rather quickly. In addition, when you're dealing with a vaccine that's extraordinarily as successful and protective vaccine where the immunity also wanes there. And you have then the third ingredient is a virus, which as was recently described by several of the panellists, myself included, which has this extraordinary capability of mutating, developing new variants, and the new variants can be eluding the immune response. We're seeing that with Omicron, where Omicron, fortunately, is not as pathogenic inherently. But when you look at its protection, particularly against infection to a lesser degree against severe disease, it does elude the immune response. That's a different scenario than what we see when you have a virus like measles, which does not really change very much, and gives you almost lifelong immunity. And you have a measles vaccine, which does not give you anything changing but allows you to have rather lifelong protection. That's the ideal herd immunity. We're dealing with a very complicated situation here that makes our classic definition of herd immunity very elusive.

Francine Lacqua: Thank you, Dr. Fauci. Annelies, this is another question which we've touched on, but this person is maybe turning it a little bit more political: should we be worried about future variants, and, this person writes, sometimes it feels like big pharma companies are taking advantage of the situation. Let me ask you, and then we'll go to Stéphane on this, how can we bridge the divide between believers and non-believers?

Anthony Fauci: Because there are some inherent non-believers that, no matter what you say, they're going to give you a real problem. You know, one of the things that I believe the entire world is facing, but we certainly are facing it in a very, very disconcerting way in the United States, is the amount of disinformation that is accompanying what should be a problem where everyone pulls together against the common enemy, which is the virus. We have disinformation that is entirely destructive to a comprehensive public health endeavour. And I'm not sure how we're going to account to that, except by getting out as much correct information as we possibly can and use the social media in a positive way as opposed to in the somewhat destructive way that it is being used right now.

Francine Lacqua: Annelies, your thoughts. And also there's a difference between what virologists say - so looking at how worried we should be about these variants - and what some politicians say, because they focus more on re-opening the economy?

Annelies Wilder-Smith: Well, let me share a word of optimism. We are in a different space than we were two years ago. Two years ago, we had a population of 7.7 billion people with zero immunity to this virus. Now, more than 50% of the world's population has received two doses, and this is further strengthened with now the rapid autoimmunity being built up by natural infection. So we're in a different space, and we now need to rethink and re-evaluate some of our strategies.

Francine Lacqua: Stéphane, first of all, there has been quite a lot of questions on pharmaceutical companies, but also how do you encourage vaccination? Is there a way that companies such as Moderna need to communicate differently or put up data differently that encourages people to get vaccinated?

Stéphane Bancel: Yes, the vaccination question is, of course, a very complicated one. Many public health experts and governments have tried really hard for now two years to get people to believe in the vaccines. And of course, there's always a better job that we can all do, starting from the companies - explaining the science, explaining the side effects, explaining the long-term benefits, and the risk-reward of getting a vaccine versus not getting a vaccine. I think a lot has been done, but clearly more can be done. But as Tony said, what he said is all the misinformation that we are seeing every say online and sometimes on TV about the vaccine and what they do and what they don't do is really sad in today's world.

Francine Lacqua: Stéphane, can I ask you something specifically about some of these vaccines? And this person who is also writing in - does a vaccine designed for Alpha or Delta also work well enough against Omicron? And how much faster have you been able to adapt some of these vaccines for every new variant?

Stéphane Bancel: Sure. So the vaccines that are currently available were for the original strain. They have not been adapted, that I'm aware of, to the Alpha or the Beta strain, at least ours was not. As we've seen and shared the data very quickly when we had it - we had a strong partnership with Dr. Fauci's team on the data generation in the Fall around Thanksgiving when Omicron appeared. What was seen is we saw an important drop of neutralising antibody after two doses of the vaccine. But what we saw, thankfully, is after a third dose, there was very strong protection, which is why you saw around the world all the public health experts and governments urging people that have not been boosted to get a third dose to protect them, especially people at high risk. What we're doing - and we started this the Wednesday before Thanksgiving, the day we saw the sequence - is developing a new Omicron-specific vaccine. The vaccine is being finished to be made. It should be in the clinic in the coming weeks, and we're hoping in the March timeframe we should be able to have data to share with regulators to figure out the next step forward. And that's always been a great partnership between public health experts, the regulators and vaccine makers, to figure out what's the best path. As Tony said, for two years we've all worked literally seven days a week together to figure out how to fight this common enemy, the virus. The enemy is not another company or another group. The enemy has only been the virus, and is still the virus.

Francine Lacqua: Richard, a better, more broadly protective vaccine that would be effective against all future variants, of course, everyone's hoping for - how far away do you think we are from that goal, and what more is needed to make that vision a reality?

We really don't want to get into the whack-a-mole approach towards every new variant.

Richard Hatchett: I think the first thing that's needed to make the vision a reality is investment in the research and development, and Dr. Fauci and his team at NIAID have already begun to make investments. We've already begun to make investments. There's some private-sector partners that are pursuing it. There's a lot of a lot of science that we still need to sort through to figure out how to capture the benefits that we have seen, and I'll talk about that in a minute, in a specific vaccine. There was the really important proof of concept - biological proof of concept - observation that was reported from Singapore. Linfa Wang is a scientist, very prominent in the coronavirus research community, actually administered mRNA vaccine to persons who had actually survived Sars-1 back in 2003 and 2004. He administered an mRNA vaccine to them - the Pfizer vaccine - and then looked at their antibodies. They produced neutralising antibodies, not only against Sars-1, against Sars-2, against MERS and against a number of other known animal coronaviruses. So that proves that the human immune response can generate neutralising antibodies against coronaviruses broadly. How we capture that, put that into a vaccine, is something we're looking at in a variety of different ways, a variety of different approaches. I would say that that would be the holy grail because we really don't want to be in a position where we are chasing the new variants that are going to come when they will and unexpectedly and potentially would quite - even if they're milder as Omicron is - the capability potentially to overwhelm healthcare systems. And so I think that needs to be, even as we support the vaccines that we've got, which is, as Tony says, are very, very good vaccines. They have done a great job, particularly in preventing severe disease and death. But we don't want to be in a position where we're having to vaccinate everybody in the world every three or six months or even annually, ideally.

Francine Lacqua: I'm not a virologist. Everybody thinks they are virologists, very few people are virologists. But you know, there have been reports that actually say if you boost too much, then it's counterproductive to the immune system. Richard, where are we on that?

Richard Hatchett: It's going to vary from agent to agent, pathogen to pathogen. I'm not aware of any data that strongly suggest that the administration of the third dose or the fourth dose in any way weakens the immune response. What we're seeing is a very robust response with the administration of the booster doses.

Anthony Fauci: You're absolutely correct Richard, there really is no evidence that if you boost... I mean, obviously, if you just overwhelm the immune system by just giving the person an antigen all the time, you get a hyperactivity of immunity. But giving boosters at different times, there's no evidence that that's going to hinder it. One of the things that we've got to be careful of, and I really want to underscore what Richard said, we really don't want to get into the whack-a-mole approach towards every new variant where it comes up and you all of a sudden have to make a new booster against a particular thing because you'll be chasing it forever. So that's the reason why one of the things we are really all pushing for is what Richard just mentioned, of finding out what the mechanisms are that induces a response to a commonality among all of the different - real and potential - variants that we're seeing and that can occur. And that's something that I think is a very, very important scientific goal, to be able to do that. Once we get there, whether or not you have to intermittently boost someone with that - you use the word universal - I think before we talk about a universal coronavirus [vaccine], we want to get a universal SARS-CoV-2 virus. Let's take it one at a time. Otherwise, I think we're really going to be jumping ahead of ourselves. But what we really need to also point out to people: that when you have a virus that has such a high degree of transmissibility, a very good vaccine may not necessarily prevent initial infection and may allow it to be very mild. But what you really want it to do is to prevent you from getting significant systemic disease. That would be a very, very successful pan-SARS-CoV-2 vaccine.

The key message remains: the vaccines still really work very well against severe disease.

Francine Lacqua: Stéphane, are you working on this better more broadly protective vaccine to outdo them all or is it something that we already have because it has been pretty efficient in tackling the variants that we've had so far?

Stéphane Bancel: As Rachel and Tony said, we definitely all of us want better protection for people and broader vaccines. There's a lot of work going on in academia around the world. We are looking at partnering with a lot of people, but unfortunately we are not there yet, but hopefully we're making progress toward that direction.

Francine Lacqua: Annelies, what do you do differently in terms of maybe explaining some of these variants to the broader population?

Annelies Wilder-Smith: The key message remains: the vaccines still really work very well against severe disease. And what we really want, the primary objective, is we want to avert deaths and protect healthcare systems. We're still in an epidemic, our healthcare systems are still overwhelmed. We still need to continue our public health and social measures. But as population level immunity is increasing, both through natural infection and vaccines, we now have a stronger hybrid immunity that will protect us against against new variants. So even if we have more severe new variants, this population now is different. We do now have a cellular immunity from background exposure - be it vaccines or infection - that will protect us against more severe disease.

Francine Lacqua: Dr. Fauci, I'm also getting a lot of questions from the US, so for the US specifically. Why is the US, a 'first world', developed, rich economy, struggling to contain COVID?

Anthony Fauci: That's a very good question, and I think some of the answer to that question has already been articulated by our panel members. One of the most important things is that we have, somewhat of a fractured and disparate accessibility to healthcare in our nation. We have a great disparity. We have individuals who don't have access to care. We have a higher degree of hospitalisation and death in our minority populations as we do in the general population. But we also have, what I mentioned earlier, and it's very disturbing, I believe, to all of us as public health officials and scientists, such a degree of pushback against regular normal, easy to understand public health measures. Reluctance to wear masks. Reluctance to promote vaccination. Reluctance to do kinds of public health measures that really we know if we all pull together as a society, we would be much, much better off. I mean, even at its best, this is such a formidable virus in its ability to do the things it's already done, with multiple waves and multiple surges and multiple variants, but you make the virus have an advantage when you don't implement in a unified way all the very well recognised public health measures, particularly the vaccines. And I think that's one of the reasons why it's so unfortunate for the entire world, but even for a rich country like the United States that supposedly was the best prepared country for a pandemic. We are among a handful of the countries that have actually suffered the most. When you look now, 65 million cases and close to 900,000 deaths in our country, that is really, truly unfortunate and something that we would have hoped would have been avoided.

Francine Lacqua: Dr Fauci, why does the U.S. not have free testing, free tests?

Anthony Fauci: Well, we're getting there very, very quickly. In fact, President Biden has made it very clear that he's put out by this month, a half a billion free tests. There will be now an online capability of getting online and having free tests sent to your home - eight per household per month. And then we're talking about in the next months or so to have the capacity to get anywhere from 200 million to 500 million tests per month. Many of them will be free. Many of them will be reimbursable through insurance. So although, as the president honestly said that we could have done better with free testing right now, we are still in the process of getting the tests widely available and free for individuals in the United States.

Francine Lacqua: I'm getting quite a lot of questions on tests, which will come back to. Annelies, would it make sense to include vaccine education in schools, for example, to try and keep some of the misinformation out there?

Annelies Wilder-Smith: Start with the medical schools! We need to educate a lot of doctors and medical students and the scientific community because they are part of the conspiracy theories. So yes, education on vaccines and the benefits and cost effectiveness, but the safety, the public health benefits, need to be strengthened around the globe.

Francine Lacqua: A lot of questions about testing what works - PCR, rapid antigen and their efficiency with Omicron and new variants, I don't know, who would like to get us started on this. Richard, is it something that you look at?

Richard Hatchett: We work with our partners at an organisation called FIND, which is a foundation for new diagnostics under the ACT-Accelerator, the WHO-led effort. They are really leading on diagnostics and in trying to get things distributed globally. Just to come back to Tony's point, the importance of having rapid access to diagnostics is absolutely critical if citizens are going to govern their own behaviour. One of the challenges with Omicron is there have been reports that the lateral flow tests have a slightly lower sensitivity and thus are not capturing all of the positive cases so you can have what are called false negative lateral flow tests. The understanding is they still work, but there is a lower sensitivity and those tests can be updated and I think are in the process of being updated. PCRs, of course, still work quite well. Access to PCRs can be challenging in many environments. I was home, I live in the UK, but I was [away] over the holidays when Omicron was peaking and had what I think was a cold because I found a PCR that was negative. But it took me five days to gain access to a PCR, which in a period when you think you might have Omicron can... I was behaving well and staying home, but not everybody would. And that could lead to further spread in the community. So diagnostics, - access to diagnostics - and updated diagnostics are absolutely critical to managing an infectious disease crisis.

Anthony Fauci: Big challenge, Francine, that we really do need to get, we need highly specific, highly sensitive, easy to do at a point of care setting. We're not there yet. The PCR are highly sensitive. In fact, in some respects can be a bit misleading because you could recover from the acute phase and not have 'replication competent' virus. And since the PCR doesn't tell you whether it's replication competent, it tells you have nucleotide fragments there. On the other side of the coin, the antigen tests are less sensitive if you give just one. But if you can do it in a sequential way, they become cumulatively as sensitive as a PCR. But there are considerable numbers of false negatives when you have a less sensitive antigen test. So you have two ends of the spectrum, you have one that's highly sensitive but, as Richard said very appropriately, sometimes it's difficult to get and you have to wait a few days sometimes to get the results. The question is, what do you do in the meantime? On the other hand, the easily accessible one has a lesser degree of sensitivity and could give you a false negative. So that's the reason why we're putting a major investment in trying to get those tests that are sensitive, specific, point of care, and easily accessible to virtually anyone who needs them. We're not there yet.

Francine Lacqua: Thank you, Dr. Fauci. Annelies, part of your research really focuses on modelling the reopening of travel, based on virus transmission risks on flights and cruise ships. What are your predictions for 2022 in terms of disruption to travel?

I think we need to be creative now that we have Omicron, to really rethink what has the highest public health impact without harming trade and travel.

Annelies Wilder-Smith: The short answer: I am optimistic. The longer answer is, we have to balance the relative public health benefit of travel restrictions and border measures against its harm for trade and travel. Travel restrictions and all these measures only really make sense if a country has a much lower incidence and wants to protect itself from importation from a higher incidence. But as we are now two years ahead, we will get to an equilibrium where most countries will have similar incidents, but we are not there yet. We still have an absolutely inequitable distribution of vaccines, and this drives all these problems with travel. So I do believe that we that we need to apply, and that the current Omicron base should be a stimulus to rethink some of our travel restrictions and remodel it, really trying to minimise the very harmful quarantine, versus maybe a higher frequency of testing and and travel bubbles, et cetera. I think we need to be creative now that we have Omicron, to really rethink what has the highest public health impact without harming trade and travel.

Francine Lacqua: Thank you Annelies. I'm getting a lot of questions on vaccine equity. Stéphane, where are we on vaccine solidarity? So far it feels like we failed. Is 2020 to going to be more of a balance?

I don't think the problem is access to doses anymore. That was last year's problem. I think it is really getting them into arms.

Stéphane Bancel: I think so, and I think - and Richard and I were discussing this actually last week - I think things really changed in the Fall, it's tough to say precisely when. But we clearly went from a time where there was clearly a big issue to get the vaccine to low-income countries. There's just not enough vaccine. As you know, mRNA technology was a new technology and so there was no manufacturing capacity idle, waiting for a pandemic. And so everything has to be built and increased by the month and the quarter. If you look at what the industry has done, I think now it's more than a billion doses made across the planet on a monthly basis, which is just remarkable. Just to give the order of magnitude, the entire flu production on an annual basis is around 500 million doses. So when you have a billion doses a month, it's quite remarkable.

And so what you saw in the Fall timeframe is starting actually to have the product in the warehouse, which is the first time we had this happen during the pandemic, which is, as you can imagine, every time a product was approved, it would be in a truck going somewhere. But we started to have warehouse space issues because the issue will become the ability of countries to get the vaccine, from a storage standpoint, from a delivery standpoint. In the November-December timeframe, any given day we had 50-100 million doses waiting to be shipped to COVAX because there was a lot of work being done with different countries. And another data point, which is actually from two weeks ago, which is a good sign for where the world is heading, is the African Union indicated to us that they do not want the vaccine that we had reserved for them for the second quarter of this year. And so I think it's just a good confirmation that thankfully vaccines are getting to the entire planet. I think now what I'm hearing from colleagues on the ground is the issue in low income countries is how do we get dose in arms? In terms of warehouse, medical professionals. And I think the rich countries, the high-income countries need to do more to help low-income countries in terms of getting doses in arms because I don't think the problem is access to doses anymore. That was last year's problem. I think it is really getting them into arms, and I think we should be able to do more.

The last mile is going to be the major challenge for 2022.

Francine Lacqua: Richard, do you agree, first of all, are you optimistic about vaccine distribution? And if we're not aiming for a temporary waiver of intellectual property, then what would be the best way to actually ensure that there's vaccine distribution in lower-income countries?

Richard Hatchett: Let me celebrate an important milestone that was passed actually on Saturday. COVAX, which is the CEPI and Gavi and WHO and UNICEF-led effort to distribute vaccines globally, particularly to lower-middle and low-income countries - passed the threshold of having delivered to countries a billion doses. And I think it speaks to the point that Stéphane was making. We now produced over 11 billion doses of vaccine. Since the beginning of the pandemic, 9 billion doses have been administered. The supply constraints that dominated the situation in 2021 and were a huge problem. a heartbreaking problem, have eased. And where supply was the major challenge for 2021, I think, as Stéphane was saying, the last mile is going to be the major challenge for 2022. And you know, the major thing that the world is going to need to do to make vaccine available to everyone who wants it - primary vaccination and booster doses available to everyone in the world who wants it, which I think is an achievable goal in 2022 with the vaccine production that we have - is helping countries, particularly the less well resourced countries, build their capabilities to do mass vaccination programmes and to deliver vaccine to their populations at speed. There's been a lot of focus on what hasn't been accomplished and and the equity gap that has emerged, and that is real, and that gives us plenty of opportunity to improve for the future. But I don't think there's been enough focus on what has been accomplished. HIV medications, effective HIV medications, there was a gap of a decade before those became widely available in many parts of the world, in Africa. Tony led the effort on PEPFAR which really was game-changing for many, many African countries in terms of making those vaccines available. In the last pandemic, after 13 months of a vaccine donation programme, only 78 million doses delivered outside of the wealthy countries. This time 13 months in, we just delivered our billionth dose, and those numbers are going to continue at a very substantial pace as we go into 2022. So you mentioned the TRIPS waiver. I think there's an important discussion about how do we achieve a more globally, more equitably distributed manufacturing capacity and many, many partners, governments, financing institutions, private sector partners. I mean, Stéphane has announced that Moderna will be building facilities in Africa and elsewhere. We're working on this and I think, you know, a trips waiver may have a role in that, but there are other paths up that hill too. And I think we really need to explore all of them. I don't think it's necessary right now in terms of making vaccine available. I think it's the last-mile challenges.

Francine Lacqua: Thank you, Richard. Dr Fauci, we talk a lot about the new normal. How do you define the new normal? How do you see us? Wearing masks? Travelling? How often will we get vaccinated? And does it make sense, for example, getting tested every week if it's a, you know, a virus or a COVID-19 that may be less deadly than the previous one?

Anthony Fauci: Again, it is very difficult to predict what a new normal is going to be until we get ourselves out of this pandemic phase that we're in. But a new normal, I believe, will have a much, much greater attention to the capability of respiratory viruses to spread as they do. I think the new normal will be, I hope, a greater degree of interconnectivity and solidarity throughout the world when we're talking about the possibility of pandemics. I don't think people are going to be walking around with masks all the time. I mean, I think that that's very much out of the question. That's not going to be something that the world will accept as being normal. But I think a normal will be a little bit of, Francine, related to your original question of me of 'what does endemicity mean?' And if and endemicity means such a low level of infection that, as Richard and others have said, you're going to get people who are going to be sick, it's not going to be that you're going to eliminate this disease completely, we're not going to do that, but hopefully it will be at such a low level that it doesn't disrupt our normal social, economic and other interactions with each other. To me, that's what the new normal is. I hope the new normal also includes a real strong corporate memory of what pandemics can do so. We don't just go on, when we get this under control, forgetting how we have to do better in both the scientific preparedness, the public health preparedness and the public health response. If it were not for the decades of investment in basic and clinical research that ante-dated this pandemic, we would never have been able to hit the ground running and within such a very short period of time, get a highly effective and safe vaccine that goes into the arms of individuals 11 months after the virus was first identified and put on a public database,

Francine Lacqua: Dr. Fauci, are we advancing toward some kind of global financial architecture to be able to fund pandemic preparedness for the preparation and response to the next one?

Anthony Fauci: Well, again, when you talk about pandemic preparedness, there are certain aspects of pandemic preparedness. One is scientific and one is public health. And I think that the kinds of things that Richard has been doing in collaboration with other organisations is really part of the public health preparedness that links up very closely to the scientific preparedness of getting better platforms, better immunisation design, the ability to get production literally within a very fraction of the amount of time that it takes to go from the recognition of a new pathogen to the ability to get vaccine. And one of the things that Stéphane mentioned is to get a global production capacity so that you don't have to wait until hundreds of thousands, if not millions, of people die before you can get vaccines out. That's where we should be heading.

Francine Lacqua: We have a minute and a half left. So, Stéphane, are you optimistic that we'll do better in the next pandemic? And what are you worried about that we won't learn from?

Stéphane Bancel: Yeah. So I'm optimistic. I mean, I'm an entrepreneur, so I'm optimistic by nature. But I'm optimistic that what is being done today is going to help tremendously. As you know, we're working with Dr. Fauci and his team, we're working with Richard to work on many more pathogens that we know - the entire scientific community has known - for years, and there's a list of around 20-ish pathogens that are at risk for which we need vaccines. You know, we have a Zika vaccine in Phase 2, we're working on the Nipah vaccine. Those are viruses that not everybody has heard of. Because we need to have the data - what dose, what construct from a genetic standpoint is required, and at what dose, so that if a new pathogen emerges of that that family we can very quickly move into a Phase 3. I think we could potentially shape up to six more versus what we're able to do in 2020, which, as Tony said, was already a world record by any stretch. The other piece is manufacturing. If you look in 2020, we were able to ship 20 million doses to the U.S. government when the vaccine was authorised. That is not a lot. But because this year we're going to have 2-4 billion doses of capacity in a six month timeframe, which is what I believe would take us to get authorisation of such a vaccine if all the work has been done before in preclinical and clinic, you could have 1.5 billion doses available in six months. And it's just from Moderna. And then you have all the platform. I think it would be a much bigger number. So I think we have all the means to do that, and we're investing heavily also in plants in Canada, in Australia, in Africa, to be able to have a very decentralised manufacturing network.

I think we have within reach if we work towards it, the ability to make vaccine available to everyone in the world who wants it in 2022.

Francine Lacqua: Great, thank you, Stéphane. Annelies, in 45 seconds, what are you most optimistic about?

Annelies Wilder-Smith: Travel will resume. I think we will have a better summer. We need to respond to the pandemic preparedness in addition to biotechnological solutions - we need better approaches to communication. And really social science - openness and preparedness should now be better embedded in social science.

Francine Lacqua: Thank you so much. Richard?

Richard Hatchett: I think we have within reach, if we work towards it, the ability to make vaccine available to everyone in the world who wants it in 2022, and we should strive to achieve that. I also think to some of the points that Annelies, Tony and Stéphane have made, that there are many, many lessons to be learnt from the response to COVID that will inform how we go forward and think about pandemic preparedness, not just for COVID or coronaviruses, but for other threats. And we need to capture that, institutionalise it. And we need to have the long view even while we address the near-term problems of COVID.

Francine Lacqua: Great. Thank you, Dr. Fauci, maybe the last 45 seconds to you: with hindsight, what should we have done differently? One thing?

Anthony Fauci: There are several things we should have done differently. I think we should have had a much more coordinated global response. As I've said so many times, a global pandemic requires a global response. And we have to keep in mind the issue of equity all the time because you can't have a situation where you have virus circulating freely in one part of the world. One - because we have a, I think, almost a moral obligation to the lower and middle income countries to make sure that doesn't happen. But also it's for one's own self-interest, because as long as you have virus anywhere circulating freely, you're going to get virus that will ultimately impact all of us. We've got to do it as a global community. That's what I think is such an important lesson.

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