World Health Organization (WHO) Media Briefing on Global COVID-19 R&D Forum July 2

Fadéla Chaib: (00:26)
Good evening and welcome to all journalists and our speakers. I’m Fadéla Chaib, WHO media officer in Geneva. Sorry for the delay. We are here today in Geneva to brief you about the main outcomes of a two day forum on global research and innovation on COVID-19 that has just concluded. The subject of our press conference is of great importance, update on COVID-19 research and development, the science, the health tools, and course of the pandemic. Our main speaker is Dr. Soumya Swaminathan. She’s the chief scientist at WHO. We have also a panel of WHO experts ready to answer specific questions.

We have Dr. Maria Van Kerkhove, technical lead on the COVID-19 pandemic, Dr. Ana Maria Henao-Restrepo, research and development blueprint WHO, Marie-Pierre Preziosi, colleague at the research development blueprint, [inaudible 00:01:38] in the same department. [inaudible 00:01:41] she’s technical lead infection prevention and control, and Dr. Janet Diaz clinical care at WHO and Peter Ben Embarek. He’s a food safety and cyanosis expert. Journalists can join us through Zoom and follow this press conference on our social media channels and platforms.

Today’s press conference will be in English only, no simultaneous interpretation. Our apologies for that. Without further ado, I will give the floor to Dr. Swaminathan. Soumya, you have the floor.

Dr. Swaminathan: (02:28)
Thank you very much, Fadéla, and good morning. Good afternoon. Good evening. Greetings to the journalists who are online. And it’s a pleasure for me to provide a very brief overview of what happened over the last two days. Many of you may remember that in February, WHO convened the first global research and innovation forum that brought together over 400 scientists and researchers from all over the world. At that time, we had just learned about this new virus, the SARS-CoV-2. And the idea was that we need to get together to really discuss what are the major research priorities, what do we need to learn about this virus and how it’s impacting us.

This resulted in a research roadmap that was released at the end of February and that I think has shaped the global research agenda to a large extent. It also resulted in the creation of nine working groups, and we’ll run through the topics around which the working groups were created. Each of these working groups was coordinated by WHO staff member, but basically consisted of experts from around the world. Some of the working groups have more than a hundred people. Some are a little smaller. But experts from all around the world voluntarily joined these working groups and over the last few months have been working on their own areas of expertise and topics.

Today, it seems incredible that it is just six months ago that we actually learned about this cluster of cases of pneumonia, originating in Wuhan. And none of us could have, I think, imagined when we woke up on the 1st of January, that six months along, this is where we are going to be grappling with this pandemic. We’ve learned a lot, and so we decided that it was time to reconvene these experts from around the world to take stock of what we’ve learned, what are the gaps in knowledge that we’ve actually been able to fill, to address those.

So to sort of get a state of the science, a position at the beginning of July and importantly, to also lay out the existing knowledge gaps and the emerging research priorities, and what are the critical research questions that need to be addressed by people all over the world as we go forward. It’s clear that research and innovation and science has played a leading role in this pandemic and that the public more than ever has been closely following the science and this has had its advantages. And it’s also some downsides because the way science usually progresses is by scientists putting forward their findings and those being peer reviewed by their peers and then getting accepted for publication.

And then these findings are sometimes questioned by future publications that come out and then eventually there’s a consensus that forms around a particular question. Now, in this case, everything is accelerated and moving really fast and we’ve seen a huge explosion of scientific publications and knowledge. A lot of it is in the pre-publication or in the pre-print stage. And we see, because we review this on a daily basis, 500, sometimes up to a thousand publications on a daily basis. So it’s also very challenging to keep up with the science, but also being able to judge the quality of the products that are coming out, not all out of the same high quality.

We’ve seen incredible willingness for scientists to collaborate. So from the time that we started the research and innovation working groups, we’ve seen people collaborating on all aspects, and I’d like to say particularly something around therapeutics and vaccines a little bit more than that. We’ve also had the research funders involved from the very beginning through the network that’s called GLOPID-R, which is a consortium of research funders that are focused on infectious diseases research. And they will present at our February conference and they were also present yesterday and today and they shared what they are doing in terms of funding research into these priority questions.

So it’s really important that we’ve had them. We’ve also had the private sector participate. We’ve had developers and manufacturers of vaccines and therapeutics and other new technologies. We’ve had social sciences represented with a working group on social and behavioral sciences, and as well as an ethics working group, which has been an extremely vibrant and productive working group that has come up with papers on ethical aspects of this pandemic ranging from the ethics of doing different kinds of clinical trials, including human challenge studies, but also talking about the ethics of contact tracing using apps, for example, or the ethics of a fair allocation of scarce resources.

So a lot of the difficult topics that we come across in our day to day work have been addressed by this working group. We’ve had almost 1,300 participants. So this has been much more successful than in-person or a face to face conference because I’m sure we would not have been able to get 1,300 people into this room. It only accommodates a couple of hundred, so there’s been incredible participation. And as we’re all getting used to these virtual conferences, we realized how much we can actually achieve. So we’ve had chairpersons and panelists and participants waking up at early hours of the morning and staying up late in the night to participate, and I must say the technology worked well.

It’s been very smooth. We were able to stick with time. We were able to go through all the presentations as well as take questions and having the chat function on Zoom was also very helpful because we could also all follow the questions and comments that participants were making. So of the 1,300 participants, they came from 93 countries from all the WHO regions. So if I can give you the number of percentage of participants by region, 29% came from the European region, 20% from Southeast Asia region, 21% from the Western Pacific region, 8% from the African region, 20% from the Americas and 3% from the Eastern Mediterranean region.

We also had a very wide spectrum of people participating. We found the gender balance was excellent, 46% female and 54% men. And about 50% of the registrants were either from academia or representing member states, intergovernmental organizations. We had non state actors, 11% of participants from the private sector, about 3% from the UN. We had national committees, observer member states. So we had a number of, a huge spectrum, as I said, almost a hundred countries participating. So, that was also very gratifying. Some of the issues that that came up, of course, were the fact that we’ve learned a lot, but we’ve still a lot to learn about this virus.

And as I mentioned, we have a number of working groups that are looking into more detail, and we have the experts here, the WHO focal points who can answer your questions. There’s an area of work around clinical characterization, pathways and management, and how do we improve clinical care and reduce mortality amongst people who develop this infection. There’s another working group, a very vibrant one, active one on epidemiology. And this has been one of the most hotly discussed and debated topics about how does this spread. How does this virus spread?

What are the modes of transmission? What precautions do people need to take? What are the public health measures that are working or not working? So that whole area of epidemiology and transmission, then we have the animal and environmental research on where did the virus originate from, how is it spreading, the viral diversity itself based on the huge amount of data we have on the genetic sequences of these viruses. The management at the human animal interface. We’ve also learned a lot about which animals seem to be susceptible to this virus, in other words, getting it from humans.

But we still have to get to the bottom of how it actually crossed the animal human barrier when that happened. And that’s important because we want to prevent further spillovers and further pandemics from rising, so it’s important to understand that. Then about the virus itself, as I mentioned, the natural history, the transmission, and very importantly, diagnostics. We have the molecular diagnostics, you have the antibody tests, antigen tests, you have other new technologies for detection of and what we really would like to see is a very good point of care test, a sensitive and specific point of care test that would make life a lot easier for the healthcare workers, as well as for patients.

Then infection prevention and control. What have we learned about how to protect healthcare workers in healthcare settings, but also how does a public, how do people protect themselves in other settings? So there was a lot of discussion about that. Then, as I mentioned, we had a lot of discussion on ethics and where the ethics working group has contributed and how they could contribute further. Social sciences, I must say it was very welcomed to see a huge amount of discussion on why it’s important to focus on social and behavioral research.

Because a lot of what we’re talking about involves behavior change and why it’s also important to involve communities and get their views on vaccines and therapeutics and the new technologies that are being developed. And finally, we had two longer sessions on the first day focusing on therapeutics. Where are we with the repurposed drugs that were put into trials a few months ago? What have we learned from the ongoing trials? And I must say that I was very grateful to all the researchers who share data with us for us to do pooled analysis, to know where we are, so this can inform better patient management.

And then we had discussions on what next, what are the therapeutic agents that should now go into trials, whether they’re antiviral agents or immuno modulators or antithrombotics, or the new monoclonal antibodies. And then today we had a fairly long and excellent session on vaccines starting with the vaccine trial designs. And again, 15 of the 17 developers who are currently in human clinical trials shared their vaccine design protocols with us. So we were able to compare and contrast and make a presentation on the kinds of trial designs that are being considered by different promote sponsors or developers of vaccine trials.

And we also then discussed in a panel, the various initiatives that are ongoing and how best we could come together in terms of researchers, funders, sponsors, and developers of vaccines to conduct speedy trials, but with the scientific rigor that would be needed to establish both efficacy and safety beyond doubt. And there was a very good discussion on how focusing on the science of what kinds of trials would need to be done and what we need to avoid, what are the pitfalls that we must be aware of where we could actually trip up if we do things in the wrong way.

And there was a discussion on how can we use existing networks. One thing that did come out was the fact that a lot of the research seems to be happening in the high income countries, at least from the data that we have from the GLOPID-R network of funded research and that we definitely need to have more research addressing questions in low and middle income countries, but also involving researchers and institutions from low and middle income countries. And therefore a lot of the networks spoke about the capacity that they have and the interest that they have to collaborate, and so that’s something we will be focusing on.

And the other message that came was to improve the interdisciplinary science work. So while each of the working groups has been focusing on their areas of work, perhaps there’s a need to also have these dialogues between the different working groups and have more interdisciplinary exchanges. So the biomedical group, which is looking at clinical care and management speaking with the social sciences group, the vaccine trials that are being planned definitely need to engage civil society, community advisory boards and things like that.

And then to focus more on the needs of low and middle income countries because the pandemic obviously affected Europe and North America, and now it’s spreading through the world and is more and more impacting countries with less resources, bigger populations. And therefore, the priorities are also changing as time is going on. So I will stop there with those opening remarks to say that it was an incredible two days. I don’t think anybody left their seats. It was four hours on each of the two days, yesterday, and today. We’ve just come out of the meeting, so everything is fresh and we’ll be happy to take your questions.

And as I said, we have the experts here who could address some of the more specific questions that you have. Thanks. Over to you, Fadéla.

Thank you, Soumya. Just, I would like to remind our journalists to click on the raise hand. This will put you into the queue for questions, and please don’t forget to unmute yourself when you are called or to ask a question and finally indicate to which expert you are addressing your questions. I can see that Jamie Keaton from Associated Press would like-

I can see that Jamey Keaton from Associated Press would like to ask a question. Jamey, can you hear me? Jamie?

Jamey Keaton: (18:10)
Yes I can Fidela thank you.

Thank you.

Jamey Keaton: (18:13)
This is for Dr. Swaminathan. Thank you very much for taking my question. We’ve seen the United States two days ago, announced an arrangement with Gilead Sciences about being able to obtain supplies of Remdesivir particularly the equivalent of a hundred percent of production for the month of July if I recall correctly and 90% of production for the months of August and September. I’m just wondering yesterday, doctor, DG Tedros mentioned that solidarity remains to be the buzzword for for countries. How concerned are you that solidarity may be lacking in some cases, particularly with regard to Remdesivir? And what do you know about the stocks that may be needed in other countries that are developing countries that may need it? Thank you so much.

Thank you Jamey. And I reiterate I think what Dr. Tedros has been repeatedly saying that global solidarity is important and not just for this drug, but also for other drugs and for vaccines that are likely to be developed over the coming months. This is a test I think for all of humanity, but specifically on Remdesivir as you know there are many trials still ongoing on Remdesivir including The Solidarity Trial that’s looking at mortality benefit. What we know up to now is from the publications that came out of China that did not show any benefit for Remdesivir and the publication from the NIH which showed a reduction in hospitalization of about 30%. So patients who got Remdesivir had an average hospitalization of 11 days versus 15 days for the ones who did not receive it.

We know Remdesivir is an antiviral drug but we don’t know what its efficacy is. The plan is really to continue with the clinical trials that are ongoing because we definitely need to answer the questions on efficacy of Remdesivir, looking at mortality, looking at other clinical outcomes, but also establishing the impact that it would have on public health. Because the benefit risk and the cost benefit ratio of interventions is extremely important when we talk about an intervention that’s going to be rolled out across the world. So in the coming weeks I think we’ll be in a position to come to sort of a meta analysis of the ongoing trial data from published and ongoing studies, to make an assessment of its impact on mortality as well as on other clinical outcomes. We know that Gilead has licensed this drug to several generic manufacturers so I imagine that in the coming weeks and months we will see an increasing supply of Remdesivir being made available.

But I think it’s really important to reiterate again the importance of establishing the benefits of using a particular drug through clinical trials and this was one of the points that came out very clearly from our Therapeutics panel. There were many repurposed drugs that were put into trials at the beginning of this pandemic based on some in-vitro data or based on some small anecdotal clinical data. And many of those questions today have been answered thanks to the large trials that have been performed. So again going forward they’re going to be other antivirals tested. They will be other drugs tested. We need to ensure the same robust trials are performed to answer the questions. Thanks.

Dr. Maria: (22:09)
I’d just like to supplement not about the Remdesivir but about solidarity and the question of solidarity. This press conference today is about the findings and the completion of the second large research forum that we’ve had from COVID-19. And those of us that are sitting up here are representing literally thousands of scientists across the world and the solidarity and the unity and the collaboration that we have seen for science and the advancement of science in this virus that we knew nothing about six months ago is really incredible. It’s tremendous. And as Soumya has said, the accumulation of data and knowledge and papers and teleconferences that we have had to try to coordinate this research from willing researchers all over the world in so many different topics to help advance our understanding of severity of transmission, of interventions that depend on medical interventions, public health interventions that are helping us suppress transmission and save lives is outstanding.

Dr. Maria: (23:18)
And I think all of us here really are honored and grateful to be part of a time where people have come together to advance this at an incredible rate.

Thank you Maria. Next question is from John Zarocostas. John, [inaudible 00:05:39]. Go ahead John.

John Zarocostas: (23:48)
Yes. Good afternoon. Can you hear me?

Yes. Perfectly. Go ahead, John.

John Zarocostas: (23:53)
Yes. I would like to get a bit of a read out on the presentation by the 15 of the 17 vaccine manufacturers. What was the take away from that? How close are you to getting that short priority list where the money can be allocated going forward? Did you walk away with a short list from this meeting or not? And secondly, why was this meeting also closed behind closed doors like the one in February when there’s such big interest by the scientific world?

I’ll just start and Ana Maria can add on the vaccine trials. So it wasn’t a closed meeting John. It was open, but it was not open to the media. We had an upper limit of a thousand and we really wanted the academics and researchers and others to really engage. So in fact, while the first conference brought together about 400 people, as I said this one brought about 1300 and probably much more were observing. And the idea was not to have a closed meeting or anything like that but just focusing on the scientific topics that were discussed and we had a very tight schedule as you can imagine. We have nine working groups so literally had 10 minutes for presentation and about five minutes for discussion. So we couldn’t have the kind of discussion and we thought that this might be a better forum.

On the vaccines I’m going to ask Ana Maria to comment on what the analysis was. This was not a forum to make decisions on funding or anything like that. It was more a forum to discuss, what are the kinds of designs that are out there and how can we best inform those designs so we get the kind of results that would be needed both by regulators and by WHO to make decisions on the use of vaccines? Ana Maria, you want to say a little bit about-

Dr. Ana Maria : (25:52)
Yes. Thank you Soumya. So I just want to clarify WHO has published in our website, the target profile for vaccines that provides the public health perspective of the kinds of vaccines that will be important for public health. It was developed through a wide consultation with experts around the world. In addition to that, we have published the criteria for the selection of candidate vaccines that could be prioritized for clinical trials. The 17 vaccines we were talking about today are the 17 vaccines who are already in clinical phase. It means they are in phase one, phase two, or phase three trials. What was requested from the developers and we are very grateful to them, was to share openly the design of the trials, the phase three trials that they plan to implement.

It was an excellent exercise of transparency and communication because it would allow all of us to contrast the different designs, to look at the trade off of different designs and to have a conversation about what can be done to ensure that we indeed have the best clinical trials. That we have compatible exercise of speed and robust designs so we come out with robust estimates. So the main takeoff from this is that overall all the researchers were proposing randomized clinical trials. That’s a very good thing. The number two is all the researchers were targeting the critical populations and thinking of end points that are compatible with the public health needs. And third, there was an open and robust discussion about the need of having a stringent success criteria that will allow not only to have robust estimates, but will help regulate some public health officials make informed decisions on the deployment of these vaccines.

So we just want to say thanks to the developers, thanks to the researchers who participated because now we have a transparent process of what is in front of us in terms of assessment of this candidate vaccines. But these 17 are going to be joined by other vaccines as they move into the clinical evaluation phase. So 17 are the ones today but probably next week and in the weeks to come, this number will increase. Thank you.

Thank you Ana Maria. Next question is from Christian [inaudible 00:10:15]. Christian, can you hear me? Christian is from DPA.

Christian: (28:23)
[inaudible 00:28:23] much. DPA German Press Agency. I would just like to follow exactly on what Ana Maria just said. Can you give us some more specifics on the vaccines that are on the table now? Are there are several promising candidates? Are there not? Do you expect rapid progress? I think in your last briefing Dr. Soumya you said, if we are lucky we might have a several million doses ready by the end of this year. Is this timeline still valid or did you get new information that might have changed it? Thank you very much.

Thank you for the question. So I just want to say that we are very lucky in a sense because there is a very broad pipeline of vaccines. We have four types of different types of vaccines. We have virus vaccines using live attenuated virus that are commonly used also as platform for vaccines we use today. We have viral vector vaccines which use replicating or those that use non-replicating vectors. We have modern platforms, nucleic acid vaccines, DNA and RNA vaccines, and we have protein vaccines using protein subunits and virus-like particle vaccines.

As I said an increased number of these vaccines are moving forward from phase one into phase two, 17 of them. Of those who are in the clinical phase, we have one candidate vaccine from the University of Oxford, the ChAdOx1 that you have commented a lot in the media that is moving into phase three. But we have other five vaccines that are now into phase two. We don’t know if the race is what pays until we get the results of these clinical trials. So we are very encouraged by the progression of this candidate vaccines across the clinical phase evaluation and we are looking forward to have the results. Whether or not we will have the vaccine in a given timeline depends on factors that cannot be anticipated. What is good is that there is a lot of consensus, a lot of work together, a lot of collaboration. As Soumya mentioned, there is a number of global enterprises and collaborative efforts to accelerate the evaluation of these vaccines and moreover the availability.

So for now on, the pipeline continues to be a healthy pipeline. We have nearly 150 candidate vaccines moving forward with evaluation and every day gives us more hope, but we will not know when we will have the vaccine until we have the results on efficacy.

Thank you Ana Maria. We will move now to Jim, Jim Roope from a radio in the US. Jim, can you hear me?

Jim Roope: (31:30)
Yes. Thank you very much and hello everyone. Thank you so much for making yourselves available. I have so many questions but I guess you’re-

Just start by one please.

Jim Roope: (31:43)
I promise. I know you’re getting to the vaccines and you’ll get to the therapeutics. I guess my question is, what exactly is the state of the science now? What is known about the virus that wasn’t known before? Are there things that you thought you knew that you know better now or that were discounted? Where are you in knowing exactly how this thing behaves and what we can look forward to in the future?

Good and interesting question. Maria?

Dr. Maria: (32:12)
Sure. So Jim, nice to hear your voice and a good question as always. Probably one of the most interesting and difficult ones to answer succinctly because I think every single person up here could give you an answer about what we know now versus what we didn’t know before. As I’ve mentioned previously, the acceleration of the science around SARS-CoV-2, the virus that causes COVID-19 disease is really incredible. So my area as it relates to the R&D blueprint, in the R&D forum is around transmission, around severity, which of course overlinks with several different pillars and around the evaluation of the impacts of interventions. And I could probably speak for an hour on each and I won’t. For another time Jim. But one of the most interesting areas right now that I think is really critical for us to understand besides transmission and severity is around the evaluation of interventions.

Dr. Maria: (33:14)
As we wait for therapeutics and for vaccines which are advancing at an incredible rate, we have tools right now that can break chains of transmission and can save lives. And so through different groups, through our mathematical modeling network, and through the collaborations we have with academics and our member states is to really do much deeper dives into understanding the use and implementation of different interventions. When were these interventions used? How were they used? The combinations in which they were used as they were implemented, but also as they were lifted. Because we all know that we have a long way to go with this pandemic and in many countries which are seeing success and suppressing transmission, others are really dealing with overwhelming outbreaks at the current time. And so as countries are lifting some of these so-called lockdown measures, we need a better understanding and more detailed analysis about how countries are actually lifting those, in what way they are doing this, just as they introduce them, how they lift them as just as important.

Dr. Maria: (34:23)
And so we will be working very closely with member states in doing much more deeper analysis about the use of these interventions so that when we think about going forward in this pandemic and when we do see resurgence in some areas, we can have better advice and use the experience of other countries about how we could use interventions hopefully not needing to do these widespread lockdowns as we go forward, because it isn’t a matter of public health versus the economics or social impacts, we have to find a balance between both of them as we move forward. But others may want to supplement.

Janet Diaz, Clinical Care.

Dr. Janet Diaz: (35:08)
Hello there. So thank you. Gosh, what have we learned? I think what we have confirmed that over time that severity of disease seems to be standing with what we initially saw in China, which means about 20% of patients. So a subgroup of patients are developing severe disease and a smaller subgroup developing critical disease. So I think that’s what we have learned and confirmed over time and seeing that same type of breakdown in different countries. We have also seen that we have learned with the recent release of The RECOVERY Trial, that corticosteroids seems to be reducing mortality. And so why is that? So what is the mechanism for that? So I think that’s something we still need to figure out more and understand more. But it does lead to the hypothesis that-

And understand more, but it does lead to the hypothesis that some virus-induced inflammatory state that is suppressed, that happens in a subgroup of patients, that we need to better understand with the treatment of … That leads to hypoxia, leads to needing oxygen, needs to potentially needing ventilation with the use of corticosteroids. That is a suppressed, and potentially reducing mortality. So that’s something. And over time, people were describing an inflammatory response to the virus. And I think we still need to further understand that what biomarkers are elevated and correlating with severity of disease, to help us identify these patients earlier so we can apply treatments earlier. I think that’s important.

What else have we learned? Oxygen therapy? And I guess we go back to the basics. Until we have other known therapeutics that will treat the virus, we do know supportive care. So identifying patients early, those that are with complications, those that have hypoxemia, that need oxygen. To that, the early interventions with oxygen therapy can be lifesaving. And that for countries that have limited capacity with oxygen, have resource limitations, that really surging oxygen systems is important. And making sure that the staff is trained in how to deliver oxygen, how to maintain oxygen supplies, and how to surge oxygen supplies is also critically important. So thank you.

I think we have also Dr. Benedetta Allegranzi. She is Technical Lead infection prevention and control, who wants to say a few words. Benedetta.

Dr. Benedetta Allegranzi: (37:49)
Thank you. One of the major concerns of the international community in this outbreak has been health workers’ infections. And I think that now, following reports and studies, we know that personal protective equipment, in particular medical masks, respirators, eye protection, gowns, gloves, do protect health workers, if appropriately used. Also, we have learned and confirmed that appropriate hand hygiene protects healthcare workers. Conversely, also we have now evidence that shortages and inadequate practices, for instance, for hand hygiene, do put health workers at risk. And so I think that this is clearly a call to all those invested in this outbreak, in particular governments, but also the international community, to really continue to take care of personal protective equipment procurement. In the context of access equity among countries around the world. So this is a first message that is really key. The attention about this problem should not decrease.

Dr. Benedetta Allegranzi: (39:20)
The second point we worked on from WHO with institutions, academic institutions, was to find out what is the best way to make masks, fabric masks, for the population, the community, to protect them. And we achieved very interesting results in terms of knowing the type of materials, the number of layers to be used, the shape, the level of protection, or especially the level of filtration, allowing source control that is needed. And that is available using specific materials. So all of this can be found indeed in WHO guidance that has been informed by this research. And we have a recent document on masks, in particular with focus on the general public. So these are some key messages that have emerged from research, and from the discussions during this meeting.

I think I’d like to mention one other area, [Afanella 00:40:36], and that’s the area of genetic sequence data that we’ve got. I think this is probably the first time that we’ve seen all countries, almost all countries, willing to share the genetic sequence data of this virus in a public database. Through GISAID, through GenBank, we have over 60,000 sequences currently shared. And this has allowed scientists to do a couple of things. Most importantly, it’s allowed epidemiological tracking of how … Because there are different clades, because of the natural mutations that occur in the virus, they’ve been divided into different clades. And by looking at the proportion of these clades in different parts of the world at different times, you can actually try to put together a story of how this virus moved around the world. And where it came from, where the outbreaks actually originated from.

So that’s quite useful to understand. And also to try and go back to see when the first few cases may have been introduced in a particular geographic area. But also it helps us to track the mutations itself. We know that there are certain parts of the virus, which are more critical, like the spike protein and the receptor-binding domain that are also the targets for vaccines today. So if major mutations occurred in those domains, it might actually affect the development of vaccines. Similarly, there have been hypotheses by people from different countries, seeing a particular mutation corresponds with a particular clinical profile, less severe, more severe disease. So it allows us to study. And so this kind of pooling of data, both clinical data, as well as sequenced data. And if the two could be combined, then it gives a very powerful database to actually see if actual specific changes in the viral genome mutations actually have impact or not on clinical outcomes.

And this is only possible when you have large data, it’s not possible with a few tens or a few hundreds of cases. So that’s, again, I think for the first time we’ve seen. And this is a very good model, I think, for future. For the world to think about future pandemics or diseases which can cause potentially epidemics or pandemics. And having a mechanism for global sharing of genetic sequence data gives you an opportunity. In fact, the genetic sequence data was made available by Chinese scientists on January the 11th. On January the 13th, I think, we had the first diagnostic essay that was published. WHO working with a lab in Germany published the first. And that allowed countries to get diagnostics up and running.

And similarly, the first vaccine candidates were also being made in January based on the sequence data. Because as you know now, sequence data allows you to do a lot of things. So the RNA and DNA vaccines were all being prepared in the lab within a matter of days of getting the sequence data. So it just shows how powerful this is, and how essential this is, and why the world needs to think about some of these mechanisms, and how to support mechanisms. Platforms like for GISAID, for example. To make it easy for scientists to share this. Because GISAID was set up for influenza data sharing, but very quickly they were able to expand to accommodate the SARS-CoV-2 virus. Thanks.

Thank you, Soumya. Now we will move to Nina Larson from Agence France-Presse. Nina, can you hear us?

Nina Larson: (44:24)
Yes, hi. Can you hear me?

Yes. Perfectly. Go ahead.

Nina Larson: (44:29)
Okay. Thank you for taking my question. So related to what was just being said, I was also wondering if there was any discussion about the studies of wastewater that have shown indications that the virus may have been present in European countries, for instance, last year. If that was something that was discussed. And I also was wondering on the issue of asymptomatic transmission, if there was a discussion about what seems to be, perhaps the case, that when you have asymptomatic people, that if they transmit to someone, they are themselves asymptomatic. If there’s anything to do with that. Thank you very much.

Maria will take this question.

Dr. Maria: (45:24)
Thank you. Thank you very much. So yes, there were really rich discussions about transmission in general. About how the virus can be transmitted, the different modes of transmission, when people transmit the virus, whether when they have symptoms or when they don’t. And then the context in which transmission occurs. So your question specifically about asymptomatic transmission, yes. People who are infected with the SARS-CoV virus, many of them develop symptoms, but some do not. And when someone does not develop symptoms, we call them asymptomatic. Meaning that they don’t have those symptoms. And some people can transmit. We’ve known since February that individuals can be infected, not have symptoms, and possibly transmit to others. And that has been confirmed through studies. These very detailed investigations that are ongoing.

Dr. Maria: (46:18)
What we’re really trying to understand is the relative importance of when people transmit and how they transmit, and the context in which. What we know is that this virus transmits through respiratory droplets from an infected person, most often when they have symptoms, but it can happen just before they develop symptoms, or right at the time of them developing symptoms. Meaning they’re very, very mild. And it can happen with when people are infected and don’t develop symptoms at all. And so that makes control measures that much more challenging, which is why we make a comprehensive set of measures in place to be able to break chains of transmission. Including making sure we find those cases that we know about, we find all of their contacts, and we quarantine those contacts. And by doing so, you effectively isolate people so they can’t pass the virus to someone else, whether they have symptoms or not.

Dr. Maria: (47:10)
And so what we really need to better understand is how often that is happening. How often does it happen that someone that doesn’t have symptoms, and never has symptoms, transmits further? How important is it that someone, just before they develop symptoms, passes to someone else. And we know that is important. And how does that affect our control measures? The other thing that we spoke quite … We need to spend much more time talking about are these events in which transmission occurs. We know that it happens between close contact with people, when they’re within one meter, prolonged contact. That means more than just in passing. And we’re quite alarmed by a number of super spreading events that are happening in a large number of different types of controlled closed settings.

Dr. Maria: (48:01)
So for example, we’ve seen outbreaks in longterm living facilities. We’ve seen outbreaks in healthcare facilities. We’ve seen some clustering events in mass gatherings. In different types of religious events. In meat processing plants, in expatriate dorms. There’s a number of settings where we need to do much more detailed analysis to really understand why and how transmission is occurring so that we can prevent this from happening going forward.

Dr. Maria: (48:28)
And then just briefly on the wastewater. So, this is an area of interest that we are looking at, and that a number of countries are looking at, to potentially look at testing of wastewater for the SARS-CoV-2 virus. To see if that could be a Sentinel signal for whether or not the virus is circulating. There are some papers that have come out recently, and we are aware of those papers. We’ve actually reached out to a number of those authors to get more details. Some of those are in pre-print, which means they have not gone through peer review. And so we reached out to those authors to really understand how they’ve conducted those studies, and what those can inform us going forward.

Dr. Maria: (49:12)
Benedetta, I don’t know if you want to add anything about, okay.

Okay. Thank you, Maria. We will now move to Kai Kupferschmidt from Science. Kai, can you hear me?

Kai Kupferschmidt: (49:24)
Yes. Thank you very much for taking my question. This one’s probably for Ana Maria. I just wanted to ask whether there’s any news on, first of all, the Lopinavir/Ritonavir arm of The Solidarity Trial, given the results from recovery. And any discussion of how to move forward with, now that recruitment is going well, how to move forward, prioritizing the next drugs to test?

I think Ana Maria will respond. Thank you.

Thank you, Kai. So first on the solidarity trial, we are very pleased with … And we’re very grateful to all the researchers from the 31 countries who have now approvals for participation in The Solidarity Trial. So they have the national regulatory authority approval, and the ethics review approval. Of those, 21 are already randomizing hospitalized COVID patients in nearly 400 hospitals. And we have a global network of about 1,300 clinicians. So we are active in the six tablature regions.

We are very pleased about that because that gives clinicians and researchers from all around the world the opportunity to contribute to The Solidarity Trial. We are also very pleased with the increase in the recruitment rates. So we are now getting to 5,500 patients included in the trial. And unfortunately, we have high rates of transmission. But the good scene, and this was discussed during the forum and encouraged by several of the speakers, is that given that the virus is moving around the planet, and that the rates of transmission are uncertain, it is very important to use global platforms like The Solidarity Trial to be able to evaluate not only therapeutics, but also vaccines. Because that will allow us to have the therapeutics and the clinicians in the places where the incidence rate is high at the time of introduction.

In terms of the results, there were two presentations on the data that is available, because it was important for the community to learn what we have learned from the therapeutics that have been evaluated so far. As you probably know, that are nearly 1,700 clinical trials that are registered. Unfortunately, the majority of these trials never started, they were started and were canceled, or recruited only a few hundred patients. So in total there was an independent review that suggested that the three major trials contributing to the evidence for hydroxychloroquine, lopinavir, retonivir, and the sSteroids, including dexamethasone, were the recovery trial from the U.K., The active trials from the NIH and NID, and The Solidarity Trial led by WHO. Of these, there was a discussion of the preliminary results of these trials that suggest and confirm the hydroxychloroquine, unfortunately, doesn’t have the positive effect that we were hoping on mortality for COVID patients.

There also discussions on the potential effect of lopinavir. And the preliminary data suggest that this effect is not there, but we are looking at the analysis. And then there was the discussions on how to look into the sSteroids. So the recovery trial resources that are publicly available, were again discussed, and WHO put forward a proposition for a full systematic review of the data on remdesivir and on sSteroids. That we will be shortly share with the community because we value, and we think is important for all of us to look at the integrated, critically appraised evidence. Thank you.

Thank you, Ana Maria. I will take now a question from Bayram Altug from Anadolu Agency. Bayram, can you hear me?

Bayram Altug: (53:23)
Yeah. I can hear you. Thank you so much for taking my question.

Yeah. Go ahead.

Can you hear me?

Yes. Perfectly, Bayram. Go ahead, please.

Mr. Ghebreyesus stated that 60% of all cases, so far, have been reported just in the past month. Relating to state data, I don’t know why these cases jump by more than 50,000 for the first time yesterday. On the other hand, while the number of cases increases rapidly across the globe, the mortality rate drops significantly. My question is so-

Mortality rate drops significantly. My question is, can we say that the COVID-19 is losing potency as it spreads more, or what we know or what we don’t know? Thank you.

Thank you, Byron. Maria or Soumya?

I think we have to be very careful when we talk about mortality rates, because it’s calculated in different ways by different countries and at different times. Case fatality rate is, you have the number of people who die divided by the number of people who the diagnosed disease. But you also know that there’s a gap between somebody getting the infection, progressing, and then dying usually two or three weeks later. Unfortunately, that happens, and so it also depends on what denominator you take when you calculate case fatality rate. It’s been suggested by scientists that really to get an accurate idea of case fatality rate, you should divide by the number of cases two weeks ago, not the number of cases today.

There’s also infection fatality rate, and there was some discussion on that during this forum. That probably gives you a better idea of the actual mortality, so the number of people who are infected in the community. Now, this number is not often known, because what you know is who gets tested, and those are only those who get really sick or those who are able to access testing. In places where these seroprevalence studies have been done to look at the prevalence of antibodies in that population, it’s clear that the number of people infected often is about 10 times the number of people who actually get diagnosed as cases, which is what gets counted.

So if you look at infection fatality rates, then that is a much lower number, and the figure that was presented was an average of about 0.6%. So that’s much lower than the case fatality rates of 5, 6, 7% that we’ve been talking about. But, again, this depends. Again, pooling all the data that’s still coming in from studies on the seroprevalence in communities will give us a better idea.

But the bottom line is that there is a significant proportion of people who die. Even if it’s 0. 7 or 1%, that’s still high, and that it disproportionately affects people with certain risks, underlying conditions, including obesity in young people. We have to remember the young people are not immune from severe disease or death. It’s less common than in older people, but we should not become complacent that it’s fine for young people to get infected, because there is a subset, particularly those with obesity, those with habits like smoking, for example, who are at higher risk of complications and death. So I think when we talk about death rates and mortality and we start comparing, it’s really important to really look at how that’s been calculated before we do comparisons.

The other thing we’ve seen is many countries have been able to update their death counts later. So it’s not on a real-time basis. But even in high-income countries and certainly in the lower and middle-income countries, the death reporting is not real time. It takes time to catch up, particularly when people die at home in the rural areas, there’s often incomplete cause of death reporting. So we have to keep all of those things in mind when we talk about case fatality rates, and especially when we start comparing between countries or between regions.

Thanks. You want to add anything, Maria?

Dr. Maria: (57:50)
Thank you, Soumya. That articulated very well, the challenges of estimating and comparing mortality. As you’ve said, they’re very difficult thing to calculate. I wanted to touch upon the question around the potency of the virus and the questions… We’ve received that question quite often, is the virus changing? And you mentioned the mutations, the changes. These are natural changes that we’re seeing in an RNA virus, changes that we expect. And there’s a large group of scientists that are part of this group that are looking at these viruses very, very carefully and looking at what these changes actually mean. We have not seen any indication that the changes, these mutations, these changes, confer any difference in terms of transmissibility and severity, but it is something that we are very carefully watching.

Dr. Maria: (58:43)
Then it’s not just a matter of comparing the sequences themselves, but more work needs to be done to really understand the viruses and what these changes mean, if anything. And so I think that’s just an important thing to add. And then just to mention on the serology, because this is part of the core work that we do within the EPI working group. And again, given we’re six months in, it’s pretty astounding that we have seroepidemiologic studies that are underway. And WHO is working in three different areas with our partners on serology.

Dr. Maria: (59:17)
The first is to evaluate the serologic assays that are currently in development and working with partners at Find and other collaborating centers across the globe to look and see how well do these serologic assays perform against real samples? The second area of work is around what we call the Solidarity II collaboration, which is developing an assayst and having a panel to be able to develop a standardized serologic assay. And we have more than 110 collaborators from 43 countries in this collaboration.

Dr. Maria: (59:52)
The third area of work is what we call our unity studies, which is WHO has drafted these core generic protocols for six different types of studies on healthcare workers or on household studies or on cases and contacts to support countries in conducting serious epidemiologic investigations themselves. Currently, we have 45 countries that are actually implementing these studies right now, and we have an additional 34 that are intending to implement them. And so we’re building research capacities, we’re supporting countries in conducting these so that they could better understand what is the extent of infection for SARS-CoV-2 among certain populations to better inform their next steps as they move through this pandemic.

Fadéla Chaib: (01:00:43)
Thank you, Maria. I think we will take the last two questions, one from [Tomo Degushi 01:00:48] from Kyodo News. Tomo, can you hear me?

Tomo Degushi: (01:00:56)
Yes. Can you hear me, Fadela?

Yes. Perfectly go ahead. A short question on the participants. I believed in February meeting, we had experts or official from Taiwan, but was this the case this time as well? Thanks so much.

Dr. Ana Maria : (01:01:18)
Thank you for this question. As Dr. Swaminathan mentioned, the forum was open to researchers all around the world. We circulated an open registration tool in which experts, regardless of whether or no they were in our list of experts, could register. This is how we have experts from all around the world. And we know that some of the experts participating actually were from Taiwan. Again, Dr. Swaminathan insisted we make a big effort to have experts from all around the world and they could on their own register. It was open to all researchers.

Thank you, Ana Maria. We will take maybe the last question from Helen Branswell. Helen, can you hear me?

Helen Branswell: (01:02:05)
Yes. Thanks very much for taking my question. It’s for Ana Maria, please. Ana Maria, is anybody in phase 3? And if I can sneak in something else in terms of vaccine, did you hear anything that relates to the question of whether or not any of these vaccines are inducing… If there’s any risk of a vaccine-enhanced disease associated with any of these vaccine candidates? Thank you.

Dr. Ana Maria : (01:02:38)
Thank you, Helen. The theoretical risk of enhanced disease has been the object of extensive discussion in our expert groups and also in the expert groups by other collaborators. And indeed, all the protocols that were presented or the majority of them has the potential to evaluate enhanced disease. I just want to explain there are three levels of the evaluation. First, is during the preclinical phase. So there are ongoing efforts to try to establish animal models that will allow us to evaluate enhanced disease in animal models. That has been accepted as a potential way to evaluate, but it’s not sufficient. In addition to that, you have to start by going through the clinical evaluation phase and evaluated in humans. The most important part of the clinical trial is to be able to document enhanced disease, is to have longer term followups. And most of the trials that are being planned include 12, 15 and two-years follow up.

Dr. Ana Maria : (01:03:36)
And in addition, it has been clearly identified that there is the importance of postmarketing surveillance, so safety as an additional element to document enhanced disease. So most of the sponsors or potential sponsors, developers and researchers are fully aware of the importance and majority of them are making provisions in the protocols for the phase [inaudible 01:03:59] trials for longer term follow up, for measures to document information from vaccine use in hospitals, et cetera, so that this can be certain. I insist, it remains a theoretical challenge, a theoretical possibility, but it’s well considered by all.

Thank you, Ana Maria. I think we will stop here for today. It has been a long day for everyone. Thank you for your interest. I don’t know if one of my colleagues want to say final words, if not, we will conclude this press conference. Maybe Soumya, final words.

Dr. Swaminathan: (01:04:43)
Yeah, maybe just as final words. We did also have some discussion on the transmission from human to animals. This may be of interest to some people, and it’s clear that there are some animals like the felines, cats and the ferrets and even tigers, that can get infection. So human to animal, but very little evidence of the reverse. And also interesting data presented on the virus and how long it can survive on the fur of animals and so on. So there’s very little risk from domestic animals because there was some concern about domestic animals becoming a source of infection. However, you would have seen the reports of minks in mink farms, actually getting the infection and even perhaps being able to transmit it to humans. So this is again an active area of research. As I mentioned, the animal-human interface, and it was a robust discussion because of course it’s relevant, not just for this outbreak, but also for the prevention of future pandemics.

And so the whole issue of how does one not only have surveillance for these emerging viruses that can cross the barrier, but also surveillance among different species of animals to see what viruses are circulating? And importantly also, to think about how markets that deal with meat and food need to be regulated, what are the minimum hygiene standards that need to be put in place, and also the illegal trade of wildlife, which can actually aggravate some of these conditions. That whole area of research, the One Health where the group actually has people from FAO and OIE, in addition to scientists from around the world was also one of the areas that was discussed.

Overall, I think we had, as I said, in a limited time covered a huge area of topics, and we’re able to get glimpses into what’s going on in these different areas, but we will probably follow up with more in-depth interactions with the scientists within the working groups and perhaps also between working groups, there’s the interdisciplinary work that was very much encouraged and welcomed by the participants in order to take all these areas of work forward, and we’re happy that WHO has been able to bring together scientists from around the world to collaborate, but also to accelerate, I think, the science.

And our goal is to see that the learnings from science are as quickly as possible channeled into impact for patients and communities. That’s the goal of this research. It’s not an academic exercise. It’s how do you take the learnings, put it into interventions, either in clinical or in public health, so that we start seeing an impact on the pandemic. And that’s why WHO is so involved in this and key to try to make this happen in the best way possible.

Female: (01:08:01)
Thank you very much for all of you for having come and for those excellent questions that you had today.

Thank you for your attendance, journalist as well as our colleagues from WHO. As usual, we will be sending you the full audio file and the transcript will be available as of tomorrow on the WHO website. So see you next time and have a nice evening. Thank you. Bye.

World Health Organization (WHO) Media Briefing on Global COVID-19 R&D Forum July 2

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