18th April 2020 Webcast
Fighting Global COVID-19 Together: Clinical Experience Sharing and Discussion

The content is intended for HealthCare Professionals for medical educational purposes only. The content is from a webcast that was initiated, organised and funded by AstraZeneca and was broadcasted on 18 April 2020. Expert opinion of the participating physicians are based on their experience to date managing COVID-19 in their respective home countries. Some therapies and product classes may not be available in your country. AstraZeneca is not responsible for, and may not necessarily agree with the views and opinions expressed by the participating physicians, and does not recommend any treatment or course of action. Please note the date and time of the webcast recording and seek local governmental advice for latest advice on diagnosis and treatment”.

Mr. Pascal Soriot
AstraZeneca CEO

How a pharmaceutical company can support the fight against COVID-19

How Pharmaceutical companies can support the fight against global COVID-19

Pascal Soriot:: [00:00:00] Thank you, Prof. Hui, Prof. Zhong and to all of you for the opportunity to speak with you today, but most importantly, for everything you're doing to fight COVID-19. The work you're doing today really showing your experience is critical to the global effort to defeat this pandemic. In difficult times, the whole world should actually come together, and it's really energizing to see the Health Care Community take the lead and collaborate with each other. We are really grateful for all the experts, like all of you, willing to invest their time sharing their knowledge today.

[00:00:40] The pharmaceutical industry worldwide has also stepped up to contribute in many different ways, and it really has been a team effort. We've seen companies work together without worrying about who owns what and the information has been shared for everybody to use. If I speak about  AstraZeneca and how we stepped up ourselves, first of all, let me address what we've done as a contribution to the efforts of what I would call the heroes of today, the healthcare care workers around the world, who take care of patients.

[00:01:12] First of all, we bought 9 million masks very early in the epidemic, and we donated them to health care providers around the world. We've done that working with the World Economic Forum  (WEF), the World Health Organization (WHO)  of course, governments and yeah, high in the U.S to decide where the masks should go because we didn't know where the needs were. The great majority of those masks have been now distributed.

[00:01:35] The second thing is that many of our employees, medics, or nurses and other people would actually have volunteered their time. And our teams are supporting local communities who [inaudible] many of our doctors work in hospitals and we've put in place a program to allow them to do this, and of course, continue to be paid by the company.

[00:01:54] Our teams have done many different things for instance, in the UK, our organization has come up with the idea of refurbishing iPads and iPhones that we have donated to the NHS to enable people in hospitals to connect with their loved the ones that cannot visit. That is, as you know, better than I do an issue for patients who sometimes die without seeing their families.

[00:02:18] Another example of what our people have done in those [inaudible]. I have many other examples, an AZ employee in the U.S has developed a headband to help healthcare workers wear their masks, day after day without hurting their ears. We've had lots of great ideas coming up from the bottom up, from grassroots.

[00:02:39] We are also working hard trying to decrease the pressure on hospitals. You know very well, better than me, that health care systems are stretched. And in many countries, we have partnered with technology companies and hospitals to develop digital tools that facilitate remote follow-up of patients who have chronic conditions such as asthma.

[00:02:59] We've have advocated with governments for the temporary reimbursement of home injections of some products. For instance, in the U.S., you may know Medicare is now reimbursing the use of home administration of the so-called Part B products that are injectable products.

[00:03:14] Finally, we also shared our knowledge with health authorities for instance in the UK and Sweden. We've been collaborating with the health authorities in the development and implementation of an antigen testing and now we are working on that antibody testing. In the UK, in particular, we've been collaborating with GSK and The University of Cambridge to set up a testing center in Cambridge, actually, that just started operating and we aim to deliver 30,000 tests a day by early May.

[00:03:45] Well, this has been a really collaborative effort that was put together in about three days with GSK and The University of Cambridge and nobody's thinking about who was in charge of what the team really got together very quickly and we will deliver these 30,000 tests a day by early May. We are very much on time, and of course, we are donating the resources involved in this effort.

[00:04:08] Let me now turn to what - beyond donations - what we've done internally as a company. First of all, as you can imagine our absolute priority has been to maintain the supply of our medicines. We know very well that patients who suffer from an underlying condition such as Asthma, Hypertension, and Diabetes are more exposed. So we manufacture our products for the treatment of Asthma, COPD, Hypertension, Diabetes, Cancer, and many other chronic conditions. This really has been a key priority for us, to ensure that our supply chains are not disrupted so patients can continue to receive their therapies.

[00:04:45] It may sound easy, but I can tell you it has been quite challenging because we have hundreds of our employees who had to be quarantined because they felt unwell went home and could not come back because our policy, based on CDC recommendations, was to stay home for two weeks. We got to a stage where we had 112 employees unable to come back to work in our factories, and we didn't have the tools to test them and so we didn't know whether they were infected or not. But our employees have really done an absolutely remarkable job and we've had no shortages. We were even able to supply the surge of demand for Asthma and COPD inhalers that we've experienced in many countries.

[00:05:27] What we've also done is we've supported our employees by protecting them. We use masks in our plants, not only in the GMP side of the plants but everything around the plants. When people are working there, they have to wear a mask now. We, of course, have made hand sanitizer and we have to manufacture them ourselves because they're on shortage. We are practicing social distancing as you can imagine and we're asking our office staff to work from home.

[00:05:56] We implemented childcare support for our employees who had their children at home in many countries where schools have been closed. As you know very well for hospital it's an issue but for companies, it's also an issue, people struggle with having to manage their job and also their kids who are at home. We offered childcare support. We even offered, in some countries, homeschooling for the children of our employees. We've rolled out additional video conferencing tools around the company to enable our people to work at full capacity.

[00:06:29] Finally, we developed our own antigen testing that has started working and we are offering this service to our employees at our main sites with, of course, the priority given to manufacturing sites, so we can now offer people the ability to test themselves to know whether they are infected or not when they have a doubt.

[00:06:50] Another important priority, of course, has been to think about the COVID negative patients. Everybody is so focused on COVID positive and new doctors in hospitals I'm sure you know better than me that COVID positive patients are the potential next health issue. And for us, developing medicines, new medicines, for severe diseases, our key priority has been to keep our projects going and our products, our new indications for our new products developed and approved. Of course, we've had to stop or pause a number of trials around the world, but we've tried to keep going with trials in countries where the epidemic was less impacting.

[00:07:34] Finally, I'd like to say a few words but we have also done addressing the disease itself and working on the disease and what we could do. The way we've looked at it has been kind of threefold if you want. Our view has been, that we need to deal with the virus. We also need to deal with the immune response that is [inaudible] killing patients in some cases. Finally, we thought, can we protect the organs during the course of the treatment.

[00:08:06] We are working on a monoclonal antibody. We have very talented antibody engineers and they're working on a long-acting antibody that actually can be used for prophylaxis but also treatment and we hope to have this in the clinic by the summer.

[00:08:37] For the immune response we have launched a randomized study using a BTK inhibitor. As you probably know, the BTK pathway is very upstream from this inflammatory cascade, and actually, we believe turning off this main switch will downregulate the production of many cytokines and chemokines. Not only IL-6, which everybody is focused on, but also IL-1, IL-7, and many others.

[00:09:13] Finally, in the hope of protecting kidneys and heart, we are using SGLT-2 inhibitor. We just launched a phase three randomized study in the U.S to explore the potential organ protection that this antigen could offer  COVID-19 patients.

[00:09:49] This is really the extent of what we've done and I have said it many times to our teams at AZ, they're really, truly, putting a heroic effort. Maintaining, keeping the company going, but also investing a lot of time and effort in fighting COVID and coming up with potentially new solutions.

[00:10:06] I find that the title of today's session is very appropriate and I have no doubt that we will soon come out of the darkness. And I can see plenty of light already, not least with how we are united to respond, but also there's a lifting of restrictions in Wuhan and many countries in Asia, but also, progressively, in Europe today.

[00:10:27] With your collective efforts, and your input, and your great experience, I'm sure we can accelerate the fight against COVID. Again today, I would like to thank you very much for your time and I look forward to a very stimulating session.

Academician Nanshan Zhong Guangzhou , China

Scientific update on the China COVID-19 situation

Prof. Nanshan Zhong:: [00:00:00] Okay. I just have to make two points because of the time limitations. First of all, I think the follow up too from the States and UK, we talk about how they are going to deal with the COVID-19 infection. That's why I would like to mention very briefly about the strategy in controlling further spreading in China.

[00:00:36] This is the picture coming from the UK, how control measures may reduce the spread of the virus in the UK as we relate the new cases overtime here. So no action, everybody knows will be an outbreak. When out of the control of the National Health System Capacity. Somebody else should take some control to reduce the spread so the include self-isolating curfew, so social distancing of vulnerable and whole household as a result if one member is ill. I suppose this kind of policy may not include close contact. That's a big problem China is facing.

[00:01:27] One of the policies is Suppression. Another one, Mitigation. I think the suppression takes a very strong action towards the pandemic. But of course, in the other way, it will make a great impact on the economy. The other way the mitigation, just make a delay of the outbreak, but because of the high reproductive ratio that may not work. So what China had been doing.

[00:02:00] I think, just very briefly, I'm going to mention four measures. So note down, Wuhan, because at that time, at the end of January, only Wuhan had an outbreak and not other places. And then the more transparent, real-time announcement of the number of diagnosed patients every day in each city. And that the most important is the so-called Inter-agency Mechanism. They launched the early self-protection and early detection, early diagnosis going just to the large hospital rather than getting final approval by the CDC and early isolation. That action is down to the community and also PCR has a check-up in all close contacts including those without symptoms.

[00:02:55] This is something that happened that day on that day in Wuhan. The point is very briefly saying - the newly diagnosed cases increased since the 23rd of January increase. So two weeks reaching the peak, some more than 3000 per day, and then going down, going down. Then after another two weeks going through the formal level and this is the situation in China. So it only took one month. This is the curve of that. I think some outside China, I think the majority of the country, they have taken some action as early as February, but the majority of the countries take a little bit stronger action in the beginning of March, but I think it's not strong enough. So that's why after one month, the inclusionary [inaudible] still going up.

[00:04:05] Maybe I'm wrong, but the curve or something like that - and early beginning, I mean, Wuhan has lost control in a very short time. And then when it's being obstructed. So for more than 50,000 medical staff going from different parts of China, and then support Wuhan. And the situations quickly could be in control. I think at the moment in Europe, as well in the United States, I think at the moment, at this stage, I suppose if we lose the role I suppose maybe we'll have a further curve because the number is still increasing, so that's something worrying me. I hope in Europe, we're going to the plateau and then going down in the next one or two weeks. I don't know what will be happening in the USA it is what I suppose.

[00:05:09] The next point I would like to mention about the asymptomatic COVID-19 infected patients. Whether they, how many patients there, and then whether they [silence] in China?

[00:05:30] First of all, I would like to mention the so-called [inaudible] definition of asymptomatics with COVID-19 infection. Of course, the first is the presymptomatic patients, they are in the incubation period.

[00:05:45] The second, asymptomatic with COVID-19 infected, in other words, PCR, but just asymptomatic.[00:05:54] The third maybe patient with very mild symptoms being neglected by the patient themselves. That's [inaudible].

[00:06:05] Fourth, no symptoms at all. When you are following up... [silence]

[00:06:18] Dr. Christopher Hui::

[00:06:18] Hello, Prof. Zhong...

[00:06:19] Prof. Nanshan Zhong::

[00:06:19] Sorry. Can you hear me?

[00:06:23] Dr. Christopher Hui::

[00:06:23] Yes, we can, we can.

[00:06:25] Prof. Nanshan Zhong::

[00:06:25] Okay, okay, okay.

[00:06:26] So this patient should be diagnosed as having COVID-19 infection. We have seen very few patients with long time of positive PCR and the serum antibody always show negative, both IgM and IgG. Maybe we will call this patient with the so-called virus career or something like that. So remains to be solved. So that the transmission is as you know [crosstalk]. As you know, the presymptomatic [inaudible] to this transmission is not infected, and then symptomatic are infected. So how about this kind? Asymptomatic patient. So transmission of virus from a person who does not develop symptoms that remains to be discussed.

[00:07:19] As you know, we have some data showing the incubation period of the patients. So for our data, when 1099 patient beginning the medium incubation time is 4 days, we have found 13 cases with approximately 1% with the so-called asymptomatic presymptomatic.

[00:07:48] The Next one is just in pre-print. So they were 7.45%, with pre-symptomatic. Another paper showing 12.6% of cases indicate pre-symptomatic transmission. That varies a lot. That's from China CDC in February, they had made a survey, within 72,000 report cases and they have found 889. That's only... let's see, 1.2% with this kind similar to our data. In some very special groups like in New York City. So, 215 pregnant women, they have found 33 PCR positive among them, so 88% asymptomatic... [silence] ... PCR positive. That's a lot. So that's the significance of the asymptomatic carrier, so whether- what kind of role they are playing in the transmission. We need to have a national wide survey. How many asymptomatic patients. The so-called patient with COVID-19 infection. That's one study just coming out. So last week, that's a PCR test I've been carrying out in 275,400 workers, civil servants in Wuhan and among them, so 182 have tested positive. The 6.6 per 10,000 - 10,000 right? No, 100,000, and that's data. We just want to see the so-called background of the serum positive rate. This is in Wuhan area.

[00:10:08] There's also Hubei area, the CRF, the case fatality rate, is pretty high in Hubei area and pretty low in other areas. And then we have made a survey in about 300 patient insight that's inside hospital, not the whole Hubei inside hospital. In Wuhan, one hospital that's in our hospital 2000 in March, at this time. So that's CFR. And also the IgM, IgG positive, shows 2.5% in Wuhan area and 0.9% in other areas. In other words, the so-called [inaudible] immunity is far from reaching there.

[00:11:03] Whether this kind of asymptomatic patient will be capable of transmission, I suppose this is the first paper from Chris and Prof. Chun. And the six family members, Australia, Chinese, five of them being in Wuhan. And for instance, one of them, who had not been in Wuhan and just before the syndrome occurred. That's I'm not going to talk too much about that.

[00:11:29] Another example is Asymptomatic Carrier Transmission. So that's a [inaudible] asymptomatic carrier transmission. Again, a familial cluster of five patients with COVID-19 pneumonia in Anyang, China, at the contact before their symptom onset with an asymptomatic family member here. Also, show asymptomatic patients will have some infectivity to the other person.

00:12:04] This is another case showing a gentleman who attended a meeting in Germany with some partners, and then when he flew back he developed symptoms and eventually he was diagnosed as having COVID-19 infection and others contacted without symptoms. However, there is some study not showing this as the case. They claim that new Coronavirus can be transmitted by the asymptomatic by people without symptoms was flawed. Why? Because in this study showing that according to the people familiar with the call, she felt tired and suffered from muscle pain and took paracetamol and fever-lowering medication. In other words, this patient actually is not asymptomatic, but very mildly symptomatic transmission.

[00:13:12] China CDC announced we should endorse close surveillance and observation of the close contacts since four days before illness onset. And during this symptom onset 1-2 days before and after symptom onset, that's very important.

[00:13:35] Another study just showing that the support these. This is actually some patients who had already had symptoms, but the first 3-5 days, their virus load in the nasal and throat - so it's pretty high after 5 days, and then going down and then the very week in this way, in other words, so it really means so we'll be - we will have some infectivity of the asymptomatic person, but as I know. The big proportion of work is in pre-print status, has not been certified by peer review. So we need a big number of screening at longitudinal study. Can the asymptomatic infected person spread the virus, and how efficient?

[00:14:37] So we need to have further study, big data study to prove that. So actually to identify asymptomatic infection isolation for two weeks. So that's what I had mentioned. I should thank all my colleagues from Zhongshan University from my hospital as well as H. Zhong from AstraZeneca. Thank you very much.

Dr. Fernando Martinez USA

USA situation update: Prevention measures, current treatment protocol and key challenges with managing severe COVID-19 patients

Dr. Fernando J Martinez:: [00:00:00] Thanks so much for allowing me to participate with such an august panel of individuals. And you provided a wonderful introduction regarding the global impact of this pandemic. Sadly, the U.S has become the epicenter, globally now, with 30% of the overall cases. And in New York city we, sadly as well, attend to being the epicenter of the United States.

[00:00:33] We have had quite a bit of experience over the last 5-6 weeks, which has proven to be quite a challenge. The characteristics of the population in the U.S particularly in New York City had been published in the last couple of days by our group in The New England Journal of Medicine, so you could look at that particular communication - Parag Goyal is the first author.

[00:00:56] The characteristics, as you can imagine, are very similar to the characteristics that have been reported from other groups with a slightly higher incidence of gastrointestinal presenting side effects in the U.S and associated with worse outcome. And a much more significant role of obesity that has really become a very strong predictor of bad outcomes in the US. I suspect there are some important mechanisms behind that, but I leave that to my translational scientists to aid in defining.

[00:01:26] The approach that has been taken at our institution to the management of a multi-fold increase in hospitalizations - thousands of hospitalizations - and critical care hospitalizations, has been published in the Blue Journal in the last several days. So I would encourage you to look at the paper by the Intensive Care Directors at my institution - Kelly Griffin is the first author - because it provides very granular recommendations regarding how to consider surging an ICU plan in anticipation of the impact of a pandemic on critical care resources. It's a lovely piece of work that has quite a bit of very practical details. Again, it's on the Blue Journal website online, so you should take a peek at that. The approach to the management of the individuals, particularly those with severe disease, since those are the ones that we tend to see in our pulmonary critical care group, as all of you realize, is rapidly evolving.

[00:02:28] Even though there are recommended guidelines, including a practice guideline, that our group is in the process of revising, all of these are based on relativelypoor data and anecdotal experience. I've spent my life designing and conducting randomized trials and so the database that is available is weak for making strong recommendations. The ventilatory strategy is one of those areas of controversy. And you've seen that playing out in the literature even in the Blue Journal in the last couple of weeks, there've been contrary recommendations. There is a series of 200 ventilated patients from our institution that is in review, which demonstrates that, by and large, the ARDS syndromic picture that we see with this particular virus from the point of view of ventilatory mechanics is actually remarkably similar to what has been previously published with quite a bit of heterogeneity. And one of the major differences, I think is the component of dead space, which does seem to be quite a bit higher, and it raises important biological mechanisms and alterations in the therapeutic strategy. I'll get to those in a second. So once that paper is published, you'll get a better sense, a much more comprehensive sense of the potential ventilatory approaches that are taken, or should be considered in this particular disorder.

[00:03:58] The approach that's taken at our institution has been that following the ARDSnet criteria that some of us published many years ago, which regarding a low tidal volume ventilation, the majority of people - a fluid strategy that fits with the ARDSnet strategy. With the understanding that in the first day or two, these patients generally have been febrile and have had quite a bit of insensible loss, and so their fluid status is a little bit more liberal early on, a little bit tighter later on. With an understanding that renal involvement is quite frequent and that it has to be kept in consideration as you're defining a fluid strategy.

[00:04:35] Generally, the approach that we've tried to follow has been that that has been confirmed in prior randomized control data, with my experience being predominantly with the ARDSnet. The pharmacological treatment of these patients remains completely conjecture. In fact, there is a lovely review in JAMA, two days ago, from a group at The University of Texas which is titled, "Pharmacological Treatments for COVID-19." Their conclusion is, no proven effective therapy for this virus currently exists. And so I think that that has been one of the major limitations that all of us have had - and Pascal, I appreciate your company getting involved in this component - and that level of heterogeneity in therapeutic approaches is reflected by a long meeting that we had yesterday at our institution. We were trying to define the approach to steroid therapy in managing the cytokine storm, that I'm sure all of you have seen at week 8 - 10 in a day, 8 - 10 in the syndrome of this particular infection. And in New York City, every single institution has a completely different steroid protocol of when they use it, how they use it, what dose they use, what age do they use, and how long they use it. So our conclusion was there was no conclusion, the approaches to dealing within a much more targeted fashion to this cytokine storm that we see that has some features consistent with a Macrophage Activating Syndrome have varied from IL-1 to IL-6 to GM-CSF. Pascal, you offered new potential options, again, with an understanding that, within New York City, every institution, does something completely different in this regard.

[00:06:28] All of you have seen, and this has been reported in multiple groups, including some of the authors that are speaking today, a very strong hypercoagulable state in a series of patients, both clinically and in pathological samples from patients who have succumbed to this disease, and so there has been a tremendous interest. Also, in systemizing, providing a cohesive approach to the management of that particular aspect of this disorder.

[00:06:57] Sadly, again, on polling every institution in New York City, there's a completely different approach that's taken to that as well. But it is clinically and syndromically a very important component to this disorder. So my sense has been that COVID-19 is here to stay guys. It is not going to go away. We need to develop a system to manage it, to mitigate it and suppress it and whatever terminology you would like to use, but also to develop a series of cohesive approaches that allow us to target the heterogeneity of the presenting features of this disease, which likely reflect heterogeneity in biological mechanisms. And the optimal approach to achieving that is global collaboration in defining approaches, that includes all of you on this call, and an approach that is collaborative across institutions, federal in our case, federal sponsor of studies. And Pascal, you and your colleagues from the point of view of industry all have to collaborate to be able to develop a series of evidence-based approaches to the diagnosis of the disease characterizing the clinical and biological heterogeneity of the disease and allowing us when we have this presentation next, they have a series of evidence-based recommendations that clearly can be applied broadly, globally, that will improve the outcome of this particular infection. Now, having been involved in the care of hundreds of these patients, it is an impressive sight to behold. I am old, I've been doing this a long time. I have never seen anything like this. And so I think it's a charge to all of you to collaborate and to define better sets of approaches to these patients because sadly, I suspect that this particular Coronavirus is here to stay and we have to be able to develop better approaches to management. Thanks.

Professor  Mike Grocott UK

UK situation update: Prevention measures, current treatment protocol and key challenges with managing severe COVID-19 patients

Prof. Mike Grocott:: [00:00:00] Thank you, Christopher, for the opportunity to contribute to this seminar and particularly to AstraZeneca and Pascal for supporting this sharing of learning. I'm going to change tack a little bit and talk principally about intensive care, critical care, and COVID-19 and in particular in relation to our experience in the United Kingdom.

[00:00:29] My slides seem to have frozen up. But, I'll tell you
what... I'm okay. If

[00:00:39] I start with the challenge, which is novel disease with extraordinary epidemiology that threatens to overwhelm, and in some cases does overwhelm our health systems. The potential for novel phenotypes, and I'll come back to that later, particularly in relation to severe respiratory illness.

[00:00:58] The interaction with politics, policy and people that we often don't have in medicine in terms of the necessity for dramatic social change. I'll also talk a little bit about our response, the surge in activity in all aspects of how we run health systems as a reply to COVID-19, and some of the differences in clinical care and decision making. I will focus principally on the epidemiology in the UK and our clinical experience then a couple of personal reflections at the end of the presentation.

[00:01:33] If I start with the epidemiology, you will probably be aware that the UK is sick now in terms of total number of cases, but I think in comparison to many countries, we have done relatively few tests and sadly we are fifth in terms of the total number of deaths with approaching 15,000 deaths in the United Kingdom now. We commenced lockdown and social isolation on the 23rd of March, and you can see in the upper black and white graphic the continuing increase in the number of daily cases for at least a week or 10 days after that before they start to plateau. And then tailing that in the lower black and white graphic the number of deaths increasing until a plateau probably two and a half weeks later. In the colored graphic, you can see total NHS bed usage, and reassuringly that has started to plateau and indeed the most recent data suggest that started to decrease. If we look at our intensive care bed usage in terms of you can see on that vertical axis there up to 4,000 beds, that is also clearly starting to plateau, and in some centers, they're starting to see a modest decrease in intensive care bed usage, which is overwhelmingly by COVID-19 patients at the moment.

[00:02:53] Like many countries, we have a high degree of diversity in terms of the experience of people around United Kingdom with hotspots in London and some of the other major metropolitan centers and you can see with three local critical care networks that have been most severely affected are all in London. London led us temporarily into this epidemic and it may be that some of the areas outside of London will be fortunate because social isolation was effectively earlier in the growth curve of the spread of this virus.

[00:03:27] These are data from our Intensive Care National Audit & Research Center showing not surprisingly, the overwhelming, the indication for admission to intensive care with respiratory support of which about two thirds, three quarters was invasive ventilation, the remainder being non-invasive ventilation, CPAP and BiPAP.

[00:03:46] Many patients requiring either simple or advanced cardiovascular support and a significant incidence on average about 20%, but with some centers seeing up to 30% or more of renal impairment. And in terms of survival, although we have relatively few completed episodes, you can see at the moment that our overallsurvival is about 50% of those episodes that are completed and if you were not ventilated within the first 24 hours, your outcome was substantially better than if you were.

[00:04:18] If I focused on our clinical guidelines now we've shared a lot of information about how to deal with the surge in demand related to COVID-19, and that's involved as it has in many places around the world expanding the locations in which we deliver critical care both within the hospitals, onto other critical care units, onto normal wards and indeed into new facilities, the so-called Nightingale hospitals, which are converted non-hospital facilities with a very large capacity for looking after critically ill patients.

[00:04:52] We've had people coming into critical care to support the specialists, many anesthesiologists, but also other specialists, including surgeons and physicians. We've procured a huge amount of equipment and consumables as everyone else has. And we've had some very interesting discussions around decisions - and I'll come back to that at the conclusion of this presentation.

[00:05:14] I think the three key lessons have been, first of all, the importance of communication, clarity of communication and kindness, compassion and communication when we have so many different people coming into critical care, some of them who haven't been exposed to it before or not for a long period of time.

[00:05:30] The importance of mutual aid, which is how we described the sharing of resources between different parts of the hospital and between different hospitals should an individual hospital be overwhelmed in terms of critical care demand and indeed around the country, including the notch and go facilities. And increasingly our recognition that this is going to be a very long and drawn out experience, it's a marathon, not a sprint and we need to be careful and marshaling our resources over a long period of time.

[00:05:59] As it's been talked about already, there are no known effective treatments or prophylactic measures for COVID-19 or the SARS-CoV-2 virus. There are several candidates and we are investing a huge amount of effort into nationally approved platform trials, evaluating different aspects of therapy, including antibiotic therapy, direct antiviral medication, steroid use, and other immune modulators. And we're achieving a high degree of recruitment to these,
REMAP-CAP being the International Critical Care Platform Study most patients are going into.

[00:06:36] We are struggling a little bit with antibiotic therapy. I think we all believe we probably shouldn't be giving antibiotics when patients first come to us. Current infection rates for bacteria are relatively low, but it can be very difficult in a [inaudible] patient with a pneumonic process not to administer antibiotics.

[00:06:55] We're increasingly leaning on procalcitonin and we're very conscious of the importance of antimicrobial stewardship, both at the population level, but also for individual patients. The patients are getting a lot of antibiotics earlier we'll say, we're starting to see like fungal infections. We're not recommending routine steroid therapy, but clearly, a replacement should be continued and anything that would normally require treatment with steroids that should be treated in that way.

[00:07:24] In terms of the management of respiratory failure, I think we've got competing challenges. The risk of disseminating infection through so-called Aerosol Generating Procedures. They're all potential resource constraints. Several of our hospitals have exceeded their oxygen supply due to the use of invasive ventilation and high flow CPAC devices along with lots of [inaudible] oxygen, and there's a lot of focus on how to manage that. And the question of
how to manage different clinical phenotypes.

[00:07:50] Well, as a clinical reflection, I'm a research doctor, but I have to say the most important thing I think for us has been the reliable and effective delivery of normal care that we're used to doing and including normal care for the Respiratory Distress syndrome ala net, as it's been discussed already.

[00:08:08] There is some move to lower oxygen therapy targets. In general, we're aiming for about 92-96%, but in carefully monitored environments national guidelines now except 90-93% and there are undoubtedly individual clinicians who are aiming for targets lower than that with uncertain efficacy.

[00:08:26] We are in general avoiding high-flow nasal oxygen because of both the risks of aerosol generation and infection spread and the use of oxygen, potentially scarce resource, but there's a substantial amount of non-invasive ventilation CPAP going on and some patients are undoubtedly avoiding invasive ventilation through that route. And obviously many patients are invasive ventilated but there's a spectrum of approaches to the timing and thresholds through mechanical ventilation.

[00:08:58] There's a huge amount of prone positioning going on, including self proning prior to intubation in patients on NIV. Some use of pulmonary [inaudible] and increasingly, I think, tracheostomy as a means of supporting patients who have a high incidence of failed extubation and often a long period lots of sedative drugs and it's a means of managing limited drug supplies. I've touched on corticosteroids and incidence of fungal infections already.

[00:09:28] We do recognize as many others have these potential two different phenotypes, but I think many people's belief is that the low elastins high compliance, non-recruitable and pneumonitis phenotype probably progresses towards the ARDS phenotype. A few patients are lucky enough just to get a pneumonitis phenotype, but most in our experience progress through the ARDS phenotype. And the two striking non-respiratory organ failures we've had have been the significant incidence of renal failure.  And others have touched on the thromboembolic components, and we've definitely had a shift towards more generous thromboembolic prophylaxis earlier implementation of anticoagulation.

[00:10:13] To conclude in terms of clinical decision making, we are definitely not business as usual, but we are also definitely not resource-limited. The total number of patients as well within our current capacity and all that was local resource stress we are decision making as normal, both for COVID-19 and we're trying to do the same for Non-COVID-19 patients. We're increasingly aware this is going to be a long journey and we may have parallel COVID and Non-COVID health systems looking months or even years ahead. And once again, I emphasize the importance of clear communication. Lots of different people coming together to treat these patients who may not have worked together so much before and compassion and kindness dealing with our colleagues it's never easy under such challenging circumstances. Thank you very much for listening.

Professor Jieming Qu Shanghai, China

Medical strategy for city-wide defense in China

Suppress Strategy for city-wide defense in China by Prof. Jieming Qu

Prof. Jieming Qu:: [00:00:00] Hello, distinguished monitor, chairman, and colleagues. Today, I think it's an honor to have the opportunity to exchange the experience from Shanghai China, for a [inaudible] gesture of the COVID-19.

[00:00:31] Since July 23, 2020, Shanghai launched Level-I Public Health Incident Alert. I think this is the top level of China's public health alert system. According to this public policy, Shanghai established a very integrated strategy. You can see here we combined integrated government, hospital, and the community as the integrated body against COVID-19.

[00:01:18] For example, you can see here the government defense for COVID-19 in Shanghai, we focus on the five aspects. Just so you can see here,  the strict management of the access to Shanghai, just so for airport and the railway station and temperature monitoring was carried out for all kinds of access into Shanghai. So everyone with fever or symptoms would be sent to the isolation site promptly.

[00:02:04] Another very important thing by the government issued the surveillance of personnel. You can see people who want to get into Shanghai, every people should submit their travel history and health information online.

[00:02:35] The third - is an important issue. We established the coded-electronic data system called QR Color. You can see the different colors - green, yellow, or red. This data system could electronically -  See color green? That means the person has no abnormalities and has been cleared of the medical management measures. If this shows the yellow, those who have come to Shanghai, I think from the key epidemic areas, less than two weeks. If there's a red color, the people should be quarantined. So people who have not been freed of the medical management measure, and have been diagnosed and not been discharged, so whose infection has not been ruled out. There are three different colors. It is very obvious representing different situations.

[00:03:53] Restricting gathering for people is a very important approach. You can see this is Disney land, and this is the restaurant, subway, and the [inaudible] of the Shanghai Market. There were no people gathering. So I think this was a
very important approach for stopping the spread of the COVID-19.

[00:04:21] The other very important issue just for the government for performing disclosure of the daily report. It can reduce the panic and stabilize social mood through daily report, I think it's a very important function for this disclosure.

[00:04:47] Another very important function for disclosure of daily reports this can do some very important things. For example, they can disclose the information of the COVID-19 patients of the cases. And the public health education and
refutation of rumor, et cetera.

[00:05:14] Another very important policy for Shanghai against COVID-19 for the hospital defense, you can see here these are three aspects, including patient management, human sources management. And it's a very effective strategy for screening strategy. You can see here fever clinics set up, and isolated ward and designated hospital.

[00:05:59] We have established this very effective strategy for hospital. You can see here the achievement of COVID-19 defense in Shanghai. You can see Shanghai exhibited very high-efficiency epidemic controlling ability and it stopped the exponential growth. And the total confirmed cases just only 628 cases by April 15th. Among them, just nearly 290 cases imported from abroad.

[00:06:43] Here are some pictures showing community management. You can see every resident they walked into the community to be screened for temperature and the information register. Also, you can see here the community management the person to do some checking or to go. Another very important scenes is the propaganda for community among the areas.

[00:07:26] Another very important thing for the community activity, I think it's the public consciousness. This is very important for the citizen, for the public civilians, they should do the wearing mask, hand hygiene, reducing contact with
others and also do some self- isolating and self-monitoring. You can see in this picture this is social distancing, like two meters apart.

[00:08:02] Control strategy for the imported cases as another very important for the government and the community controlling policy for the imported cases.

[00:08:22] The last thing I think especially in Europe, and in North America, there will be [inaudible] epidemic period. It's a good experience for the Fangcang  shelter hospital establishment. They are the largest-scale temporary hospital and rapidly built by converting existing public venues such as stadiums, exhibition centers, et cetera. So, this Fangcang Shelter Hospital served to isolate the patients with mild to moderate COVID-19 from their families and community.

[00:09:10] There is a summary, several functions. Function one is the isolation, and the second function just the triage. The third function I think separated the kind of the disease co-infections, so this is very important. After this Fangcang
shelter hospital establishment, you can see the results. This map showed the results, the progressing of bed capacity, and occupancy of the Fangcang shelter hospital over time. You can see here early descriptive evidence, the Fangcang
shelter hospital, was a major reason for successful COVID-19 control in Chinabecause you can see here more beds waiting for patients of the COVID-19.

These are for my tops conclusion. Strategy for COVID-19 defense in Shanghai of
China depending on the efforts of the government, hospitals, and the community
as the integrating body. So Shanghai exhibited high-efficiency epidemics
control ability. Thank you!


Professor Wenhong Zhang Shanghai, China

Strategy for preventing mild COVID-19 to severe conversion

Strategy for Preventing Mild COVID-19 to Severe Conversion

Prof. Wenhong Zhang:: [00:00:00] I'm very glad to share some strategies for preventing the mild COVID to severe
conversion. I think that recently, it's very important for us to stop the progression of the disease because globally there are so many patients. If we want to decrease mortality, I think it's very important for us to keep the number of critical AR patients, not so many.

[00:00:37] Recently, we also observed that in some countries the mortality's much higher but other countries just like Germany and China and also China -Hong Kong, I think we found that mortality is not so high.

[00:00:57] Majorly, I think the cause for this phenomenon is that we always keep critically ill patients, not so many. Prof. Hui, also mentioned that they had to because we control that, the numbers of the patient in Shanghai. So they are not keep our case number not so many and keeps a very low level. However, recently we noticed that the first week of Shanghai, all the patients from China Wuhan Epicenter, but now today, we almost cured all the patients from Wuhan. But today, we just treated the cases from other countries. Certainly, all the cases in Shanghai recently are imported cases. So we just to get us some experience from our fiscal wave of the disease, we just think it's more important for us.
Recently, we just want to stop as a progression of the disease.

[00:01:56] According to our observations from our first wave, the treatment, we found that according to the timeline of the COVID cases at the onset of the illness we found that the median time for the patient, the progression for the mild or moderate to severe is around 7 - 10 days after the onset of symptoms. Therefore, we want to stop the progression at a very early stage, it's very important for us.

[00:02:32] But what's the mechanism for the progression of the disease? According to some basic research and also from an autopsy, we found some inflammatory mechanisms associated with the progression of the disease. This study is from China, I think it’s the first data from the autopsy we can find is that in the critical ER patients, they are patients with ARDS, we found the hyaline membrane formation, interstitial mononuclear inflammatory infiltrations, and also we can see that the thrombosis in pulmonary arteries also is very significant. Therefore, I think the cytokine storm and the inflammatory mechanism and the coagulation mechanism is very important.

[00:03:27] Today we know that in the COVID disease, immune-defense phase, a protective phase as the adaptive immune [inaudible] in the very early stage it will be surprised by the virus.

[00:03:38] However, it was [inaudible] as the [inaudible] of the mechanism of immune function, we will see the inflammation-driven damage of phase, we can call it the proinflammatory cytokines and also the innate immune will be strengthened by our hosts.

[00:03:56] Therefore, I think at this stage, we should suppress some kind for the initial immunity,also inflammatory cytokine, but what kind of the cytokines...

[00:04:07] Dr. Christopher Hui::

[00:04:07] Prof. Zhong please if I can interrupt your slides aren't rolling.

[00:04:10] Prof. Wenhong Zhang::

[00:04:10] Okay, okay. Can you see now? Okay, okay.

[00:04:14] There are lots of predictors for progression, the D-dimer and Lymphocyte, the Ferritin, LDH, and the IL-6. The
D-dimer, I think also very important. The IL-6 present a standard for the inflammatory cytokines level. So these two can indicate, I think is the most important. Therefore, there's some strategy we can take.

[00:04:39] First of all, we will give all patients anticoagulants in COVID according to the level of the D-dimer. So we will control the coagulation level to the very satisfactory range is very important for us to keep the progression of the disease. Meanwhile, some patients we're working with biological antagonists just like IL- 6 and IL-7.

[00:05:03] Of course the corticosteroids also will be used in some patients at a very shorter window. Just a very narrow window in the patients if the disease progress very fast in the CT scan as we can see a lesion expansion very fast.
Also, the LDH increase,  we won't give the short duration and a low to moderate dosage of the steroid for the
patients. So these kinds of intervention, I think it can you give us some help for keeping the progression of the disease. So I think in the future to save the critical ill patients, well, not decrease the mortality very fast. However, controlling the progression of the disease is more important. So this is our experience recently. I think it maybe will help us to decrease mortality in the future. Thank you.

Professor Gary WK Wong Hong Kong, China

Management of COVID-19 infection in children

Dr. Gary Wong:: [00:00:00] Thank you for the opportunity. I think overall if you look at the pediatricians in terms of the work in hospital they have a slightly less difficult, because first of all, the number of children affected is a very small fraction of the total number of patients. If you look at the data in China it's something like 2% under 20 years of age. So in order to get a good experience of what exactly is the disease, a clinical manifestation and how to manage them properly we get a group and initially we analyze the initial dataset coming out from Wuhan Children's Hospital, which is the only vaccinated hospital looking after children under 16 years of age with this infection.

[00:00:51] And prior to our analysis, there have been a few reports with very limited number of patients so it's very difficult to see. But the impression seems to be, first of all, the disease is uncommon in children. And second, even if they get it, they are not very sick. When we look at this initial cohort from Wuhan Children's Hospital was close to a hundred, a little over 170 of them. And one thing very clear early on in the outbreak is children seemed to get the disease from infected adults within the same household.

[00:01:32] Mind you in this initial cohort, though, there were four children actually within the same family, but the children developed the symptoms first before an adult within the same family, developed the symptoms. And of course, they can be exposed to the same source such that the incubation period may be shorter for the children, than the adults, but we really cannot rule out the possibility that actually the children were infected first and then passed the infection to the adults.

[00:02:05] With that initial impression that it tends to run in the family, later part of the outbreak, we start screening all the children regardless of whether they have symptoms or not. As long as within the same household there is an infected adult, we screen them. And that probably explains some of the results that when we analyze this initial data. As you can see here, the median age is around 6.7. One thing I would like to point out actually the children or infants under
one year of age tend to be overrepresented in the pediatric age group. As with many other respiratory infections in children, you see a slight male predominance.

[00:02:52] As you can see here with the age breakdown, you see children are susceptible to the infection regardless of the age. In fact, as I said earlier, almost 20% of this cohort under one year of age and subsequently this data had been
replicated in the UACDC data.

[00:03:14] Now one thing very clear in children is the symptoms are rather atypical and in fact, only about 40% of them presented with fever at any time during the illness. And many of them, they may have a little bit of cough, very mild. Now one thing I would like to point out in children actually that GI symptoms actually are a little bit more common than in the adult population. Very few of them actually are sick when look at those with really quite some oxygen
therapy, invasive or noninvasive ventilation, only 4 out of the 171 patients actually required such treatment. So in the end, in this cohort, three of them required invasive mechanical ventilation.

[00:04:05] I like to point out because the earlier discussion about the severe cases in the adults that they tend to have a concomitant renal problem among these three children were required mechanical ventilation, two of them actually required renal dialysis, and one of them died. The laboratory features are very similar to the adults, but in the milder form among this cohort, only 6 of them had lymphopenia.

[00:04:39] When I analyzed those with the symptomatic disease - Prof. Zhong earlier pointed out a very important aspect - in this cohort, 16% of them are asymptomatic, they have no symptoms whatsoever. And I would like to also point out among these 107 children with pneumonia, actually, 12 of them were picked up radiological investigation they had no symptoms either. In fact, if I add those two groups up actually around 20% of the children actually are asymptomatic.

[00:05:21] And that, as we can discuss later, marks a very important role in how we look after that group of children. And among those with symptoms, by and large, they recover rather unevently within very short duration of period. The majority of them, they would get better within a week, and for those with fever, which is 40% of them, they have a fever of a few days and then from the onset of symptoms to their PCR-negative from their respiratory sample, it took around
two weeks. And a few of them continue to be detectable in terms of PCR in their stool samples.

[00:06:09] The CT abnormalities are very similar to what's been describing the adult population. As you can see here, actually this one is the, one of the more severe cases and this is the 14-month-old who required invasive ventilation and
dialysis. Again, the ground-glass abnormality is the most common finding in the CT scans.

[00:06:36] Now, there was another report with more or less the number, the initial numbers around Wuhan and Hubei region with 731 confirmed cases. As you can see here, also replicate our findings that those under one year of age tend to be over-represented. And I would also say they tend to be symptomatic, although the symptoms are rather mild, a little bit of fever, cough, lethargy, decrease in the appetite.

[00:07:07] And the severe case - now in China there is a total of around 1600 children under 20 years of age infected with the virus and there have been two deaths. One had underlying leukemia, the other one in our cohort, actually, that child primarily presented with GI symptom. In fact, it was intussusception, and the child had a very stormy cause. The respiratory symptom came a little bit late, and then we investigated the child and found to have nasopharyngeal aspirate to be PCR-positive for the virus. And she went down a very stormy cause and then developed renal failure and then DIC and after about five weeks died from the condition. I'm aware of another case in Middlesex Hospital in London, also an infant presented with intussusception, but very mild respiratory symptoms.

[00:08:07] I think the important point here would be for the children, a large fraction ofthem are asymptomatic. We really need to figure out their role in terms of propagating the infection within the community. When we look at the early CDC data from the U.S are close to 2600 cases, very similar in their series, around 2% of children and within their datasets, three pediatric deaths and they're still investigating. In this report, they really do not have a lot of clinical
details about their patients.

[00:08:47] Similar to our cohort, 2% of them required admission to the ICU and by and large, theyhave an underlying comorbid condition. Also in their dataset, again, they find over-representation of infants in the pediatric age group.

[00:09:12] As far as infection in pregnant women, as far as neonates are concerned, it seems now this is one of the largest studies with 33 pregnant ladies infected in late pregnancy. First of all, the ladies are not very sick and only 3 out of the 33 mother-infant pair got infected and two of them were terms and one of them, preterm. And the preterm, the degree of illness that's similar actually probably explained by the prematurity rather than infection, by and large, infants when they got infected, they're not sick and they get well rather quickly.

[00:09:59] Of course, throughout different parts of the world there are reports of children who died from the infection, and apparently these infants, children, and adolescents are otherwise healthy. So fatalities in otherwise healthy children
are rare but they do occur.

[00:10:23] By and large, for infected children, they run a very mild course, and I think the most important point about this infected population is we need to figure out their infective potential, their role in spreading the infection in the community and of course we need to watch out for children of comorbid conditions and those infants are at risk for more severe disease, and they tend to present more atypical with GI symptoms. So a clear understanding of the
immune response, really, between the children and adults probably will give us a little bit of insights in the development of effective treatment and how to control the cytokine storm. Thank you!

Dr. Christopher KM Hui Hong Kong, China

Host-Immune responses and lung damage induced by severe COVID-19 infection

Dr. Christopher Hui:: [00:00:00] Just to recap, because, we were discussing this before last time at the end of March. And looking at the Host Immune Responses and Lung Damage Induced by Severe COVID-19 Infection. So the first slide shows you the CT scans that we're very familiar with and the progression from mild to moderate to severe. And we can stage this roughly into three stages now with the asymptomatic incubation period, moving onto the non-severe symptomatic patients, and then those who develop a high viral load and a cytokine storm with acute lung injury and end-organ failure on intensive care.

[00:00:46] Moving forward to the next slide, the SARS-CoV-2 virus does divide very nicely into early and late-stage or severe stage inflammatory responses, and this was shared with Prof. Helen Lachmann at the UCL Institute for Immunology. We do know that lung inflammation remains the primary cause of life-threatening respiratory the endpoints in the ITU or ICU stage and that once this lung damage occurs, efforts should be made to suppress the inflammation, but corticosteroids are obviously a very blunt instrument. And as Dr. Martinez said in New York, there isn't a congruous application of steroids that we can apply coherently in terms of different management strategies and individualized treatments.

[00:01:35] The other half of immunity, of course, is to look at it from both parts of the innate and adaptive immunity. And we can look at this, we can study this from the systemic autoinflammatory diseases, mutations that affect the innate immune response and the cluster HLA, the non-cluster HLA associations, gender predisposition, autoantibodies, and antigens specific T-cells, et cetera. These are the so-called experiments in nature.

[00:02:04] Moving  forward, we've been talking a lot here about the cytokine storm in London and the life-threatening and excessive inflammation that is driven by the cytokines. They are existing scores in rheumatology, such as the H-score, which was published in rheumatology in 2014, which looks at different metrics that we can measure, but there are still too many confusing terms.

[00:02:30] I think that the discussion comes back to the many potential target agents, and we're still many of us dwelling on the application or the potential for blockading targets such as IL-1 receptor, IL-6 interferon-gamma and so on and so forth, China's kinase inhibitor, et cetera.

[00:02:48] But the problem is that, as it has been said so far, we haven't found a sort of magic combination or a way of applying these levers and brakes on the inflammatory response in a cogent way. And I wonder whether or not it's not
just the method or the drug, but whether we can apply it in series or in parallel to apply sort of stops to individual parts of the pathway, and there is, a great need is as been mentioned for many more clinical trials.

[00:03:23] In terms of IL-1, we said last time that they have been sort of ad hoc clinical trials in Anakinra and the use of it appears to be safe, but again, these are in the range of any course three at our own institutions here in London at the moment. There is a clinical trial that's due to start at the end of the month and I think a lot of the questions we'll be looking at sort of the stage at which this is most applicable, whether it's early application of the IL-1 target inhibitor or later on. And I think this is something that we have to look at going forward.

[00:04:04] If we can move to the sort of next slides, please. Just going forward you can go through to the, I think it's the 10th slide now. The summary is that there's too little data on any of this for anything other than speculation at the moment, but we do reiterate that IL-6 is not the only target potential, there are others. Again, what we have to consider is the safety profile in all of this. There are anecdotal stories in one or two cases where this appears to have been workable. But again, I think the outstanding issue is going to be on patient selection, timing and dosage, and the interaction of different agents as it has been said before. So with that, I'm just going to tie up that conversation so that we can move and enjoy 20 minutes or so for the question and answer section.

All Experts

Scientific Discussion

Dr. Christopher Hui:: [00:00:00] I'm going to invite all the panelists together to answer these in turn and I'm going to try and curate some of the questions that we have. We have collected a bank of 60 questions here from all countries around the world, and I'd like to just start with Prof. Zhong, please, first if he might share with us some of his thoughts on what the most important strategies are to improving the outcomes in severe COVID-19. What do you think on the basis of what's been discussed so far today? I apologize if the sequence has been a little bit out of order. What do you think Prof. Zhong, the most important strategies are for improving outcomes with particularly with the mortality that we see at the moment.

Prof. Nanshan Zhong: : [00:00:47] Well, I suppose two points. First of all, I think that Prof. Zhang although I haven't looked at your slides very clearly, because it doesn't work, but I think early detections are really important. I think if we can find out the patients earlier, so the patient can receive some medical care whatsoever care, so less patients will be getting to the servere situation.

[00:01:22] The second point may be important is to prevent those patients from developing critical ill situation, those who can reduce the mortality. So all of our actions, one of our measures, is to give this patient hydrogen plus oxygen gas inhalation. When I was a student, so 60 years ago, so we have heard some treatment of the inhalation with helium plus oxygen. That means that the decrease in the density of the inhalation, but actually helium molecular weight is much higher than the hydrogen. So hydrogen-oxygen mix inhalation is much better. In summary, we have found a lot of patients when they inhale hydrogen and oxygen inhalation will decrease the extent of dyspnea which may, in turn, prevent them from getting to severe situation. That's two may be important.

Dr. Christopher Hui:: [00:02:48] Well. Thank you very much, Prof. Zhong. I'd like to just extend one more point on that with the number that you've seen of non-symptomatic transmitters or minimally symptomatic, and we see this in many populations, they may account for the mild to moderate cases that cover over 80% of COVID infections. Do you think we've come to the point now where we are looking at screening entire populations with testing to confirm or refute their COVID status?

Prof. Nanshan Zhong: : [00:03:14] Yeah, yeah, I suppose yes. I don't know whether I can catch your question or not, but anyway, we are now doing a survey on both sides,  RT-PCR and serum antibodies. I think if we have some background data, it will be much easier for our policymakers, to work out some other policy and how we are going to go to do mix. Because as you know, although in the first phase in China seems to be quite successful, but we are aware we are facing a more dangerous situation in the second step because the majority of the Chinese people are known with no immune response to COVID-19. So that's the point in China, as I mentioned before so the background of anti-bodies the percentage is pretty low in Chinese.

Dr. Christopher Hui:: [00:04:26] It does seem to be the case that the presence of antibodies or infection doesn't necessarily confer clinical immunity on the population. So there was previously a brief discussion about herd immunity, but I think we've moved past that and I think I would reflect on very much on what you said about how we might generate some data quickly to compare the respective strategies between [inaudible] population testing and subset population testing, so selective testing because I think as you said, many policymakers do require some of this data to help guide the way we approach this across different countries. Thank you very much. I'm going to move on now to - thank you, Prof. Zhong. I'm going to move on now to Dr. Martinez in New York.  I just wonder, this is a question from the UK actually, have you seen similar off with the data that's coming out now with the predominance of significantly more male deaths in the UK ITU system. Are you reflecting on this in North America as well? And what are your thoughts on the bias between male and female infection that we're seeing in the data that's coming out now? More and more, we think this has to do with perhaps potentially the ACE2 pathway of entry for the virus which is X linked, of course. And I've had very interesting discussions here about skewed lionization where selective copies are taken off in females which may confer some protection. What are your thoughts on the male-female split?

Dr. Fernando J Martinez: : [00:06:04] Well, I think that your colleagues in the UK have made a very similar observation to what we've made here and what we've recently published on our evolving data. There is an imbalance between the genders with respect to certainly hospitalized patients. The imbalance is a little bit less dramatic with regard to overall infections. And Prof. Zhong's comments regarding asymptomatic infection who knows what that's going to reflect. And I totally agree with his thoughts that this is going to require widespread either population-based or population sampling-based testing both serologically and with RT-PCR to be able to get a sense of what the distribution is. But we have a lot more data within the hospitalized setting and in the hospitalized setting and certainly in the U.S there does seem to be an imbalance, and that imbalance is more dramatic in critically ill individuals. I cannot imagine that there's not going to be a biological rationale for that. So I think some of the components that you've described regarding ACE2 and ACE2 processing and signaling has to be reflected, it or has to be influencing what we're seeing in terms of disease severity and clinical manifestations. And so the fact that you're doing that work, I'd encouraged to collaborate with some of the folks over here that are doing some similar work so that we can generate data relatively rapidly. The same component comes to the issue of obesity. Obesity, certainly in the U.S seems to be very strongly linked with negative outcomes, and so I would again, suspect. Maybe for the same mechanisms that there will be a mechanistic reason for why that's the case. All of those components that reflect mechanisms and provide biological insights as you can imagine, I don't know who you can because you've done this will be reflected in targeted therapeutic strategies. That to me has to be the aim that we have in the future.

Dr. Christopher Hui:: [00:07:59] Thank you very much, Dr. Martinez. I think one of the very early conversations I had regarding ACE2 was with a colleague who said, "Well, the solution then is to put everybody on an ACE inhibitor", but I think it might be more complicated than that because the hypertension signal would suggest otherwise. I suspect that hypertension associated mortality figures would point us in the direction of a group of people who are already on ACE inhibitors and therefore perhaps potentially up-regulating their ACE2 expression by negative feedback which would perhaps make them more vulnerable in some way to COVID infection. I don't know again, these are old very limited hypotheses, but we have discussed a lot of different ideas in terms of the mechanistic biology behind this as you say...

Dr. Fernando J Martinez: : [00:08:44] Listen, when I walked to the ICU every day, I wonder whether I should be taking my ACE inhibitor or not. So it's a normal, practical component.

Dr. Christopher Hui:: [00:08:52] Thank you. Thank you, Dr. Martinez. That's you and me both in practice. Actually, I do wonder if ACE inhibitors are influential at least in this context. I'm going to move forward to talk to Prof. Mike Grocott in Southampton about treatments in intensive care. Now, we've moved past the early stages Prof. Grocott with Hydroxychloroquine and Kaletra. I remember early discussions with my colleagues in Shenzen about using Lopinavir and Ritonavir. And we are concluding that none of these agents independently worked very well or very clearly in all critically ill patient groups. What are your thoughts about the inflammation that you described and the discussion about where we need to go with this? Do you have any thoughts of where we might direct our energies and trials?

Prof. Mike Grocott:: [00:09:48] Yeah. I'm not sure I have any answers.  I think we need to have attention to the critical care interventions that we are providing. So what are thinking carefully not just about drugs from pharmacology that will modify inflammation, but also the consequences of, for example, ventilatory strategies in terms of driving inflammation? We know about ventilator- lung induced injury. That does seem to be a bit of a flavor from different groups who are either strong protagonists of avoiding ventilation through quite persistent use of CPAP and others who are - as you will know across London different groups - other groups who are very keen to go for intubation early and avoid noninvasive ventilation, and both argue that there's a potential pathophysiological basis to what they're doing. So I think there's some interesting questions there. Some of the things that we've previously discarded in relation to management of laryngeal LDS may have a role. So I'm thinking of things like SOF active therapy and nitric oxide therapy. And we have a direct and trusted base of those. But nitric oxide particularly interesting because it potentially has direct antiviral effects as well.  Well, it's clear that so far we have no magic bullets, so I think we're going to be looking at all aspects of care, including antivirals, different approaches to immune modulation and anti-inflammatory
pharmacology. And then being very careful about all the other things we do to minimize promotion of inflammation.

Dr. Christopher Hui:: [00:11:30] Thank you very much, Prof. Grocott.

Prof. Nanshan Zhong: : [00:11:32] Yeah. Well, I would like to make a...

Dr. Christopher Hui:: [00:11:35] Yes. Hello? Yes. No? As an extension of that Prof. Grocott, I just wonder we've all seen the benefits of prone ventilation in certain of these groups of patients. And I'm certainly more and more convinced that this adds a ventilatory benefit. What are your thoughts on this and in terms of the nature of the gas transfer deficit and the lung ventilatory mechanics on intensive care? Are we looking at really a policy or universal approach to these patients who come into intensive care?

Prof. Mike Grocott:: [00:12:18] Practically, despite being a little skeptical early on, we are proning almost all of our patients now. And what we're typically seeing is that there's variability in response to proning, but typically they respond better early so we would go for three spells of 16 hours, an eight-hour break. By the time we get to the third spell, quite a few patients seem to be not responding as they get a bit sicker.  We're having a lot of... Well, we feel, clearly, there's no clinical trial, but, experientially it feels like the conscious priming. So, patients who are self-priming themselves on an IV, which is -  if I'm frank something, I had not thought of before and I haven't come across before
clinically, but we've adopted from others and, but on the patients seem to really like it. They seem to feel more comfortable and some of them can sleep like that. And then my impression is we may be avoiding inflammation - sorry,

Dr. Christopher Hui:: [00:13:19] Okay.

Prof. Mike Grocott:: [00:13:20] ...on similar approach. [crosstalk] get more advanced in this.

Dr. Christopher Hui:: [00:13:24] Certainly here at the Royal Free in London, we were also proning many of our patients, probably the vast majority of them and we're very grateful to our surgical team headed by Bimbi Fernando who has been leading the proning teams going round ICU. Obviously, this is very labor-intensive, and so we've drawn everyone in the building in to help with the proning operation as it were and that's a separate [inaudible].

Prof. Mike Grocott:: [00:13:52] I mean, we have the same, it's a huge logistical challenge.

Dr. Christopher Hui:: [00:13:55] It is a huge logistical challenge. I'm going to move on now with the next question because we only have a few minutes left...

Prof. Nanshan Zhong: : [00:14:03] Can I make a point? Chris, can I make a point?

Dr. Christopher Hui:: [00:14:09] Sorry, sorry. Please do.

Prof. Nanshan Zhong: : [00:14:13] Can you hear me?

Dr. Christopher Hui:: [00:14:15] Yes we can. Okay.

Prof. Nanshan Zhong: : [00:14:25] Can you hear me?

Dr. Christopher Hui:: [00:14:28] Yes. Can you...

Prof. Nanshan Zhong: : [00:14:28] I want to make a point, very brief. So I quite agree with what Mike mentioned here. I think the most common involvement [inaudible] other than the lung is the kidney. I agree with that. So you had mentioned about your involvement complications about 20% from our data, from the critical ill patient with no more than 400 close to 40% of patients with different extent of kidney - basically necrosis of kidney tubules. So that's why we suppose - sometimes if we can see the tendency of the deterioration of the liver [inaudible], CRRT so be putting on as soon as possible. Thank you.

 Dr. Christopher Hui:: [00:15:20] Thank you very much, Prof. Zhong, for that very clear summary. Moving on to the next
questions. I think we'll draw on our experience of our colleagues in Shanghai Prof. Qu and Prof. Zhang, if you could share with us [inaudible] there have been a lot of questions from Japan and Spain here where the clinicians locally are asking about the benefits of Tocilizumab, so anti-IL-6 and the targeted sort of anti-inflammatory agents. Firstly, they question how and why we think it might work and whether or not in your experience with perhaps larger numbers as a denominator, you think there's value in pursuing these directions of therapy.

Prof. Jieming Qu:: [00:16:06] Professor Zhang, could you answer this question first?

Dr. Christopher Hui:: [00:16:13] Professor Zhang?

Prof. Wenhong Zhang:: [00:16:16] So you want to answer your question about IL-6 yeah?

Dr. Christopher Hui:: [00:16:22] Yeah, IL-6 and IL-1. Yes.

Prof. Wenhong Zhang:: [00:16:27] I did not hear very clearly.

Dr. Christopher Hui:: [00:16:30] Sorry. Just to repeat that it's for Tocilizumab and IL-6, do you think this improves the prognosis of patients with severe viral pneumonia?

Prof. Wenhong Zhang:: [00:16:40] Yeah, yeah. Yes, yes, yes. I mentioned there that in some sides in China, my colleagues use it in Wuhan Epicenter of China. There are some cohort that they compared with other therapies, so we can see their outcome may be better than the control. However, in Shanghai, because we only have 600-700 we just use some cases here. However, I think -  of course, by the safety of this agent is good. However, we do not think it's just
like improve the symptom very quickly, or it can stop the faster progression of the disease. So recently we just used that in very ill patients. According to my experience in Shanghai, not so many experiences and also some data from my
colleagues in ICU. Up to now, I cannot recommend as the first line of therapy for my critically ill patients. So this is my opinion, recently. 

Prof. Nanshan Zhong: : [00:17:56] The paper about IL-6 receptor antibody, will be coming out soon. So there are two viewpoints inside China. One is only in those patients with enhanced IL-6 can be an indication of that. The results seem to be promising. The other point was if you have some cytokines storm, IL-6  receptor antibodies should be used. I don't think there's so much positive evidence concerning that. Okay.

Prof. Jieming Qu:: [00:18:32] I totally agree with Prof. Zhong's comments about the therapy of the IL-6 receptor antibody of the Tocilizumab. According to the experience of Wuhan and other sides of China, we just use for the patients with the measurement of the IL-6 level. If the IL-6 level is quite high or maybe clinical efficacy is key. I think we should do this at once.

Dr. Christopher Hui:: [00:19:09] Thank you very much. And just to extend on that, there's an outside question here from Serbia. They're asking, "Did your experience in China or Europe", I think they're asking here, "extend to using agents such as nonsteroidal anti-inflammatory. What are your thoughts on using ibuprofen, for example? Or the COX inhibitors for COVID-19 positive inflammation. Do you feel there's any benefit to using nonsteroidal?"

Prof. Nanshan Zhong: : [00:19:37] Yes, yes. As some of the small groups have been doing some inhibition of COX-2, so that kind of pain-killing set-up. And then because they have measured the urine, prostaglandin metabolites are pretty high. So that's why they use this, it seems to be useful in relieving the symptoms, in particular, high fever of course and other symptoms in the early stage, their conclusion, may be positive in using this kind of agent.

Dr. Christopher Hui:: [00:20:16] Thank you very much. Prof. Zhong. May I direct the last question here I think to Dr. Martinez and Dr. Wong in Hong Kong. Just very quickly this is a question from Hungary. "We learned about diabetes as comorbidity associated with worse outcomes in COVID-19. Do you feel that it's worth investigating the effect of glycaemic status in diabetic patients?" And what are your thoughts in your experience in New York, Prof. Martinez with the diabetic and perhaps overweight population that you see?

Dr. Fernando J Martinez: : [00:20:49] Yeah, no...

Dr. Christopher Hui:: [00:20:49] I assume they're talking about Type 2 diabetes. I've not seen many Type 1 interestingly.

 Dr. Fernando J Martinez: : [00:20:54] Actually, if you come to our ICU now, we have three DKAS in the ICU that are actually COVID infected, so just goes to show. And so I agree completely. I think that from a mechanistic point of view, the link between obesity and diabetes, which actually holds in multivariate analysis, suggests that there's likely going to be an important biological and a plausible relationship. The management or the assessment of glycaemic control is something that has been studied intensively in the ICU, as you guys realize, in critical care, with varying results. I think that that area is an area that is very, very important from an investigational perspective. And when I give a long-winded answer to a very good question it genuinely means I have no clear idea and it requires your insights and systematic collection of information to be able to address that question. I think there will be a strong relationship.

Dr. Christopher Hui:: [00:21:57] And Dr. Wong, do you see any signal for diabetes in the young, perhaps with the type 1 diabetics?

Dr. Gary Wong:: [00:22:05] Not at all. Of course, the majority of cases have occurred in the early period. They were in China and the type 1 diabetes in children in China it's very rare. The prevalence is about 120th of what people see in Scandinavia and the UK, so there was no signal there. But one special thing. [crosstalk] Yeah. But one special thing would be actually, in general, asthmatic would develop attack precipitated by the virus, but there is no signal in the disease in children that none of the cohort in Wuhan Children's Hospital they have underlying asthma. And in general, also the children do not present with the disease primarily is in the lung parenchyma and the airways are spare.

Dr. Christopher Hui:: [00:22:59] Yes. I very much agree with that. I mean we've seen the same diabetic profiling of patients here obviously, and there have been quite a few DKAS as Prof. Martinez has mentioned already. We haven't seen very many type 1 diabetics, but again, as you said that might be because of background prevalence rather than anything else, or perhaps there may indeed be a difference between type 1 and type 2 diabetes. I am just going to extend because we've caught up a little bit just in terms of the last question. "What does the panel of experts
believe or think about the associated coagulopathy or the thromboembolic phenomenon that we're seeing because, in the last few weeks in London, I've seen a lot of subsegmental embolization of the lung. And if you look on the CTPA, they are the second, third, fourth-order branch vessels at the periphery almost just to the limit of what CTPA is able
to resolve. And it's very interesting to us because obviously there's this whole discussion about hyaline, thrombosis, immune complex deposition, or whether or not there's an inflammatory response that drives this apparent predisposition to [inaudible] in the lungs. We did three CPAs upstairs. I think it was day before yesterday, and three for three they were all positive. So as an anecdote what does the panel feel is the background to this
and why, and how can we treat this better?" 

Prof. Mike Grocott:: [00:24:32] I would agree. There seems to be an increasing signal that this is a coagulopathic or even vascular coagulopathic illness, at least in part. We've had a similar experience in all hospital and adjacent hospitals in terms of much higher incidence of PEs when we're doing the CTPAs, they're much more likely to be positive. There seem to be quite a few thrombosis generally in terms of lung-related thrombosis that kind of thing and we've definitely shifted everybody if you like, right a bit. So we're giving a higher level of thromboembolic prophylaxis and we're focusing much more attention on that. And in those patients who are properly sick with multiple organ failure and either high or rising D-dimer, we are formally anticoagulating with an aPTT target of about 1.5-2. I think it's becoming more common. We'll see [inaudible] the benefit.

Dr. Fernando J Martinez: : [00:25:29] That's same in the U.S. The other thing we've seen is a lot of problems with renal replacement. Cartridges clotting off and lines clotting off. It's become much more of a challenge for our nephrologists to be able to appropriately do renal replacement in this setting. There's clearly [inaudible] fraction of individuals and impressive hypercoagulable state.

Dr. Christopher Hui:: [00:25:45] Right. So this is a consistent signal and Prof. Qu and Prof. Zhang, Prof. Wong in China, do you feel the same way?

Prof. Nanshan Zhong: : [00:25:53] Yeah, I think micro thrombosis in the lung is a big problem.

Dr. Christopher Hui:: [00:25:59] It'a big problem.

Prof. Nanshan Zhong: : [00:26:01] Yeah, yeah, yeah. Also, we can see some of the patients with massive hemolysis with complications. Actually, they are [inaudible] during the - it's massive micro necrosis. And also this patient has shown a very high type of D-dimer. So that's why some of the hospital they try to use low dose heparin to treat those patients, but anyway, there's no any control studies. But I think, as compared to other kinds of ARDS it did play an important role in the pathogenesis of COVID-19 infection.

Dr. Christopher Hui:: [00:26:44] Thank you. I think as Mike said, we are setting a very low threshold now [inaudible] because obviously if you don't look you don't find so we screen more regularly. And the other thing is also we're treating with a lower threshold and perhaps with a slightly higher level of anticoagulation support with these things in consideration. I think this is impacting our clinical practice in all these directions. I'm going to invite each of our panel of experts now to give us a final comment for what they feel is the most important direction to take this forward. So starting with Prof. Zhong again, if you'd like to share with us some final parting comments before we move on to the subsection conferences.

Prof. Nanshan Zhong: : [00:27:27] Well, very interested in discussion as I mentioned before, but the quality is improving one by one, but these times I learned a lot of these fears from others. So I suppose next time we will have more concern about the mechanism and then the immune response about this kind of research. So rather than just thinking about the clinical trial or some others. So this is because it's a long run, I suppose that Prof. Martinez mentioned about it's a marathon and not a sprint. I quite agree with that. Thank you.

Dr. Christopher Hui:: [00:28:09] It is very much a marathon. Thank you very much, Prof. Zhong. Prof. Martinez in New York, would you like to share with us some final low key thoughts about where you'd like to see this go.

Dr. Fernando J Martinez: : [00:28:19] Yeah. I won't take Grocott's marathon line. That was his line, which I would love to say came from me cause it's a great line. As I've told all of my colleagues here at our institution, this is a problem that isn't going to go away. It is a problem that will not be resolved purely by epidemiological studies. And it is not a problem that's going to be resolved by anecdotal experience. This is going to require a combination of very good epidemiologists. There are certainly some on the line, Christopher, people who have a good understanding of translational biology. That's going to be crucial to be able to link and define mechanisms, and then finally, coordinated integrated approach between multiple investigative sites across the globe. With partnering with societies with their own federal governments and - Pascal, you're still on - with industry to be able to define appropriate therapeutic strategies based on the combinations of the epidemiology, clinical observations, and the biological constructs. This is the perfect model of what that type of approach is going to be vital for us to be able to get control of this challenge.

Dr. Christopher Hui:: [00:29:33] Thank you very much, Prof. Martinez. And as you say, as we stare down the barrel of this new normal, I do reiterate the science paper I'd like to share it with everyone by Steven Kissler and Marc Lipsitch on "Projecting the Transmission Dynamics in the Post Pandemic Period." I think this is something that's foremost on everyone's mind, and we need to see how this pans out because obviously there is the potential for transmission in cycles now once it's established in the population. So we do have to be very careful about how we proceed and, perhaps, develop the science and the data to support policymakers in their very difficult decisions.

Dr. Fernando J Martinez: : [00:30:16] Better said than I could have said.

Dr. Christopher Hui:: [00:30:18] Thank you. Prof. Grocott, please.

Prof. Mike Grocott:: [00:30:23] I think I would make three points. One, I think this is going to be an enduring challenge and I'm not a great fan of the military analogies, but I think it's going to take our combined efforts to fight. I do not know if we are ever going to defeat, but to come to some kind of living arrangement with this virus. And I completely agree with the comments about coordinated research.

[00:30:46] My second comment would be, we are all very lucky speaking from positions of relative wealth. Globally. And I think the consequences from some of the poor countries may be terrible and attention to the types of interventions that could be effective in those environments I think is very important.

[00:31:06] Finally, as physicians, as healthcare workers, the person is going to be very important. It's going to be a very challenging time because of all the social consequences of COVID. And it's very challenging, the different ways of working professionally. And I think professional compassion is going to be a very key element.

Dr. Christopher Hui:: [00:31:25] Thank you very much, Prof. Grocott. I think perhaps really what we're looking for is some sort of etente cordial with the viral the enemy, as it were. Moving on to Prof. Qu then, and Prof. Zhang in Shanghai. Could you share with us your final thoughts on where you'd like to see things go from here?

Prof. Jieming Qu:: [00:31:44] Yeah. I think during the past 2-3 months. Just the way we knew about COVID-19 gradually, especially I'm thinking for the virus and [inaudible]. I think that's a very big challenge, up to now. Just, I think we just only familiar with very late to COVID-19. So actually, we should do a lot of things stop this spread of the COVID-19, just like public prevention policy or strategy. Another very important thing is we should further investigate the [inaudible] of the COVID-19. We can find a very precise and effective and targeted therapy for COVID-19.

Dr. Christopher Hui:: [00:32:46] Thank you, Prof. Qu. I think we would echo. There are many of us who believe that in the absence of any effective therapy, falling back to the first principles of infectious disease management, which is to identify, test, isolate, and then treat is the right way forward. Absolutely and I do fall back on first principles in these very difficult times. Prof. Zhang please if you share with us your thoughts.

Prof. Wenhong Zhang:: [00:33:11] Yes. Yes, yes. I think now the way of controlling the disease, I think is so far away. I think it's much longer than marathon itself, and I feel very lucky this time we fight against the virus together this time. Not only China fighting against the virus. Today we also will learn a lot from our colleagues from other countries. I think the next time we can see more information about the virus. Even though today we do not know where's the vaccine, where's the promising agents, but I think maybe not far away that we will have it. So I really hope that next time we'll know more about the virus and the way more agents and more strategies to fight the virus. I think we will win in the future. Yeah.

Dr. Christopher Hui:: [00:34:06] Thank you, Prof. Zhang. I think we're going to have to ask Pascal and our support structures industry partners to help us here. One of the things that come to mind is that the last three webcasts we've done have grown in size, but also we always inevitably run out of time to share more and in-depth in terms of our data. I suppose the other problem is we're so busy doing that we don't have time to undertake the necessary analysis and I'm sure we all struggle with that, but you're absolutely right. I think there needs to be more sharing and we need to make this open. I think perhaps if Astra can consider setting up some platform to link everybody together after these three meetings. We should stay in touch and really open the channels of communication widely to ensure that we have free transfer of information and the necessary research and data sets to support everything. Prof. Gary Wong, please. Dr. Gary are you there?

Dr. Gary Wong:: [00:35:04] Yes, yes, I'm here. As far as the role of children within this disease is concerned we really need to figure out a large number of these mildly affected children, asymptomatic children, as well as the young people in the analysts and what is the role in terms of spreading the infection in the community. And of course, we need to understand the biology, why the disease behaves so different compared to adults. And we must not forget actually on top of all these children that we need to look after there are millions and millions of children now they are not allowed to go to school, they're locked up in homes, the psychological effect and the detrimental effect on their learning and we must pay attention to that too until there are, in fact, vaccines to protect people.

Dr. Christopher Hui:: [00:36:03] You're absolutely right. Unfortunately, vaccines appear to be a good few months away, if not a year down the line or more. I think we do forget that the social and psychological impacts of these decisions basing it on the science and the data is very good, but certainly, we need to consider the impact on children. And certainly, with the numbers that you've seen already, there is a clear signal coming through that we need to pay attention to so we'd be delighted as adult physicians to work with our pediatric colleagues to drive this all forwards.

[00:36:38] Unfortunately, in the interest of time, we did have prepared a polling section, but we're going to skip through that now to the closing remarks because the section seminars are now prepared and ready to start. So it remains for me to thank each and every one of our panelists, Prof. Zhong, Dr. Martinez in New York, Prof. Grocott in Southampton, Prof. Zhang and Prof. Qu in Shanghai and Prof. Wong in Hong Kong. Thank you very much for your time and your sharing. I hope we can really take this forward now, we've had three meetings today, they've all been very similarly successful and we really need to merge these ideas and discussions into something more solid now, perhaps in terms of the data and the science of driving forward some of the discussions on policy.

[00:37:27] We have to thank also AstraZeneca and Pascal for their incredible support in coordinating this very timely and meaningful event. Thank you, Pascal, and his entire team at AZ. They really should be applauded for taking the lead on this. We wish everyone here, including all our partners in industry success in our individual and respect to fights against COVID. This section of the webcast is now ended in the interest of time, you will be directed on your screens now to select one of three breakout sessions covering specific areas of interest in the context of COVID-19 under the headings of respiratory medicine, cardiovascular disease, and oncology and I'll hand you over to their host separately. Thank you very much for joining us today. Bye, bye.

Prof. Mike Grocott:: [00:38:15] Thank you.

Prof. Nanshan Zhong: : [00:38:16] Thank you.

Dr. Gary Wong:: [00:38:16] Thank you.

Session Breakouts

Professor JunJie Zhang China

Lecture-1: CSC Consensus on Principle of Clinical Management of Patient with Severe Emergent CVD During COVID-19

Prof. Junjie Zhang:: [00:00:00] It's my great honor to present the CSC consensus on behalf of Prof. [] and Prof. []. To date, COVID-19 has been a great threat to global public health. So far more than two million people suffer from COVID-19 among those, unfortunately, 139,000 patients died.

[00:00:36] To date, in Chinese mainland with the leadership of government and also our beautiful medical staff, now the COVID-19, has been on the control. So far, we only have 1000 remaining infected, and among these patients only 85 severe cases in ICU.

[00:01:05] So actually COVID-19 had 78% of nucleotide analog with SARS, and the 50% with MERS. Similar to the SARS, COVID-19 combined with ACE2 on the surface of epithelial and [inaudible] cells. And also ACE2 can be expressed in the heart, kidney, and intestines.

[00:01:32] SARS and MERS had a cardiovascular complication, including, myocarditis infection and exacerbation of heart failures. Previous autopsy show SARS RNA was detectable in the heart of 35% of the SARS patient. So previous data also shows COVID-19 infection may result in a high risk of acute adverse events in patients with coronary heart disease and heart failure.

[00:02:03] Early autopsy from Wuhan showed inflammatory infiltration of monocytes in cardiac tissue, without obvious histological changes. Recent pathology biopsy also reveals that endothelial shedding, endocarditis, and the thrombosis
formation in the cardiovascular. However, there's still no clear evidence show inclusion body of SARS-CoV-2 in the heart.

[00:02:38] This is an academic study from 17,000 population from Wuhan. The mortality of COVID-19 patients with cardiovascular disease was more than 10% compared to only 0.9% in patients without any comorbidity.

[00:03:03] This is another cohort from Wuhan ICU patient. Totally 1090 patients with the COVID-19. Among these patients comorbidity 48%, 30% patients with hypertension, and 20% with diabetic and also CAD patients, 8%. Heart failure and acute cardiac injury were more frequent in death group compared with survivor group, you can notice it - 50% versus 12% and also 59% versus 1%.

[00:03:42] This is another cohort study just published in JAMA Cardiology from our Wuhan colleague. You can see there's a total of 416 cases with the confirmed COVID-19. Including 82 patients with cardiac injury, with a relatively troubling high 20% and also 334 cases without cardiac injury. Compared with those without cardiac injury you can notice the patient - the COVID-19 patients - with cardiac injury was associated with significant low rate of [inaudible] at 30 days, only less than 50%.

[00:04:32] This is another group from Wuhan ICU cohort patient. You can notice the patient shows CVD co-morbidity, and also with elevated TnI, TnT. This means the patient with the cardiac injury was associated with the extreme high mortality, up to 70% compared with only 7% for those patients without any CVD comorbidity and normal troponin gene.

[00:05:07] The CSC expert consensus on the principle clinical management of patient with severe emergency cardiovascular disease during COVID-19 epidemic was written by 125 medical experts, including 23 front-line experts from Hubei, Wuhan. And mainly it's from the front-line expert experience, which has been published in circulation in March.

[00:05:40] There are four general principles about this CSC consensus. The first is epidemic control as the first priority. Before we make decisions for CVD patients or COVID-19 patients with severe cardiovascular events, we should do a prompt risk assessment. So the preference for conservative medical therapy was the first option. Strict measures to limit infection spread within the hospital and also to the health care staff.

[00:06:19] In terms of risk assessment, we should first, diagnose the COVID-19, such as confirmed case or suspected case. We should also balance the benefits of the treatment for severe emergency cardiovascular disease. We also should
comprehensive consideration of differential diagnosis.

[00:06:45] I've seen the fourth principle is always protecting our medical staff, not only medical staff but also for patients. Protective quarantine measures should be adhered strictly throughout the process of the treatment in all patients, including those with severe emergency cardiovascular disease, so as to minimize the risk of disease transmission across the patient and in medical staff.

[00:07:14] This algorithm for management of critical cardiovascular disease in regions with a high incidence of COVID-19 in Wuhan and also in Hubei province. Confirmed or suspected cases, which case we should be located in isolation ward and also in the COVID-19 designated hospital. Also, single room for suspected cases, and I've seen the first option is medical treatment. If still after the treatment the patient is still unstable like cardiogenic shock-like high-risk NSTEMI patient. So we should start the emergency procedure plan third-grade protection cath-lab with negative pressure ventilation and also we should get the consent of health administration, then we can treat this patient with the emergency invasive treatment.

[00:08:17] Otherwise, after medical therapy, if the patient is stable, we can still treat this patient with medical therapy and after maybe the patient recover the COVID-19, we can do the elective invasive intervention treatment.

[00:08:37] For the patients who have not reach the suspected cases diagnostic criteria in Hubei province, we can transfer these patients to the non-designated hospital and also the lung CT scan and RNA test to truly exclude the COVID-19. If these patients, unfortunately, with confirmed or suspected with COVID-19 in this scenario, these patients should be transferred to the designated hospital. Otherwise, we can still treat these patients in the non-designated hospital.

[00:09:24] This is another algorithm for the treatment of critical cardiovascular disease in a region with a low incidence of COVID-19, which means besides the Hubei province. If patients have fever, these patients were referred to Fever Clinic. Nowadays, seeing all over the international, all the hospitals have a special fever clinic. And also we have the COVID-19 expert panel stand by. If these patients are confirmed or suspected cases, then these patients were transferred to a designated hospital.

[00:10:08] Otherwise, if patient cannot be fully excluded temporary, so we're still [inaudible] a consultant of the COVID-19 experts and at these times a single room in an isolation ward should be mandatory with the second-grade protection until this patient is finally excluded from the COVID-19.

[00:10:33] If the patient with severe cardiovascular events. However, the principal treatment options still the [inaudible] option. Like the patient with STEMI for whom thrombolytic therapy is indicated. Also, STEMI patients actually exceeding the optimal window of time for revascularization and also including the high-risk NSTEMI patients. All these patients were treated with medical therapy.

[00:11:04] Otherwise, acute myocardial infarction with the hemodynamic unstable and also like STEMI, NSTEMI patient indicated for urgent revascularization like Stanford A or Complex type B acute aortic dissection, severe Bradyarrhthamia complicated with syncope or unstable hemodynamic, [inaudible]. In short, with all
these patients, we should start our emergency cath lab intervention.

[00:11:36] So if emergency intervention or surgical procedure required all the following conditions should be met. First, transfer the patient to a designated hospital of COVID-19 and also [inaudible] the cardiac cath-lab, followed by strict peri-procedural sterilization. And also [inaudible] is mandatory.

[00:11:59] In term of referring patient through the designated hospital, in principle, I think, patients with severe emergency cardiovascular disease who has been ruled out for COVID-19 should be treated locally. Otherwise, confirmed or suspected COVID-19 patients with a critical cardiovascular disease should be transferred immediately to a local designated COVID-19 hospital.

[00:12:26] Protection also was mandatory for patients with confirmed or suspected COVID-19 undergoing an emergency cardiovascular interventional procedure, Preestablished [inaudible] for COVID-19 should be initiated. This should include all aspects of pre-operative preparation and comprehensive peri-operative management of the patients, medical staff, environment, and also operators, emergency supply equipment, and consumables. So it's also, we can recommend you use telemedicine for remote consultation. This is the case, a STEMI patient, we use telemedicine for remote consultation in our hospital.

[00:13:20] So ladies and gentleman, let's gather summary. The COVID-19 outbreak has substantially increased the difficulty of treating patients with severe emergency cardiovascular disease. Individualization, diagnosis, and treatment measures tailored to specific local epidemic situations should be developed. Thank you for attention.

Professor Otavio Berwanger Brazil

Lecture-2: COVID 19 and CVD--What do we know so far?

Prof. Octavio Berwanger:: [00:00:00] Thanks very much, Prof. Zhang for this very clear presentation. We are all learning a lot from the Chinese colleagues, and it needs to be acknowledged the great work that you and your team did during this pandemic. I think the world has a lot to learn from these guidelines that China wrote. It's been very useful globally.

Prof. Junjie Zhang:: [00:00:30] [inaudible]

Prof. Octavio Berwanger:: [00:00:33] Thank you.

[00:00:35] I will now try to share my screen here. If I - let me see, one second. Hopefully, everyone is able to see slides should come up in a minute. Yeap.

[00:00:48] So I think I'm here more to learn than to teach anything, but I just need a quick summary of cardiovascular consequences of COVID-19 and also future targets for randomized clinical trials and potentially preventive therapies.

[00:01:12] As we just heard, it's been less than four months since we learned about COVID-19 so, in reality, we know very little. As I just mentioned, we're learning a lot from colleagues from China. We are now learning a lot from Europe and the U.S.

[00:01:31] In my country, Brazil, the first case was actually in my hospital. My hospital is still one of the hospitals in Brazil with the largest number of case, the Albert Einstein Hospital in Sao Paulo. The first case in Brazil was, February, 26th and was a gentleman who came from Milan, in Italy. But now, of course, it's all over the country in Brazil with the peak expected for late May or early June when our winter starts to begin. We have over 30,000 cases in Brazil as per yesterday and over 2000 deaths, so it's still not chaotic, but of course, people are very concerned.

[00:02:19] What we've seen so far here, it's similar to what other countries have seen. About 69 of 80% of the patients will have no or mild pneumonia with small symptoms, about 15% will get severe disease, and 5% who ended up having critical disease and need for ICU beds and mechanical ventilation.

[00:02:44] This is just a quick summary. I'm sure by this point everybody knows, but just as a summary presentation, which is what this presentation is intended to. The most common symptoms are still fever in 88%. Here in Brazil, it's pretty much the same. [inaudible] in almost 70% of the patients in fatigue, in about 40% of the patients. This is still the most common symptom, and it seems to be similar in our regions of the globe.

[00:03:18] Something that we also learned from China, and in this Lancet publication and what we're observing here in Brazil, there's some Brazilian papers about to come out with not only a national registry with describing the cases, but we have some outcome and some randomized trials ongoing in Brazil, currently all over the country. But we learned that especially for survivor sepsis and ARDS would happen around day 10, and we also know that late complications in non-survivors, like acute cardiac injury, acute kidney injury, water secondary infections, start to occur after the second week, although in some parts of the world, including Brazil, we are also seeing some early acute injury happening around the 4thh day I'm not sure if that's the case in other countries, but we have some cases of early cardiac injury even in patients without previous cardiovascular disease. And this were mainly patients over 65-70 years in the

[00:04:28] You already saw that with the complete publications that Prof. Zhang just showed us, but especially in non-survivors, about 10% of them have cardiovascular disease, diabetes in more than 7%, hypertension in at least 6%. So it has something going on specifically with the cardiovascular system, we're still trying to learn about it cardiovascular disease, hypertension and diabetes are independent predictors of mortality and also are independent predictors of bad
outcomes and especially in the ICU as we've seen.

[00:05:12] There's something going on and we need to deep dive into it and try to understand it further. You're already seeing that - I'm sorry Prof. Zhang I mean, China generated the most important publication so far, unfortunately, I will repeat some of your graphs. And as I mentioned, we are learning from China and trying to apply the concepts everywhere. As they also mentioned, Brazilian data is coming out very soon, but I can tell you that it's what you're observing here, it's very similar. Although our mortality it's slightly lower, so far, than European countries, even in the elderly.

[00:05:52] But I think one important concept is that in terms of the cardiovascular system, I think the interactions of the Coronavirus and the COVID-19 in cardiovascular systems can go two ways, which are not necessarily independent.

[00:06:12] One, the cardiovascular system as a primary target, I mean, the COVID-19 disease-causing directly some sort of cardiovascular insult or injury. And that can include hypotension, arrhythmia, and of course, sudden cardiac death. And what had been discussed so far is both laws Prof. Zhang already showed us about the protein spike of the Coronavirus binding the ACE2 receptor, which is expressed in the heart and also in the lungs and intestine and kidneys, as you just heard, but also some form of systemic inflammation in cytokine storm seems to play a role. We're learning about it, but that seems to play a role, and obviously in patients who already have cardiovascular comorbidities, which as I mentioned, are still the key factors independently associated with mortality. Of course, as we just learned cardiovascular disease, diabetes, and hypotension are common in these patients. These patients are at higher risk, and of course, systemic inflammation, for example, with the high cardiovascular risk patients can cause pro-coagulant effects so thrombosis seems to play a role. Yesterday just came out a very nice paper in JACC explaining that further and then anticoagulation may be a target for therapies, but also systemic inflammation. We know that inflammation can lead to [inaudible] rupture and on a lot of fodder mechanisms, and the cardiovascular system. So we need to think of the cardiovascular consequences, both in terms of a primary target, but also in patients who already have comorbidities.

[00:07:56] In terms of the primary targets, you've seen this data before also from Prof. Zhang, but over 16% of these patients develop arrhythmia and over 7% of them develop some form of acute cardiac injury. There seems to be some early cardiac injury and also some late cardiac injury leading even to heart failure. We're still learning about it, but theoretically, what we learned so far, it approximately commensurate with what we've seen with SARS, MERS, and other influenza analogs. But this is a big problem because, of course, myocarditis can lead to cardiac arrest and acute illness and this is also an independent predictor of mortality. And you've seen Prof. Zhang's graphs in terms of elevated troponin T in this patient population.

[00:08:50] This in terms of direct effects as a primary target, but it's very important. This is from the ACC and AAJ, but also it's consistent with the Chinese Society of Cardiology Guidelines of course. We have these patients coming to the hospital every day, so we need to make ones to quickly identify and isolate them. We know that these patients are at higher risk, and it's very important to keep current with other recommendations in terms of vaccinations, including a pneumococcal vaccine.

[00:09:23] One phenomenon that is happening in Brazil and is happening elsewhere is we have a lot of people who are scared of going to the hospital, elderly people, so we are seeing, paradoxically, a lower number of myocardial infarction [inaudible] coronary syndrome and being reported. But the concern is that it didn't go away. Probably a lot of these patients are having ACS or dying at home. We just received some reports, given in the late press and in New York City, the number of cardiac arrests have over rocket, and probably it has to do with patients avoiding seeking the system. So this is also happening in patients with acute strokes. So that's worrisome, that's a major concern besides, of course, the
direct concerns associated with the COVID-19 disease.

[00:10:21] Of course, we are using a lot here in Brazil, and we also learned from - - and this is the case in China and the U.S - telemedicine and telecardiology, different forms of digital health and telehealth are being applied.

[00:10:37] The ministry of health in Brazil has a huge program in Albert Einstein for these patients. We have even in Brazil changed our regulation because, in Brazil, the regulation requires that telemedicine was provided from physician to physician, and now there are some exceptions because we need to follow these patients with diabetes, with chronic cardiovascular disease, other patients with hypertension who are not being at a hospital. We need to make sure that we
can follow them up. And of course, it's the triage of COVID-19 that should include all the comorbidities that are independently associated with bad outcomes as we just heard. So it's general recommendations because once again the evidence is anecdotal. It's very limited. We have some cohorts publish it, but the reality is we still don't have sound evidence because we know this for the last three months and a half, four months at most. I think one question that everybody's asking what about stopping ACE inhibitors and ARBs in patients with hypertension, in patients with heart failure, in patients with diabetes?

[00:11:54] We know that, once again, the proteins spike of the Coronavirus binds to ACE2, and by using ACE inhibitors, it's a paradox because mechanistically you could make things worse, but also, on the other hand, ACE inhibitors or even the ACE analog can be a way to reduce the risk of acute lung injury and other cardiovascular consequences.

[00:12:24] The reality is this is mechanistic insights, both in terms of worsening the prognosis - because of the time's sake I'm not going to the mechanistic details here, but I would like to highlight that this is pathophysiology, it makes sense both ways of reducing events or increasing the risk of events. So since we don't have any randomized trials, we are starting to see some real-world evidence studies with some limitations suggesting that stopping actually may be worse, but this is very controversial because of very limited evidence.

[00:13:01] In reality, we need some randomized trials in patients comparing stopping versus not stopping ACE inhibitors and ARBs. There's a large ongoing trial in Brazil about it if I'm not wrong, there is one trial also being conducted in the U.S if I'm not wrong. But our society here, this is the recommendation from the Brazilian societies, we should not withdraw or stop at this moment without having sound evidence.

[00:13:29] And I learned that from the European Society of Cardiology, CCNA, AAJ recommendations are currently the same. So practice in Brazil now is to not stop ACE inhibitors or ARBs unless the patient is being included in a randomized trial addressing this question. I think this is more or less similar everywhere. It's part of physiological insights we simply don't know. I think you also learn that there's something interesting going on in these patients when we compare survivors with non-survivors in these Chinese Lancet Publications. We know that these patients, the non-survivor has an important increase in the D-dimer levels. They have an important increase in IL-6 levels and we've already seen that in terms of the cardiac injury, they have an important increasing troponin - here for Troponin I, but you just saw that also holds true for Troponin T.

[00:14:29] There's something going on here and all these markers being elevated together points to the direction of some sort of systemic inflammation in a cytokine storm. So, LDH used to increase in some patients, we're seeing ferritin increase so cytokine storm in a pro-inflammatory state may be the case here, but also - this just came out yesterday in JACC - as you know, also there is a pro-coagulant and a pro-thrombotic state in these patients.

[00:15:07] It's interesting that this systemic inflammation, cytokine storm, and also pro-thrombotic effect may play an even greater role than the direct acute lung injury. So there's more to come here. So there's trials on anticoagulation are being proposed at trials with IL-6 antagonists are being proposed it, besides, of course, antivirals, chloroquine, hydroxychloroquine, azithromycin, and several components. But I'm very involved with - this is my last slide - I'm very involved in the conduct of large trials and we are having to adapt to conduct adaptive trials and also to conduct pragmatic trials to try to answer these questions. Several of these trials with flexible designs are ongoing. They are a big challenge. I know that China is conducting a lot of trials too, as the UK, in the U.S. So we'll learn more in the days to come. So this is what I had to present today.

Professor Jaime Davidson USA

Lecture-3: COVID-19 Diabetes and HTN--Considerations for Health   Care Professionals

Prof. Jamie Davidson:: [00:00:00] Good morning, good afternoon, wherever you are, and you are learning as much as I'm learning. I enjoyed the previous two lectures. And this is a learning curve, we're going to continue to learn. And now I will talk a little bit about COVID-19, diabetes, and hypertension, and considerations for healthcare professionals. This is where I work. Actually, the Touchstone Diabetes Center is in the back of the building on the fifth floor, and we have actually many Chinese people working with us in that department.

[00:00:50] Well known is that COVID-19 is a virus belonging to the family of Coronaviridae. The previous member of the family includes SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East respiratory syndrome) The big difference is COVID-19 is one of the most contagious viruses ever seen.

[00:01:13] Everyone is at risk, but who is at higher risk based on the data that we have reviewed? Older adults (65 years and older) people of any age with underlying medical conditions, cardiovascular disease, diabetes, hypertension, et cetera. People in nursing homes or long-term care facilities - this is one of the biggest issues that we're confronting in the United States - and people with disabilities.

[00:01:46] What are the symptoms of significant concern? If the patient starts having lung symptoms, severe cough spells, shortness of breath, persistent pain or pressure in the chest, bluish lips or face because of lack of oxygen, confusion or inability to arouse. Time is crucial, take action, that patient belongs in the ICU of a hospital trained to deal with COVID-19.

[00:02:21] I recently wrote a small piece on COVID-19 and I called COVID-19 a pandemia plus diabetes mellitus, the metabolic syndrome, hypertension, and epidemia, and I put that as a bad marriage. It was published about two weeks ago.

[00:02:40] Let me tell you what we're dealing with here in the United States. The COVID started in the state of Washington, in the city of Seattle, and on April 2nd, 2020, we have 240,000 total cases. And that day we have 25,000 new cases. 15 days later, it tripled. By April 16th, we have 674,000 patients so cases, but interesting thing is that the total number of new cases started to go down.

[00:03:24] If we look at data from Wuhan, we look at who is at risk of cardiovascular disease, that was well-covered, hypertension, that was also very common. It's hypertension and diabetes, those are the comorbidities that are most commonly seen in those patients in Wuhan.

[00:03:48] The next question that I asked, "Is diabetes and hypertension risk factors for mortality in hospitalized patients with COVID-19?" Now on the left-hand side, you see age and once you reach patients with COVID-19 age 50 and higher,
you can see that between 40 and 49 is 0.4%, between 50 and 59 it tripled to 1.3% and any decades of life after that it doubles or triples. By the time we have patients in the 70s is about 8-10% and in the 80s is about 15%.

[00:04:34] If you look on the right-hand side, other than cardiovascular disease, the next one here is diabetes and hypertension. If we look at the clinical course and risk factors for mortality in inpatients in Wuhan China, again, what do you see here? In the non-survivors in this particular study over a total of 191, and the non-survivors, 54, hypertension accounted for 48%, and diabetes for 31%.

[00:05:10] We move now to Europe, and this is the case fatality rate and characteristics of COVID-19 in Italy. Now you want to see here that the average age here the meanage was 79.5 with a standard deviation of 8.1. Older people and 35.5% have diabetes.

[00:05:38] If we look at clinical characteristics and outcome of severe COVID-19 in patients with diabetes. Here, what we see, there are more males. If you look at the age, they're older. Fever is no different. There's slightly more cough in patients with diabetes, there's more dyspnea. And if you look at the random blood sugar is really high, 11.3 versus the non-diabetes patients 6.5 and the A1C is 7.2 versus 5.8.

[00:06:17] If we look now at diabetes and comorbidities, if we look at hypertension, that combo is not that good. 50% of patients with diabetes in this particular study had hypertension. Now the use of ventilators was also high, 81.3% versus 57 of the total and 49 in then known [inaudible] patient.

[00:06:44] Now when you look the length of stay is shorter in patient with diabetes because the death rate is higher, so they die before other people do. And if you look at the mortality is actually identical to those in the ventilator, 81.3%. And obviously, we need to have more information, we need to learn if the ventilators are helpful in patients with diabetes or not.

[00:07:19] We want to learn from previous epidemics. This is some study that was published in 2016 and is the glucose level and diabetes mellitus at independent predictors of mortality and morbidity in patients with SARS. If you look, actually, you can see the big difference in fasting glucose, in the survivor's patients versus in the patients that died and had diabetes.

[00:07:52] Do we need better care before people get infected? If we look at Wuhan's health care system hospital admissions, obviously we think we do. Again, here the median age is 69 (54-81) the hyperglycemia was seen in 56.6%, of the people with pre-prandial in almost 30%, and postprandial in about 65%. Also, hypoglycemia, which is also a risk factor for many other things, in about 10% of the cases.

[00:08:41] What do we recommend in patients with diabetes? Like in any other patients, general recommendations for patients with hypertension [inaudible]. Everyone clean the hands often with warm water, liquid soap for 20-30 seconds. And be sure the nails are clean. If water and soap is not available, use hand sanitizer with at least 60% alcohol or if Clorox wipes are available, use them. Avoid touching your face, your eyes, your nose, and your mouth. Well known by
all of us.

[00:09:19] In addition, social distance. Very important to keep people from not living in the same home 6ft away from you, which is almost 2 meters. After sneezing, coughing or blowing your nose, use disposable tissue, and discard them immediately. Do not share cell phones, tablets, etc and clean them on a regular basis. Very important. Do not share cell phones. Use protective gear when available and hopefully is now available everywhere. Because patients with less than
desirable glucose control are usually behind in fluids. It is well known if a patient has an A1C of 8, versus somebody that has an A1C of 7, the one that has an A1C of 8, is behind in fluid. So drinking water rehydrating is very important.

[00:10:17] Have them call you if glucose levels are increasing for no reason in 3 consecutive days. We tell them if your glucose is working the control of 140 and now in 3 days in a row, you're fasting is over 140, I know your postprandial is greater than 180 please give us a call. And therefore, SMBG is extremely important in getting your patients under control. For any reason, if they have nausea, vomiting, diarrhea, have them go to the closest emergency room because it's imperative that they get rehydrated and tested as soon as possible.

[00:11:05] The recommendation for prevention in hypertensive patients. Remind your patients of the importance of taking blood pressure medications daily and at the time you recommend it. If you prescribed a low sodium diet, remind them that most canned foods or pre-prepared ones have a high sodium content and to please read labels and avoid the ones with high sodium content. Have patients do blood pressure monitoring and if their values are escaping for 3 consecutive days, have them call you for advise and adjustments to medications.

[00:11:48] Myths. Blood pressure medications make people more susceptible to the virus. You heard a lot more than I will tell you. At this point in time maintaining desirable blood pressure control is very important. Emphasis on taking the medication is a must. Some medications to control blood sugars should be discontinued to help fight the coronavirus. On the contrary, taking all the medication at the appropriate time and improving glucose control is essential. In the U.S for a while, we said masks are not helpful and smoking kills the virus. Those are myths.

[00:12:32] Facts. No country in the world was prepared for such a contagious virus. New data show masks do work, but not every mask is the same. Use a mask when going to the pharmacy, grocery shopping, et cetera. That's what we need to tell our patients to practice social distancing. Gloves are important that all surface is a great place for viruses to attach. So we need to tell people if you are going to use them, use disposable and trash them before getting into your car. Otherwise, you'll bring the viruses into your car, and into your home.

[00:13:15] COVID-19 and diabetes: Clinical implications. Higher prevalence of diabetes in patients with COVID-19 infections. Patients with diabetes have worse outcomes compared with those without diabetes, with higher hospital admissions and among hospitalized patients, higher ICU, higher ventilatory support and higher mortality. Inpatient hyperglycemia is associated with poor outcome. Inpatient management of diabetes we need to target the glucose whenever possible to below 180 or better yet.

[00:14:04] Insulin therapy is the preferred treatment regimen. In the ICU, continuous insulin infusion. If we have patients that do have DKA episodes, and there are expected, proper hydration with insulin infusion should be the standard. Please apply the DKA standards of care for your country. In addition, patients with diabetes should have frequent blood glucose monitoring, SMBG or CGM, depending on the patient and the country.

[00:14:42] Hypertension and COVID-19. What are the clinical implications? As you saw, there's a high prevalence of hypertension reported in several studies in patients with COVID-19. It is important to monitor blood pressure once diagnosed. There's no scientific evidence yet, you heard that very well that the ACE inhibitors or ARBs use is harmful. It could be beneficial, it could be harmful. We need a lot more information and a lot more data. In the meantime, tell you patients, control your blood pressure and take your medication.

[00:15:20] I know there is data on hypertensive episodes and the contribution of hypertension to that. I could not find any data, but it's clearly due to volume depletion and the status of the patient. Before we need to emphasize the importance of staying hydrated. Patients with hypertension have the worst outcomes. Highest hospital admissions and mortality. Prevention is best. Don't forget to emphasize to your patients to take medications properly and to stay physically active. It is very important for our patients with diabetes and hypertension, especially now in the U.S we're confined there are ways to do exercises at home.

[00:16:11] I want to finish by my concerns of what I see the 4th wave and here we may learn from our Chinese colleagues. I think that the biggest concern I have is psychological issues. I know we're going to have an economical injury is already known and burnout not only by medical people but also by patients.

[00:16:39] Today and the future. Prevention is the most important way to fight COVID-19. Control the best possible blood pressure and glucose - fasting, postprandial, and A1C. Good hydration is imperative. Rapid Diagnostic Test is now available. It should become the standard. Other tests are also very, very valuable. The vaccines are in different stages of development and will be ideal for high-risk populations and eventually for all of us.

[00:17:16] Therapy. There were some studies that came out recently, small antivirals with good results from The University of Chicago. There's data on Hydroxychloroquine and Azithromycin and others. We need to stay tuned to see what works best. Thank you so much for the invitation.

Discussion for All Cases from Dr. Jing Chen China

Panel Discussion--Cases from frontline
Treatment of COVID-19 patient with severe CV diseases

Prof. Jing Chen:: [00:00:00] Okay. Good evening, good afternoon, and good morning everyone. Today, it's my great honor to show the case of the emergent PCI of [inaudible] during the COVID-19 epidemic in Wuhan. This is a 48 years old man and he suffered from chest pain for two hours and was admitted to our hospital. The past history is Hypertension, Type II diabetes, and smoking. What is special is that he works as a volunteer at the Fangcang Hospital and has a history of the close contact with the COVID-19 patients.

[00:00:53] For the physical examination, the [inaudible] rate and the blood pressure is normal, but the heart rhythm is very slow. And no cardiac murmurs and no rales on lung examination. You see the 12-lead ECG of the first medical
contact within 10 minutes. So the heart rate is about 44 per minute in the lead and the reason is third-degree atrioventricular block. And in the lead of the two, three, and AVL there is a significant elevation of the ST segment.

[00:01:40] In all the chest leads, we can see a slight ST elevation observed and with biphasic [inaudible] waves in lead II and lead II leads in ECG. Since he has close contact with COVID-19, he received chest CT and admission within 30
minutes in an emergency room.

[00:02:09] This is the CT results. Here, is a modeling shadow in the right [inaudible]. And at the same time, this is what is the label said and a sample was taken off for the new [inaudible] assay and as well as the antibody detection taken at the same time.

[00:02:30] This is a lab finding and admission. Because the time of onset is only two hours so the cardiac [inaudible] is normal. In the test of the blood counts, the numbers of the white blood cells in the neutrophil is in the normal range. We pay more attention to the lymphocyte. Luckily, the numbers had not been declined. Only the serum the potassium level was seriously decreased. The primary diagnosis is acute inferior STEMI Killip I, [inaudible] hypertension, diabetes. There is still some doubts about [inaudible] anterior STEMI.

[00:03:25] Here is the workflow for the management of STEMI patients during the COVID-19 epidemic. For this patient, they had just suspected COVID- 19 but there is no severe pneumonia and the time of onset is only two hours, so we decided to take the thrombolysis strategies for him.

[00:03:52] This is the details of the thrombolysis. The thrombolysis was taken with a full-dose Alteplase with a 90 minute accelerated dosing. At the same time, heparin was used and the APTT was monitored to reach the target values.

[00:04:20] This is ECG at 30 minutes post thrombolysis. So we can see the admission ST elevations was increased by more than 50% in the 2, 3, and [inaudible]. The rhythm is back to the sinus heart rates.

[00:04:46] This is ECG under 60 minutes. At that time, the chest pain has been relieved. Although the ST elevation was back to normal, but there is a very strange here in the V2 and V3 leads. Poor heart rate progression was observed here. After two hours, the chest discomfort occurred with peaked T waves in the chest leads.

[00:05:20] From this ECG, we speculate that there is something happened for the LAD. So, if the spasm of the plaque rapture leading to the occlusion of the secondary ischemia but since the blood pressure is normal, so the third one is impossible. And that turns the results of the COVID-19 have not worsened. We consider the spasm, spasm is first considered reasons.

[00:05:56] So the diltiazem was immediately intravenous pumped, but at that time the patient suffered from the ventricular fibrillation suddenly.

[00:06:09] This is ECG after defibrillation. So we can see in all of the chest leads the [inaudible] segment was elevated very seriously. So it's very, very dangerous.

[00:06:27] Last approved by our hospital health commission and under the third-grade protection, the rescue PCI was done. In the other two scenes at hand [inaudible] under [inaudible] the left coronary angiography with the guiding, we
use the Transradial approach (TRA).

[00:06:56] So from the caudal position, there is no stenosis in the LCX. And the TIMI flow is TIMI III. But, of course, nearly, almost 99% stenosis in the mitral segment, and the with the [inaudible] limiting. So this is a process of the PCI, and this is the [inaudible]. And then, the drug-eluting stent was implanted and this is the post examination. There is a final result with no residual stenosis.

[00:07:39] Because the RCA is also the time factor related vessel, so the guiding was used directly. In the proximal segment of the RCA [inaudible] stenosis was unstable, plaque here.

[00:07:56] So this is also the process of the PCI is very simple. A stent was implanted. You see the final results of the RCA. So from the angiography results, although there is no residual stenosis in [inaudible] and LAD, but the blood flow
could not reach the [inaudible] totally.

[00:08:26] We preferred - the reason is micro thrombolysis. So the Enoxaparine was used for three days. This is another strategy, a therapeutic strategy. ECG post-PCI all the ST has returned to the baseline. After two days after admission, the
nucleic acid of the SARS-CoV-2 [inaudible] and these results have been checked repeatedly for three times. And this is the dynamic of the troubling.

[00:09:12] Before discharging, from this ECG we can see all of the ST segment have [inaudible] baselined and there are inverted peaked T waves. The results of the bedside USG showed the inject fraction is normal. The decreased wall motion in inferior and interventricular [inaudible] at back to normal after seven days. So within - almost 30 follow-up there is no ischemia, no bleeding, and no heart failure.

[00:09:55] So from this case I want to share our experience from [inaudible] hospital. In general speaking, for the emergent cardiovascular disease, the risk of the COVID-19 and the cardiovascular should be evaluated immediately in 30 minutes after admission. But for the regular examination for the cardiovascular system, it should be simplified, including the ECG, UCG, cardiac enzyme, all the D-dimers. For the COVID-19 examination, the test should be done with enhanced CT scans, blood cell count, nucleic acid, and antibody. Due to results of SARS-CoV-2 are not immediately available, we recommend the risk evaluation depending on the clinical manifestation, chest CT finding, and antibody.

[00:11:02] In such situations, in our experience, there is [inaudible] possibility for SARS-CoV-2 infection including, negative IgM without close contact with a confirmed case, no fever or respiratory symptoms and no ground-glass opacity in CT chest scan.

[00:11:30] Here is a workflow in our hospital. During the epidemic, if ASC could not be ruled out for the COVID-19, an optimized medical therapy strategy should be preferred in order to limit the hospital infection. Only in some cases, the emergency PCI could it be considered. The first one is failed thrombolysis or is not suitable for thrombolysis. Or very-high risk NSTE-ACS it's only been ischemic symptoms was difficult to control or hemodynamic or electrical instability persistent existed.

[00:12:19] As for this patient we decide to do the coronary intervention. So this is a message of the transport. In our center, the isolation ward in CCU is on the fifth floor, and special lab is on the first floor. We use the special-purpose elevators, and the transfer route is simplified.

[00:12:48] As for the - throughout the entire process, the third-grade protection for PCI should be enhanced. And the terminal disinfection must be guaranteed after PCI including the air, the instrument, floor, and the wall. All of this should be disinfected thoroughly after PCI.

[00:13:16] Here, I will show the results of the evaluation of this experience in our center. As we know, during the epidemic, all of the STEMIs within the window period was changed from the primary PCI to the thrombolysis combined with a rescue PCI or selective PCI. For the following NEST-ACS, anti-ischemic medication is considered as the first choice if there is some life-threatening situation, the emergent intervention therapy was affirmed. We defined this strategy or provisional intervention. We compelled these results as traditional emergent in intervention.

[00:14:08] We combined - the clinical follow-up was performed at 30 days. We see there is no significance between two groups about the compound data of the deaths, class IV heart failure, cardiogenic shock, re-infection, refractory ischemia, the intracranial hemorrhage, and the major systemic bleeding. So these results showed this experience is feasible in such special situations. This is my only question about that, is that which [inaudible] which is infected. [inaudible]. And so we can discuss later. This is my presentation, thanks for listening. Welcome to questions. Thank you.

All Experts

Scientific Discussion

Prof. Octavio Berwanger:: [00:00:00] We have just one minute left. Anyone who would like to do a comment in the case? Prof. MA, Prof. Davidson, Prof. Zhang, any remarks in terms of the case that you would like to make or some of the discussions?

Prof. Jamie Davidson:: [00:00:18] This is Davidson. How about diabetes? The patient had type 2 diabetes was on lead
foreman. I don't have an A1C. I know of that in China, most of the patients with type 2 diabetes that I saw totally different to the U.S because they're leaner, but they have abdominal [inaudible]. So we have data on the A1C?
Do you have data on how the patient was treated for his diabetes while in the hospital?

Prof. Jing Chen:: [00:00:59] In this patient there is glucose. He has a history of diabetes, but the glucose is normal, under the previous medications. So we continue with our previous strategy of before for this patient.

Prof. Jamie Davidson:: [00:01:22] All the stress that he was having did not make his glucose abnormal, and thenduring the hospitalization, he was not taking Metformin. Correct?

Prof. Jing Chen:: [00:01:38] Right. You're right. Yeah.

Prof. Jamie Davidson:: [00:01:39] Okay, okay. Thank you.

Prof. Jing Chen:: [00:01:41] Yes, yes. Okay.

Prof. Jun Jie Zhang:: [00:01:45] I have one comment. First of all, congratulations on the fantastic case and also your analysis, your data [inaudible] center and the results show actually [inaudible] with analytics therapy a prime PCI represents no any difference in term of 30 days of mortality. According to your case, I think combining with the clinical information and the angiograph results, I think both RCA and LAD is a capped vessel.

[00:02:16] If I do these PCI similarly with your procedural, I will perform ARD first because ARD, at that time, is a capped vessel. Then, I will also check the RCA angiograms because their radial stenosis is more than 15, so I will still treat the RCA.

[00:02:38] In terms of the reason for the anterior [inaudible], I think, actually, it's difficult in the [inaudible]. Maybe, I think, this younger patient has comorbidity, like hypertension and diabetes. So he suffers from acute inferior MI with a low BP. Maybe [unintelligeble] induce a spasm just as you mentioned. Finally, the occlusion of the AIV. That's my point.

Prof. Jing Chen:: [00:03:14] Yes, thanks, Dr. Zhang. The first ECG, [inaudible] like the RCA [inaudible] alteration of the ECG from the LED. So maybe these pull of these two yet. Yes.

Prof. Octavio Berwanger:: [00:03:39] Wonderful. I think it's a spectacular case, congratulations Prof. Chen we really learned from it and from your experience, and congratulations to your team, for handling the pandemic in China we have a lot to learn from people of Wuhan and Hubei.

[00:03:58] We are out of time, but I'll just like to hand back the words to Prof. Ma so he can finish the meeting. Thanks very much for everyone. I just landed over 7,000 people were with us. Basically, it was a big attendance. I have the number here or something. 7175, and the total registrations over 12,000. So it was something. A lot of people are following us. Prof. Ma, thanks very much once again for our invitation on behalf of the Chinese Society of Cardiology to have us here with your society today. Thank you.

Prof. Changsheng MA:: [00:04:36] Thank you. Today we have a wonderful session for international cooperation for COVID disease. Many mentioned in COVID-19 era. I think lastly, I'll invite Prof. Davidson you can give us closing remarks for today's session.

Prof. Jamie Davidson:: [00:05:08] Okay. I want to thank all of you. I've learned a lot from everybody. In the U.S I think we're reaching the peak and started to level and hopefully from all the lessons that we have learned from you, we can do better in the future. Thank you very much for inviting me to the session.

Prof. Octavio Berwanger:: [00:05:41] Thanks very much and have a great evening/afternoon.

Prof. Jing Chen:: [00:05:44] Thank you. Bye.

Professor Haiquan Chen, China

Topic #1: Lung cancer management during COVID-19 pandemic

Prof. Tony MOK:: [00:00:00] Yes. I think we've tried that. Yes.

Prof. Haiquan Chen:: [00:00:07] Yeah. The COVID-19 infection disease is suddenly come out. Nobody is ready for this pandemic disease. Early in the Wuhan area-. So this is the paper that just came out from the JTCS reported several experiences from the colleagues from Wuhan Tongji University. They reported a clinical course of Coronavirus disease 2019 in 11 patients after thoracic surgery and the challenges in diagnosis.

[00:00:52] So this paper - they invited me to give a commentary and the changes to the [inaudible] during the global Coronavirus pandemic. In that paper, they reported COVID-19 disease in January. They encountered about 11 patients after thoracic surgery they got COVID-19 infection. That accounted for about 9% of the whole surgery. The 11 patients finally got a severe illness about 36.4%, and mortality rate is 27.3%. So it's very a serious disease if the patient got the infection after surgery, so it's a big challenge for us.

[00:01:57] In China, especially in East Asia, there are a lot of GGO lesions turning out to be lung cancer. Unfortunately, at a very early stage, COVID-19 pneumonia seems like the early stage of GGO. Sometimes it's very difficult to make a differentiated diagnosis at first. But we don't have to worry about if the patient got the GGO lesion lung cancer. This kind of lung cancer is indolent, we don't have to worry about it, and we can have enough time to wait for some

[00:02:48] To our experience, if we cannot make a clear diagnosis, we can just wait for a period. So the lung GGO we can just follow-up for COVID-19 infection. Maybe several days later, patient got severe - maybe patient got fever, got pneumonia - serious pneumonia. But if the patient with the GGO lesion lung cancer, maybe the [inaudible] stayed there for a very long time.

[00:03:25] We got to wait for several weeks to find out the patient benign if the benign COVID-19 pneumonia got disappeared or got severe. And even benign pneumonia maybe so after the lesion will disappear. COVID-19 it got severe pneumonia or disappeared.

[00:03:54] If the malignant for several months the lesion will be [inaudible] there, so don't have to receive surgery immediately. For patient with sudden lesions of patient of lung cancer, a sharp period of follow-up or needle biopsy may be considered. We don't have to [inaudible] special time, we don't have to worry about this lesion.

[00:04:22] In some circumstances, where surgery cannot be delayed or some emergency cases. I think there should be a strict measure to prevent COVID-19 transmission. Two, the patient with epidemiological history should be observed for at least two weeks before the surgery. Three, for suspicious patients, nucleic acid test should be performed before surgery. During anesthesia in emergency surgery, the endobronchial blocker may be the better choice and also strict infection control practice should be followed. And make sure during this special time, you do everything, every procedure, every contact with the patient, make sure you are protected. Thank you.

Professor Yeon Hee Park South Korea

Topic #2: Breast cancer management during COVID-19 pandemic

Prof. Yeon Hee Park:: [00:00:00] Thank you for having me here, this very valuable opportunity. Can I show my slide?

Prof. Tonny MOK:: [00:00:15] You have to share your slide.

Prof. Yeon Hee Park:: [00:00:24] I can control my slides, right?

Prof. Tonny MOK:: [00:00:27] Yes, that's right.

Prof. Yeon Hee Park:: [00:00:28] Okay.

Prof. Tonny MOK:: [00:00:29] Right now, I'm not seeing your slide as yet.

Prof. Yeon Hee Park:: [00:00:34] Really? I already shared my slide.

Prof. Tonny MOK:: [00:00:37] Okay. Let me, at this moment, I can see your face, but not the slide yet.

Prof. Yeon Hee Park:: [00:00:47] Okay.

Prof. Haiquan Chen:: [00:00:49] I think in the bottom of your screen there, share your screen.

Prof. Yeon Hee Park:: [00:00:58] Yeah, I already shared my slide.

Prof. Haiquan Chen:: [00:01:01] Just click at the bottom.

Prof. Yeon Hee Park:: [00:01:08] So can you see my slide? My screen says that another participant is sharing their slide, so I cannot share my slide, the screen said.

Prof. Tonny MOK:: [00:01:24] Okay, can you try sharing again, please?

Prof. Yeon Hee Park:: [00:01:36] Okay. It's working. Okay. Thank you.

Prof. Tonny MOK:: [00:01:38] Excellent. Let's start.

Prof. Yeon Hee Park:: [00:01:41] Thank you. So let me make [inaudible] My area is breast cancer patient. I am a medical oncologist. So let me start with the screen saver of my institution computer. The screen saver shows like this.

[00:02:04] Every individual in our hospital, entering the hospital, is being screened with the constant update. For those that need to be examined further, they are given a wristband to wear and sent to the Febrile Respiratory Infectious Disease Unit at the ER. Anyone with a wristband is not permitted to enter the hospital. There is a kind of a screen at every gate that every individual who is entering the hospital, should be screened like this.

[00:02:49] Today, our key question is about the key challenge of the breast cancer treatment in terms of certain patient screening, prioritizing, and any change of the protocol, like that throughout the stages. But to me, I have no patient who tested positive up to now, because of our infectious pandemic, mainly focused in Daegu/Kyungpook province, but we have a protocol so I can share today. And lastly, I can share that our institution, their protection policy for healthcare professionals.

[00:03:35] Can we do the best for management of cancer patients as before? Or any compromise? So this slide is actually my summary slide from today. The lesson from MERS outbreak in Korea especially in SMC, Samsung Medical Center, in 2015, and countermeasures for the COVID-19 in 2020.

[00:04:01] At that time, 2015, I was quarantined two times because my patient and their guardians have been infected in ER. The infected patient had a critical ill stage IV breast cancer patient with MERS pneumonia. She died of MERS pneumonia, anyway, not because of the breast cancer.

[00:04:22] Another infected guardian of another breast cancer patient had serious MERS pneumonia needing ventilator care. From that time on, we have learned a lot and trained well. And now the protocol for COVID-19 is the older breast cancer patient from outpatient clinics were screened in advance for their symptom, including fever and their travel history when they're booking an appointment for the doctor's clinic. We screen using the call center and also the screening chest Xrays and also CT scan. If they have a fever or every other respiratory symptom, or travel history or residency in high COVID area such as Daegu/Kyungpook province, they are not allowed to be in the clinic for two weeks at least.

[00:05:17] All the breast cancer patients who will be admitted should receive SARS-CoV-2 RT-PCR testing, irrespective of any symptom. COVID-19 negative confirmed cases are only allowed to admit. And you may agree, in Korea, the rigorous RT-PCR screening for any suspected case, irrespective of patient and caregiver without limitation. I have experienced, one of my patients had three times of RT-PCR testing during these two last month. She presented at first with neutropenic fever, but anyway, she was screened. And then after- three weeks later, she also has a respiratory symptom, and then again, RT-PCR tests, and like that.

[00:06:08] It takes only four hours for the results to come out during the time. The suspected cases cannot enter inside the hospital, but in case of a serious case, they are admitted to a negative patient bed first and then confirming negative cases, transported to the routine oncologic bed.

[00:06:33] I'd like to share our screening questionnaire. According to the patient and caregiver guardians, we prepared it in English, Korean, and Chinese form. Also, you can fear, but it's Korea. I'm sorry, but this is our employee's screening
system. Every day I receive these messages two times a day with my cell phone and then I report my fever, and any respiratory symptom, and any travel history.

[00:07:11] Our institution has set up the protocol and countermeasure for each possible scenario. Listed chemotherapy process for clinical research and treatment flow of suspected COVID-19 mother and newborn. And any during treatment the COVID confirmed case is medical countermeasure, and each case without any symptom after surgery, as Dr. Chen has mentioned. I'm more focused on the chemotherapy process for clinical research.

[00:07:45] Let me introduce today's trial case. She's 57, female, triple breast cancer patient with De Novo stage IV metastatic breast cancer diagnosed in August last year, and like this. And then she enrolled in the Begonia clinical trial, randomized to Durva, Pacli, and Capivasertib arm. And very good PR showed but as scheduled, check the CT scan, but radiologists [inaudible] She has atypical pneumonia, including viral infection and DDX like COVID-19 also. We called her and the history travel, and any respiratory symptoms, but she was very steady and stable at the time.

[00:08:37] Anyway, we did the whole COVID-19 test, and finally diagnosed as drug-induced pneumonitis. Actually, retrospectively, she has also this kind of atypical pneumonia since December last year. But anyway, any suspicion, I should check their SARS-CoV-2 test anyway. And then, she luckily continued planned chemotherapy. You can find here, very faintly show here, but any GGO anatomy.

[00:09:14] So whenever I see that is it is like a test CT scan, I call them my nurse in my clinic [inaudible] of COVID patients and then sometimes stop to visit our hospital and sometimes regularly CoV-2 [inaudible] scheduled chemotherapy.

[00:09:38] I have actually two deviated case in on-going breast cancer clinical trial, both the DSA tool was scheduled, patient. Also a similar pattern, but her residency in Daegu province, that's why she postponed the two weeks later and then reported she delayed two weeks.

[00:10:06] In another case, no symptom and scheduled her visit on March 2, but the patient went to Japan and got back on February 27. Because of the outbound traveling, her cycle was postponed for two weeks. And finally after two weeks later, she had to receive her scheduled chemotherapy.

[00:10:37] For both of these cases, the investigator documented these on the medical record, and the study coordinator reported this to the study team, and in the protocol deviation due to delay dosing and out of visit window.

[00:10:51] So let me summarize my presentation. Impact of COVID-19 BC management in Korea. If a patient is not suspected as COVID-19 positive, she does receive her scheduled chemotherapies during adjuvant, neoadjuvant, and palliative chemotherapies with targeted therapy and or IO without any compromise. But if there is any suspicion, care schedules are compromised according to the protocol.

[00:11:21] In the clinical trial base, recruitment is impacted, but monitoring hold everywhere recently re-open, but discontinuation of study treatment and no COVID-19, COVID case in my clinical therapies patients luckily.

[00:11:44] Lastly, I'll just tell you a brief into the regulation of the Samsung Medical Center healthcare professionals for prevention of COVID-19. We have emergency call centers according to the symptoms and also their family member has COVID-19 predictive or not. Also the family member in his or her self quarantine. Also [inaudible] the department head and call center contact again. And every entrance is like this, there are several levels of COVID-19 equipment like this. They need to wear their personal protective equipment according to the area and the security like this. And it's so kind of similarly the employee with the symptom, we need a call to the different call center to 2115 like this, and they find that according to the call center guidance. [Inaudible] the clinic outside of the hospital and isolated area like this.

[00:13:03] Let me finish with kind of restaurant silent meal campaign for prevention from COVID-19 here. We have a very unique and simple and homogenous healthcare system, you may know that, so. Korean government is the only insurance company in Korea so that's why this system is possible. Also, we established a reputation and availability of the high-technology diagnostic tool. Also, very uniquely, we learned a lot and well trained from MERS outbreak in Korea in 2015.

[00:13:44] We are very familiar with the triage outside our hospital. And adherence to regulation. Keeps social distance and daily screening and also the report of the symptom and contact tracing using IT and self-quarantine. When you also the help of many negative pressure beds prepared. We use this 3T system, now I guess the COVID-19 in Korea has settled down but keeping social distancing continues. Let me stop here. Thank you very much.

Professor Matthias Guckenberger Switzerland

Topic #3: Delivering radio therapy during COVID-19 pandemic

Prof. Mattias Guckenberger:: [00:00:00] Thank you, Tony. Thanks for giving me the opportunity to present just a recent consensus statement we have published together with the European and American Society for Radiation Oncology and others mostly focused on lung cancer, but you can assume that many of the basic concepts, you can only also transfer to other cancer entities. I would like to thank, at the very beginning, David Palmer, who contributed tremendously to this project in the [inaudible] course, as well as the, contributed in a very strong amount.

[00:00:33] So the background, I think there's not much to discuss about it. It's become a pandemic defined by March 11th. There are certain risks populations which we are well aware of the elderly patient and patients in particular with
cardiovascular comorbidities. And that's also some indications that, in particular, cancer patients might be at increased risk for a severe development and a severe course of COVID-19 infection.

[00:01:04] What we know is that in particular in cancer care, but also in radiation oncology, we are facing different challenges depending on the phrase of the pandemic. And in general, we distinguish between an early pandemic phase, a contingency standard of care where resources are still being available, but our goal is to slow down the spread of the virus. And this later phase, so-called crisis of standard of care, where we have a lack of resources, where we have to prioritize patients and where we have to triage.

[00:01:36] In radiation oncology, we have the specific citations that patient has to come rapidly and repetitively to radiation oncology. They are exposed to additional risk, risk for the patient themselves, but also to radiotherapy staffing. And there might also be an altered risk-benefit ratio for patients based on this traveling and based on thoracic radiotherapy.

[00:01:59] Of course we have to address the question, "How do we handle cancer patients in a scenario of crisis? How do we triage patients?" We address the questions we have risks that need to be balanced - the risk of the COVID
infection and the risk of cancer. And how do we balance them? Do we need to- can we allow ourselves to adapt radiotherapy practice beyond current guidelines? That's why we actually use the consensus process, very similar to our guideline process, but a modified one for developing rapidly.

[00:02:32] The aim was to provide rapid guidance on the potential need to adapt practice which is the indication and also the fractionation of radiotherapy for lung cancer in the COVID-19 pandemic. We aim for endorsement of both societies -ESTRO and ASTRO societies. We had 32 international participants involved in this project, and it was in total of three rounds of surveys rapidly done between 23rd and 27th of March.

[00:03:01] We did the survey in a practical way. So we assessed six cases, typically cases for lung cancer. Stage I non-small cell lung cancer, inoperable, where radiation oncologist standard of care would be stereotactic body radiotherapy.
Case two was a stage III non-small cell lung cancer locally advanced, bulky N2, where the standard of care would be a concurrent radiochemotherapy followed by development. Case III locally advanced, non-small cell lung cancer being
resected and now being referred to postoperative radiotherapy. Small cell lung cancer limited-stage treated with concurrent thoracic radiochemotherapy. Patient having finished thoracic radiotherapy for small cell lung cancer and
chemotherapy, having a good response now being referred for prophylactic cranial irradiation. And last, the palliative case-patient with failure after first-line chemo-IO and now developing symptoms due to mediastinal and hilar disease progression and having severe cough and moderate dyspnea. We assume that all these patients would be standard and have average patient characteristics.

[00:04:14] The first question we addressed is how do we handle COVID-positive patients before we start treatment? The question was, do we defer treatment and wait until the [inaudible] patients become asymptomatic and COVID-19 negative. And there was a strong to very strong consensus for all six cases. We should not kind of rush into treatment with thoracic radiation in any of these cases [crosstalk] until the patient becomes COVID negative and becomes asymptomatic.

[00:04:46] The second question we asked was, what happens if we've already started radiotherapy and the patient becomes infected during the course of radiation? Do we interrupt treatment and wait again until patient becomes asymptomatic in COVID-19 negative. Here, we saw a mixed picture. We saw that there was consensus to interrupt and wait until the patient becomes negative in port, PCI, and then the palliative case, but there was no consensus for the radical treatments for early-stage and for locally advanced non-small cell lung cancer and the same for limited-stage small-cell lung cancer.

[00:05:23] We further addressed the question. How do we handle now this patient becoming COVID-19 positive during a radical course of radiochemotherapy for stage III and limited stage non-small cell lung cancer? What are the factors which influence our decision-making process?And we were able to identify three factors which we should consider in our decision-making process. Of course, the severity of COVID-19 related symptoms, the severity of lung cancer symptoms, and also whether we are at the beginning or near the end of our treatment.

[00:05:59] Another question we asked ourselves as well, maybe we could just postpone treatment - the start of treatment, maybe the pandemic becomes less severe. Why not postpone it by a certain period of time, 4-6 weeks.

[00:06:13] Again, there was a mixed picture based on the patient we saw. There was a strong consensus not to postpone treatment in the radical treatment, again for stage III non-small cell lung cancer and limited-stage small cell and also not for the palliative care, but the very strong consensus of 96%.

[00:06:31] There was consensus to postpone for port and the PCI, and there was no consensus being reached for the early-stage non-small cell lung cancer. So for that stage 1 case, again being inoperable, that we will treat with SBOT. We
asked for factors influencing the decision-making process to postpone radiation. And there was one strong factor, which was the growth rate - strong consensus of 87%. And there was some support for patient preference, solid versus GGO component, patient performance that's T1 versus T2, and current versus future status of the pandemic whether or not to postpone treatment.

[00:07:13] Another question that is heavily discussed in the radiation oncology community is whether we should alter our fraction, meaning whether we should squeeze the dose of radiation in a smaller number of fractions and each time delivering a higher dose of radiation.

[00:07:27] Again, we saw a picture that most people consented that we should not leave standard of care. For cases three to cases five, there was a consensus not to pursue any hyper fractionation. Even in this early phase of a pandemic, there was a consensus to go for hyper fractionation, either in five or down to a single fraction for the palliative case, and there was no consensus being reached for non-small cell lung cancer in stage one and stage three.

[00:08:00] Another question to be addressed is the multimodality treatment strategy for stage three where the standard of care would be concurrent rate of chemotherapy for the [inaudible]. There was a strong consensus for continuing and doing concurrent radiochemotherapy as a standard of care, not switching to radiotherapy
alone, and also not switching to sequential chemoradiotherapy.

[00:08:24] That was no change in treatment strategy depending on the EGFR status and also not on PDL1 status. And we also address the questions," Are there certain chemotherapy combinations, which might be at a higher risk in this pandemic scenario?" And there was some concern about carboplatin pact attacks, potentially due to increased risk for pneumonitis and [inaudible] suppression. Now I would like to switch to the later pandemic scenario. Remember, this is the scenario where we do have a shortage of radiotherapy resources where we have to prioritize patients, where we have to triage patients. Again, we asked about hyper fractionation and here if we have less radiation resources being available, there was consensus in four out of six cases to go for more severe to go for more hypofractionation.

[00:09:15] Not in port, and not in PCI, but in all other four cases, we should go for hyper fractionation in this later and severe phase of the pandemic. We also ask, "How do you prioritize patients having lung cancer compared to all other cancer patients, which are referred to a radiation oncology department?" And then we saw a very interesting picture. The radical treatment for stage three non-small cell lung cancer, and for limited small cells, they were ranked as having the highest priority. Stage one was still kind of intermediate. Interestingly, for the palliative treatment, we did not observe any pattern. Some members and participants rated it as very high priority. Some said, "Well, it's only palliative. We should have it low priority." So there was a widespread dispersed response.

[00:10:05] Low priority. That was consented for the post-operative radiation and also Potter prophylactic cranial irradiation. And lastly, we address the question what effect does which are influencing the triaging of your patients. And we did an open survey at the beginning and then the ranking them in decreasing relevance at the top number or the top question, which was influencing triaging of patients was the potential for cure, relative benefit of radiation to any other treatment options, active COVID-19 infection or its absence thereof, life expectancy and performance status. And here you can see the kind of ranking of these different factors being strongest for the potential of cure and factors.
Just like comorbidities and age down here, having a very low priority.

[00:10:53] Let me summarize. First of all, I think it's important to make sure to make clear that there is not a standard of care. Even in this pandemic, we have to adapt our practice to the local situation where the pandemic is actually running. In an early risk mitigation scenario, we saw that efforts should be made not to compromise the prognosis of lung cancer patients by departing from guideline-recommended radiotherapy practice. But postponement or interaction afraid to therapy for COVID-19 positive patients, that was generally recommended to avoid exposure of cancer patients, but also to protect our staff from COVID-19 infections such that they can continue their cancer treatment.

[00:11:37] In the latest severe pandemic scenario, which [inaudible] the rise for reducing resources. If patients must be triaged, we were able to identify parameters that allow us or support us to perform this prioritization, these
three arms of the patients. Thank you very much.

All Experts

Panel discussion and Q&A

Prof. Tony MOK:: [00:00:00] Thank you so much, Matthias, for the excellent summary. It's amazing how you guys can pull a consensus together in such a short time. It's truly amazing, and this is very helpful as a guideline to our radiation oncology colleague.

[00:00:15] Now we're going to move on to the discussion, but before we do that, I would like to take just one minute to cover the systemic therapy for lung cancer. I mean, in a way that Dr. Chen talked about lung cancer as a surgical side. You talk about radiation side, but for systemic therapy for lung cancer, I just want to share with you briefly on what happened in Hong Kong.

[00:00:35] Currently, we don't have a very serious situation right now, but we're taking all the recautions just like what they have done in China and Korea and other parts of the world. And we also try to mandate to cut down the visit of other patients.

[00:00:47] In general, for lung cancer, we categorize them into three groups. One is the patients who keep on active treatment. The other group is the patient who actually just on maintenance treatment. The third group is the patient who actually on follow-up.

[00:01:00] Patient on followup we basically defer them. We just tell them not to come back for follow-up for quite a while until things settle down.

[00:01:07] Then on the patient on active treatment, we try to give them exactly what they used to get. However, we tried to cut down the visit by avoiding the [inaudible] because they did come down on day 1 and day 8. And so in a way of them to Cabos red, to bleed nontoxic. So we choose the therapy that makes it easier, lesser toxicity in terms of

[00:01:29] Now the biggest controversy is the patient on maintenance therapy because we've got a lot of patients on TKI, we got a lot of patients on immunotherapy, and also maintenance [inaudible], that's a large number of patient. A lot of work that you come with this group.

[00:01:43] The question is, can we reduce the frequency? It's controversial. We are not as good as you are to take on a consensus, but we do take out within the hospital consensus to reduce the frequency. Usually, these may come back to every 6 weeks for the medication we extend that to 12 weeks. So in a way that we can just renew the order by the phone or by the relative data so patient doesn't have to come to the hospital.

[00:02:08] Maintainance therapy for the immunotherapy. We basically can reduce - that increases frequency to every 4 weeks, every 6 weeks, and hopefully that we will just minimize the number of these patients. And in fact, this is actually quite possible.

[00:02:21] That briefly summarizes, what we do on systemic therapy for lung cancer. Now, let's go to some of the questions. Let me just throw in the first question to Dr. Park. It's very interesting that you are actually providing tests to all breast cancer patients who come to the hospital. My question is, "Is it necessarily the case, you have the patient asymptomatic and no exposure, or would you recommend that to all the other cancer patients to receive the COVID-19 testing before they get admitted to hospital?"

Prof. Yeon Hee Park:: [00:02:58] Not all the patients, not all the kinds of patients, but the patient who is admitted to the hospital and also the surgery - any surgery patient, they should. It's not my guidance, but our institutional policy. The asymptomatic outpatient clinic patient is okay, but if they hyper checked their routine no respiratory symptom, no travel history, and no kind of contact history, they can be allowed to enter the hospital without COVID test.

Prof. Tony MOK:: [00:03:41] I see. Okay. Thank you.

Prof. Yeon Hee Park:: [00:03:43] Okay.

Prof. Tony MOK:: [00:03:44] Dr. Chen, in China, what can a patient do the testing on? Do they have to have symptoms first or do we just do it in general?

Prof. Haiquan Chen:: [00:03:52] Yeah. Tony, I think you asked a very good question. At the first in February or early March, all the tests are not available in every hospital. In Shanghai, we got a very serious quarantine policy. So the hospital opened out time and, if the patient will be hospitalized, we do the same. We check the patient's temperature and the blood routine, and also the chest CT for the chest CT screen. If your temperature is normal, your blood count is normal and your chest CT is normal, then the patient can [inaudible].

[00:04:53] And actually before that, also outpatient epidemic history. Have you ever contacted a patient or a highly suspicious patient? After that, if all the tests are negative, then we can hospitalize the patient.

[00:05:14] Tony, you know why we do that? It's very serious in Wuhan area. At first, there are a lot of hospital staff, hospital employees, they got infected. And if the hospital is infected, all the employees infected, there are other serious
consequences, no doctor to see the patients. So I think it's understandable we took this very serious policy.

Prof. Tony MOK:: [00:05:46] Right to protect the staff is very important. Matthias, I got a difficult one for you. Now I can see the high consensus that you will continue with the routine standard dosage of radiation for stage three lung cancer, which actually I agree with you because potentially curative. Now, what if a patient, during radiotherapy develop upper respiratory tract infection and a fever? Will you stop the radiation? What would be your management?

Prof. Matthias Guckenberger:: [00:06:16] Actually, we had few of these cases who developed kind of fever like symptom and kind of coughing, which is not untypical for patient's having lung cancer that they do cough, that they might develop a kind of a slight fever during a radiochemotherapy.

[00:06:31] So what we've done is in this case, first of all, we've done a proper screening by our RTTs. They come to radiation on a daily basis and they are kind of asked by RTT daily whether they develop any symptoms. If they develop any symptoms, we test send them for testing immediately and we interrupt treatment until well, 24-36 hours. That's how long it took, so far, to get a test. If the test was negative, obviously, we were able to continue treatment. If the test was positive, well, we would have to consider where we currently are in our treatment protocol. Most likely we would try to finish treatment, but if we would be very early in the beginning and would expose our staffing to a large number of [inaudible] to COVID-19 positive, we would interrupt and then restart if the patient becomes asymptomatic again.

Prof. Tony MOK:: [00:07:22] Let me push this a bit further. Prof. Zhong Nanshan from China just talked about a silent carrier or asymptomatic patient. Now in a way, is that, will one testing negative be sufficient to assure you that it's safe enough that it is a negative case? We've got a false negative and some patients got delayed in terms of their rise in the viral load. So that may take 4-7 days. How will you manage that? Because there's always a worry that you are subjecting the patient to a radiotherapy machine, that every other patient may get exposed to the same area.

Prof. Matthias Guckenberger:: [00:08:01] That is a true concern. And we have considered that very carefully. We have a similar practice. Every patient being admitted to inpatient care, he's going to be tested. And we know that the sensitivity is not perfect, maybe 70-80% if we even know the sensitivity. For the outpatient treatment. We do not have a standard screening being implemented yet. Mostly due to a lack of M screening resources and testing resources that will be implemented by next week.

[00:08:27] What we currently advise is to do every kind of proper hygienic measurements for RTT so they are all wearing their gowns, they're all wearing the eye protection, they are all wearing their masks and that we do a kind of M disinfection after every patient treatment. That's how we kind of try to minimize the risk, knowing that we don't have a risk, which is minimum, considering that we have patients going into our treatment room for 30 days in a row over six weeks, and they just come from the outside. That is a true concern and risk.

[00:09:00] Interestingly enough, we have not had COVID-19 positive patients so far. And also, if we look at our oncology board, we have seen very few COVID-19 positive patients that having a severe kind of infection. So I'm not really convinced that the cancer patients are truly at a much more increased risk for having a severe course of disease. I think this start is not really strong I would say. They are at risk, but we don't know how large this risk actually is.

Prof. Tony MOK:: [00:09:29] Thank you. Now, Dr. Park, I have not treated breast cancer for a while, but I still remember the good old day of Adriamycin and Docetaxel, which is really quite myelosuppressive. In an adjuvant setting and view of the pandemic, you try to avoid neutropenia. Would you either effect- Question number one is that, would you delay the adjuvant chemotherapy for patients with breast cancer early stage? Number two is that would you reduce the dose such that you would avoid the risk of neutropenia during this period.

Yeon Hee Park:: [00:10:01] It's really a good question. So Docetaxel also induce the kind of a drug industry [inaudible] long, so this is another problem. But as I introduced the mention in our guideline, according to the guideline, if there is no kind of any suspicion, if I introduced, we have no delay. And if there is any suspicion, it delayed two weeks and then be evaluated. And then we assist, like that. And then in terms of total reduction, that actually recommended up to now. But it's a really the physician's discretion. So according to the patient age, and the situation, and her residency, these days like that. Really, like personal discretion.

Prof. Tony MOK:: [00:10:57] Yeah. You personalized on the individual situation and make the decision accordingly.

Prof. Yeon Hee Park:: [00:11:01] Yeah, yeah, yeah.

Prof. Tony MOK:: [00:11:03] Going back to the lung cancer situation, Prof. Chen, if there is a patient with a stage two disease, would you consider new adjuvant chemotherapy so that you can delay the surgery, which is the high risk. Are you going to, in a sense that if there is an epidemic going on, we'll still subject the patient to surgery or delay it with adjuvant chemotherapy?

Prof. Haiquan Chen:: [00:11:27] Yeah. I depend on different situations, and age of the patient, and academic logical [inaudible], patient no fever, and the chart show that no [inaudible] patient pneumonia, we don't have to wait. Under our [inaudible] we get to quarantine the patient for two weeks. We can delay the surgery for two weeks. That intubation time before the COVID-19 virus infection. Two weeks, just before the surgery workup, maybe one week, and then did it for one week. They're not a big deal. We can schedule the patient one week later. Not a big deal. I think we do the surgery first now. Also, the chemotherapy has imposed the same [inaudible] on a patient that is COVID-19 infected in the intubation time.

Prof. Tony MOK:: [00:12:37] So this is one question for everyone. Should we start immunotherapy now? I mean, in a sense is that if the patient got an indication for it. Do we worry about the intersection of pneumonitis related immunotherapy, which can confuse with the COVID-19 picture? Should we avoid it, or should we just business as usual to start, I just like the way used to do anyway.

Prof. Haiquan Chen:: [00:13:00] You mean China Mainland?

Prof. Tony MOK:: [00:13:04] Yeah. In China Mainland for example.

Prof. Haiquan Chen:: [00:13:06] Yeah. I think it's the patient highly suspicious of COVID-19, you look for one week. You just watch the patient one week. If he got COVID-19 infection patient getting serious pneumonia getting better or getting worse, I think...

Prof. Tony MOK:: [00:13:30] [cross-talk] Immunotherapy. Should we start immunotherapy? That was the question. Yeah.

Prof. Haiquan Chen:: [00:13:37] Actually, and I'm sorry, I have...

Prof. Tony MOK:: [00:13:39] It's okay Chen, I know.

Prof. Haiquan Chen:: [00:13:44] Yeah, yeah.

Prof. Tony MOK:: [00:13:44] [cross-talk] Would you prefer the patient to start immunotherapy at this time, or just say avoid immunotherapy completely, Matthias and Dr. Park?

Prof. Matthias Guckenberger:: [00:13:53] Well, in radiation oncology, we have only one indication for immunotherapy,
which is in the kind of adamant new maintenance setting after stage III radiochemotherapy. And considering the large benefit in terms of overall survival by adding Nivolumab up in that situation, I would not expose the patient to a risk of not experiencing that overall survival benefits. I would continue to give him, MIO. Maybe I would be more cautious with the time of starting. I'll see if the patient would have some mild symptoms after chemoradiation, maybe some radiation-induced pneumonitis, I would wait a bit longer to the patient for recovery, but I would not offer him such a treatment
with such proven benefits. So I would continue.

Prof. Tony MOK:: [00:14:34] And Dr. Park?

Prof. Yeon Hee Park:: [00:14:36] Yep. Actually to me, the main breast cancer beta IO population is trial based patient to up to now. So typically, I follow the strict protocol. Also whenever I have a question I asked to talk to the protocol team. So, and these days, most of the protocol has COVID-19 guideline also, though. Approximately adaptive to the guideline and breast cancer - triple breast cancer, first-line [inaudible] in Korea, a tocilizumab. In that case, if our patients agree that they are risk, and then most of the population who the other indicative that regimen as very young premenopausal patients. So to me, we can continue.

Prof. Tony MOK:: [00:15:36] Thank you so much. Under the note, I would like to thank you all for participating in this podcast conference on management cancer patients in the COVID-19. I've actually truly enjoyed this meeting, I learned a lot from each one of you and I certainly appreciate all the participants who will listen to our discussion.

[00:15:54] Hopefully this is just the beginning. I think this is going to be a long battle. Cancer patients would be around, COVID virus is going to be around, and we're going to mingle what this for the many months to come.

[00:16:06] And certainly I think although we are distant socially, and we cannot meet each other, but certainly while united in the heart, in this war against the COVID-19. So thank you very much for your time. I wish you would have a good evening and a good afternoon. Thank you.

Prof. Yeon Hee Park:: [00:16:22] Thank you very much.

Prof. Haiquan Chen:: [00:16:23] Bye.

Prof. Matthias Guckenberger:: [00:16:24] Have a good evening.

Prof. Tony MOK:: [00:16:25] Bye-bye.

Prof. Yeon Hee Park:: [00:16:26] Bye-bye.

Prof. Haiquan Chen:: [00:16:27] Bye.

Professor Mary IP Hong Kong, China

Management of chronic airway diseases during COVID-19 period

Prof. Mary IP Sau Man::[00:00:00] I will briefly talk about COVID in patients with asthma or COPD, that is the association and then focus on the management of asthma and COPD patients without COVID.

[00:00:18] I cannot see the slides, but I assume we're going onto the second one.

[00:00:22] Now regarding the association of COVID with the comorbidity of asthma or COPD, largely in the early case series from China, Europe, or even the USA, there was not any excessive representation of asthma or COPD as comorbidity.

[00:00:40] Although a very recent data from the USA on the COVID net surveillance, and they only had the data for about 178 patients out of their whole cohort of 1,500 in March. About one third had chronic lung disease and 17% had asthma and about 10% had COPD or depending on which age group too. But now this is of course only an association and it's really difficult to know whether this is an underrepresentation or what are the factors that affect this reporting.

[00:01:17] Well, on the other hand, we are also interested whether if you have asthma or COPD, then you would get more severe COVID. Again, the early reports vary. In the smaller reports from China, there was no particular association, while the most recent China nationwide report of 1,590 COVID positive patients.

[00:01:42] One can see that adjusted for age and smoking stages, COPD was a risk factor for admission to ICU or invasive ventilation or death. Although - actually the most common comorbidities or was not COPD, it was actually hypertension. But the message was that the more comorbidities you have, the worse the prognosis. And having COPD, obviously, will not improve the prognosis if you catch COVID.

[00:02:13] However, we are now going to talk about the large populations of non-COVID patients who are suffering from asthma and COPD. And we have to know what are the basic principles of management. And I would say it follows the basic principles of managing almost any other disease. First, we would like to avoid the risks of catching the virus and that we would all follow the usual principles right of wearing masks and social distancing and isolation if you have been close contact, et cetera. But, the more important point is that we must actually maintain the stability of the airway disease. Because obviously if you have an exacerbation of the management will be a bit more complicated. So for that, we have the GINA guidelines for asthma and the GOLD guidelines for COPD.

[00:03:18] Now, if we look at the asthma patients our maintenance medications, we know that many of them will be on inhaled corticosteroids, or the combination of new corticosteroids and LABA, which previously was introduced in the more moderate cases in step three but now it may be taken on necessary basis in step one.

[00:03:45] So the other, such as the short-acting beta-agonists, the LAMA, the [inaudible] and the oral theophyllines are also used. So far really, I think the major focus is on inhaled corticosteroids. On whether they would do any harm. Or actually, there is another school of thought, whether they would be of benefit in preventing the COVID. I think right now the belief is still that there is no evidence that it would cause any harm, and therefore it is most important to keep using the maintenance therapies that the patient has been taking and not to allow abrupt disruption or they are taking off the medication so that the exacerbation will come later on.

[00:04:42] In severe asthma, these patients may be on low dose oral steroids, long term of biologics. Suppose we always worry about the issue of oral steroids as an immunosuppressant in COVID infection, but again, the same motto applies. That if the asthma needs to be controlled on that low dose, we can only do the usualtitration trying to keep it as low as possible, but not to just take it off abruptly and because the patient will then go into uncontrolled asthma.

[00:05:21] For the use of biologic there has been also some concerns, for example, that these patients may generally with COVID have a low eosinophil count already so would they be actually not needing the biologics or they would actually be more prone to the infections.

[00:05:42] Again, there is really no evidence that biologics would be promoting their susceptibility to COVID. And the fact that [inaudible] is low maybe just a general response to the infection. In fact, many infections and also that being a biomarker in biologic therapy [inaudible] does not mean that it has any pathogenetic significance necessarily either in the COVID situation.

[00:06:18] We are on to the maintenance medications in asthma. And as I was saying that it's most important that we maintain stable asthma with whatever medications, including the inhaled steroids that the patient will have. Because it is well established that viral infections, in general, maybe a trigger for asthma exacerbation so we would not want them to catch any virus not only COVID but others.

[00:06:47] Therefore, COPD actually - of course, the medications are, in one sense, sort of similar. The LABA/LAMAs taking the priority, but some of them may be on inhaled steroids only on the theophyllines or the [inaudible].

[00:07:02] And again, there is no evidence that any of these medications would be not good for COPD patients during the COVID period. And therefore we must keep them on the medications as much as possible. And in Hong Kong, the hospital authority has been very prompt in that at the beginning of the COVID epidemic, they asked that patients who are coming to the clinics for follow-up can be allowed to just call in and come for drug refills without really attending the clinic. And so that they can have their medications, maintain their treatment, and yet not crowd the hospitals at the outpatient clinics. And anyway, many of them are quite scared of the healthcare setting as well.

[00:07:51] Then we go onto the acute exacerbations of asthma in COPD. And from our data, in the recent months about the A.J. Hospital admission, there's actually no obvious increase in admissions due to asthma or COPD exacerbations.

[00:08:10] In fact, there may be a decrease in the COPD exacerbations and resulting in hospital admissions that we usually see year-round. And compared with the same period last year, this actually is no increase but or even a lower admission. Well, we think maybe the patients are too scared, they don't want to come to hospitals, but in that case, they still would be having exacerbations, and they have to go somewhere. So is it because of all the other measures to prevent COVID? So they stay home, they are not exposed so much to the triggers, and therefore they really don't get as many COPD flare-ups. That is something to be explored.

[00:09:00] So if a patient comes in with an acute exacerbation either of asthma or COPD what do we do? Because the symptoms of COVID infection may be quite similar to that of an exacerbation except that they may have fever or they may have myalgia if they do have a viral infection.

[00:09:25] But on the other hand, they may be quite asymptomatic. We know that there are so many asymptomatic carriers. So basically what we do is, we definitely screen for COVID with nasal parenteral spray or a swab, but to make sure that they do not have COVID infection. And then we can go on to the standard treatment of an acute exacerbation.

[00:09:49] But we may need other investigations to prompt us or to exclude the possibility of a COVID like a chest X-Ray, or in some typical cases, even a CT thorax. And of course, we will do the usual microbiological [inaudible].

[00:10:06] Now, for airway management, it would be airway management for acute exacerbations as usual. For inhaler therapy, we would certainly use all the beta-agonists or maintain - continue the inhaled steroids.But one word is
there's no nebulizers. In fact, we have no longer used nebulizers ever since the days of the SARS in our public system.

[00:10:34] And systemic steroids would be given as indicated. And for giving oxygen, we would use supplemental oxygen through the nasal cannula, but we will have to be careful about using further devices, which I will briefly look to later. And of course, we would like to treat any other infective trigger because there may still be bacteria or other viruses.

[00:11:00] And for the device usage, as I said, we would not use nebulizers. We do not do any peak flow measurements anymore because although they are not exactly aerosol-generating, nowadays, there is more evidence that these deep flowing measurements may lead to some form of COVID spread, and so being more clinical in our assessment.

[00:11:29] And also the use of non-invasive ventilation in COPD is actually a big issue because we do not want to use non-invasive ventilation in the general wards without negative pressure. Earlier we talked about screening out COVID first and then patient can be using non-invasive ventilation, especially adding on a non vented mask and filters. And that will help to reduce any potential spread, and of course, the idea is that it is done in a room with negative pressure
facilities, which is a luxury which may not be affordable. High flow oxygen, again, avoid the high flow oxygen devices as you heard from other speakers.

[00:12:22] At this point, it is a good reminder but although it may be a little bit late sort of to do it right now in the rush, is that we should vaccinate our patients against influenza and pneumococcus so that they would not get superinfections which are associated with the worst prognosis if they are COVID. Or at least it is very common as a superinfection in COVID and especially in the elderly. And also that they would not have influenza to sort of mix up the picture. And also we will always advise stopping smoking and there is some suggestion that smoking may predispose to COVID infections.

[00:13:07] So with this, unfortunately, I may not have been able to show my slides I hope I've shared with you my views on the management of chronic airways disease during the COVID period.

Professor Xiaoxia Lu

Management of pediatric asthma during COVID-19 period

Prof. Xiaoxia Lu:: [00:00:00] Hello everyone. Today is my great pleasure to be here to give a representation. My topic is Pediatric Asthma Management during COVID-19. I will talk about it from the two parts. The first is background and the other is our experience.

[00:00:26] It's well known that an ongoing outbreak of pneumonia associated with a novel coronavirus was reported in Wuhan, China in December 2019. In the following weeks, infections spread across China and other countries around the world.

[00:00:44] On February 12th, 2020, WHO named the disease is COVID-19. On March 11th, the WHO announced the COVID-19 outbreak a pandemic. WHO Director-General remarks on the disease like this. He said, "We are at war with the virus." And he used the four numbers to describe the disease. That is, "67 days, 11 days, 4days, and just 2days." That means the first 100,000 cases took 67days, the second 100,000 took 11 days, the third, just the 4days and the fourth, just
the 2days. That means the pandemic is accelerating.

[00:01:37] So, Wuhan is the center of the outbreak... and control the disease effectively the government make a very big and important decision that Wuhan is to shut down. So everyone in Wuhan just like me, stay at home and avoid face to face contact. The big city is in silence. Wuhan Children's Hospital is where I worked. It's the only center assigned by the government for treating COVID-19 children. This is our team - so from there on we together to treat the COVID-19

[00:02:23] Next, I will talk something about our experience. Everyone knows asthma is one of the most common chronic respiratory diseases. From the figure, we can see the prevalence of asthma in China's children is increasing by about 50% every 10 years. There is- In 2000, the prevalence is 1.97%, but 10 years later, it's 3.02%.

[00:02:55] This is a study about asthma control. From the frequency, in the past 12 months among the children, about 27% had visited emergency department. About 70% had been hospitalized. And about 10% had visited emergency department and be hospitalized. Because of asthma attacks, almost 37% of parents were absent from work. So that means the current level of asthma control is not optimistic.

[00:03:34] During the COVID-19, there are several challenges in the management of asthma, such as all of the people stay at home all the time. And the reduction of exercise. And it's very inconvenient over visiting a doctor and so on. So failure management in asthmatic children can lead to an acute attack. So we should pay more
attention to long-term management.

[00:04:04] Based on this background we have, we should, we could follow the three principles to the management of asthma. The first is standardize treatment. The second is the family management, the last is online management. Let me talk about it one by one.

[00:04:25] The first is standardize treatment. As we know, the latest version of GINA has published the COVID-19 and asthma. It suggested that the world patients with asthma to continue with their prescribed medicine, particularly inhaled corticosteroid  (ICS) and oral corticosteroid  (OCS) It is said asthma medicine should be continued as usual. Stopping ICS often leads to potentially dangerous worsening of asthma. And it is suggested that make sure that all patients have a written asthma action plan and we should avoid nebulizer whenever possible and so on. So according to the GINA analysis suggestion, we have some management tips to reduce the risk from Coronavirus.

[00:05:26] I have listed some advice here, but in my opinion, I think the most important is the four parts. The first is because we stay at home all the time we mentioned we should have a very clear head that we should continue asthma controller inhaler daily. Third, we can use action plan to help us to recognize and manage. At the same time, we can start a peak flow diary if we have this.

[00:06:01] So for the China Asthma Action Plan, we have two versions. One is the paper version and the other is the app version which prepared in 2016 and app released in 2017. It used the color of traffic lights to manage asthma. They
have three zones, the Green zone, Yellow zone, and Red zone. For example, let's take a quick look.

[00:06:32] If we are in the green zone, that means asthma is well controlled and we should just maintain controlling dose daily. If we are in the red zone, that means acute attack of asthma, we should use emergency medicine and ask for help. So it is an effective tool for both doctors and patients to strengthen the management of acute asthma attacks.

[00:07:01] For the family and treatment, first we suggest the doctors and the parents form a partnership. Then let the parents know the performance and the principle under the doctor's instruction, the parents can choose the appropriate inhaler or nebulizer because it's specialized for the acute attack. Nebulizer is easy to operate for parents and the children can better cooperate with inhalation in a familiar environment.

[00:07:36] The second we can choose the appropriate medicine and we can choose the right course of treatment. All of this, we should let the parents make plans for regular follow-up.

[00:07:52] For the online treatment and management in the outbreak, many parents are afraid to visit the hospital and the pharmacy. They can get medical consultation and medicines through an online form, just like the WeChat and the online. So we think COVID-19 pandemic promotes the development of internet and the medical model.

[00:08:17] So all of the work and during this time, we are very grateful to Dr. Gary, Dr. Sau, Dr. Shin, and Dr. Yung and all the medical nursing and the supportive staff on the Wuhan Children's Hospital for their dedication in looking after the patients during their epidemic. That's all for my presentation. Thank you for your attention.

Professor Huiqing Ge

Management of Covid-19 patients with asthma and COPD in ICU

Prof. Huiqing Ge:: [00:00:00] Thank you. Thank you, Prof. Sau, and our narrator. Thank you, everyone, for inviting me to participate in this discussion. And it's my pleasure to share my experience about the management of critically ill COVID-19 patients, with asthma and COPD in ICU.

[00:00:28] According to the meta-analysis, which published online at [inaudible] academic emergency medicine on March 24, 2020, the [inaudible] prevalence of smoking history in people infected with SARS-CoV-2 were estimated as 7.6%. COPD was among the most prevalent underlying disease among hospitalized COVID-19 patients.

[00:00:57] Previous epidemics of novel Coronavirus disease such as severe SARS and MERS, they still share with the similar clinical features and outcomes. One might anticipate that patients with COPD and the other chronic respiratory disease would increase the risk of SARS-CoV-2 infection and more severe presentation of COVID-19. However. it is striking that both diseases appear to be underrepresented in the comorbidity reporting for the patients with COVID-19
compared with the global burden of the disease estimates of the prevalence of these conditions in general population. Maybe they are some reasons.

[00:01:51] I think I want to share the experience about the COPD patients who suffered from the severe ARDS the critical ill patient for the COVID-19, these kinds of patients. For COPD patients, Coronavirus pneumonia there's a part treatment in ICU that is the same as the other patients.

[00:02:17] We have paid more attention to the patients with airway resistance - may be the higher airway resistance and more obviously respiratory distress. So they're severe hypoxia and hypercapnia in the critically ill COVID-19 patients. So the [inaudible] and the gas exchange of these patients with chronic lung disease should pay more attention.

[00:02:45] And the non-invasive ventilation will consider the first choice when patients have the respiratory distress. We supply the patient by the non-invasive ventilation, we should focus close monitoring or when the NIV is ineffective
for the patients and then respiration is not improved the hypoxia and hypercapnia of [inaudible] are not improved. it is necessary for active intubation for the patients.

[00:03:24] In addition, we need to carry out effective aerosol therapy for the COPD patients including inhalation bronchodilators and ICS. Although inhalation treatment may increase the aerosol dissemination, it can still be carried out under the effective prevention and control of infection. For example, we can choose the nebulization driven by the ventilator and hydrophobic filter through the exhalation [inaudible] ventilator, put on the general surgical mask for
the patients, keep the negative pressure ward or room ventilated.

[00:04:05] So when the patient with the history of COPD has been admitted to our ICU just the one patient the patient's PF ratio is not so bad, is above 150. High flow oxygen therapy and the nasal cannula exhalation inhalations where therapy was used alternatingly. The patient's condition was stable after inhaled SABA and ICS the patients were better and transferred to the ward after improvement.

[00:04:45] The other scene moreover - although the NIV might be reduced intubation and the mortality in the mild ARDS, it is associated with higher mortality in moderate to severe ARDS. And a high risk of failure of MERS and that's including the COPD suffered by the COVID-19.

[00:05:08] Delayed intubation as the consequences of its use might increase the mortality That's very important That's the most important point. That's NIV and the high flow nasal cannula should be reversed for the patient with mild ARDS with close monitoring.

[00:05:27] Intubation of the patients with COVID-19 also poses the risk of viral transmission to healthcare workers, and the intubation drills are crucial. Most killed operators available should perform that test with four PPE and the necessary preparation for difficult airway. Number of the assistants should be limited to reduce the exposure.

[00:05:53] The other thing is the bag-mask ventilation which generates aerosols should be minimized by the prolonged pre-oxygenation. A viral filter can be placed between the exhalation valve and the mask. A [inaudible] injection with the muscle relaxer will reduce the coughing and the [inaudible] Cabon dioxide detection and observation of the chest rise should be used to confirm [inaudible] placement

[00:06:28] They also have closed suction system posts intubation that will reduce aerosolization. Major focus of mechanical ventilation for the COVID-19 is avoiding ventilator-induced lung injury while facilitating tests exchange their lung-protective ventilation. And the prone position should be applied earlier. Giving us associated with the reduce the mortality and other causes of severe ARDS. Although the outcome that a prone position in the COVID-19 is currently lacking, but the tendency for the SARS-CoV-2 to affect the peripheral and dorsal areas of the lungs provides the ideal conditions for the positive oxygenation response to the prone position.

[00:07:24] And a VV-ECMO is reserved for the most severe ARDS patients in view of evidence that it might improve the survival. The other very important point is rapid liberation from the invasive mechanical ventilation to reduce the incidence of the VAP and the VIDD.

[00:07:49] In our ICU we try to determine the time of intubation, through trend assessment and the support treatment through non-invasive ventilation and extending the ventilation support steps. And the oldest patients with success story incubated and they're finally discharged. That's what I wanted to share with you. Thank you.

All Experts

Scientific Discussion

Speaker 1:: [00:00:00] Thank you very much. Now actually, it seems the pandemic of COVID-19 destroys everything including all our routine life. In my department, there are 236 beds, but only one-third of the beds are occupied. Now we have regulation - hospital authority. Other week, we are not allowed to hospitalize the patient over 50%. So that could be a huge challenge for the doctors to manage chronic airway diseases.

[00:00:49] Actually, we have prepared a couple of questions, but I don't think that they are not prepared for discussing, just for asking. I have two questions for Prof. IP. In mainland China, among COVID adult patients who are over 20 years, the prevalence of asthma is 4.2%. Unfortunately, only 5 or 6% can have an opportunity to take standard therapy. Means only 1 of 20 they have inhale steroid. What about such a situation in Hong Kong?

Prof. Mary IP:: [00:01:48] I think the use of inhaled steroids would be more common according to the stepwise approach in the international guidelines. So we do have many more patients on inhaled steroids, but the basic principle is still that they would follow the severity of their asthma control and how well it is to use the steroids. Yeah, inhaled steroids.

Speaker 1:: [00:02:18] Yeah. I have been told there are many Hong Kong people they do believe that traditional Chinese medicine. How about today, why do they still use steroid just taking traditional medicine?

Prof. Mary IP:: [00:02:35] Yes, there are some, but I wouldn't say they are a very big group, but some may take it as an adjunct, hopefully, that the tonic effect would take place and they can reduce on the inhaled steroids. Yes, there are such patients, but overall, not really say as bad as 90% not taking the inhaled steroids, even when it's indicated. Yes.

[00:03:04] I guess in this COVID period, we would really just do the usual education. Well, but this time, even our patient education sessions have been closed up because we would be practicing inhaler technique, etc, and somehow, although there's no proof that these would be really aerosol-generating or transmitting COVID these are considered some elective things. So, we have suspended most of that, but we do encourage our patients to take their inhalers as appropriate according to their previous prescriptions or if they have exacerbations that will step up the therapy.

Speaker 1:: [00:03:51] Okay. Thank you. In my own experience, I think that the [inaudible] is a really important factor to check the onset of asthma. Ten years ago where I was working in [inaudible] China, I did not have asthma. But now, where I work in Beijing, every day I have to inhale steroids including cortico. So I have final questions for Prof. Ge. Because even now, it's said to me this, there was no single publication concerning steroid use in the treatment of the COVID. All the evidence comes from the profession - the observational studies. How about when a patient has both COVID and COPD? How about the ER [inaudible] concerning the steroid in COPD or the COVID-19.

Prof. Huiqing Ge: [00:05:12] Yeah. Thank you for the question. We just have the one COVID-19 patient, he has a history of COPD. And during that - he's not so severe ARDS so it's better for us to just use the nasal high flow nasal cannula for him, and use the ICS steroids inhalation to him. And his good response to the inhalation treatment. So, that's good for him. And we also use the oral steroid at first and then change to the inhalation therapy. Thank you.

Speaker 1:: [00:05:58] Okay. Thank you very much. It's already very late at night, it's 10 o'clock. So we had a wonderful opportunity to talk about the management of chronic ill airway diseases tonight. I think it was just for this section tonight. Thank you very much.