The Science Behind the Coronavirus, Series II

[Music] my name is dr. Patrick soon-jong I am executive chairman and CEO of a company called nan twerks whose mission is to find solutions for patients suffering from life-threatening diseases such as cancer and infectious disease I'm also the executive chairman Los Angeles Times and I'm here today to present more information and updated series on understanding the science behind the corona virus very recently my executive editor norm pull Stein shared with me a comment that unless we understood the dynamics of this virus we could provoke an existential crisis with that comment I realize there's huge amount of fear and consternation and rightly so but I wanted to present this episode today so that we can understand that we need not panic the fear that is out there has been accentuated by three factors I believe number one the unknown meaning who's infected who's not infected the unpredictability as a consequence of that number two how long will this nightmare pandemic last and number three the thought of the feeling that this virus is uncontrollable I'm here to assure our readers and those listening that the scientists of the world are hard at work 24/7 and are more confident than ever that we have now enough science and knowledge about this virus to beat this thing unfortunately because the way the virus has occurred through this ace receptor the infectivity of this virus is enormous and as I presented in our last episode this virus has found a way to activate and hijack our body by taking on this ace two receptor which is in our lungs knows and in other areas of our body and therefore become highly infective yet because it's done that it is an Achilles heel and we have an unity to stop it and attack it in addition this ace receptor doorway so to speak was the same in saws 2003 which means we as scientists and had a jumpstart and understanding how to attack this virus so today my goal is to present you some more elements about this covert nineteen and unfortunately it is my belief in my opinion that this virus is here to stay it doesn't mean however it's yet to stay and we can't defeat it it's yet to stay as a human to human transmission and it's here to stay because it will mutate but we will have and I will share with you our strategies in which we can overcome this virus ultimately and convert what we consider now a fatal disease of Righton disease to a virus that we'll be able to manage like that of the flu especially as we learning day by day in most rapid fashion what's going on with this virus what's going on clinically how we can understand it and how we can move on I also want to share with with you that is my belief now that we can categorize this virus into three conditions firstly the asymptomatic patient it is one of the differences with regard to this virus infective 'ti that a patient could be infected and yet asymptomatic I believe however that this is also one of the reasons why it is so infected we don't know who's infected and the asymptomatic patient inadvertently could be transmitting this infections through travel through their droplets that actually contaminate surfaces and inadvertently creating the spread of infection and will speak to this asymptomatic patient which happens to be I believe over fifty to sixty percent of the patient population ultimately and what they can do to help us control the spend emic but then there are patients who are infected with mild to moderate symptoms who I call the symptomatic patient and that's going from yellow to orange and this symptomatic patient will have an opportunity today with the rapid onslaught of the clinical trials as well as our knowledge from SAS 2003 of what drugs that could be repurposed for the purpose of mitigating this disease and not allowing these mild to moderate patients to become critically ill which then takes us to the critically ill patient which what I call the red and unfortunately these critically ill patients have such severe lung injury and damage because of this virus and the desire of the body to fight it because the immune system is fighting so hard it creates tissue injury in its own right and fibrosis and requires oxygenation and ventilation sadly the results today are for these critically ill patients almost 50% of them succumb in on these ventilators and they succumb rapidly and in New York that number is even higher according to physicians working there and sharing some of this information with me the fatality rate among those on ventilators is as high as 80 percent so if you look at this yellow orange and red we are now very rapidly understanding clinically what's going on with these patients and we are developing strategies for each of these groups my job today is to describe these three groups and the strategies of how to go about addressing the asymptomatic patient the symptomatic patient and the critically ill patient however at the end of the day in order for an inflection point to occur where this pandemic will end and if the next pandemic occurs we'll have ways and prepared to fight it where there is a light at the end of the tunnel is this race for the vaccine and you've heard multiple reports of varying timeframes of when a vaccine will whether it'll be 12 months 18 months 24 months I want to present to you some data today that there's some hope that'll be even sooner than that but I need to also put into perspective of what a vaccine is how does it work what's the difference between short-term immunity long-term immunity what's the difference between what we call humoral immunity is cell mediated immunity and in fact what's exciting is how does this vaccine so to speak not differ very much from the attempts that we're trying to do with immunotherapy in cancer today to generate what we call a memory vaccine so I believe that this race for vaccine is while exciting for scientists we'll be the basis for the end of the nightmare so my proposal today is to spend time going through these elements of explaining about the pandemic presenting elements of strategies which are very real in learned since 2003 that we can address and beat this virus describing for you the differences of this asymptomatic patient the symptomatic patient when does the patient has to go to hospital the severely ill patient what opportunities there to save that life and reduce the fatalities and finally the lighted in a tunnel that in fact a vaccine is at hand let me turn first to why I believe covert is here to stay not to alarm you but to present to you the science of how this virus is evolved and more importantly how it is now a human to human transmission and we have to deal with it but more importantly we now have to understand it and we can deal with it this all started in 2003 this virus we believe emitted from the bat bats have such an amazing number of species across the planet so transmitted between bats and multiple viruses within the bats and the bat virus and found a intermediate host in a form of what they call crickets or cats and that resulted in China in 2003 of one of the first transmissions from intermediate hosts of a mammal to a human fortunately SARS 2003 stayed contained in a sense that the SARS was not that infective and was able to be contained and as you could see 774 deaths there is a silver lining in that because this SARS Cove in 2003 is the parent of SAS Cove - because mutations occurred which means the scientists have had a head start of about 16 years to understand how this virus attacked the human body and how it hijacked the human body in the interim in 2012 it transmitted from bat to a camel and in Saudi Arabia to the Middle East and that's called MERS which is a variant of this between SARS and Merced hit 30 countries in 27 countries and limited exposure and that's what we meant by an epidemic and not a pandemic all of a sudden in 2019 it went to human and then from human to human and that is when this became really because now there's for the first time a real human-to-human of a virus it's never been seen in in us as a host and by 2019 in China there were 5,000 deaths so that was the first evolution of this virus from human to human and because none of us had ever seen this virus and the ability of this virus to not only become so highly effective but so toxic the Furious in the United States we may even possibly hit a high of hundred thousand two maybe even two hundred thousand deaths and that is why I think this is great fear about this pandemic but I think there's an opportunity for us to understand this pandemic as we work through the science and what we've seen through the science is the ability of this virus to mutate and this is a amazing graph of all the genomic sequences since the initiation in China of the first virus as you could see in purple are the beginnings of these mutations and what mutates mainly is the surface of the virus the spike and as you could see as it mutates and goes around the countries there's ongoing mutations and I believe the amazing thing about this virus it has to be Tate in a funny way in order to survive because if it's as aggressive as it was in China it would creates its own extension by not having a host survive so it mutates and as you could see the red is the mutation in the United States and what do we mean or understand by this mutation is the good news there's significant number of base pairs or parts of the genome that are conserved the thing called the receptor binding domain the domain of the virus it binds to the ACE receptor the domain inside the structural protein of the virus called a nucleic caps that are conserved why is that important well the reason that's important is that we now have ways to attack these conserved portions so we can actually end this pandemic and this is what the pandemic looks like this is what we call the evolution of a pandemic starting in China for the first human to human transmission of a virus it's never been in the human population therefore none of us had immunity and the rapper had spread around the world and all the way now in the United States I think this map clearly shows the evolution of this spread it's a remarkable testimony that we are one community one global community and as it spreads from China to Europe to the United States to every part of this world we have the pandemic and this is why I believe this virus is here to stay from the world to the United States unfortunately one of the epicenters is New York and whether New York has hit its peak yet is hard to know and credit to the Governor of California we have significantly lower numbers perhaps we haven't touched the peak yet but I think one of the lessons that we learnt in California was the very early announcer my governor Newsom to create the state home policy to limit to the beaches to limit exposures of crowds the NBA that canceled all games it is our hope that this limitation of contact will mitigate this this spread clearly one of the fears we have is not only as as far as highly infective it is a highly toxic and the toxicity we haven't yet worked out because we don't have enough data what percentage of patients who are getting infected are toxic there were estimates that it was 20 times that of influenza but what we do know is that if a and enters into what we call the critical phase the ICU phase sadly the survival rate or the death rate of a talented rate is 50% which is an enormous number if you look from California to our local areas in Los Angeles you begin to see in the highly dense populated areas both of LA and LA is now a hot spot relative to California and within LA thus the the areas of Brentwood Santa Monica and Long Beach it is our hope however that the work that both the the mayor and the governor has done to mitigate the spread by creating this state home policy will keep these numbers down so as we present this Cove it is here to stay an idea that this human-to-human virus now will not only continue to mutate may but may come back again I want to assure the community that the scientists are learning so fast about how to attack and to mitigate that and I believe that the inflection point of getting to a vaccine possibly before the next season if there is a next season of this pandemic that we will be on the cusp of vaccine or close to a vaccine before that happens so while we should be fearful about this virus we shouldn't panic I understand that there are great fears both mentally socially economically financially about what will happen but we will deal with that in some of these other episodes but for now I want to show the community that both the science the medical community are hard at work to find solutions [Music] let me discuss the therapeutic strategies in motion as we begin to understand this disease the three stages we've been discussing whether it be yellow the asymptomatic patient Orange the patient that is really infected with varying degrees of symptoms and then finally the critical illness or severe so these therapies or these strategies I believe have to be tailored temporally based on where you are where the patient is with regard to his state of infection obviously an asymptomatic patient has the ability first not even to know he's infected even though they may test positive or COBIT but the ability to basically self isolate not go to the hospital not burden the healthcare system but then we have the patient in the intermediate phases what I call the orange and then obviously the patients in the red phase the reason for this temporal nature or temporal understanding of which strategy to use when is because the patient goes through various stages of the immune response is my belief that patients who have a compromised immune system are much more susceptible to this disease because they have absence of what we call the innate protective system of the natural killer cell that floats around our body protecting us not only from cancer but from any infective disease so it is in these patients whether the patient be elderly with diabetes with cancer or some form of image suppression that the virus takes advantage of and in the early stages I believe these patients could be benefited from having some form of activation of the NK cells on the other hand once the virus has spread within the body and replicated to such an extent that the patient cannot breathe oh I have difficulty breathing on her second in ammonia the patient's body now takes over the immune system takes over and fights so hard that there's what we call a site storm and clearly in those instances in order to reduce the cytokine storm to allow the patient to breathe get off the ventilator we need a different strategy not a strategy oh I believe of immune activation but in fact the quite the opposite their strategy of immune deactivation the tamping down or cooling down of that period so that the patient then could fight so I think the complexity of what I call this temporal nature is something we as clinicians are now beginning to learn but we need to tie that to the treatments or the treatment strategies of the drug development strategy to the molecular strategies with regard to the disease itself so let me turn now to the strategies with regard to the patient's the question is and that's now pertinent to discussions in the news are there drugs that are approved for the indications that we could repurpose well for patients that are in this moderate or where they call orange phase indeed there are drugs that firstly was needed to be in clinical trials and now has been recently approved under the emergence itting this chloroquine and hydroxychloroquine and how do these drugs work well chloroquine hydroxychloroquine actually works by preventing the fusion of the virus and preventing the packaging of the virus in these things called endosomes by affecting the pH of that virus and this is really why in patients that potentially are in the yellow or in the orange have the ability to maybe take part into the clinical trial or be part of the treatment of hydroxychloroquine in this early phase of blocking the fusion and packaging of the virus the next opportunity is could one block the entry of the virus itself into the cell and again these are Unity's for patients in the yellow and the orange to participate in which this ace receptor in which the virus activates and takes on this ACE receptor and finds a way to enter the cell is an opportunity now for drug developers molecular biologists to understand the dance of this receptor as it interacts with a spike protein this is really exciting because we now have at our hands these supercomputing GPU systems that can model what we call dynamic modeling every nook and cranny of the sequence of these proteins amino acids and find the ability to block the entry of this spike protein into this ACE receptor and in so doing create a sponge or trap and prevent infection in the first place or for patients who already are infected with symptoms from from getting any more virus from entering the body and these will serve as what we call antibodies or traps the next opportunity in patients who have again symptoms is to look at this machinery and as we discuss in the last episode the virus once it enters can only survive and replicate when it hijacks as it hijacks the machinery of our own human body so it takes over the machinery it comes in it breaks up into its different parts and now take over the machinery to replicate and through what we call the golgi apparatus and the ER and reassembles and in this replication of taking our machinery packages and now spreads to the rest of the body so there are what we call these antiviral drugs approaches oma inhibitors or the adenosine analog such as rim desert view where these can block and trick the virus so that it actually miss reads who creates an incorrect reading and does not assemble unfortunately I believe once the patient hits the phase in which the virus has replicated such an extent that the patient is in the red phase that it'll be very hard to overcome that until you get the patient out of that red phase and then the other opportunity is to find a way in which patients can now activate their own immune system so again this is where it becomes tricky because this natural killer cell I believe needs to be activated in the very early phase and maybe as a last resort at the later phase in which the natural killer cell which is in your body is there to protect you from infection and can then be given early on so that it could kill infected cells through this natural killer cell activity and destroy the infected cell and prevent from you from getting into the red phase so I think the off-the-shelf natural killer cell or an activation of this natural killer cell by a protein called as super agonist are opportunities again in these early phases to prevent you getting into the red phase unfortunately patients go into this red phase and when they go into this red phase this is where disaster hits this is where the virus I believe is replicated to such an extent in these patients who are elderly in these patients with pre-existing conditions and unfortunately these patients who are deficient in the first place of their natural killer cells what happens to these patients is in fact they have what we call full-blown saws which is really an inflammation and a cytokine storm in the lungs what do I mean by cytokine storm will be going into that much more detail in the following chapters but cytokine storm is when the patient's own immune system is fighting so hard to try and protect itself it causes tissue injury and ultimately death so what is happening as this patients have what I believe these huge numbers of viruses the huge viral load and the viral load occurs in these patients with pre-existing conditions it occurs in the elderly it occurs in patients diabetes with cancer and I believe that happens because these patients in the first place had a poor immune system or lower NK cell activity but ironically because they have a lower NK cell activity with the on slot of this huge viral load it takes over this lung what you see on this left is what I call a normal alveolus or the air sacs inside your lung these air sacs have a very special macrophage within them called we I believe in m2 macrophage and thus macrophage is not designed to kill and remove debris and as you have this massive infection you have this debris formation occurring and with the debris formation occurring you have fibrosis and with fibrosis you have scarring and prevents oxygen from entering from the air into the blood you have then the immune system trying to fix this problem and this is what you mean by cytokine storm so interestingly enough now is not the time I believe to activate the immune system now is the time to dampen the immune system so this phenomenon of SARS is very similar to another disease we know in medicine call a RDS in which the patients again have cute lung damage based on sepsis it's very similar I believe to other inflammatory diseases such as graft-versus-host in which patients are after transplantation the patient's own immune system starts damaging the body and we can learn from this that there are mechanisms and methods to tamping down the storm and have antibodies aisle six monoclonal antibodies for example to block this inflammation block this fibrosis there are mechanisms to activate or change the polarity of these macrophages so that they can actually remove the debris there are mechanisms to increase the tgf-beta so that we can actually slow down and tamp down the inflammation in China they attempted the transplant or injection of a stem cell called amis in camel stem cell which has been used for a RDS which has been used for patients with graft-versus-host disease and I believe under these circumstances there are methods to quiet the inflammatory storm and to overcome this terrible event and have the patient come off the ventilator quickly and live to fight and activate at that point the patient's immune system will give best supportive care to get the patient out of the ICU so we have now presented today the therapeutic strategies in motion while I've shared with you we have this pandemic and this virus here to stay I'm extremely confident based on all these strategies and based on the amazing speed with which both the regulatory the government the private sector and most importantly the healthcare and the scientists have moved to actually put in motion these strategies in real time whether you have severe disease moderate disease or critically ill disease that we will have the insight and the understanding to overcome this disease I'm confident however that the in order for us to change this inflection not for just now but for the future is a vaccine is needed I'm confident based on what I now see that the vaccine is close at hand so these therapeutic strategies are real knowledge that we gain from the saws 2003 and with the power of the super competing in our hands and with you effort the collaborative effort of the world I think we will have a chance to deal with this virus [Music] let's turn our attention to the asymptomatic patient the patient that is infected is Kovac positive but is asymptomatic I want to remind everybody what I feel there are three stages of this disease we've termed yellow orange and red in yellow you have what I call stage one where patients in fact are positive infected but without symptoms don't even know sometimes if they infected and their job is to limit spread and we'll get into that that's their only job is to limit the spread on the other hand patients have flu-like symptoms they have muscle aches some myalgia a minimal cough not greatly short of breath and what we called mild and our job is to find ways to reduce their viral load so that they don't go from orange to red and then finally these patients were in full-blown saw's the elderly view pre-existing conditions and I think we have yet now a real challenge is to overcome the lung damage reduce the fatality rate in these patients so if we categorize or create these buckets it gives us as both scientists and medical scientists and clinicians an opportunity to understand what I call the temporal spatial nature of the disease and we're in the spectrum of the disease we need to treat and what treatments to use obviously at the end of the day we want to find a vaccine to really prevent anybody from getting this infection and it turns out that I believe forty to sixty percent of the patients Y infected asymptomatic and eighty percent of patients are in this bucket of flu-like symptoms or asymptomatic but the terror for for our loved ones for the elderly is that these patients in the stage three disease have such a high mortality rate that we need to find a way to even prevent this what is most disconcerting is that while the started stage 3 the red in the elderly it's now moved in our country to some of the young and sadly even the youngest child has now suffered a death as a result of full-blown sauce so on that basis I will not like to now start on trying to break up these categories and speak to each of these categories of the stages of kovat and let's start now with the asymptomatic patient I believe this is why we have this immense spread because these are the what I call the super spreaders the patient being infected has no idea that they infected so they may have minor or have no idea but I think this is the value of the state home policy until we can do all the tests until we know who's in fact are not infected the only policy to provide containment and flatten this curve and not overwhelm the system is this self isolation or stay at home policy these patients because they're infected should truly be with face mask so the purpose of testing now is to identify this patients which who should self isolate which would use separate rooms and bathrooms would and as we talk to be in the pass wash their hands constantly and this is what this is also different with the regard to this virus it appears now from studies that the viral load in the respiratory system of patients who are asymptomatic can be as high as if they had symptoms this video was taken at 2,000 frames a second from a healthy person during a violent sneeze and as you could see as the sneeze progresses it goes 20 inches and then goes on to progress to 43 inches and the remarkable nature of this is if it's taken then by a plume what they call the physics of a gas plume it could go as far as 20 feet while this is unlikely that most needs go that long or far as much as 26 feet I think the point of this video is to say that within 26 feet of this infected person surfaces can be contaminated pavements door handles paper this is why we need to understand that these patients weigh symptomatic in environments like this have the capability of spreading and in generating this pandemic this video taken again by another company I am I can vouch for the veracity of where the data comes from other than according to the reports of this company it comes from mobile telephone data but I think the point again here is at Fort Lauderdale this is one single beach at spring break a single beach at spring break in which potentially these young people are asymptomatic traveled and you now you see their phone records in a very short space of time across the seaboard and the eastern seaboard of the United States and even up to the Midwest on the other hand if you took the approach as we've done now in California and again credit to the governor and the mayor of our towns we've closed beaches we've actually closed parks we've banned gatherings we've asked families to stay at home for the first time there are very little traffic and credit to the community they've actually accepted this because we are all in this together this is the importance of us flattening of the curve and causing the extension of this virus we have in our control the ability to cause an extinction of this virus by not giving it a host to survive these young people at least are wearing masks the idea that if you're infected and you wear a mask is not just to protect yourself thinking you're not infected because you ain't symptomatic but to protect others from the droplets that can come from your sneezing or coughing but I don't think it's very clear to most in the public that there's a very much difference in the mask you wear if one were to look at this person's mask you would see a great difference between this person's mask and where the difference is this exhalation valve what this means is that in this exhalation valve that is present in this person's mask both in 95s is that the droplets can emerge from the exhalation valve so the opportunity unfortunately completely defeats the purpose of this person protecting the rest of the community so I would urge those who are infected and understand that they infected that this is the master should be wearing and not an exhalation valve as has been attested by the CDC who have shown that through these exhalation valves in order to maintain a sterile field the exhalation valve itself does not protect that and why is this also important why am i emphasizing the importance of the responsibility of those that are asymptomatic and infected to stay at home protect the others through appropriate wearing of the appropriate mask the fitted mask for medium small and large is because of the health care workers these are the professionals that are necessary and need to treat even the the moderately infected but more importantly those severely infected with a fatality rate of 50% as can be seen from this Instagram and Twitter posts here you have these professionals were on the front line and they put their lives at risk to save all of us and this statement says we stayed at work for you you stay at home for us so I cannot emphasize more the importance of the young people understanding how difficult it must be that they are asymptomatic feeling good that is their responsibility to stay at home stay isolated and unfortunately the period of time while the median goes 14 days there's evidence of 20 days and even evidence or 30 days in which the virus stays within your body so the longer yourself isolate the better so that we can protect the healthcare workers and protect the community and protect your loved ones [Music] let's turn our attention to the symptomatic patient and unfortunately this particular virus appears to have a high incidence or prevalence of patients who are asymptomatic yet infected and until we can test everybody which unfortunately is not possible today the only way for us in to contain this virus is to make the assumption that the young people even though asymptomatic are positive and only by doing so could those who are asymptomatic and possibly and don't knowbut prevent the spread so I wanted to make sure that everybody understood the word asymptomatic did not mean non infected quite the contrary we need to emphasize that a large proportion of patients are infected but have no symptoms and therefore can be these spreaders but let us turn our attention to the symptomatic patient and by that I mean the patient that has the feeling of flu-like symptoms and who has a real important need to reduce their viral load and the reason for that is we need these patient to recover and not progressed to read so these are the patients we call Orange and very much like the asymptomatic patient need to self isolate inside their homes but require supportive care they should I and I emphasize this avoid home remedies which we'll talk to a little bit as we proceed through these symptomatic patients who are managed at home because of the danger of so-called home remedies it is important for these patients to know when they should reach out to their physician and in fact when they should be hospitalized even because the onset of pneumonia from orange to red could be very rare and from red to an event late it could be extremely rapid the other issue that I want to discuss with regard to the symptomatic patient is what drugs are on the market today that are repurposed for this disease and then finally the opportunity as I said for us to avoid the fatalities of these patients will reduce the fatality of the patient who go into the red face and who have this severe lung damage and who are hospitalized is is clearly the goal to take a patient from red back to Orange and to prevent a patient from Orange becoming red so let's start a little bit on these patients who are symptomatic and the questions that they need to understand first of all let me just revisit again the difference between orange and red and how a symptomatic patient gets infected through the nose through the mouth through the eyes through the mucous membranes into the lungs and once into the lungs these viruses attach to the ACE receptor and once and the ACE receptor it starts infecting the alveolar cell you will see this alveolar macrophages and we will over the next few series talk a little bit more detail about what is this alveolar macrophages Abel is m2 and what's it doing there this is your normal macrophages that cleans up what's inside your lung and these mild-to-moderate patients have some level of infection in the lung but not overwhelmed this ACE receptor is here to protect the lung with mucus and the surfactant layer is a protective layer of the of the lung so that the oxygen can be passed from the lung to the blood vessels and to the rest of the body this is the alveolus this is what we call the alveolar sac and this is what happens in the infected patient so we begin to understand the basis of this infection and and how it occurs in the lung so what are the symptoms well I say follow the ACE receptor and this receptor sits at the base of the tongue at the in the nose and because it sits at the back of the tongue of the nose there are now reports of loss of taste and smell so that could be a symptom of an infection a positive Covidien faction the receptors are in the alveoli of the lung and that's why a dry cough which actually goes all the way on to difficulty in breathing with a respiratory rate which is higher which will get into the ACE receptors are in the GI tract so diarrhea and stomach cramps could be a symptom and then they are in the blood vessels and patients with hypertension a higher risk of this because there's higher exposure of a scepters and then finally these ACE receptors are in the what are called the immune cells themselves and there's even a back door to the immune cells where the viruses figured out a way how to actually evade the immune cells or kill the immune cells but the body fights back as you get this is infection and the secondary infection and you have a temperature so if you look at the what happens in patients with these symptomatic infections you could have loss of taste and smell you could have a dry cough diarrhea hypertension and high temperature these are clear symptoms that you may have an infection and need testing so what happens when you need these testing and you know you are positive how do you know that you have to go into the hospital what requires hospitalization well as I said this is a very dangerous disease and you really need to understand how rapidly this can progress if you're not careful so a positive Cova test could be asymptomatic or you could be just mild to moderate presence of a high fever clearly begins a demonstration that is pneumonia occurring is a secondary infection occurring which Wren requires hospitalization for you to go and see your physician a high respiration what we mean by that as your lungs have much more difficulty in terms of inflammation and fibrosis and fluid the passage of oxygen requires much more of a rate the normal rate 8 to 12 goes to 20 so the counting of your spirit of need to take much more breaths more rapidly in order for you to feel comfortable is a not a good sign saying that you need to be in hospitalization the oxygen saturation where you can measure the oxygen saturation from your blood levels these are all a consequence of now the lung becoming affected and a chest x-ray that shows pneumonia and then finally a hundred percent of patients with a positive kovat 19 infection have this appearance on CT scans of a ground-glass effect and fibrosis that occurs while this is a test that absolutely confirms the positiveness of severe kovat it's not recommended for everybody because the radiation effect of a CT scan in its own right is not safe so the medical signs that require a patient that is symptomatic in this Orange state to be very aware that could go very rapidly to the red state that with Huayra spirit rate low oxygen saturation evidence of an infection difficulty in breathing these patients need to very quickly get to the hospital so in this instance of a patient in this orange state what have we learned from SARS in 2003 and that's been at least the blessing of some level of experience that sauce 2003 and code 2 sauce Cove to have the commonality of the fact that it's an ace receptor and that the virus in his replication stage has some of the same characteristics and we talked about how chloroquine and hydroxychloroquine and now as earthworm Ison have been talked about with regard to opportunities to reduce the replication Ram desert vehicle etre these are two antiviral drugs which we'll talk about and there's a whole slew of other drugs methotrexate amiodarone and the question which is much more complex about where the one should be on an ACE inhibitor and ARB inhibitor for hypertension these are questions that frankly we do not really have full answers these are questions that require clinical trials these are questions that require clinical understanding of the clinical practice level but in times of desperation it is clear doctors hospitals and even patients themselves are taking on these drugs that are on the market for their own use so let's talk about some of them chloroquine hydroxychloroquine Plaquenil they're basically the same chemical structure and this is chloroquine which is discovered for malaria so it's an old anti-malarial drug and then the hydroxychloroquine which is derivative the chloroquine was developed so that you could have a better solubility and it appears to have a higher efficacy and I say there were it appears because we're not sure even of the true efficacy of this and told me to the clinical trial so there's chloroquine hydroxy Korakuen and the trademarked name of hydroxy Gordon is called Plaquenil there's been a very small study that says if you combine Coral when hydroxyl working with this antibiotic there seems to be even a synergistic effect there may be some evidence that this is anti-inflammatory mechanism but is really unclear how and why this combination works if it does but before we move on from this chloroquine story I do want to emphasize that this drug hydroxy Kolko no patent all is actually approved for patients with lupus and patients with rheumatoid arthritis so it is very important for us to understand in the community that these drugs are in great need for patients who really do need them on a day to day basis so luckily or happily I think the pharmaceutical companies are now increasing the manufacturer of these two drugs so that we do not route run out of supply for those who really need it in its approved state what is the theories of how hydroxychloroquine works well one it actually affects this ACE receptor through thing called Lac oscillation - it affects the fusion of the virus into the membrane because of the pH it changes the pH and three it actually fixed the endosomal packaging as well as this thing called RNA polymerase so these are the theoretical reasons of why these findings prompted the early testing of chloroquine Fuko vat19 and was regard to the effectiveness well from china they were conflicting results on the one hand there were some results as is effective on the other hand when they did a randomized study they showed no difference so this is why it's important for us to understand that it's correct for the FDA to say we need randomized clinical trials with this against placebo there's been a report widely touted report from France that only in six-page when you do combination of chloroquine and zephyr myosin by day three the viral load with significant decrease compared to controls this looks promising it's the best way I could say but again until you would do two clinical trials we won't know having said that one has to be super careful because one of the problems with hydroxychloroquine in its side-effects is in arrhythmia which is a rhythm of the heart which kid himself could be fatal when combined with ezra the licen that arrhythmia complication increases because both could have such an effect before I go beyond just the chloroquine this is the danger of I believe television of an uninformed audience what was remarkable when the chloroquine phosphate idea came out there was a run on cork and phosphate that was used to clean fish tanks and people will be taking this Corrigan phosphate in water and drinking it as if this would be a prevention for covert 19 and sadly a person died so a great warning no hone remedies and chloroquine phosphate is not fit for human consumption another warning as I just shared with you that the combination of hydroxychloroquine and as ether Meissen raises the risk of heart irregularities so it's not without risk even though there may be a desperate need to try and self remedy if you are going to go on these two drugs you should do it with the coverage of a physician inside a clinical trial having said all of that amidst these controversies FDA has now issued an emergency authorization allowing this hydroxychloroquine to be used in the treatment of kovat 19 so I leave you with the hydroxychloroquine that it is proved under these emergency conditions but he stole without not without risks and has to be fully proven which then takes us to the next set of drugs called REM des via which some of you may have heard what REM des of you is an antiviral drug that was developed for by Gilead for Ebola and it is what we call a nucleotide analogue in layman's terms it's here to decrease the viral replication by tricking the virus into creating a version inside the machinery which inhibits the replication so this complex science here called RNA dependent RNA polymerase is inside the machinery and that's what REM deserve you potentially does and also this proofreading capability of this amazing virus it actually may inhibit that there is good science about why this would work having said that again it's unproven until the clinical trials are completed and there's a large REM dezer via clinical trial going on the solid algae trial is a trial where all the known antivirals such as renders via such as Calitri which is an anti HIV drug as well as the anti Muriel's are all being tested and that will brings us now to kill etre and interferon beta so Calitri is a combination of two molecules or two chemical agents one called la piel de Navarra and one called route anova and these molecules are really anti retrovirals it's still complicated because HIV is a different kind of virus of what will a retrovirus and they used in HIV the thought process being here that these drugs why effective against HIV may be effective against covert virus by inhibiting these things inside the cell again through the machinery called these proteases we don't know this yet these drugs however are toxic have severe side effects including things like pancreatitis again should only be considered inside the world of clinical trials while I've summarized in a very limited fashion some of the well-known drugs that could be repurposed there are many being considered some like amiodarone which is used for arrhythmias they may also have a role in preventing fusion and then there's this whole discussion about ACE inhibitors versus all be inhibited what I mean by that patients now on hypertension antihypertensives there's a drug that inhibits ace ace is separate from Ace to ace 2 is protective of the lungs aces injuries to the lungs ace 2 however is where the spike protein binds so should you be having an ACE inhibitor or an ARB inhibitor with regard to these two receptors should you be on these drugs at all should you change one for the other the answer to this is all unknown at this point these are interesting scientific questions and the recommendations now for the american heart cardiology associations are in fact you should not make any changes at this point so these are complex discussions about repurposing old drugs which says that there are treatments for drugs that could affect the machinery diffusion or the endosomal packaging all for the purpose of reducing the viral load inside the infected cell by the virus so that these patients don't go from orange to red as I said before the inflection point for us is to get to the vaccine on the other hand there are treatments on the horizon which will speak to that can even treat these symptomatic patients before they have this cytokine storm so that we can actually kill the factory and that is potentially the use of NK cells or the use of al 50 but that again should be a subject of clinical trials in the future so with that we will then move on next to the critical patient [Music] I'm now going to turn my attention to what I called red or the critical patient these are the patients for which we are really worried about as health care professionals as surgeons as scientists as an EC ologist as nurses because these are the patients who end up tragically not only on ventilators not being able to be seen by the loved ones but a 50% fatality rate it is really important for us to not only understand the pathogenesis of why these patients died but how can we stop it how can we actually get them out of this terrible situation call SARS which is severe acute respiratory syndrome for full disclosure I as a physician and scientist in our organization immunity bio made a concerted effort at least for this particular point in time to focus a huge amount of our effort to see if there's any way we can mitigate this to this terrible event of high fatality rate of close to 50% so let's discuss these critically ill patients as they enter the intensive care unit these are patients who have severe lung damage and require ventilation just to keep alive I think one of the goals for us as physicians is to find a way to rapidly discharge this patient from ICU they are hospitalized in intensive care and in these instances I think next generation immunomodulators are needed and I'll describe what I mean by immunomodulators let's first try to understand what's going on in these patients and as you recall I was explaining how this virus enters and it binds to the ACE receptor and how it gets in and it fuses with the membrane and with the spike protein and it breaks up and it takes over and reassembles and creates rapid replication and then there's endosomal transport and out of the lung and it sheds all of that is what happens until you get this huge replication of this virus inside the cell with inflammation and tissue damage and lung damage and fibrosis and once you get to this stage you end up in this statement of saws in a normal circumstance your lungs have this pockets called alveoli that's how these pockets of alveoli actually take in air and the oxygen is transported very carefully back and forth into the blood and that's how your body's organs are oxygenated when the virus enters and enters and hits these alveoli cells through the ACE receptor it turns out in this area of the type 2 cells macrophages call em 2 macrophages which are not quite designed to clean up debris they their sentries but more as suppressors than activators of the immune system so when the cell is overtaken by this virus the body then reacts that allows this virus to create fibrosis and damage but it's not just the virus that's causing the damage unfortunately it's your own body creating the damage in the sense that it's now releasing these what we call cytokines and creating fibrosis and when it creates a scarring all of a sudden is impossible for the oxygen to easily travel to the blood and this is why the patients require ventilation to open up these Airways in this instance what is needed is to tamp down this inflammation to tamp down the ability of this self tissue destruction from occurring and there are other diseases that look like this some of them they called a RDS which has happens when patients have sepsis it's also called graft-versus-host where patients have their own transplant takes over and the the body itself causes the same kind of damage what has been used in those calamities have been ways of actually transplanting cells that would enter here that would tamp down this storm and these cells are called missing comma stem cells so this opportunity to take this horrific episode that's overwhelming the system and take these patients who are in ICU and ventilation and bring them out of this 50 percent survival rate and increase that survival rate to reduce the time they've spent on ventilators it's reported they spend 14 days on ventilators that's one of the reasons of why they overwhelming the system in order to reduce that the opportunity is to look at selected trials in motion so some of the trials in motion is this drug called an anti il-6 or il-6 antibody that tries to block the storm and it's now in clinical trials and used for patients with severe disease whether this is effective fully effective yet again is is not known there as you know now talks about using convalescent plasma we will get into that in more detail as we get to talking about the race to the vaccine but convalescent plasma means that these patients who had the disease having their blood antibodies that could basically ameliorate the infection and stop this inflammatory storm what I'm most excited about however is to find ways to one kill the factory itself but as we difficult to enter into this environment from which there's huge storms to add yet another potential storm with a natural killer cell I think probably this natural killer cell and who needed to have been there before the storm occurred in the moderate phases ironically what is needed right now is not to increase the cytokines but to dampen it down and one of the opportunities is a concept of mesenchymal stem cells in which means and camel stem cells could be grown from a patient's bone marrow any donor bone marrow or adipose tissue could be taken and these stem cells actually exerts a system secretion of a protein called tgf-beta and that tgf-beta would actually reduce this storm and has been used in patients with graft-versus-host disease in a or D s7 patients have been treated with this in in China with severe Cobra draws what was exciting at least is that these patients all significant improving in two days after this transplant of a single injection of these mr. carmell stem cells were able to leave the ICU it remains to be seen whether this is a real effect but if it is a real effect here is truly a way to mitigate the death of these patients for which we have a 50% death rate and we are working diligently and have created again with full disclosure in my own company over 10 years built this machine with artificial intelligence that actually could take bone marrow from a donor and through this machine grow stem cells automatically and within seven days generate a dose that could be used to treat patients we are applying for clinical trial approval and remains to be seen the effect of this as a stopgap measure I say that as a stopgap measure because our goal is not to wait till patients to get to this stage our goal is to prevent a patient's get to this stage and our ultimate goal is the race for the vaccine so that everybody is protected from this disease before infection occurs [Music] this is where it becomes really important the race of a vaccine because without a vaccine will be forever fearful of a pandemic like this again so I will spend some time on the section but really warrants a full episode in which you will talk about the progress made as we monitored the progress made on this vaccine so what are we trying to vaccinate against as I said the corona virus is an RNA virus but this is the nuclear capsid inside and this is actually what we call a structural protein of the virus and then these are the membranes on the outside and this is the spike protein so between these two proteins there are conserved areas what we mean by that is that whether it converts from SARS Cove and SARS apparent to the door to sauce Cove and these spikes are mutating as we speak there are certain proteins in the virus that are necessary for the survivors to replicate itself when we call structural proteins so the ideal vaccine would be to create a vaccine against a structural protein and a vaccine against spikes or some of these other proteins that are on the surface and that is the race today we've never seen this virus but we have thanks to the Chinese presenting very early on the genetic signature the genic code of the capsid and of the spike having said that this is a huge virus when I said huge amines about 30 kilo bases which is pretty large for a protein so we have to find a way to create a vaccine that could teach our own cells about this protein and recognize it as foreign this is akin to cancer because when you have cancer you have imitation in your normal cell and that mutation in the normal cell very much like a virus is an abnormal mutation that resides in you sell that can induce the cancer we call that the neo antigen and we need to engage our t cell as a new epitope there is no difference between that challenge versus this challenge of trying to find a vaccine against the equivalent of a new epitope by finding a way to teach our T cells to recognize either this or recognize the nuclear protein and kill the virus itself or kill the cells which are infected with the virus there is this concept of neutralizing antibodies and what do we mean by that blood from people who cover from the corona virus actually develop these antibodies so it is possible then to take the blood from a patient that is survived or the plasma that has these antibodies and infuse it into patient that's infected and allow these antibodies to neutralize so to speak the virus these antibodies then are seen by our macrophages call em ones in these cases that phagocytose and kill the virus by actually eating them and breaking them down and destroying the virus itself or taking the cell that is infected with the virus and these antibodies would attach to them and then we have our natural killer cells that bind to these antibodies and kill the infected cell this is killing the factory so this is what we call B cell mediated immunity or humoral immunity so the opportunity then to take as a short blood from people who have recovered as neutralizing antibodies and use these neutralizing antibodies to either kill the virus itself induce macrophages to eat the virus so to speak and induce our natural killer cells to link to these antibodies and kill the infected factory itself if we then say okay we would like really longer-term immunity and that is called cell-mediated immunity meaning you want to get to a point where your t-cells have memory so that the next time you have this infection your body is ready for it and you do not get a severe case of the infection very much like how we treating influenza today we have now used and are using a modernized version of this common cold virus called an adenovirus and so ironically we using a virus to kill a virus and this ad Nevarez could be then taken and engineered not with its own code but with the code of that of the corona virus so the first step is to find that code that sequence which the Chinese have done and shared with the world and now taking those sequences of either the N or the spike or the membranes and putting these sequences into the adenovirus so you now have a vehicle of vector with this particular injection of this vehicle to infect your own dendritic cells so this is the educator cell this is the cell that needs to be trained so that you could take a t-cell that is naive and start educating the t-cell about this virus once you have this educated t-cell you have what we call activation and clonal expansion resulting in the memory t-cell and now you are vaccinated so this is what we mean by cell mediated immunity the irony is that this virus vaccination is no different to what we are trying to accomplish we regard to cancer because we could use this exact same vehicle put in a the cancer sequence which is unique only to that cancer injected into the patient educate the dendritic cells and now have educated t-cells to go after the cancer cells so this is a universal mechanism of your body protecting yourself not only against infection but protecting yourself also against cancer so to summarize let me speak to the two mechanisms of how the vaccine works against covert on the one hand you have b-cell immunity and you have these neutralizing antibodies that either could be obtained from a patient's blood that's recovered or what's exciting is actually being generated if one could sequence the spike and go into a library and find these neutralizing antibodies one could generate these neutralizing antibodies and now these neutralizing antibodies would be able to be combined with natural killer cells these could either be natural killer cells that your body is making naturally and that could be stimulated with proteins that you could inject call island 15 or you could give natural killer cells that you could grow off-the-shelf so this is one way of inducing killing as well as a vaccine through what we call B cell immunity this killing of the natural killer cells tied to the neutralizing antibody has a special term called ADC C and then finally within the neutralizing antibody there's the opportunity to have this macrophage going from an M 2 to an M 1 to also kill so if you look at this board you begin to see the beginning what I call the killing fields of the triangle offense because you've got one and you've got two and now coming to the third which is the T cells so between the neck and the natural killer cell the macrophage these are to the killing cells but what's very exciting is the opportunity to induce longer term things we call t-cell mediated immunity and as I said your body has never seen this covert virus so you have what we call an immature dendritic cell and in drit Excel is ignorant about this virus so how do you educate it well if you had a virus that is not the covert virus but a virus that is safe to give and that has been depleted of its ability to replicate and such a virus exists called the adenovirus and you place inside the adenovirus the covert sequence now you have the ability to take this aDNA virus injected subcutaneously and allow that aDNA virus to educate these dendritic cells now you have a dendritic cell that is educated about covert and now we have the first time than an opportunity to take in dendritic cell and activate a t-cell and causes t-cell to become a killer t-cell so that this Killick t-cell then can go after a cell that's infected and induce what we call amana Jetix cell death kill the factory and at the same time generate memory so these are the two mechanisms of killing I call that the triangle offense on the one hand you have a net and natural killer cell then you have m1 macrophage you have the dendritic cell in the killed T cell all to get you to the memory cell so this complex science this complex board should give all of us hope that this virus is not going to beat us we have well established methods now to be able to rapidly get to a vaccine and manufacture it in the past manufacturing of vaccines as you could see install is very cumbersome the herpes vaccine the pox vaccine the influenza mumps back Sene etc well manufactured through eggs and stole our so that's a huge challenge in terms of scaling the manufacturing of these vaccines until now where we've now modernized using the adenovirus as the vector fitting the gene sequence into the aDNA virus growing these aDNA viruses and large vats and injecting doses so their opportunity now to get millions of doses and even billions of doses are very real and I was excited to see that Johnson & Johnson and Barda entered into a billion dollar vaccine research trial to achieve exactly that in full disclosure we have exactly a adenovirus vaccine we have tested in cancer patients and we are completely committed as well to be looking at our platform in the meantime this video put out by Johnson & Johnson & Johnson very nicely demonstrates not only how this adenovirus platform is scalable as demonstrated safety and can bring the vaccine to us earlier than expected this vaccine video demonstrates very clearly how this antigen is built onto this aDNA virus and how it can be used what is really important as a flexion point is the race for a vaccine only then could we change the path of this pandemic and be ready for the next hundred years but then we will really be in in so advance and be prepared for anything that comes along and no way will the virus be able to take over mankind I don't think our scientists of the world will ever tolerate that in summary we spent time in the series first saying that the code word is here to stay but presenting at least therapeutic strategies that says help is at hand we understand this we can get there we game do be able to treat the patient with Mal disease we can treat the patient with severe disease we can try and reduce the fatalities that happen today but most importantly we have a race for the vaccine which we believe is close at hand again with full disclosure our scientists and our organizations at immunity bio 9 quest and ant works are working 24/7 to take on this race we will be back in the coming weeks with another installment of the series in which you will look closely at the race for the vaccine for now we'll say goodbye with these images of healthcare workers here in California across this country working at great risk to themselves on the front lines of the fight against kovat 19 indeed these are the warriors and the heroes of our time [Music] [Music] you

Channel: LA Times Studios

Views: 412,661

Keywords: Los Angeles Times, LA Times, L. A. Times, coronavirus, science, dr. patrick soon-shiong, vaccine, science behind the coronavirus, covid-19

Id: rRMkEDwJxbU

Length: 84min 53sec (5093 seconds)

Published: Mon Apr 13 2020