Understanding COVID 19 Virtual Town Hall

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Understanding COVID 19 Virtual Town Hall

good evening and welcome to understanding coated 19 a virtual town hall event hosted by the University of South Carolina office of the vice president for research our presenters this evening are dr. melissa nolan from the Arnold School of Public Health dr. Prakash Nagarkatti USC’s vice president for research and dr. Helmut Albrecht from the USC School of Medicine and Prisma Health we will begin tonight with a talk on the epidemiology of covid 19 presented by dr. melissa nolan good evening i would like to thank dr. nagarkatti for the invitation tonight I plan to discuss salient virology topics define epidemiologic terminology you are likely reading and hearing about in the news and close with some disease trends nationally statewide and within our campus population next slide please SARS COVID 2 is a novel coronavirus that causes the infection known as COVID 19 this virus is a single-stranded RNA virus which simply means its genetic material can serve as both a blueprint for making more viral copies and as messenger RNA which can be made directly into protein corona viruses are large with the genome sizes roughly double that of influenza viruses this fires can be pleomorphic meaning that the shape can change but generally appears spherical the envelope and membrane proteins are instrumental in forming the outer shell and the Spike proteins allow for the virus to attach to human or animal cell receptors we are already seeing genetic variation of this novel virus with regional variants noted that meaning as new cases are diagnosed we are seeing slight variances in the genetic makeup of the virus these variances tend to aggregate by geographic location a preliminary study suggests that type L appears to be more frequent and possibly more aggressive in its ability to affect new people the clinical implications of these different genetic types are still unknown next slide please coronaviruses as a family have four genera the figure on the right is a phylogenetic tree which represents genetic similarity each virus is like a leaf on a tree and leaves on the same branch are more genetically similar than leaves on different branches alpha and beta genera infect mammals whereas gamma and Delta genera primarily affect birds SARS COVID 2 belongs to the beta coronavirus genus and is genetically related to the original SARS virus from 2002 to date seven different chrono viruses are known to infect people with four causing mild infection and three related to high mortality in large outbreaks there are 33 corona viruses that can infect a wide variety of animals with varying clinical presentations Crona viruses can have notable economic impacts on the farming industry with outbreaks having been reported in poultry swine and bovine populations next slide please it should be noted that all four of the mild corona virus types are regularly circulated in the United States in fact an estimated 15% of the common cold cases in the United States are due to corona viruses I’ve seen in this figure from CDC we see seasonal Peaks of varying coronavirus types that fluctuate each October to April these four types are known as 229E, NL63, OC43, and HKU clearly we scientists need a better PR person to help us with naming our corona viruses next slide please the zoonotic disease can be transmitted from animals to humans typically these diseases naturally exist in animals and spillover into humans spillover in the context of zoonotic transmission relates to an unintended consequence examples of zoonotic spillover can be when people eat wild animal Bush meat when they come in contact with wild animals during the deforestation events or have extensive animal contact due to farming or ranching an amplifying host is one that provides a large one that produces a large number of viral copies making it significantly more likely to transmit infection to others and contrast an intermediate or reservoir host can harbor infection without getting sick itself finally indeterminate hosts are animals that can get infected but do not create enough viral copies to infect others okay enough with the academic lessons back to covid 19 team from the viruses have a long history of Co evolving with bats and avian species in regards to the original SARS virus it was thought that in live animal markets facts and palm civets closely lived in shared spaces allowing for cross-species transmission

an amplification of that strange in civets these tickets then served as an intermediate host for viral evolution of the strain that eventually went on to infect humans with MERS camels served as an important intermediate host with SARS COVID 2 we are still trying to understand what animal is serving as the intermediate post next slide please SARS COVID 2 has an affinity for pulmonary epithelial cells which allows it to transmit via respiratory mechanisms dr. Nagarkatti will detail the mechanistic pathway but for now I want to clarify how transmission of the virus occurs between people respiratory droplets are small drops of liquid release during everyday body functions and social interactions that are heavy enough to drop to the ground in contrast aerosolized droplets have a more specific definition namely that they’re small around 5 to 10 microns in size allowing them to stay in the air longer SARS COVID 2 has incorrectly been described as being airborne transmitted which is an indirect route that does not require droplets an example of airborne transmission would be dust that can be carried around by air currents in closing the average sneeze contains an estimated 1 trillion viruses that are circulated in a mixture of respiratory droplets and aerosolized droplets combined next slide please respiratory transmission is the main way people are getting sick however as our pandemic continues we’re starting to understand other possible rare routes of transmission in the United States pregnant women account for approximately two percent of reported cases we are still in our infancy of understanding whether mothers can pass infection to their babies while pregnant during vaginal delivery or through breast milk studies in South Carolina and New York and California are ongoing to better understand the viral kinetics around the pre and post partum period next studies dating back over a decade demonstrate that corona viruses can be detected in fecal material oral people transmission can occur in animals while SARS COVID 2 virus particles have been detected in human feces it is not believe that they are infectious however we believe that these virus particles could serve as an indicator of transmission in an area studies are working and understand calm monitoring of wastewater of virus particle levels could relate to the number of people that are infected in the area our very own dr. Shawn Norman as part of these important studies going back to respiratory transmission fomites or inanimate objects can harbor infectious particles for several hours initial studies suggest that stainless steel and plastics can Harbor infectious particles for hours or possibly days while perfect laboratory conditions suggest that a doorknob could harbor SARS COVID 2 to for days it should be noted that these studies also demonstrate that the transmission risk is highest within the first eight hours the take-home message clean your frequently touched surfaces often next slide please the first time in my career people actually know how to say epidemiologist and that epidemiologists don’t study skin it’s been a pleasant surprise that so many people know about the topics I learned about in school I would be remiss however if I didn’t include a slide the correct definitions that we’re all reading and seeing these days first a basic reproduction number is a complicated metric that can vary based on the given point the two are within a pandemic the population that’s being studied and a variety of additional assumptions made the take-home message is this a basic reproduction number sometimes called an R nought can tell you how infectious a pathogen is or if you’re in the up side on the back end of a pandemic and when expressed as a range you can have a better feel for the pathogens potential next incubation period this is the time in which someone is exposed until the time their symptoms start the incubation period is one way we determine how long an exposed person should be in isolation to monitor if they develop symptoms for SARS COVID 2 to the average symptomatic person begins to show signs of disease within four to six days after initial exposure but it can be up to two weeks which is why quarantine has been recommended for two weeks an infectious dose is the amount of pathogen needed to establish an infection an infection dose can vary from person to person and is likely related to underline immunologic and genetic factors we do not know what the infectious dose of SARS COVID 2 is we believe it is quite low which explains why we see great disease spread viral

load is the amount of virus in a sample this information helps us understand how contagious saliva blood or other biologic samples are lastly there are preliminary studies that suggest that high heat and high humidity can reduce the viability of the virus in the environment one possible good outcome for our famously hot and humid columbia summers next slide please unlike influenza we are starting to see that asymptomatic infected people play a very important role in transmitting this virus studies suggest there are no statistical differences in viral load between patients with severe disease versus mild disease as indicated by the top left graph there’s no difference in viral load between healthy patients versus those with underlying healthy conditions bottom left graph and between those with symptoms versus no clinically apparent disease on the right one thing we are seeing however is that viral load increases with age as seen in the central graph suggesting that older people might be shedding more virus thus more likely to infect others than their younger counterparts next slide please health care workers have always been known to be a high-risk group for transmission given their increased close contact with infected people what is unique about this pandemic is the expansion of additional occupational groups there have been a few accounts of asymptomatic nursing home workers and asymptomatic prison officers that have introduced infections into institutions that have rapidly spread among these populations and we are still learning just how many jobs and occupations require close contact that might be putting essential workers at risk next slide please okay switching gears we’re gonna finish with some trends from the initial phase of this pandemic nationally we’ve seen a flattening of the curve as indicated from the CDC daily counted in the incident cases to date we have over a million reported cases with 6% of these cases resulting in death but as you can see we’re flattening that curve with less of a peak next slide please similarly in South Carolina we are seeing a reduction and a hopeful continual downturn encases as indicated by this week recent report from DHEC this figure shows the incident case burdens by week since the beginning of local cases next slide please this figure from DHEC shows the percent of people who test positive out of all of those tested this figure shows testing from the last two weeks the take-home message from this figure is that we’re seeing an expansion and our ability to test statewide and an overall decline in cases next slide please this graphic from DHEC refers to hospital surge capacity a primary concern we had a beginning of this pandemic was whether we would well more Hospital resources and not be able to provide supportive care to all those in need thankfully from this first phase of the pandemic we have not reached peak capacity even at the height of peak cases used a fraction of our resources given great promise that’s statewide we have the resources needed to handle any future spikes in cases next slide please lastly we see that every county in our state has reported infections as indicated by the darker blue shading the majority of cases have been reported from metropolitan areas so far we have an estimated 4% case fatality rate that is lower than the national figure next slide please so bringing it back home on our campus we have had a small number of students staff and faculty reporting infections students as demonstrated by the top blue line represented the highest burden of infections these cases peaked in late March and we’ve had a minimal number of cases reported since campus was closed next slide please infections among our campus body includes students that live in different states including a fifth of cases that reside in the northeastern United States it is belief that half of infections among our campus body occurred in our state versus exposures that occurred following campus closure and with that I will pass the baton on to dr. Nagarkatti thank you thank you that is an excellent so in my talk so far we heard you know how where the virus originated and how the virus

is spreading so in my talk if I can have the next slide what I’ll be discussing is can I have the next slide yes and so I’ll be discussing is how your immune response reacts to the corona virus infection and particularly I want to share you know the exciting concept that your immune system against the corona virus is like a double-edged sword that on one hand you need the immune system to protect you from corona virus infection almost 80% of the population can overcome this infection but in about 10 to 20 percent of the patients who develop a severe form of this disease it is actually the immune system that is responsible for causing damage to your lungs as well as other organs and cause you know sometimes death as well so therefore I’m going to share with you the concept of immune system acting as a double-edged sword if I can have the next slide please so when you inhale the virus it gets into your respiratory tract and the virus expresses what is called as the spike protein and this spike protein binds to the host cells through a receptor called as ACE 2 and ACE 2 receptor is expressed extensively throughout the body in particularly into your respiratory tract and so that virus is using the spike protein as a key to open the lock so that you can get into the cells once it gets into the cells it can it can replicate rapidly and can further spread the infection right so what does your body do at that time is that it produces B lymphocytes – it triggers the B lymphocytes to produce what I call as antibodies so antibodies are molecules that can bind to her example the spike protein and prevent that protein from binding to ACE 2 in other words the antibodies can block the key so that it cannot open the lock anymore now our immune system produces a variety of antibodies directed against so many different molecules expressed by the virus but the most important antibody is called as the neutralizing antibody so this is an antibody that specifically binds to the spiked protein so that it cannot enter the cells so therefore immunologists when we are trying to look for vaccines we want to make sure that the vaccines trigger is neutralizing antibodies so in this slide basically it shows that if you produce an optimum immune response it can clear the infection and therefore you’re going to recover fine in the next slide I also wanted to show you that in addition to the antibody molecules our immune cells also produce other protein molecules what I call as cytokines and these cytokines when they are produced in small quantities they can get rid of our infection they can bring other immune cells to the site so basically they are the ones which you know make you get fever and you know you get inflammation and that is because of these cytokines that are produced in by your immune system the lower panel shows what happens when a patient is immunocompromised that means in a patient maybe elderly or has certain other comorbidities and if your immune system is not functioning and you’re not producing enough neutralizing antibodies initially when you are infected then what can happen is your infection can keep spreading into the lower part of your respiratory tract next slide can I have the next slide please okay so it’s important to remember that while the virus enters your respiratory system and acts through the ACE 2 receptor interest rate is 2 receptor the h2 receptor is also expressed on other immune cells as well as other types of cells so it’s been shown that ace 2 receptor is expressed in the brain in the heart in the kidneys the GI tract all the blood vessels the endothelial cells that line the blood vessels also Express the h2 receptor now you have heard a lot about the antibody molecules but you’re not heard about another type of immune cell what is called as the killer T cell so the killer T cells also play as important a role as the antibody

molecule and what these killer T cells immune cells do is that they can sense when a normal cell gets infected with the virus so as soon as the cell gets infected with the virus the killer cells get a signal and they kill that infected cell before the virus has an opportunity to divide and multiply so therefore the killer T cells are also important having said that these cells kill the cells that Express h2 then you can imagine as the infection spreads the killer T cells are also going to cause damage to your heart your kidney other organs brain and and so on so forth and you suffer from the clinical symptoms that are associated with you know these killer T cells destroying your own cells next slide please so in addition to that what is happening now in the lungs is that your lung has what is called as the microbiota it has got millions of these bacteria and viruses that live in harmony and normally but when there is an active viral infection and when there is severe inflammation that is going on then what happens is the microbiota get disturbed and that leads to the pathogenic microbiota or pathogenic bacteria and viruses taking a dominate roll and start causing more of infections so at that time what happens is the immune system gets worried and it says you know oh my gosh there is not only this viral infection now the bacterial infection other things are going on so it goes into full gear and starts producing tremendous amount of cytokines that attract other immune cells to the site so it leads to a condition clinicians call it as a cytokine storm and that combined with the killer T cells what happens is the immune cells start releasing these toxic chemicals to kill the virally infected cells or kill the virus in the same time at the same time what is happening is there is friendly fire that means significant damage caused to your alveoli and the lungs so therefore the oxygen levels drop and you can have you know loss of blood pressure and so many other things that are associated with a cytokine storm so this also can lead then to multi organ failure and once you have all this it’s difficult to kind of save the patient’s next slide please so let’s move on to some of the tests that are used to for diagnosis of the code 19 the first test which is very popular is called as the nucleic acid cell test so what it does is you take a swab nasal or the oral swab and you can then use what is called as the rt-pcr reaction what it does is it can help detect even a single virus particle because it’s so sensitive that the virus particle RNA gets amplified and you know you can detect that now interestingly many of you may not have known this that the PCR reaction the following polymerase chain reaction PCR reaction was discovered by dr. Mullis who was a Nobel laureate and I’m sure you didn’t know that he studied in Columbia he went to Dreher high school and unfortunately last year he passed away but it’s so exciting to see you know the entire globe is using the PCR reaction to detect this infection and this was contributed by dr. mark mulli s from Columbia South Carolina so that is pretty exciting so now the advantages of this test is that is highly sensitive as I said you in one part where is particle it can detect but the problem is that it needs special equipment like I’ve shown you there it needs special reagents and it takes a long time and what if the test does is basically it helped can it can help isolate the patients and it’s important to remember like dr. Nolan said that sometimes the patients can be symptomless but still shedding the virus and so therefore you can detect using this particular nucleic acid test next slide please so this is another test what is called as the antigen test and what it does is basically it does not detect the RNA or the nucleic acid but it detects the foreign the other antigens or molecules expressed on these virus particle so it can for example it can detect the Spike antigen so this test is very simple and it can be as simple as like a pregnancy test and what you can do is

you can take a swab and put it on a strip and based on the change the color or false tree or negative it can tell you that so that’s the advantage the disadvantage it’s not very sensitive mostly like you know 80 percent of the time it you know a person who’s really infected shows up as positive but the advantage is that everybody can you know you know down the road everybody would be able to do it even at home by yourself if it’s possible next slide shows you what I call as the antibody test so these are tests that measure the amount of immune response that is triggered by inside the patient right so there are two types of tests one can detect the IgM that is produced early on and/or detect the IgG antibodies which are it takes at least two weeks sometimes to develop these antibodies now there are 12 approved tests by FDA but there are over hundred non-approved tests and that is because they wanted to make sure that they release all of these tests so that you know people can get benefit out of that but you know the feedback has been that lot of these tests which are not approved by FDA might give you high false positive or high false negative responses so you must be careful and you try to use the antibody test that it be approved by FDA the also the drawback of this compared to the previous two tests where you take the swab is that you need to draw blood here and you can of course use a lab test like what as far as the eliza test or you can use its chip as well to find out whether your antibody positive it helps also to know whether you are currently infected or you will you where infected because even if the you’re cleared the virus you will still have antibodies because the IgG anybodies can can be there without any problem for several months so you can detect the antibody levels for up to several months there is also question about whether you know once you’re infected whether you become immune or not so against most viruses I think that you’ll have immediate lease for a year because that’s when the that’s how the how long the antibodies that IgG will will survive in your system but sometimes you know these antibodies can disappear much faster or sometimes they can live for couple of years or even sometimes several years so now this also antibody test helps the way how many people are infected and what is the reinfection rate and some saying that you know maybe this can be used as a certificate to join workforce because you already contracted the disease you’re overcome the disease now you are immune to that this test also can be used to find out you know before you do the plasma transfers you can check whether that person has the antibodies but we don’t know which of these tests would detect neutralizing antibodies because those are the ones which are very important and then you heard about herd immunity that is the immunity across the population right so because this is a new virus we don’t have any immune response against this we don’t have an immune response so all of us to begin with are at a baseline and we don’t have any immunity against this virus so the way that we can spread herd immunity that everybody has some level of immunity is by either promoting infection or by vaccination promoting infection we cannot do because even if it kills 1% of the population there is almost 3.3 million people in the United States right so we can do that and vaccines of course you are waiting right until then there are some countries like Sweden for example might want to encourage the younger generation to go and to work and contract the disease but because they get mild disease they overcome the infection and that’s another way to spread third immunity but you are to make sure that the vulnerable people are sequestered and you know that isolated otherwise that would be tragic as well and it’s we need to find out of course like how long the immunity will last next slide please so this is a graph that I have taken from the w-h-o which shows you first in the blue line when you can detect the virus you know starting with day one you can start detecting the virus up to about two weeks and then as you start producing the green one is the IgM antibodies you start producing after one

week of infection it Peaks around a 14 and then it drops by day 21 so as the end anti as the IgM antibodies are being produced the virus levels also start decreasing as the IgM levels start decreasing the immune response starts what is called as the secondary immune response where it starts producing these IgG antibodies on around day 14 and they can last for the longer time and also our vertebrate immune system is made in such a way that we developed what is called a memory response upon our primary infection so if you come across the same infection second time our immune system is going to go to mount a very strong and vigorous reaction so that the virus or the bacteria can be clear so that’s a that’s what is called the memory response because of which the vaccines work so this chart is very critical because for example if you are using antibody test to detect IgG and you start doing it within one week or even up to send seven to 14 days you might find that it’s coming negative and you may have to wait till such time you know that the person shows positive so there are a lot of issues to interpret the test results you need to be familiar with this particular chart over all next slide please so about vaccinations don’t have the time to go through all of this there are over 100 vaccines being right now being developed the important thing is that these vaccines should be able to trigger the neutralizing antibodies as well as the cytotoxic t-cells so there for some sort of an attenuated live virus would be great I have a strong feeling that the vaccine is going to be highly successful and that is because we know that this virus triggers a very strong immune response the question is of course will the virus mutate to an extent that the vaccines might fail most of the evidence shows right now that this virus does not have mutate as much as some of the other viruses and the question is why does it take so long on time to develop the vaccine actually the development of the vaccine doesn’t take much time but it is based on how long it takes to do the clinical trials because some vaccines instead of triggering neutralizing antibodies they trigger what I call as enhancing antibodies which bind to the virus in fact facilitate infection or might trigger a very strong inflammation because of which you know we want to make sure that the vaccine can be tested in in in individuals to make sure that is safe so that takes a lot of time and then of course to make millions and millions of doses of the virus next slide please yet another approach you know which is a different approach is to identify the neutralizing antibody try to know its structure and clone it and produce the same antibody by you know by culturing them using what is called as growing the single cells now you can produce tons of these antibodies that can be you know transfer back into the patients and because we know that these antibodies are directed all against the Spike antigen we are 100% sure that it is going to be effective so that’s that’s being tried out as well and we’ll see how successful this approach is going to be as well next slide please so this is my slide last lights so basically what I wanted to convey is that you need an immune response to get rid of the infection and that’s what happens in eighty to ninety percent of the population they developed the optimal immune response and they can clear the infection but in ten to twenty percent of the population what happens is because they don’t have an initial good immune response the infection spreads and that triggers other infections or cytokine storm by the immune response and that causes acute respiratory distress syndrome multi organ failure and so on so in order to boost the immune response there is not many agents which can boost your immune response and there is some speculation about trying out BCG and polio vaccines for example but importantly to prevent the cytokine storm to prevent multi organ failure you need to have very potent immunosuppressive drugs that can block these cytokines and there are some clinical trials being done in that area as well so that’s why I just want to conclude my talk by saying you know the immune response against corona virus

novel coronavirus is like a double-edged sword on one hand it is helpful it is absolutely critical but in patients who are dying this may be detrimental as well so now I’m pass on to dr. albrecht to talk about you know what are some of the clinical and treatments available for Covid nineteen thank you Thank You Duncan so I’m the clean up hitter and we’ll take you through the symptoms the course of the disease and the therapy of Covid 19 next slide please next slide most of you can probably list a couple of the typical symptoms and their patients we see in the hospital we usually see a combination of cough shortness of breath and fever actually which each one of these being present at over 75% of patients admitted to our Hospital CDC has recently added six more symptoms but they’re really dozens of other presentations and none of these are very specific with probably the exception of a peculiar loss of sense of smell which can happen without a virus is – but it appears much more common to be with this virus in the outpatient setting on the other hand and you heard that now twice before we see a lot more asymptomatic patients or if they have symptoms they may have atypical symptoms such as back pain or fatigue or nausea all in all symptoms that usually do not result in getting you tested here in the US next slide please these are some of the studies that shows that some investigators from very high percentages of asymptomatic patients some sewer surveys using the antibody test that dr. Nagarkatt i mentioned seemed to suggest that we miss a vast majority of patients if you only test patients with symptoms next slide the typical course of diseases has an incubation period that dr. nolan mentioned that so the time from infection to first symptoms of around five days but it often takes another week before patients come in and get tested either because they are getting worse or not any better this means if you look at statistics of new cases you are looking at a scenario that actually played out ten to fourteen days ago already talked about asymptomatic patients and it’s becoming clear that patients can shed the virus or start being infectious a couple days before and a couple days after their symptoms have resolved next slide please the typical diseases of pneumonia often in both lungs which is what we call bilateral pneumonia left is a normal chest x-ray with a heart in the middle and the grayish lumps on each side with the ribs showing through and the diaphragm below in the middle some of the gray is taken over by a white infiltrates which is the covert pneumonia and on the right side the disease is so far advanced that it’s hard to see the heart the diaphragm or the ribs next slide please on a CT scan we see a fairly typical pattern the glean marks there or for the colorblind what is marked with a green square is normal lung and the red circles show all the areas have infected lung with most patients having several areas of pneumonia not only one next slide please when more organs become infected or affected when patients progress the prognosis gets worse dr. nagarkatti already talked about the hyper inflammation or the so called cytokine storm which often results in the shutting down of multiple organs advanced cases the heart can be involved as can be the brain or the nervous system and several of our patients we’ve seen somewhat atypical clotting problems leading to heart attacks pulmonary embolism or thrombosis which are not fully understood yet but the presence of any of these is prognostically bad is certainly associated with a higher risk of death next slide please death rate is itself it’s very dependent at where the patients are that you’re analyzing in the ICU mortality can be quite high especially if patients are on ventilators but it looks much less threatening if you include patients who have no or little symptoms you also hurt that mortality is age dependent and often affects persons with other clinical illnesses next slide so this is a slide that compares the mortality and covet on the right with a flu on the left I’ve actually used data from South Korea Korea as they’ve done a very good job in testing patients while a couple people have pointed out how

influenza and Covid share some similarities and they do they’re probably more different than similar and both illnesses indeed most of the mortality is and in patients with advanced age you do see however covid mortality is much much higher and the age range of deaths is much more spread out next slide this is a situation in South Carolina and dr. Nolan has shown you the numbers but here in the bar graph on the lower middle you see that our situations when it comes to deaths is very similar with a majority of deaths in patients over 65 but you can also see that almost 10% of deaths are seen in people in their 50s and furthermore while deaths in younger people are still quite rare they still occur the one patient listed here in the 30 to 40 year bracket for instance was a student of ours from USC Aiken and every one of those losses is a real tragedy and the upper left large circle you see that most infections are actually diagnosed in women however if you look at this smaller left circle on the left you see that men were much more likely to die this could be because men tend to seek health care later but it may be due to horomonal or genetic factors that actually increase or decrease your risk of dying at any rate after man flu man cold now there’s also man covid and it looks like it’s real on the upper right you can see that there is also racial disparity with African Americans making up 27 percent of our population but account for 36 percent of the cases even more disturbingly 57 percent of our deaths there are certainly societal and socio-economic factors that you can blame for this but they’re probably also genetic issues that can explain some of this next slide going on to treatment I will only have time to cover four of the several hundred different treatment approaches next slide that are currently being studied I’ll start with remdesivir next slide remdesivir is a very broad antiviral that was actually developed as an Ebola drug but it also has activity against corona viruses they have been a couple studies now they’ve put together fairly hastily but we have participated and had a chance to be on board very early and several of them got to treat several patient with this drug and have gathered some experience with this in the process and understand it now much better not all of these studies actually have shown a success the first study in China and the second study comparing a high dose versus a low dose studies showed no real difference decidedly better study that was very recently released in in in early data cuts the compared standard of care with standard of care plus remdesivir finally showed an improvement with remdesivir on average it took patients 11 days to improve on remdesivir versus 15 days if they did not get it there was also a trend to lower death rate with 8 percent versus 11.6% on remdesivir next slide please so in my personal opinion I think this will actually prove effective but the effect will be somewhat limited and will probably work better in patients with less advanced disease than what we’re currently testing it in it has been now approved under a emergency authorization and it will be distributed by the feds and nobody really has a good idea how we will get access to this drug there is a federal website and we have certainly asked to be included in this but certain currently there’s nobody from South Carolina on this website and we hope that they will not all go to New York but you never know the good news is we are still participating in the studies that only a few institutions have access to and we will at least have some guaranteed access to the drug that way next slide next our biologics next slide these are actually drugs that you see on TV every night that’s the newest treatment for moderate to severe plaque psoriasis or rheumatoid arthritis or something alike there dozens of these and they tend to

work by shutting down various parts of the immune system and all of them are being studied in one way or the other with the hope that one of them or more of them will be able to to rein in the hyperactive immune response that threatens patients with Covid 19 most well-known is probably tocilizumab and like everybody else we tried this as well and I’m going to show you very briefly our early experience that dr. s Weissman and just to put together it’s only 19 patient but that’s actually nowadays a pretty decent sample size next slide as you can tell in our hands this didn’t work so well with more than 40 percent of patients dying and another 20 percent having to transition to hospice care next slide part of the problem is that as monotherapy these are probably too little too late and this will not work with any of either of them I think alone well they’re also quite expensive they also might be dangerous as they shut down parts of the immune system which is how they work but that it’s difficult to tell which part of the immune system you can and which part you actually shouldn’t shut down and anyway the immune system is a very complex apparatus and going into this with these meds we’ve to me always feels like we’re going into Swiss watch with a hammer very blunt instrument may work but usually it doesn’t clearly need better approaches like earlier therapy but we do not have markers to tell us who would benefit or we need to combine with LSD is like for instance in the next slide a new study in the Upstate so this study is planned to combine plasmapheresis which means move removing some of the inflammatory substances with one of these biologics that will suppress making them anew and while we have started enrollment it’s too early to tell if this works next slide please chloroquine and hydroxychloroquine everybody has heard of that now there let me tell you they’re very misunderstood and very overrated next slide they are actually very different drug which is the first thing that people need to understand chloroquine is indeed an anti-malarial but hydroxychloroquine is not at all and that’s what ninety percent of people actually got it actually suppresses the immune system may therefore be particularly a poor choice in early infection or even in prevention both however affect how zinc goes into the cell which may actually affect viruses but they’re not antivirals by itself they certainly had some theoretical promise but next slide it really didn’t seem to do anything in our hands study by researchers from University of Virginia and USC here dr. harden and dr Scott Sutton from School of Public Health and School of Pharmacy at USC pointed out put the final nail into the coffin not only that these drugs did not help the patients who were on hydroxychloroquine we’re two and a half times more likely to die as when they didn’t get it and it’s probably easy to see why we’re therefore hardly used those anymore after that depressing news next slide here’s actually a more uplifting story which is convalescent plasma next slide please convalescent plasma already mentioned transfusing antibody rich blood plasma from patients who have recovered to patient with acute and severe disease this is organized by the fda in the national study led by Mayo Clinic they opened this up on Easter expected twenty patients got two thousand registered on just the first weekend but we already we’re at a point where we plan to do our own study and we’re pretty advanced we therefore got a pretty early start with this and open this up here locally on the first day next slide we’re actually the first to give convalescent plasma in South Carolina first to recruit donors first to organize a plasma drive and actually today the USC Student Health Center became a collection site for convalescent plasma for recovered patients so we’re doing a lot of things on a different front we’ve now transfused over 25 patients that I won’t show you any data of that but actually we’ll show you a letter next slide this is the first patient who got

transfused wrote a letter to dr. Rainer who is the medical director of the blood connection and and me and she was the first patient in South Carolina as I’ve said she’s also a nurse at Prisma Health Richland and got hospitalized on on Friday before Easter on 410 I was found to have bilateral pneumonia very high fever and was quickly getting more ill she was about to get on intubated and put on a ventilator as she was tiring out when we found her some matching plasma next slide actually should tolerated this pretty well and while I’m running over so you will have to read this later but interestingly enough not only that she slept and we were able to get her off oxygen in a day actually her sense of smell and taste that usually takes patients weeks to recover she got back the next day and she actually went home on the next day next slide and next slide after that and skip one further one more yes thank you critical so no one back please so I want to make a short statement about symptomatic therapy not very sexy and and undervalued but so so important these patients can have no visitors the only have healthcare workers at their bedside and our mental health and palliative care providers and the nurses have done a great job to get our patients through this it’s also really important to have good critical care docs that understand this it’s even better when you have great clinic critical care docs like we have they figured this out fairly quickly and why some hospitals in North New York and Italy have lost up to 80 percent their patient on ventilators most of our intubated patients are actually leaving the unit alive their mortality is relatively low last slide please here’s actually the summary of our strategy looks complicated but we’re getting the hang of this and phase one the virus dominates and you want to strengthen the immune system and fight the virus and phase 2 you need to battle the pneumonia and in phase 3 when the cytokine storm takes over you need to rein in the inflammation easier said than done we do not not have perfect tools for this but we are making progress and are actually getting better at this thank you that was my presentation Elizabeth unmute your mic please got it we will now take questions from audience for about 15 minutes our first question is from an anonymous USC staff member what kind of mask gives the best protection dr. Nolan will you address this question please I love that question but I’m actually gonna punt it over to helmut because we’ve had several conversations about this so I can finish up anything that he might have missed so it’s very easy to answer it depends so all of us were masked all day we have universal masking in the hospital which means we’re handing out 30,000 masks we’re not getting masks to all of our providers to protect ourselves we’re actually wearing masks to to protect people that are around us patients co-workers visitors so for that you can use almost anything anything that keeps your secretion next to you if you are if I go into a room I just need a barrier I actually use a surgical mask when I go into the room when we are doing procedures that require or have the risk of aerosilization that dr. Nolan talked about we use n95 masks so there’s an optimal mask for for every condition excellent thank you dr. obrecht our next question is from Wendy a graduate student why do people who are obese diabetic or have high blood pressure seem to be at higher risk for covid and is this true dr. Nagarkatti what do you have to say about that doctor please unmute your mic this is a great question so as an immunologist

I feel like inflammation is the underlying cause of a variety of diseases such as you know obesity hypertension you know certain diabetes diabetes type 1 so many autoimmune diseases so you know there are a lot of diseases even cardiovascular disease and neurodegenerative diseases so there are a lot of diseases in which there is chronic inflammation that’s going on so it is likely that that might further be enhanced by the viral infection as I as I described but I would also like to get some feedback clinical feedback I think from dr. Albrecht to see why that comorbidities there why I think I think you you correctly pointed out that the missing link is probably inflammation the other thing is that a lot of these diseases affect the organs most important for this which are the lungs and the heart so if those organs are chronically affected you will have less reserve to deal with this disease thank you thank you very much our next question comes from dr. Susan wood a faculty member at USC for those of us who were in direct contact with a known covid positive patient is there any internal option to get tested for antibodies so that we can donate plasma dr. Albrecht why don’t you take that one so could you say give me that question again sorry I certainly for those of us who are in direct contact with a known a covid positive patient is there any internal option to get tested for antibodies so that we can donate plasma yes and actually on Friday the the protocol from the Mayo Clinic started including patients who only tested antibody positive never had a confirmatory test so that is possible now Prisma health for instance is offering this antibody test and every provider can offer that and in our research unit we have 2,000 additional tests that we’re going to be going to be using partially to qualify donors for for plasma donation thank you thank you dr. albrecht our next question comes from Regina a USC staffer when we begin to return to campus should we wear masks when we’re on campus dr. Nolan why don’t you take that one yeah I thank you Regina that’s an excellent question and one that us as the future planning group have been discussing and we’re hoping that there will be some guidelines that will be coming out to describe this but I would say will likely be in accordance with what we’re seeing with national and state guidelines at the current moment they are recommending that you have some type of face protection I’ll just go off of what Helmut said before when we talk about wearing just a general face covering that’s really not necessarily to prevent you from getting infected from others it’s for you to protect others so that if you are an asymptomatic carrier you can help create a physical barrier from spreading this disease to others and then of course there’s another level which would be surgical mask and that would be really if you’re coming in more close contact with people so I would envision that it could be we might require you to have some type of face protection the level of which we’re still deciding but again I would say future guidelines on that will be coming out but at the end of the day absolutely our most important priority to protect the safety health and well-being of all of our campus populations whether that be staff faculty or students thank you for the question thank you dr. Nolan our next question is from leuphana Sultan and the question is it has been recently found that skin lesions specifically around fingers and feet in about 30% of Covid 19 patients in this situation does that put people with skin allergy at a higher risk of infection dr. nagarkatti why don’t you start this one yeah I turn it over to dr. albrecht I think figured you would do that so actually very interesting and very

diverse and they they have very different reasons why patients such as this have skin lesions one of the types of skin lesions is a sort of allergic reaction to the virus but some of them are related to the blood clotting events and so the virus does not get absorbed through the skin not even through broken skin and unhealthy skin if you have multiple skin allergies you have a different immune system as well so if this does set you up for different kind of events but probably doesn’t make you a lot more susceptible to this so the answer would mean I don’t think so this would not make you a high risk patient thank you dr. obrecht we’ve got two more questions to go from the audience the next question is from a community member named Ed is there sufficient empirical evidence to suggest what secondary waves might occur or what mitigating strategies might need to be deployed in the future dr. Nolan why don’t you take this question please first off I’ll say Ed thank you so much for tuning in it’s really exciting for us to get to talk to the public and you know expand or beyond we recognize that the University of South Carolina is an urban campus and that we are all in this together as one large community in response to your question I would say that we are very closely monitoring the efficacy of social distancing guidelines and trying to see what’s working what’s not and I can assure you that moving forward we’re gonna do everything we can I think our ultimate goal is to make sure that as we see cases in the fall that they’re gonna be more periodic kind of isolated cases and the goal is to reduce the potential for it to be a continued sustained peak transmission thank you for the question thank you dr. Noland and our last question for the evening comes from another community member named Neil Neil asks I live in Columbia is it true that long-term quarantine such as we have been going through can weaken our immune system overall dr. nagarkatti this questions for you oh I couldn’t hear that properly can you sorry can you repeat that again certainly Neil lives here in Columbia and he’s wondering if it’s true that long-term quarantines like we’re going through right now can be weakening to our immune systems overall yeah mean that that’s that’s a great question so I think the way we are staying at home for you know like a couple of months or whatever I don’t think that impacts your immune response you know even if it’s whatever it’s long term or short term as long as you know we we make sure that we don’t get stressed out because stress has clearly been shown to suppress your immune response by inducing for example particle steroids and all that so as long as you eat well and you know sleep well and do exercise and and don’t get stressed out and you know go for walks or whatever I think your immune system should should should be fine it’s only if this goes on for a very long period of time where you know like say if you are imprisoned in a Cell for years then you know then what will happen is there is less possibility that you have been getting more exposed to different types of pathogens and so that time you might become more susceptible but I don’t think this sequestration the way they’re doing right now for couple of weeks or few weeks is going to impact your immune response whether it’s short term or long term thank you for that question thank you very much dr. nagarkatti and thank you to our audience for joining us this evening for the understanding covid 19 virtual town hall have a nice evening