UCSF Experts on the Epidemiology, Science, & Clinical Manifestations of COVID-19, and UCSF Response

welcome to the UCSF Department of Medicine medical Grand Rounds to our department medicine attendees as well as our many guests at UCSF for joining us today our plan is to distribute this video broadly beyond UCSF after we're done so welcome to all of you outside our community my name is Bob Walker I'm professor and chair of the UCSF department of medicine it goes without saying that these are extraordinary times even folks like me who've been in medicine for over 30 years have never seen anything like Ovid before as a clinical and a public health threat as well as a test of our political and economic systems at UCSF I have to say the response has been breathtaking everyone has rolled up their sleeves and just done what needs to be done the teamwork the camaraderie the intellectual firepower being applied to these this challenge and the courage and bravery that I have witnessed has been absolutely remarkable I want to thank all of you for doing what you're doing to prepare for this crisis and to care for our patients for each other and for yourself over the last couple weeks we've received a staggering amount of new information the UCS of command center and many others throughout the organization are working 24/7 to develop and disseminate new guidelines and algorithms to stand up new services and to troubleshoot and what seemingly infinite number of challenging situations and unanticipated consequences they've done an amazing job of doing all of this and communicating it broadly to the UCSF community today we're going to focus a little bit less on the nuts and bolts of our response although we'll cover some of these in the panel discussion toward the end of this session and more on what we are uniquely positioned to do as a world leading academic department and Medical Center namely to understand and advance the science of Epidemiology biology pathophysiology clinical medicine and therapeutics we have four outstanding speakers to do that a little roadmap for this session the session will go for an hour and 40 minutes or so the first hour we'll hear from four of our expert speakers will deliver brief lectures followed at the end by a Q&A session the questions will come for the most part from our audience who submitted questions during the live session the questions are being reviewed by my colleague Queenie Chang who's feeding the most generally interesting ones or most commonly asked questions to me at the end of that which will be about an hour from now we'll have a panel discussion with five other exceptional experts covering a variety of fronts from virality to epidemiology to clinical care in the hospital clinical care in the ICU and in that session I will moderate a lively panel discussion and so the entire session will go about an hour and 40 minutes I think you will learn a tremendous amount and and I look forward to it so let's go ahead and start with the first speaker my intros will be brief to be sure we have time for the talk Stan have ler his professor in chief of the division of HIV and global medicine at Zuckerberg San Francisco General she's one of the world's experts in clinical research and the care of patients with HIV and her presentation will focus on epidemiology and biology of kovat 19 Diane Seok over 19 is the name of the disease caused by the newly discovered stars where this Q is genetically related but distinct from the virus had caused the SARS epidemic in 2002 you can see here in the cartoon is single-stranded RNA virus has characteristic crown-like from the Latin Corona spikes on its surface there's a close-up here shown of one of the spikes the structure of the spike now Tsarskoe v2 binds to the receptor epithelial cells in the upper breast if you track it long angelarts cells in the gut one of iris s were discovered in the 1960s and their widespread in humans and animals most are non-pathogenic and they caused about 10% of cols in humans however there are several pathogenic strange highly pathogenic strains that cause the SARS epidemic over 10,000 patients in 2002 and Middle Eastern respiratory syndrome in 2012 or MERS next slide please so the Kovan 19 outbreak started in Wuhan China which is a city with a population of about 11 million in probably November of 2019 the first officially reported cases to the CDC in the government were in December 27th when a physician noted three SARS like pneumonia cases in a family in the hospital cases began pouring in by December 31st there was a Public Health Alert by January 7th the virus was also isolated in sequence by January 11th there was a PCR diagnostic this is really amazing progress and all of this was shared with the world January 23rd Wuhan City was shut down for public health measures but in this time period there were there were over a hundred thousand cases in 38 under a deaths next slide please so let's look at some key of anomie illogic question what is the source of this virus but the source appears to be the rain appleís bats they Harbor a number of corona viruses but they hurt they also harbour stars Kobe - which doesn't cause any disease in them now our other SARS both stars and MERS had intermediary hosts and one of them for SARS it was the Palm Civet which is a small mammal which was actually cold during the course of the epidemic and for MERS it was the camel some early reports suggested that the Pangolin shown here whose scales are used in traditional chinese medicine were possible a secondary host however that was when only part of the virus was sequenced and that has not been corroborated so we still don't know if there's a secondary host so how is his virus transmitted the primary mechanism of transmission is through large viral a nuclei and airborne droplets when people talk with me please when they call I was transmitted people touch the secretion this is and then touch their face in their nose and this is the main mechanism now I shared with you this virus can infect gut cells and in fact it secreted it can be detected in fecal specimen however a large body I would say of epidemiologic data would suggest that this is but this is not not the main source of transmission that's I please you next slide so let's look at the Thanks let's look at the viral dynamics of this disease what we see is the virus Peaks early and at high levels on this graph you can see individual PCR levels in patients infected with koban when we compare this to SARS feet about three to five days earlier the peak levels our thousandfold higher and this may may be one of the reasons why this virus appears so much more transmissible and contagious there was also a really nice study looking at transmissibility of when this virus is most likely be transmissible that did both culture and PCR sequentially on patients after the onset of symptoms and what they showed is there was no culture positivity after eight days suggesting that transmitted transmissibility decreases after that we do know that viral shedding can outlast symptoms for days and PCR can be the virus can be detected by PCR on the stool next slide please so as we know kovat spread rapidly inside and outside of China between January to early March this is a whu-oh graph by region of the world and what we can see if the virus started as I mentioned in China it's the orange parts and also in other hotspots in Asia such as South Korea this was followed by an increase in case reporting from the Middle East specifically in Iran where the epidemic continues to be raging after this we can see the red bar which represents cases reported from Europe and Europe and this is primarily driven by the cases in Italy and finally on the far right are the Americas on which you can see are just starting now in this graph you can see green bar which is the Diamond Princess cruise ship you could finally go to the next slide and cruise ships have been a significant contributor to the transmission of this virus around the world now many infectious disease people would go on cruises because they go there's such increase risk for outbreaks of many different pathogens norovirus is self-limiting gastrointestinal Maserati rapidly can spread through populations influenza and other viruses are often outbreaks that can occur and we're coming out for killing current cruise ships cruise ships may be enriched for at-risk populations such as elderly populations also cruise ships air circulation systems do not not have HEPA filters in contrast to airplanes which have air that go through HEPA filtered originally developing as people were smoking on trains due to alter out particles with those these filters also filter out pathogens so there's multiple ongoing coated outbreaks its infect some cruise ships are still eats we all watched with duress the story of the diamond princess out Bay docked off of Yokohama and during that time period 696 confirmed cases of Kovac were found in six deaths locally here the Grand Princess was on our shores in fact I could look out my window consiga see this cruise ship it was finally docked in Oakland and March 10th of the first 42 people tested 21 were positive these individuals all of them now are being tested at federal sites the next slide please so here's the map of the global spread the reported cases are already over 200,000 we have over 10,000 cases in the United States and a couple of points here the new epicenter of the epidemic is in Europe we have increasing number of cases in the United States and in South America and in Africa we have a low but increasing number of cases of course a case detection has been limited by testing and we expect to see these numbers increase on the right side of the slide you can see the top 10 countries by cumulative cases the top three are China Italy and Iran the United States right now sits at number 8 next slide please so this graph has been widely disseminated which shows the natural history of a pandemic in the solid figure when there are no interventions what we would like to gain in our interventions is to decrease the slope of the rise of new infections and the peak and this is called been called flattening the curve we do this by a number of ways we first try to contain the epidemic using measures such as isolation quarantine infection control and public public education and unrest pretory hygiene you are all familiar with that but for some infections and some outbreaks such as koban 19 this is clearly not enough and we need to do population measures and these include social distancing community restricting community events and a new term that we all have now is shelter in place which is really widespread community quarantine next slide please many of you have heard of the term of our sub not which in the most simplistic terms is the number of secondary cases that result from an index case and our measure of how the population is how the virus is driven through a population so just just for some perspective infections like whooping cough or measles have an AR of about 18 in Koba 19 the AR is estimated to be about three we can affect our and this has been called our e by intervening on a number of points through public health measures as shown here on this slide next slide please so let's go back to Wu Han China implemented rapid and extensive universal population response with isolation quarantine suspension of public gatherings and movement restrictions it was quite amazing at one point they had asked over a billion people to stay at home for two weeks with this and you can see the graph of wu hand on the right there was a dramatic reduction in the number of cases and we just heard from china that over the last 24 hours they've seen no new cases in this region also shown on here you can see the our values decreasing over four intervals over time from three point eight six two point three two next slide please so every pandemic requires a new playbook but we look to lessons from the past for each epidemic that can what to help can that can help us to respond there was a very nice paper in JAMA that looked at the influenza epidemic in 1918 across a number of cities and I'm showing two of these cities here so this compares st. Louis where there was a very rapid response they did school closures banned public gatherings and contrasted it to Pittsburgh where there was a slow response and they did very few measures and what one can see is when we look at the excess death rate it was nearly twice as high as Pittsburgh as it was in st. Louis so the lessons from here begin social distancing interventions early and keep them going and I think we've seen some success in China and some other Asian countries such as Taiwan with this approach so this has been an overview of the epidemiology of this mighty virus and how public health measures can be effective as we work around the clock to develop treatment and vaccine for this disease Thank You Tanya thank you so much that was that was terrific I'm gonna save questions now to the till the end Marilla behind time so let me move to the next speaker who is dr. Jen Babbage and his associate program director for our internal medicine residency program and associate professor and division of infectious disease here at UCSF health and a go-to clinician educator for all of us and she's going to talk to us about some of the clinical manifestations of this new disease Jen thank you Bob thank you for that very kind introduction so I'm gonna talk today about the clinical manifestations of coated night next slide please so we'll start with the clinical presentation and I want to start with a couple caveats to this data so most of this data comes from China Singapore and Korea with a little bit of data now coming out of Italy and then another caveat is that almost all this data is from hospitalized patients with coping so I want to start by looking at the pie graph to the right to talk a little bit about disease categorization so you can see that most of the patients with Cova do have non severe disease so about 70 to 80 percent have non severe disease 15 to 25 percent have severe disease and five percent end up in the ICU in terms of the symptoms and again this is hospitalized patients most patients have fever at some point but only about 50 percent have fever on admission and that's important because the lack of fever on admission does not exclude kovat as a diagnosis cough shortness of breath and myalgias are also quite common but the triad of fever cough and shortness of breath are only seen in about 15% of cases in terms of some less common symptoms so URI symptoms including headache sore throat and Ryan area are seen in less than 15 percent and then GI symptoms with nausea vomiting seen in less than 10% and diarrhea seen in less than 25% next slide please in terms of labs in terms of looking at routine labs the median white blood cell count in most patients is normal with a leukopenia seen anywhere from 17 to 54 percent and a leukocytosis being relatively uncommon seeing less than 25% of cases lymphopenia can be seen in anywhere between 33 and 85 percent and so importantly leukopenia and lymphopenia can be important clues to : the median platelet count is normal although there can be a slight decrease in platelets in less than a third of patients and then you can see an increase in the ast alt in anywhere from four to thirty five percent there's been a lot of excitement about thinking about biomarkers to help try to distinguish between kovin and other diseases unfortunately CRP and LDH are increased in a fair proportion of patients and so don't have very good discriminatory value the procalcitonin cutoff that's used in most of the chinese studies where this data comes from is 0.5 and that's important because that's higher than the cutoff that is used in most of the algorithms in the US but they found that procalcitonin was greater than 25 in anywhere from five to ten percent of patients although in patients who were more severe or in the ICU it was higher so a low pro calcitonin and someone with mild disease may be helpful but high procalcitonin especially in severe disease cannot be used to exclude Kobuk next slide please there's been a lot of attention paid recently to the question of viral and bacterial co-infections so in published reports to date on in adults the ko infection rate appears to be between zero and six percent however it's not clear if testing was systematic in all of these studies so this is very much maybe an underestimate there are multiple cases reported a co-infection with other respiratory viruses including influenza and there is a report that many of you may have seen that is circulating now from Stanford on social media that shows that they have had a higher ko infection rate that is not yet published or peer-reviewed but something I think that everyone is paying attention to so I think the detection of an alternative viral infection makes COBIT less likely but does not rule it out and similarly bacterial co-infection likely increases with the severity of illness as we know it does with influenza so a bacterial infection in a severely ill patient should not exclude kovat next slide please we've had a lot of questions recently about asking about the clinical course for kovat so this comes from a study that came out in Lancet last week of 191 hospitalized patients in Wuhan who had a known outcome and that's important because a lot of the prior studies had patients who their outcome was actually not yet known they were still hospitalized with kovat so these are patients where the outcome was known they were either survivors and discharged or they were non survivors so they looked at 137 survivors and 54 non survivors and they looked at several parameters which are shown in the colored bars over time which is shown in me basically in the in the x-axis and so if you look at fever and cough which are the orange and the light blue bars most patients have those kind of from the beginning onwards through their course dyspnea which is the dark blue bar begins around day 7 ICU admission happened around day 12 in both groups and then for those who needed to be in 2 which happened almost exclusively in the non survivor group in this study that happened around day 15 and for the non survivors the median time of death was day 19 and for those who survived they were discharged around day 22 and you can also see they have different time points here with the arrows sepsis tended to occur around day 9 or 10 and air ds4 on day 10 to 12 and importantly we don't yet know how the clinical course will vary with different patient populations such as immuno compromised patients or patients with HIV that data is not yet out there next slide please in looking at the case fatality rates these vary depending on the country so in China it's been reported that their case fatality rate is anywhere between 2.3 and 3.8 percent the data that came out of Italy this week showed a case fatality rate preliminary of 7 7.2 percent whereas in Korea the CDC report from Korea this week showed a mortality rate of 0.5 percent and some of the differences between countries are likely in part due to testing so we know in Korea there's been widespread testing so they're likely picking up many of the mild cases so it may be that this is a more accurate number the other parameter in that may be causing some of the higher mortality in Italy is the age of their population so they have the oldest population in Europe and as we'll talk about we know that that is a factor in mortality so older age is the main risk factor for death when it's been looked at in a few different multivariate analyses other factors that seem to be associated with higher death rates are at least in China men in many studies had higher mortality rates than women and then comorbidities and the ones that were commonly reported in the Chinese literature were cardiopulmonary disease diabetes hypertension and some with cancer so I've shown a graph here of the case fatality rate with the red bars from China and then superimposed the newest Italy data in the blue text but they're very similar and you can see that the case fatality rates really start to increase once you get to the ages of 50 to 60 and really over 70 to 80 is where the mortality rates really hire anywhere from about 10 to then 20% over the age of the next slide please some of you I may have seen that the MMWR came out yesterday with a preliminary analysis of the United States cases to date so this is a look at the first four thousand two hundred twenty six cases in the US and you can see the pie graph showing the case distribution by age and there's a very wide spread of age distribution at the moment and this certainly may change as our testing strategies evolve but you can see that in importantly and similar to other data from other countries that only five percent of our cases are in people less than the age of twenty if you look at the table they stratify by age group which is the left-hand column and then they look at rates of hospitalization ICU and case fatality rate and um there's a range of data here because they had a lot of missing data so they try to give estimates but you can see that the rate of hospitalization ICU admission and case fatality rates all increase with age group and the preliminary estimate of our case fatality rate and again this is very preliminary data based on only our first 4,000 cases but was 1.8 to 3.4 percent and one of the take homes from this study is that adults greater than 65 years while they were only thirty one percent of cases they were 45 percent of hospitalizations 53 percent of ICU admissions and eighty percent of deaths next slide so I just want to end by saying I think that everyone should be thinking about taking a diagnostic time out when you are seeing patients with Kovac I think we're all bombarded with information about Kovac from all angles in every aspect of our lives right now and it's tempting when you see these patients to think in a very binary covetous no but I think it's really important to take my time out and think about all of the normal diagnosis that you're that you're thinking about and making sure you're keeping your differential broad and I personally have felt like I needed to do that when so that's my last slide thank you very one for listening thank you Jen that was that was terrific let me ask one quick question maybe it's not a quick question it's a hard question diagnostic testing and it's utility particularly since no symptom is a hundred percent sensitive or you see symptoms that are 75 percent that fever or whatever so how do you decide on diagnostic testing we're starting here about people who were asymptomatic tested and we're positive yeah that's a great question Bob and I know that I'm sure Chas we'll discuss this later on the panel as well but I think it depends on your availability of testing so I think you know we now at UCSF have quite widespread availability of testing so we're testing a lot of people because as you said it's really hard to tell whether it's coded or whether it's influenza or met a numa virus I know that other places that have more limited testing are having to risk stratify a little more carefully but that's very challenging because Kovach looks like many other respiratory diseases great thank you and again we will talk about this more during the panel and just to remind people if you do have questions to please send them in through the QA function we're seeing some chats as well but we're monitoring in the Q&A function for that so Jen thank you very much next speaker is Michael methane Michael is professor in our division of pulmonary medicine at UCSF Health he's also associate director of critical care medicine more relevant to this talk he may very well be the world's expert certainly the top handful in the syndrome of acute respiratory distress syndrome and he will talk about that with a special reference to to code Michael go ahead thank you Bob so that will be the focus ard s next slide so this isn't from the philadelphia inquirer yesterday when coronavirus kills the lung condition ard s can be the culprit here's what you need to know and so that really is the problem most of the mortality seems to be related to severe air D s next slide so what is a RDS many of us are quite familiar with this but basically it's a patient who has acute respiratory failure with bilateral infiltrates shown on this chest x-ray and protein-rich pulmonary edema it is a non cardiogenic pulmonary edema the PF ratio by definition has to be less than 300 millimeters of mercury there are approximately 200,000 cases per year in the US before kovat 19 mortality is 20 to 45 percent depending on the initial degree of hypoxemia and the clinical disorders most commonly is pneumonia second non pulmonary sepsis aspiration and trauma next slide the pathogenesis of lung injury involves injury first to the endothelial vascular barrier even if the primary insult is pneumonia and then a breakdown in the epithelial barrier there is a major role for neutrophils platelets and extracellular traps and maybe also in other cells such as lymphocytes and viral pneumonia and there is importantly direct injury from pathogens and their products and as as ICU doctors know non-pulmonary organ failure and comorbidities contribute to the higher mortality in these patients it's not just the lung injury although with a viral pneumonia such as kovat 19 it really is often an example of just severe respiratory failure next slide this slide just briefly shows that we've learned a great deal about pathogenesis of lung injury as well as repair we now have several different pathways identified it's complex because it involves the vascular and the epithelial barriers but a molecular level we have learned a lot in both of these areas next slide so the clinical features of air it is encoded 19 well some patients will present just with pneumonia that does not necessarily require ICU care but may worsen in the second week of hospital care as you care approximately in 20 to 30% of hospitalized patients air D s perhaps at about 17 to 29 percent of hospitalized patients and mortality perhaps depending on more data about 4 to 15% of various patients and as already shown by Jen higher mortality in patients with age greater than 70 next slide the next three slides will show chess radiographic and CT findings this shows on on your left hand side a chest x-ray that shows a minimal infiltrate in a cove at 19 positive patients that's confirmed on the CT scan next slide shows now bilateral infiltrates and another patient that's very evident on the CT scan they're a little bit faint but this is the next phase and then the next slide shows the infiltrates more extensive and more impressive ground-glass appearance as well as on the CT scan next slide now the lung pathology is quite interesting it shows classic features of a RDS with protein-rich edema and and fibrin debris then interestingly a lot of mononuclear cells including lymphocytes and to show that the extent of the injury the alveolar epithelial cells are denuded and there may be evidence in this recent publication of actual viral inclusions so the the lymphocyte and the mono nuclear collection the lung is is perhaps a fairly unique feature of this syndrome next slide now not everybody who develops respiratory failure will will need intubation in fact we are recommending this we'll probably discuss more in the discussion section that patients who are not rapidly progressing to severe respiratory failure be treated with high flow nasal oxygen this is the slide from the classic study from France in 2015 that showed that high flow oxygen was more effective in saving patients so that's a key alternative now for the specific respiratory treatment of patients with koba 19 low tidal volume is that is the key most important treatment peep in a moderate level neuromuscular blockade if the patients have ventilator to synchrony higher air pressures or hypoxemia and prone positioning if the PF is less than 100 to 150 next slide just to emphasize a very important point low tide of iron is really save lives in this syndrome and just to emphasize we learned that the low tide of I'm is associated with a marked reduction of aisle six aisle eight NFR one and other pro-inflammatory factors so one of the reasons it worked is that it reduced lung injury next slide provides a diagram to just illustrate how the low tide of I'm attenuates the lung injury in Iraq allows the endothelium and the epithelial to barriers to repair themselves and this is a key point in giving low tide upon the patient is set on the course of having a better chance for recovery next slide this is the slide the figure from the prone positioning trial published in the New England Journal in 2013 that showed that prone positioning definitely increases survival and patients who have moderate to severe erred yes and this is an important treatment objective and definitely is added to the treatment of these patients next slide what are the adjectives treatments for kovat 19a RDS will inhaled nitric oxide can be used for refractory hypoxemia fluid balance is probably important to use moderate fluid resuscitation for these patients so as not to overload and increase the risk for more pulmonary edema based on the New England Journal publication 2006 we know that a conservative fluid strategy targeting negative fluid balance is also beneficial dialysis can be used in continuous veno-venous filtration for oliguria renal failure pH less than seven point two and negative fluid balance and if all that fails and if the patient is appropriate ECMO can be considered there's an international group working with ECMO now and as so patients have been treated with ECMO though many can survive without without ECMO next slide what are possible other treatments for kovat 1980s well we think glucocorticoids are not recommended we can discuss this more in the panel period other experimental therapies that are being considered including anti l6 or our six receptor blocker therapy Iowan RA or interferon beta but they all have concerns and particularly the anti cytokine therapies might reduce host defense we do have a program here at UCSF that's a multicenter study for using allergen a placental stromal cells which are attractive because they have multiple mechanisms by which they can we decrease injury and increase repair and this is a phase 2b trial that's ongoing at UCSF both San Francisco General and Parnassus finally I should point out another interesting alternative which is high-dose vitamin C we're about to start a Phase two trial here UCSF and eleven other medical centers but there's a very favorable trial blinded and randomized phase two showing high-dose vitamin C reduce mortality in patients with a RDS before the code nineteen outbreak I think that's the last slide mom it is Michael thank you thank you so much that was terrific let me ask you one sort of general question and he will speak about therapeutics more specifically but from your decades of studying a RDS is the is an antiviral potentially going to be the answer here or does the virus come in and do its damage and then sets off a cascade of non viral pathophysiology that really is what's what's harming the lungs I'm going to defer to Annie on this point but I would say most likely when the patient has arrived in the ICU and has developed severe respiratory failure I would I would anticipate I wrote antiviral therapy would not be effective but I think Annie can speak to this better than I all right fantastic thank you Michael very much so our last formal speaker and then after this at talking at one o'clock we will have a panel of five other speakers just to increase the number of degrees of freedom in our resume event here but our next speaker is Annie Luetkemeyer who is professor in the vision of HIV infectious diseases and global medicine based at Zuckerberg San Francisco General Hospital where she directs the HIV clinical trials group and is now quite involved in helping to lead clinical trials around kovat here at UCSF any thank you for speaking thanks so much for including me Bob I'm going to go to the next slide so I want to talk about who we should treat when we should treat and then what we should be treating with in in this overview of Kovach treatment so Jen Babic nicely reviewed for us that the majority of people do not develop severe disease and will recover and do very well without any kind of medical intervention so this has led us to trying to prioritize who we need to develop treatment strategies for obviously it's a high priority to treat the people who are severely or critically ill in the ICU we certainly are thinking about treating people with moderate disease in other words those who have developed hypoxia and maybe hospitalized but they have not developed severe disease requiring intubation and we're trying to risk stratify those individuals by the risk factors that dr. Babic mentioned you can unanswered question is those with mild disease again we have an initial signal for those people who have risk factors for poor outcomes should we be trying to treat those individuals when they're at home we don't know the answer to this and they part of this will depend on whether we have a safe and widely available treatment in which case we could consider trying to expand to those with mild disease particularly if they have risk factors for a poor outcome many of these individuals will recover and do very well without treatment but one other thing to consider when we think about the rationale for treating people if they have mild or moderate disease that if we have something safe and effective that reduces the viral load dramatically in the beginning this can be a potential strategy to reduce infectivity and to try to break the cycle of forward transmission so we certainly would like to have a tool that would allow us to do that and then many many questions about prophylaxis post exposure prophylaxis for those who have been exposed and how do we help protect people on the front lines but I'm going to talk a little bit about that at the end of this talk that's fine so when do we treat people in the course of disease and and and dr. masse and dr. Walker brought this up you know when had the horse left the barn so to speak in terms of treating the virus and this has to do with the two phases of disease that we think of in in Cova disease as we understand it now in early disease during this first week we know that this is the time when the viral load is the highest but often times it's not when people are at their sickest so this can be a time may be the best time to intervene with antiviral approaches that may allow for a rapid reduction in viral load and the goal here is to prevent ARVs and hopefully to reduce death we know from the SARS era that the limited anti-v that we had during that time including drugs like LaPenta fear Ratana beer look like they they worked reasonably well in some studies and those with very early disease but once people had developed full on a RDS it was not effective to provide these therapies as rescue therapy when you think about later disease so oftentimes this is in the second week of disease when people's viral loads may start to come down but you start to see a very robust inflammatory and immune response this is often when people will deteriorate and become much more ill and end up in the ICU with things like a RDS at this point in time the horse may have left the barn because you have a robust cytokine response that may be triggered and frank ARVs may be present there may still be a role for treating with an antiviral we don't know we need to understand this better but the most effective approaches may be those that help to mitigate lung and myocardial injury we know that cardiac injury is a big part of what we to death particularly in older patients and that we need strategies that go beyond treating the virus that are going to be anti-inflammatory and deal with the dysregulated prior to kind overload that's happening so cytokine modulation is going to be important next slide so how do we treat people with kovat given the breakdown that I've provided of these sort of two phases of disease we've divided this into two main buckets as we think about therapy there's the antiviral approaches and then the anti-inflammatory or immunomodulatory approaches I wanted to say right off the bat that right now we don't have any approved therapies fda approved or strongly evidence-based approved therapies for for kovat right now we do have medications that have been used for other reasons that are being investigated in very actively and we do have some medications that are available and being used in an off-label way but I want to just give that caveat to what to what I'm presenting here and we'll give you sort of our best interpretation of what's being studied and what to do right now we have people in front of us for the anti-viral bucket I'm going to talk about three approaches recognizing that there are many many more than this but REM get severe chloroquine hydroxychloroquine and LaPenta beer Ratana beer I think are the ones that have really been in the forefront and I'm not going to get too into the anti-inflammatory and anti site of kine approaches dr. masse reviewed those but to recognize that there are many exciting approaches that are being investigated currently next slide so I want to start by talking about the antiviral REM Det severe this is an adenosine analogue that inhibits RNA dependent RNA polymerase it has on broad antiviral activity in vitro and had activity against other corona viruses like SARS and MERS that Diane mentioned wide activity against the number of hemorrhagic viruses including the Ebola virus interestingly REM death severe was studied in a clinical trial against Ebola where it did not look particularly effective and what we don't know is it's part of that reason that it didn't work well is that people already had quite severe disease when they were treated we know that in the graph on the right hand side this shows us that REM death-sphere has in-vitro activity against the virus that causes COBIT Tsarskoe b2 and you can see that at concentrations that are attainable with IV therapy that there is quite a robust suppression of the virus without accompanying cytotoxic cytotoxicity so at least there is an in vitro signal that REM desapear is active against this virus there are five RCTs at least ongoing around the world that are evaluating REM death severe we're participating at UCSF at both the UCSF and San Francisco General campuses in one of these in this study it provides 10 days of IV REM death-sphere versus placebo for hospitalized COBIT 19 patients and this is double blinded the eligibility includes moderate to severe disease so individuals who have radiographic abnormalities or have hypoxia if you are at one of these two campuses and you have patients that may qualify you can contact the co but ID service to discuss enrollment and you're always welcome to reach out to me directly and we could try and get you in the right direction next slide another group of drugs that has received a lot of interest at this point in time or the anti malarial drugs chloroquine and hydroxychloroquine so chloroquine is an anti malarial that has antiviral and anti-inflammatory activity there are several possible mechanisms by which this drug may impact covin it appears to interfere with viral entry by changing the acidification inside of the cell it may inhibit glycosylation of the Tsarskoe b2 receptor there by helping to block entry into the cell as well and it has immunity modulating activity and with hydroxychloroquine in particular some immunosuppressive activity and you can argue whether this may be a good thing or a bad thing and i think we need to learn more about it in vitro on the graph on the right we can see that chloroquine does have activity similar to rimmed a severe wear with orally given doses you can achieve viral aaja con suppression of the Tsarskoe b2 virus some good things about chloroquine are that it's inexpensive it's been used for many many years for malaria it's been used widely in the kovat outbreak in china and there are reports that states that it improves pneumonia viral clearance and the disease course but these have not been reported as parts have not been reported very vigorously and there have been no data to my knowledge from randomized controlled trials so we very much would like to have some more rigorous data here and there are many RC T's that are ongoing some considerations with chloroquine is that it requires a higher dose than for malaria typically in the kovat study they be giving 500 miligrams be ID which may lead to concerns about increases in toxicity and direct drug interactions and this is not a drug that we have a large u.s. supply for next slide this has led to a lot of interests in an analog of chloroquine which is called hydroxychloroquine which is molecular lis very similar with the addition of a substitution of a hydroxyl group here and this may be attractive as an alternative agent to hydroxychloroquine because you can really push the dose on orally it has less drug drug interactions when compared to chloroquine and it may be more tolerable some initial in vitro data that were just published last week suggests that it may be more potent against koba's than chloroquine and these are two graphs down below that show at similar concentrations and it looks like hydroxychloroquine may be more active in terms of suppressing the virus than chloroquine I think the jury is still out about the appropriate dose for hydroxychloroquine and it may be that we need to give it at higher doses than then then given for rheumatoid arthritis and possibly even higher doses than given for Q fever next slide there was a very interesting article that just came out yesterday and is in preprint from a group in France this is a randomized open label study I'm sorry it was a non randomized study that was open label so it comes with many caveats and it was relatively small a little over 50 patients were enrolled these were individuals who had confirmed Kovach disease and they were offered hydroxychloroquine to take orally and were given either with or without industry Meissen and that was at the discretion of the clinician people who declined to take hydroxychloroquine were in the control group and that comes with all of the potential biases and confounding factors there that being said what they were able to report out in this preprint yesterday is that those in the control arm which is in black and the top bar here 16 of those we're looking at the viral dynamic over the first six days of medication administration and you can see that the quantitative PCR for Tsarskoe b2 really did not go down by contrast those were diamond hydroxychloroquine shoter decline in the indie stars Kobe to viral load and when is it through Meissen was added and this was a very small number of people that was only six that you can see that the viral load came down even more I think we have to interpret these with great caution this was not randomized but it certainly does show a promising signal that hydroxychloroquine may indeed have in vivo effect and it's being studied very actively in a number of randomized control trials around the world just a note that the dose that they gave was 600 milligrams for five days which again is a higher dose than is given in rheumatoid arthritis this is a Q fever dose and there's some suggestions that possibly even a higher dose might be preferred to really optimize the response I think this is an area where we need to stay tuned next slide and then lastly there's been a lot of interest in LaPenta beer rattana beer which is known as Kaleta this is an older HIV protease inhibitor that we're familiar with from the earlier HIV treatment days it is still available and used for HIV treatment it has in vitro activity against other coronaviruses MERS and SARS and was widely used in the first wave of the Cova Depa Demick in in china and they've been many questions about whether or not this actually has impact on the clinical outcome so yesterday one of the first randomized controlled trials would be first randomized control trial that i'm aware of was published with results this was an open label of randomized control trial of Calitri and hospitalized COBIT patients and I just want to point out that this population had a couple of interesting points 33% were on steroids steroids remain a controversial area here it is not clear if steroids are harmful or helpful in general we have point been trying to stay away from steroids and they may impact the time of viral ah Jaques shedding so 32 percent of individuals were on steroids they started relatively late so the median was 13 days from symptoms to the time of treatment start remember we talked about whether what is going to be effective once you get into this second week and that all antivirals might be it might be more difficult for them to have effect once people are sick and importantly this was a sick population so there was a 22 percent mortality in all comers here so these were folks who are very ill and had a high mortality rate and again that may not be the group in which antivirals alone work well all of that being said we can see in the left-hand panel when you look at lepen aver ritonavir in red versus the controls in blue there was no change in the time to clinical improvement in the intention-to-treat population and this was their primary endpoint this did not change when they looked at whether people were treated earlier so sooner than 12 days or if they stratified by people who are less sick at the time of enrollment similarly if you look at the right-hand panel they looked at the viral object decline in the red which is kaliesha versus the blue which is the control and they did not see a typically significant difference in the viral load decline you can see that the viral load comes down in both arms which is expected over the course of the disease but it doesn't look like kaliya on its own is really impacting the viral object to klein here unfortunately so my take home from this is that we certainly are not saying the strong signal that we would want to see for Calitri perhaps this is because people were quite ill but nonetheless I think this dampens the enthusiasm for the use of Calitri right now but we certainly welcome more data and I know there are a number of randomized control trials that we're waiting to read out for next one many we're going to finish up and just to say yep there are many more that I looked yesterday on the WHI website 392 and Counting clinical trials they look at antivirals on the left there are many there and other mechanisms on the right next slide so how are we managing this right now given the data that we have and importantly the data that we don't have these are the San Francisco general treatment guidelines that are in evolution they're very similar to the UCSF treatment guidelines we've tried to stratify by the severity of disease so for individuals who are an ICU level care with or without intubation very important to maximize our appropriate air DF management think about a RDS targeted therapies like mizenko mole stromal cells and still consider providing antivirals like REM desapear through a randomized control trial or compassionate use just a note on compassionate use that it's only available to individuals who are intubated but they can't have end-organ disease or be on pressors so it tends to be a bit of a narrow slice there for those who are hospitalized and have non ICU level care so moderate or severe disease if possible to enroll in a randomized control trial that's the road we've been going down but we have been offering hydroxychloroquine to individuals if grim death severe is not feasible for those with mild disease but who have risk factors for progression to severe disease such as age or other comorbidities we consider hydroxychloroquine but for those who have no who have mild disease now and no risk factors at this point we are not offering them treatment next slide and this is my last slide I just want to end with just a discussion of post exposure prophylaxis there's a lot of concern about household contacts and health care workers with direct and known exposures to COBIT and how to handle this it's an area of very active investigation we hope to participate in a multicenter RCT looking at hydroxychloroquine and there are many other efforts underway pre-exposure prophylaxis is brought up I've been asked this question many times I think we need to understand and explore this more for those at highest risk who are on the frontlines and we hope to have more data to inform us here so I will go ahead and end there I think we're going to move into the question and answer period I can't thank you thank you Andy that was terrific so let's kind of we could bring up the the four speakers that's Annie Jen Dianne and Michael and we so not yet the panel this list will come to the panelists in a second so we have questions from the audience we got 143 unfortunately we can only ask about three or four given the time and we'll have a little more time with the panelists in a few minutes so let me and by the way we have three thousand four hundred and thirty five people watching this so Diane and if you can keep your answers brief which is impossible because these are really hard questions one of the questions was what do you anticipate the epidemic will look like in the US and the coming weeks to months and I'll throw in a little chase or make it even harder we see what's happened in China but we're also seeing what's happening and Italy perhaps a little bit of some of the curves getting better in Korea and then maybe getting a little worse with recidivism so as you factor all of that together what can we anticipate in the u.s. among two three four now I think what most people think it's going to get worse before it gets better we don't know how soon is going to get better and I would like to say that the the data from China are encouraging it's not just China where we've seen a decrease in cases countries such as Taiwan and Singapore we've also seen good trends the other thing about Italy there are locations in Italy that started very early with population level interventions and they have not seen the same increase in cases there so that's my answer to that okay it's - this could be either - oh this probably either to you or to any I I guess in the this is another crystal ball question in the race between effective therapeutics and a vaccine which one is likely to win and be the first thing that comes to to help us all out any you want to try that sure I mean my understanding of the vaccine development is that we are looking at at least 6 to 12 months out before we would have something that could be widely used and I think that that is probably an overly optimistic estimate there so I hope that we are well on the race to therapeutics now given the number of studies that are ongoing and the just flood of information but a vaccine is going to be really important that work is underway I just don't think there are ways to speed up vaccine work beyond how they've sped it up now because there are some steps stages that they have to go through where you can plan any comment no I think we need to do both and I also think we need randomized trials for treatments because that's going to probably be the only way if we know if something works okay Michael and I think maybe Sarah will or Deb Debbie will address this also later but the risk of nosocomial spread with high flow nasal canula or non-invasive ventilation any comment on that well just briefly I think we definitely favor a high flow nasal oxygen the more concern about non-invasive ventilation for sure so I think high flow is preferred we're still concerns of course for spread of the virus even with a high flow but it's probably probably little more limited okay and in terms of other therapeutic targets there's been some tantalizing information about nonsteroidals and also I think the target here may be a stasis and therefore people wondered about ACE inhibitors and whether anyone who happens to have gotten kovat who was on an ACE inhibitor whether we're seeing any difference in outcomes so far you know that's a that's a point of question I think that's not likely to be an issue for several reasons in interest time I won't go into but it is interesting that the virus probably in part will attach to the ACE 2 receptor now fueler epithelium but the science of this would say I mean a simplistic mind like mine would say oh put everybody in a saboteur but that would not be the right call probably not because it's the receptor that is going to determine the biologic effect of the virus I think ok any is one of the audience asked is convalescence serum being considered as a treatment option yeah I've seen that the discussion of that being used I'm not sure about the scalability there but I think right now we are looking for anything that works and then we'll sort out the scalability so yes I think that is being explored and Jen are as we're now taking care of of these patients still a relatively small number at UCSF are you getting a sense even if the data are incomplete about which patients are likely to do well which basements are likely to do poorly or are we getting surprised yeah there's a great question Bob I think as you mentioned we've only had a handful of patients that we've taken care of here and I think we've seen a couple patients who have come in who have been critically ill either when they've arrived or very soon after they've arrived and those are the patients that were I'm really worried about on the other hand we've had a couple of cases that have been very mild and have remained mild so I don't think we have the numbers yet to really be able to predict and even in the studies coming out of China it's not really been clear how to predict who's who's not going to do well except for the factors that have been mentioned in terms of age and comorbidities and the questions come up sort of when are you out of the woods in San Francisco now everyone's supposed to be sheltering in place and so there are a fair number of people that had sort of regular exposures that one would have in their normal life up until let's say a week ago if they're now home and really staying away from everybody and practicing perfect infection prevention are they out of the woods or they still need a few more days or we we figure that out yeah I mean we think the range and the incubation period is up to 14 days which is why that's been recommended as the kind of quarantine period for people who have contact with a patient with coded so I think you know our shelter-in-place order is is three weeks do I think to try to account for that but I think that two-week period is what we think is the upper limit of the incubation period okay all right we could go on but I we've got five other spectacular experts who are ready to come on for another panel discussion this one will focus a little bit more on this the the efforts that we're undertaking here at UCSF our own experience around preparation and to some extent management and treatment so let me thank the four folks who have spoken already and Diane Jen mindful and Annie for a job and I'm hearing all 3200 people out there applauding and let's bring on the next four so very brief introductions Matt Aldridge is professor in our Department of anesthesia and runs our critical care units Sarah Doran burg is an associate professor in our infectious disease division and also serves as the medical director of acute microbial stewardship here at UCSF Medical Center jazz Lango leer is assistant professor in the division of ID at UCSF health and an expert in virology and testing Brad Monash is associate professor in medicine and Pediatrics also associate division chief in the division of hospital medicine and helps run the hospital medicine response and Daddy Ocoee is professor in ID here at UCSF health and also the medical director of hospital epidemiology and infection prevention in adult medicine at UCSF Medical Center so I'm hoping we can get all of those people up in Hollywood Squares let's be sure the bet is happening and I'm I may be old enough then when I say Hollywood Squares you know people say what exactly was that it's a little concerning so thank you all for being here so we've got about 25 minutes or so to talk through the elements of the epidemic that you're seeing and preparing for I'll take advantage of some of the audience questions and throw out some of some of my own so let me start with Matt probably the scariest things that any of us here are the reports from the intensive care units at in Italy about being overrun running out of insulators and having to make choices I don't think we've ever had to make an American medicine about who gets event first of all is that what keeps you up at night second of all how are we preparing for that and third of all do you think that might happen or is likely to happen here at UCSF it is what keeps me and many people up at night I think there are certainly stories from China even before Italy I think a lot of the Italian the events in Italy and have been covered perhaps differently in the media more ask those stories but it's been it's been terrifying I mean we've we've heard stories from I think a very affecting podcast that many people saw in JAMA with an intensivist in Italy who directors leader in their regional Network so that's been a real problem they've simply run out of ICU beds and run out of valuators and patients have died and that's I don't think anything in Europe or or North America that we've seen so that is a primary concern of ours we have and so because of that you know my focus in the focus of our leadership group really from the beginning has been on securing extra ICU capacity and that began with in reduction of elective admissions Kathy over the last week but also identifying sites for additional ICU capacity and that's additional ICU units during the use of operating rooms and then in tandem with that really building building ventilator capacity I'd say we are in better shape than many I could say UCSF health right now I get a several tip get a daily event report so we know what we have in use and what's available and I just put out there right now we are tracking about 70 extra available events right now that are available we are building that vent supply we also have many more o our ventilators and these are all options that we need to consider and there's certainly options that that have been used in Italy so that's that's where we are right now I think that for me beds ventilators in PPE or the primary driving concerns that that I that I think about and that that our focus needs to be on right now thank you maybe Sarah and and Debbie what are you seeing in infection prevention I mean some ways you've prepared for this moment all of your careers and probably dreaded that it might actually happen and here it is so what hasn't worked the way you thought it might and what has been harder unanticipated challenges as you know this is all exploded on our doorstep over the last couple weeks Sarah uncork some of the wonderful things that I've noticed I'll start with those the amount of teamwork and collegiality and willingness to jump into the fray that so many people at so many levels do and I think I don't would say necessarily I think some of the challenges that Matt mentioned have been things that might have been anticipated but our biggest challenges really related to the supply chain and that impacts every single step of the way it impacts our ability to test patients our ability to isolate our access to to protective gear it is gonna affect yeah Debbie I think you're on mute but go ahead yeah I agree 100% with everything that snaring said first of all the amazing teamwork and dedication of the providers who've been taking care of these patients the physicians nurses the support staff has been really amazing and inspiring to see and also totally agree with the issues around supply chain I think that these were issues that were haven't discussed in sort of a theoretical way for many years as we've been caring for the possibility of pandemic but it has become a stark reality with our current situation the other issue that I think has been very challenging is that this is a new infections that we're learning as we go along and that means that we have to sometimes change what we're doing in terms of our protocols in our personal protective equipment and that can be very anxiety provoking for for individuals I think all of the things that we've been emphasizing in infection prevention for for a million years now around the importance of basic practices like hand hygiene adhering to careful donning and doffing of personal protective equipment that just becomes even more starkly important in the face of this pandemic you have you have gotten our attention now it took a while for Cinelli it took this one of the issues that comes up all the time is surgical masses and 95 mass and I think one of the challenges is you reach something like the New England Journal piece that came out a couple of days ago that showed that it can kind of linger in the air a little bit and yet it sounds like the epidemiologic evidence is that you really can't catch it you know wearing surgical masks is adequate unless the patient is actively undergoing some sort of procedure how do you reconcile those two pieces of information how do you tell the workforce that it's that a surgical mask is okay and convince them that that's right so I'll start and then I'll let Sarah add to my comments so as you mentioned you know based on accumulating epidemiologic data I all public health agencies agree that the evidence supports that the primary mode of transmission is through respiratory droplets and particularly among people who have close and prolonged contact for example household contacts there's also the possibility that respiratory viruses in those droplets can contaminate surfaces and some studies that support that and and that is why in addition to what we use for droplet isolation they've also included contact isolation with it use the gowns and gloves so so all of that does not mean that we don't believe that viruses can be aerosolized under some conditions and so we do have a very clear caveat that during aerosol generating procedures that we do need to take airborne transmission into consideration and and so for patients who are receiving continuous aerosol generating procedures we do require that those patients remain in an airborne infection isolation room and that everyone caring for those patients is wearing an n95 respirator plus AI protection or a popper as well as gowns and gloves think this through and what are you actually seeing on the frontlines I can imagine that all makes sense you've read the information you're at the CDC and it still feels scary to people to only quote-unquote have a surgical mask there get a little closer to the mic if you can but what I would say is that that study in the New England Journal was not cutting in and out so I'm gonna come back to you in a second let me up there are you go ahead and speak sure um can you hear me now yep okay now you know the study in the New England Journal was done in a lab setting and how it translates into clinical practice is what we've observed from the hundreds of thousands of cases now is pretty convincing that this is mainly Dizzy's and I think that are not supports that several case reports of varying exposures and the way it spreads supports that and so I think those those pieces of data are very reassuring and then the other thing I'll just say I know people are asking a lot about the funny suits that are being shown in stock photos that they're seeing from other countries having dawned and offed a lot of those in our preparations and you realize how easy it is to contaminate yourself doing that it's unfamiliar PPE and one of the real important things to remember is that you have less risk to ourselves if we ask one more question of the two of you sort of from an epi standpoint then I'll get to Chas and Brad you see you know we're being told this could be three months six months who knows and then you see the curse from China and Korea and they're fairly reassuring in terms of the sort of degradation curve and the improvements what's the disconnect there is it that they were just so good about infection prevention once everybody figured it out that they got better or that this thing can come back and we're back in a way if you sort of let your guard down after an initial period of vigilance why is it that we shouldn't expect all right this is gonna be a really bad month and then two months now if we all do the right thing we'll just be fine everyone take that sure I'll take that so I think we don't know we don't know whether our epi curve is going to be like what they're seeing in Italy or whether our Eddy curve will be like what they're seeing in some other parts of the world I do think that during the next probably two weeks we'll have a much much better idea of where we're going or they're the non-pharmaceutical interventions that we put into place including the shelter in place and the counseling of schools and in social distancing whether that has been implemented early enough to course to prevent moving into a situation a situation like they're seeing in Italy I do think that it's important to do everything we can to push that epi curve over to the triple H as you saw in the discussion by the previous speakers to really flatten out that curve to to reduce the peak number of infections and to spread it out over time so that we are not seeing a huge surge of patients requiring hospitalization and critical care at the same time and in regarding keeping our guard up I think that will be incredibly important because as was seen with SARS I think once your guard is let down once the practices go back to normal it is it is very plausible that we could see another spike in the number of cases great and what a nice question I guess for you would be when I see those that you know that flattening the curve thing I think I failed calculus I can't tell whether the area under the flatten curve is the same as the area under the steep curve is it the same number of cases just distributed so Matt doesn't get overwhelmed in the ICU or is it actually a lower number of cases I think the hope is that it is both a flattening and in a distribution of cases over time as well as a decrease in the number of total cases right all right let me turn to Chaz thank you for being here so it's kind of our expert on biology and on testing and so the world of testing it has become incredibly interesting and another area that we're all paying attention to and hadn't thought about until two weeks ago so tell us what your take is on how things are going and what the experience has been here at UCSF well diagnostic testing you know without doubt is such a critical part of the code 19 response it's really the cornerstone of any infection prevention efforts and it's so essential for preventing transmission both in the hospital and in the community you know despite that testing has really been a major challenge in the u.s. I mean if we look at some of the numbers of tests available test availability if we look at South Korea for instance 5,000 tests per million people were available the u.s. comes in right around 100 so there's there's really been an unmet need for for testing as part of the response to this pandemic things are changing as we know there have been some important milestones perhaps one of the most significant was on February 29th when the FDA revised their guidance and allowed individual laboratories such as the one at UCSF to develop their own test for this coronavirus and that's really made a major impact in terms of allowing testing to happen at a much broader rate right now testing at UCSF is at the rate of about a hundred tests per day these are efforts led by Steve Miller and at Thornborough and the microbiology lab and there's really a lot of hopeful aspects I think in terms of diagnostic testing especially during a sobering time I think one of the most exciting is the new extension of the UCSF clinical microbiology lab to the space below the Chan Zuckerberg bio hub which is on the Mission Bay campus you know over a hundred people 100 scientists physician graduates students volunteers from UCSF have come together led by Joe Teresa Steve Miller at Thornborough and have essentially built a CLIA diagnostic lab in less than a week and that's anticipated to bring UCSF testing capacity up to 300 plus tests per day within a few days and up to a thousand tests per day within a week and so that type of teamwork you know that has been discussed on many fronts the hospital infection prevention front is really one of the best aspects I think in terms of the response a few other comments I just like to make you know Jen Babic noted some of the challenges in terms of diagnosis of koban 19 given the nonspecific clinical features that are shared with many other types of respiratory infections there's really a need for tests to be able to broadly and in an unbiased way distinguish between different types of respiratory viruses and identify co-infections and then the topic of biomarkers came up that's certainly one of the key diagnostic testing challenges can we predict outcomes of patients with kovat 19:00 can we predict the risk of progressing to a RTS the risk of progressing to death especially as we anticipate a situation where resources will be limited such prognostic tests will really be essential I think as you think about testing sure has a lot of emphasis on how many and I hear less about how fast and it strikes me we'll take it to Brad in a second but there are a bunch of people in the hospital today waiting for their tests to come back I know the turnaround is 12 ish hours or thereabouts are we on the cusp of of much faster and how would that make a difference if we had it yeah I think we are so I think the turnaround time at the clinical lab now is on the 6 to 12 hour time frame on there are some exciting possibilities on the horizon for more rapid diagnostic tests one for instance developed by a group at mammoth Biosciences uses at CRISPR Cass 12 technology Charles 2 has done a lot of work on this that could reduce the turnaround time to a matter of hours and then I think rapid serologic test-- point-of-care tests similar to our rapid strep test have been developed in in China those are not yet available in the United States but potentially could be a useful tool you know the more the more rapidly that we can triage patients in terms of understanding their kovat status the better we can use limited supplies of PPE the better we can use our healthcare workforce team and the better we can understand transmission and exposures in the hospital and talk for a minute by the way where I've just gotten word that we can go past 130 so if you guys can all stay we'll go to maybe a ten minutes over is that okay I'm looking around shaking heads sorta yes yeah okay [Music] in terms of the test and talk a little bit about test characteristics that's doubly specificity and is a negative test totally reassuring can you be positive when you're asymptomatic we heard some of the basketball players seem to have been tell us a little bit about how that all works yeah that these are all very good questions very important question so asymptomatic people certainly can be positive that's now well described feature of of koban 19 in fact the ability for asymptomatic individuals to transmit is thought to be one of the main reasons why this has become such a problem so for instance in contrast to the original SARS coronavirus where patients were infectious and could transmit after they develop symptoms this appears to be happening before patients actually develop symptoms making testing of the population more relevant and important in making control of this work more challenging in terms of the test characteristics we can think about different specimen types and sampling sites in terms of understanding sensitivity and specificity by and large coronavirus tests for this corona virus are PCR based tests which are highly specific and highly sensitive but the sensitivity varies significantly depending on sampling type I think as Diane mentioned viral load is very high in the nasopharynx but looking at tests comparing a variety of different specimen types we're looking at a sensitivity on the order of about 75 percent for a single NP swab if we look at oral pharyngeal swabs sensitivity is lower than that depending on the study you look at between 33% and 65% we know that there's some added value on if you combined two types of swabs if you sample at two sites you get about a ten percent sensitivity bump so that would bring things up to eighty five percent and since this is really a lower respiratory tract infection sampling in the lower respiratory tract is optimal there was one recent JAMA paper that suggested a sensitivity of over 90 percent for be al sampling you know the exact test characteristics I think are still to be worked out the question of what is the gold standard here is often an issue is it a clinical diagnosis of Kovan 19 should a composite of all different tests be used to determine a gold standard these are important issues but I think we're talking on the order of 75 percent sensitivity for a single NP swab which is the standard sampling approach and so a negative test does not rule out infection and someone with high suspicion does that worry you I guess if I were thinking that through and saying I'm gonna get a test it's negative and I'm and the patient gets the message you're good to go you don't have the disease and then whatever flows from that maybe they're less careful from an infection prevention standpoint or don't wear a mask or whatever and there's a 25% false negative rate that that sounds a little concerning you know I think it really comes down to the need for a clinical perspective and clinical assessment of the patient at someone being admitted to the ICU with acute respiratory failure of unknown cause their respiratory virus panel PCR as negative their MP swab kovin 19 test is negative that really speaks to the need for for an additional test to be done so I think these types of pretest probability assessments are really important okay thanks Bradley Monash lovely background you are helping to run the hospital medicine groups response to all of this and most of the patients will come through the emergency department and come up to hospital medicine so I understand the entire group is lized and has created a distinct floor to cowork these patients tell us how you're thinking about it and how that's counsel for ya Bob this has been a transformational unbelievable experience on so many levels as we've seen our country our world go through this together the unit that you're referring to has been named the respiratory isolation unit the Riu 15 long has been transformed into a pandemic ward which is modeled after similar words that are exist globally including in Singapore where we've been in contact with colleagues and so a tremendous tremendous team effort to do this I won't have time to name everybody who's been involved but it took a took a village to essentially shut down the unit increase our capacity to have airborne isolation negative pressure rooms make sure that every detail every stone was left unturned trained an entire unit of staff and nurses to to care for patients with acute respiratory illness and patients who are ruling out for coronavirus and the the intention is for this to really serve as a closed a closed staffing model type unit and so providers show up they put on Scrubs a shower will be available there will be meals served in the unit massage chair I understand is is going to be delivered there as well there will be twice daily rounds with our chaplain and spiritual services and really it's this opportunity to build an incredible interprofessional team with a shared mission of caring for this population not only for their physical disease but also you can imagine with everything that is coming through the news media there's a tremendous amount of emotional psychological distress on this particular population and their families and so even those patients who have extremely mild respiratory disease the amount of time and care required to really care for them is is tremendous yes you probably mad as well about the emotional to stress one element of that is that the city of San Francisco and I guess maybe broader guidelines an hour to basically say no one can have visitors except for end-of-life care situations and so we are these patients who are scared that something terrible is about to befall them are sitting there essentially by themselves family members kept away from them that's got to be credibly hard on patients and families and the people taking care of them our you and how are people dealing with that so this is really challenging as we can imagine we pride ourselves on sort of patient-centered care and this is much more population centered care that we are practicing and these measures that are to benefit a greater community definitely come at the expense of individual interactions and so a few people have have mentioned how inspiring it how inspiring it has been to see folks spring into action and take initiative and so I saw a bunch of emails in the past week from hospitalists who really want to make an impact here and for example repurpose our video interpreter poles to have more FaceTime interaction I know there is an effort to try to consolidate iPads throughout the UCSF health to get them into patient rooms to allow more sort of FaceTime type interactions and so there's a tremendous amount of effort to preserve the critical human or interactions that are important for a regular day to day lives but also for health and recovery and Matt how are you folks thinking about this you're seeing a few patients and are they our family members being allowed to come up or not and how do you talk to a family members not being allowed to come no we've had to limit we've had to to participate in visitor restrictions like like every other unit has and for us in the ICU the impact really at this point because the number of Kobe 19 positive patients that we've had in the ICU has been relatively small the impact is really on the other 50-plus ICU patients who who don't have visitors and so we've been able to make some exceptions but it's challenging this is just it's a it's a brutal time for many patients who up until a few days ago had to have the support of their family and their friends and now don't have that anymore and so we have made exceptions at the end of life but that's also a that's a difficult clinical judgment for all of us right there are many patients who are critically ill in the ICU and and you know it is there's one circumstance where there's made a decision decisions been made a transition to comfort care and that's I think clear and that's when we've certainly made exceptions there for family visitation but then there are other circumstances where we have patients who are who are chronically critically ill and vulnerable in the ICU and they've not been able to have access to family members so that's been it's been obviously incredibly hard on patients and their families but also in all the staff that the nurses the respiratory therapists the team members who are taking care of the patients so I don't think there's an easy answer to this it's Jenna it's an unprecedented time for all of us yeah thank you for bringing us back to as I recall the world three weeks ago our hospital was packed with sick people and they've not gone away so what is your sense of you know I mean we're opening up beds for kovat patients but those other patients who used to be in our Hospital many of them are still here so what's the impact on them and also we're now turning away patients who otherwise would be here or would be getting elective surgery how are we managing this or a triage function I think we're managing is best we can I mean there's clearly some some procedures and some admissions that are that are elective and can be pushed off for several weeks to months and we've done that there are others we've you're right I mean we've there are patients with you know certainly there are surgical patients who need to come to the ICU because they have emergent or urgent needs and we need to take we need to take them to the operating room and we will continue to do so obviously it's just it's all now in our environment it's much more challenging for everybody and so we're as you know and everybody on the panel knows and ensure the mm plus participants to listen and it's a it's a daily discussion and it's so dynamic and we every day we come up with a plan and we come up with algorithms we come up with pathways and then something shifts and then you have to adjust adjust your approach with that so they're still active care for these patients with urgent needs but it's it's done and it's just simply being done in an environment that's different than any of us have ever practiced it so we only have a couple minutes left and I appreciate everybody's indulgence for going over let me just give everybody sort of 30 seconds to sum up and I understand the instinct to just say thank you and shoutouts to the extraordinary work of your colleagues it's real but probably less helpful than something that you have learned or has surprised you along the way or that you're scared about as you think about the next few weeks that you haven't already heard it heard or you haven't already had an opportunity to say anybody want to start there you want to start sure I think my biggest fear is that we stop practicing and I've seen a lot of people throwing anecdotes around and reacting to stories which are understandably I I open and sobering but I want to urge people to to continue to read the literature with a critical eye unpack that first what is a typical thing where you see people not practicing quote evidence-based medicine well I mean I just some of the treatments that are being thrown around that I've seen other centers pulling the trigger on on treatments and I really have the potential to arm to our patients things like totalism AB where there's really very little data to support it at this point I am definitely gastic about studying in rigorous trial settings but just starting to get therapy okay great Chaz anything the test could surprise you or that you're thinking about going forward and go off mute on the topic of things that that are concerning me at the moment of course there are a number but on the diagnostic testing front one is a critical need for nasal pharyngeal squad kits we've been told that the federal government is releasing their strategic stockpile of nasal swab kits I didn't know they had one but those have yet to reach us here and that may very well be a rate limiting factor moving forward but I think I think there's a lot of good things to come on the diagnostic testing front in terms of expanded capacity and availability to do more broad screening including drive-through screening of healthcare workers and high-risk populations and then the general population great thank you if we're sitting here at a five billion dollar a year operation one of the top medical centers in the universe and the fact that we're gonna get thrown for a loop because of fancy q-tips is pretty unbelievable but I think that's actually there's some truth to that right so this has been just an incredible experience in so many ways and lately I've been reflecting a lot on this concept of the cortical and limbic aspects of leadership and this has been the most challenging personal experience I've had as a leader to try to lead a division of medical service in a time of crisis and a time of panic I've learned a tremendous amount from our palliative care colleagues and how to communicate because we learn a lot about bedside communication when there's a tremendous amount of anxiety and despair in the room and this is a time when we are communicating with a health system where there's a tremendous tremendous amount of anxiety and despair and so I've been reading Harvard Business Review and thinking about how to lead in a time of crisis and it comes down to just a few key principles of slowing down of maintaining mindfulness which I recognize as a buzzword but if people really study mindfulness there's some real power to that it's about maintaining human connection and connectivity it's about the critical nature of communication and rethinking how we communicate in times of crisis and so I know many of us are turning to frequent town halls frequent communication allowing opportunities for folks to engage and interact which is becoming ever more important in an era where we are having social distancing and less and less human interaction and in the final lesson for me is just the critical importance of empathy and leading with empathy and the power of just thinking right to the person in front of you how can I make this person's day better and if we can all have that mind frame we can really I think revolutionize and and change our current mental state so this has been an incredible learning experience for me I'm learning and growing every day I realize I'm making a lot of mistakes but just trying to trying to do better thank you that's a really important and profound if you think about the importance of community and connection and the irony of we can't do it in the way we normally would do it because of the nature of this virus Matt will close with you what were your thoughts I really want to agree with Sarah same and I think especially in this time of real concern and uncertainty I think it really it's critically important that we stay focused on what we know to be evidence-based medicine and that we not that we not get distracted from that I think that certainly matters incredible care and in other other parts of treatment here and then and then for me it's just I I'm I'm grateful to live in an area where we made where our government officials made hard decisions and earlier than other areas and and and I like everybody else I really does hope I do hope that that changes it changes the curve over the next few weeks but but I also am very mindful of the fact that we over the next two weeks we are still prepared for the fact that the surges is is there and likely to come what that looks like exactly whether that's just very hard or whether that's you know potentially overwhelming we don't know yet but we need to continue to do everything we can each day over the next few weeks to prepare for that and we hope in two three weeks time you know decisions made a few days ago really start to show an impact but that's right what would really need to focus on going forward well I want to thank all of you and the prior speakers I've been at UCSF for about a hundred years and I've never been more proud of the organization and to me this is an organizational stress test and it's extraordinary the response the teamwork collaboration it's it's quite heartening we will do as long as this is going on we'll do Grand Rounds like this every week every Thursday at noon next week I will do something on the more academic missions and either on the research enterprise or on our educational enterprise or both we're still sorting it out but assume we'll be doing something and again where these are the Department of Medicine Grand Rounds but the intent here is to be for a broad audience including all of our colleagues at UCSF and maybe even even beyond so thank you all for joining us today thank you to the speakers for her presentations and everybody be safe and continue to do the extraordinary work you're doing thanks very much thanks about thanks bro you

Channel: UCSF School of Medicine

Views: 90,826

Rating: 4.7744808 out of 5

Keywords: ucsf med school, ucsf medical school, university of california san francisco, med ed, ucsf medical student, uc san francisco school of medicine, doctors, physicians, irocket, ucsf, bridges curriculum, medical education channel

Id: bt-BzEve46Y

Length: 100min 51sec (6051 seconds)

Published: Fri Mar 20 2020

Reddit Comments

[u/sixtypercenttogether]

I watched this entire video the other day and it’s quite good. There are a couple technical issues dealing with WFH for the presenters but the content is excellent. Hoping for another such video this week (I think they do grand rounds every Thursday).

[u/Offduty_shill]

Do they post the slides anywhere? I'm interested but I don't really want to watch a 2 hr presentation.