Pulmonologist Brian Block, MD, submits an enlightening analysis of U.S. COVID data, including his own work examining mortality in overburdened hospitals. Presenting the evidence on risk factors, he also offers guidance on explaining the value of flu vaccines to patients and delineates the multiple payoffs of masks.
So tonight I'm excited to be sharing some updates on covert 19 with you. When you're talking about who gets really sick, you know how to think about mitigating the risk of a dual pandemic with flu and Kobe 19. And then with a brief preview of the new information about vaccines, which we're all very excited about, I'm going to tell you again about how useful masks are in kind of the different benefits that they have. So without further ado, let's get started. So this is gonna be our outline for the day, as I already talked to you about. And so, starting with an update on the epidemiology of Cove in 19, unless you've been taking a total break from the news, it's hard to avoid knowing that things have been starting to get really bad in a lot of places. So here we are in mid November, and now we're seeing rates of growth in case numbers across the U. S. That really dwarf what we saw in the initial wave in April, which was largely confined to the Northeast and then the summer wave in July and August that hit a lot of the Southern and Southeast Southwest states and also California. But the rate of growth that we're seeing right now in case numbers over 150,000 cases the last several days is really unprecedented. And, as we all know, cases come a couple of weeks before deaths and what we're starting to see when we look nationally at Covad 19 deaths is just as there was a rise in cases we're now starting to see. A rise in death counts back persistently above 1000 deaths per day. And today, actually we crossed 250,000 quarter of a million deaths in the United States. So I had given a related talk a couple of months ago, and at that time we were on the downswing of that second wave, which really affected the Sun Belt, and things were starting to heat up in the Midwest. And unfortunately, you're looking at this heat map comparing a time in September 2. Now you can see that the pandemic has substantially worsened, with the darker red and purple marking the highest rates of disease transmission here in California and even in particular in the Bay Area numbers, they're still substantially less. And it's kind of hard to really even comprehend what the numbers are that they're seeing in places like North and South Dakota or in Wyoming, where today I saw a statistic that 70% of tests are returning positive. So here in California we are still seeing a massive increase in the number of cases. So if we look at this data from the New York Times today, you can see the case count on the left has dramatically risen in the last two or three weeks and the number of deaths has not yet started declined. But I think we're all afraid that it will begin to do so. And I think this is really a reminder that you know as much as state to state can have variability in their approach to controlling this pandemic. We're not on an island, and so as things start changing around us, we're going to see the effects of that locally. So I had mentioned that the status of things here in California is quite a bit different than it is in some of the most hard hit places, and I thought it would be useful to take a moment to just compare California and South Dakota, which is one of the most impacted places, just to get a sense of what things could look like if they got really a lot worse here. So in these figures, looking at cases, hospitalizations and deaths, this is right here for the state of California, and the dash line shows you the average for across the United States. And each of these lines is for California. So on the left, you can see that each day we're diagnosing now about 200 cases per every million residents. There's 40 million people in California, so this is about 8000 cases a day Now. If we compare that to a few weeks ago, this has doubled. As you can see in terms of hospitalizations, we have about 100 hospitalizations for Cova, 19 per million residents. So about 4000 hospitalizations. And these numbers are both lower than that dash line, which is the average across the United States. And death counts are increasing across the United States because other places have started to have the growth of this third wave earlier. Whereas the death count in the United in California has not yet begun to rise. Now compare this to the picture in South Dakota. These this Y access is a different scale here. But these air the same dash lines representing the average. So California was coming in below this. Remember that we had about 100 people per million hospitalized. They have six times as many people hospitalized in South Dakota. On a per capita basis, the rate of new cases is about seven times as high and death. They're having about 20 times as many deaths. So for every single person who's dying in California on a population basis, they're having 20 die in South Dakota. So getting into the kind of hyper local data, I did want to share the numbers that UCSF where I have some mortgage angularity that I can share with you. This is a report that we get on a dashboard looking at testing over time since the start of the pandemic and across you see, health system, we've done 72,629 tests. Almost all of those air resulted from 200 test today and you can see that we're testing both symptomatic and asymptomatic people. Asymptomatic being everyone that's hospitalized or people coming for outpatient procedures and what we're finding. This is looking at the positivity rate of testing over time. So dark orange is people presenting with symptoms and the lighter colors people without symptoms. So at the worst in August, when we were detecting the most cases, symptomatic people had about a 10 or 12% chance of being positive, meaning that even if you went to the U. C. S F. E. R or respiratory screening clinic with symptoms compatible with cove it, there was only about a one in a chance that you actually had the infection. That number went down substantially in September and October, and it has started to rise a little bit. But it's still the case that out of every 20 people presenting with symptoms compatible with co vid, 19 out of 20 actually are not testing positive Among asymptomatic people, the rate of positivity has remained between ah, half a percent and 1%. So somewhere around one out of every 150 asymptomatic people in the community is probably positive unknowingly. But in terms of our hospital burden, we had at peak somewhere in the 40 range in terms of the number of patients admitted at one time. And here you can see the distribution of patients that were in the intensive care, those who were on the general medical ward or a step down and how many of them were intubated. And we've had overall a decreased since the late summer in terms of the number of hospitalizations that have increased in October before going back down again. And I'll say that our data right now has been quite flat. But the city of San Francisco data shows that there's been a doubling in the number of infections that are being detected each day over the last 10 days. So we anticipate that this is going to rise as hospitalizations lag behind infections. So why is it important to be focusing on the burden of disease? So this is something that I'm going to focus on in the next section and detail, but just wanna anticipate here. Which is to say that there's Mawr evidence that systems that are not overwhelmed are seeming tohave better outcomes, and we've certainly had that privilege at UCSF where we were not seeing the influx of patients that they had during waves in places like New York, Florida, Arizona. So this is data over the entire course of the pandemic. At UCSF, where we've admitted 548 patients with confirmed Kobe 19, you could see about two thirds of them had not required. I see level care one third have and over 90% of people have been discharged at this time, with less than 5% having died on 2% are still admitted the like. This day is long. Those who are not requiring I see level care are being admitted for something on the order of about seven days. Those who are in the I. C. U are being admitted for a median of 24 days. So even if we don't have a high rate of new admissions, the census can stay high for a long time because thes people need a lot of care for a long time. This is a slide that was put together in September by someone with the San Francisco General Hospital comparing large cities and metropolitan areas and looking at the burden of disease. How Maney diagnoses are being made of cova 19, and what is the case fatality rate and how Maney tests are being done. And as we're heading into this winter surge now, I'm curious to see if will replicate the findings that air here, which suggests that in a place like San Francisco, where we have been doing mawr testing on a per capita basis, we have been detecting cases at a rate that is similar to some other places, but lower than those that were most burdened. But what stands out is the death rate has been substantially lower and, on a per capita basis, much lower. Our chief of medicine, Bob walked ER, you know, will frequently cite this and as a what if example saying that if other parts of the country we were having the same types of success in terms of public health and care delivery outcomes that perhaps we could have averted over 100,000 deaths because the rates and the Bay Area have been much lower. So before I go into the next section and talking about predictors of becoming most sick, I'm gonna minimize my screen here for a second and take a look at the Q and A and see if there's any questions that I can answer. I don't see any questions there. Let me quickly look at the chat. Okay? Yeah. Yeah. Okay, so that's the epidemiology of Kobe 19 as of today. And the question is, we're diagnosing 150,000 people or mawr each day now and off those How many of them are going to get sick? And what information do we have to risk stratify and predict who's most likely tohave a poor outcome. So I remember when I was first reading about Kobe 19. Back in February, there was a report that came out of Seattle in the New England Journal, showing outcomes of 24 patients each year represented by one line how long they were in the hospital and what happened to them. And you could see that many of these lines over half of them and in death the outcomes seems terrible. Similarly, from Italy, we had early reports of their disease and a quarter of people who they were diagnosing. We're having severe disease. 5% were having critical illness, and on the other side, about half were having mild disease, and they thought 7% had few symptoms. Well, it turns out this 7% with few symptoms was probably an underestimate just because test availability was limited. So they're really only detecting the tip of the iceberg. They weren't testing enough people to diagnose asymptomatic infection. There was a report that came out last week in The New England Journal looking at an outbreak on an aircraft carrier that you may recall from last spring where over 1200 people became infected and because it was an enclosed environment on an aircraft care. They could really tell everyone who was at risk map the disease spread and have kind of a comprehensive description of the outbreak. And they found that over half of these people who are mostly young men median age 27 where asymptomatic. So the point being that the spectrum of disease is broad. So there's a study out of Colombia in New York looking at patient level risk factors for Severe Cove in 19 infection and in their multi variable model, they found that older age chronic heart disease and chronic lung disease, specifically COPD or interstitial lung disease, each conferred an elevated risk of dying. They also found that diabetes, obesity male sex and chronic kidney disease. This was in a different report. Were associate ID with, ah higher risk of Severe Cove in 19. So one question I've had a lot is a pulmonologist was, Well, what about asthma? And should I keep taking my inhaled steroid? And so, with COPD and interstitial lung disease being risk factors, a lot of patients and a lot of us wondered what the outcomes would be like for asthma. And, it turns out, based on studies so far, that cove it does not seem to cause more severe disease in people with asthma. Or put another way after you adjust for other patient level factors. Asthma is not associative associate ID, with an increased probability of being sick enough that you need to get intubated. And there are some theories for why this might be the case. It turns out, on a cellular level, as you may recall, Cove. It uses a receptor called Ace to in order to enter cells and ace to expression differs in different diseases. In chronic obstructive pulmonary disease, there is increased levels of ACE to potentially providing more targets for the virus to enter cells and cause disease, whereas on the other end of the spectrum in asthma, there's decreased ace to expression. So this would be one theory for why the observation has been that asthma is not a risk factor for Severe Cove in 19. So between you know, the studies out of New York and then from the Centers for Disease Control, we have an idea of certain patient level risk factors that air associate ID with severe Kobe 19 infection. But I guess another question is, what about non patient level risk factors? What about the hospital you go to or the time when you fell sick in the pandemic? Early versus later? That's what I'm going to talk to you about now. So I've been working with a group of investigators at UCSF and also a company that collects data from hospitals around the country to try to understand how patient surges affect mortality of Copan 19. So what we did is we looked at over 100 hospitals across the United States that have admitted patients with Cove in 19, and we asked the question, What is their outcome? And we specifically looked at hospitals that admitted these patients in April because that was a time when the pandemic was relatively geographically circumscribed. In the Northeast, we can all remember pictures of what it looks like. This was some Elmhurst hospital in Queens where people were lined up outside for testing and they were just having over 2000 s a day in New York City alone. And this was just so striking in comparison to the experience that we've been having in the Bay Area at the same time. So using this data from over 100 hospitals, we asked, How does cove it 19 burden? That is the number of patients with covert 19 that the hospital admitted during the month of April, divided by that hospital size. How does that burden of admissions relate to cove immortality? So here, I'll show you a plot. This is called a Caterpillar plot, looking at outcomes for 14,548 patients admitted to 117 hospitals. And you can see this horizontal line. Here is the overall mortality rate, which was 21% for all patients across the cohort. Each of these vertical lines represents one hospital where the dot is the point estimate of the adjusted mortality rate at each hospital and the bars represent a 95% confidence interval. So what you can see right away is there is a lot of variation. Even though the average hospital had a mortality rate in the range of 21% some hospitals had 50% mortality. Others were doing better with 15% mortality. And so if we overlay information about burden here, what I've done is color those hospitals in orange that had the most cove in 19 patients while all other hospitals air in blue. And you can see that there's a skew where mawr of the high burden hospitals with the most Kobe 19 patients are over here to the right with the higher mortality rate. If we look at this in another way, where I been the hospitals into five groups with this being the lowest quintile of covert 19 burden and this being the highest quintile, the most burdened hospitals, you can see that in the lower burdens lower quintiles of burden. That mortality for each group is about the same as overall mortality, whereas in the most burdened hospitals, there's, ah higher mortality rate, and this of course, is different than what we see with things like surgical procedures or other outcomes where increased volume it of medical center is usually associated with better outcomes. In this case, we're showing that surges might be overstretching the capacity of hospitals, leading to worse outcomes. So this data that we have is supported by some other groups that have been looking at a similar question. One report over the summer found that among people admitted to the intensive care unit with Cove in 19, survival was more likely if they were admitted to a hospital that add over 100. I see you bets a larger hospital. Similarly, in a study at the state level published in the journal General Internal Medicine, investigators found that when the percentage of total occupied beds increased, meaning that the capacity of the hospital was more stretch, survival would later beef lower for people who were subsequently admitted with Colbert 19. So if I were to summarize this section of the talk, I would say that the answer to what makes someone get mawr sick from Kobe 19 is complicated. There's some patient level risk factors that we've talked about, which were things like older age, heart disease, chronic lung diseases other than asthma, diabetes, obesity, male sex, chronic kidney disease. There's also some apparent hospital level risk factors. A greater burden of covert 19 admission seems to be associated with a lower probability of survival. It's also the case that smaller hospitals with fewer ice you bed seems to be places where survival is lower for people with critical illness. Now, one thing that all mentioned briefly here. And then I'll show you some of the data that towards the end of the talk, is that there's also this interesting phenomenon. People have described where, and it seems like the overall mortality of Kobe, 19 has decreased over the last eight months. Now some of this is definitely from case detection, where we're detecting mawr cases of infection that are less severe now. It's also the case that those who are getting infected and getting tested now we're getting more young people who has early in the pandemic. It was nursing homes and other vulnerable populations that were carrying the lion's share of the burden. So there is also evidence now that even if we adjust for those factors, there have been decreases in mortality rates over time. So now here we are in the middle of November. And just like every year, we're right on the cusp of flu season. And, of course, in the era of covert 19, flu present some other challenges, and the last thing we need is another epidemic. Respiratory illness. So before Cova 19, we all were used to the pattern of hospitals being fuller in the winter because we would have so many patients with respiratory illnesses and ah, lot of them. With influenza. Turns out, flu is responsible for about half a million hospitalizations annually, and this causes a few problems. First of all, it fills up hospitals. Secondly, the types of materials we need to test people for influenza are often the same as the ones that we would use to test for Kobe 19. So such materials could run short. Then, obviously, there's the potential for people to get infected with both influenza and cova. 19. You could imagine a patient coming in and getting a rapid flu. That's positive. That wouldn't necessarily mean you're done, because you could still have thio evaluate them for Kobe 19, or you could have the opposite scenario. Diagnose someone with Copa 19. We haven't been testing all of them for flu all summer. Is that something that we're gonna have to do now? What's gonna happen when we give the antivirals for influenza and Copa 19 together thes air all unknowns? And that's reason that getting control of influenza to the extent we can is really important. So I thought would be useful to briefly kind of arm you with some information about influenza vaccines so that you can use this on the front lines when you're seeing patients and talking to them about the importance of vaccination. So each year, the components of the influence of vaccine change and they're based on what is going on in the Southern Hemisphere and predictions of what is most likely to be the circulating strains here in the Northern Hemisphere. And on average, the influenza vaccine has an efficacy of about 40 to 60% in terms of the reducing the probability that someone would have to go to the doctor for flu. Even among those who do get influenza infection despite having been vaccinated, they're still benefits because among those who are hospitalized with flu for kids. There's a 74% reduction, and I see you admission if they had the influence of vaccine and adults, there's a 40 to 60% reduction, and I see you admission or death among older adults who are often the most vulnerable and likely to have a bad outcome of influenza. There's a 40% reduction in hospitalization, even if they get their flu. So I think I'll often hear people say I'm not going to get the flu shot, it doesn't work. I still I got it last year and I got the flu anyway. Well, that it certainly isn't the case that it's gonna present prevent all influenza vaccine infection. But we can say that even among those who do get infected, there is a benefit to having been vaccinated and reducing the severity of illness. How big is that benefit? Well, if you were to calculate a number needed to vaccinate, it would be 70 meaning If you vaccinate 70 people on average, you'll prevent one case of influenza or you'll reduce a individuals risk of getting flu from about 2.3% to want to 0.9%. So despite good evidence that the influenza vaccine reduces the risk of infection and reduces the risk of serious illness amongst those who do become infected Onley. About half of people are getting vaccinated every year. So this is historical data over the last decade, looking at adults in red and Children in blue, and you could see that the pediatric population is getting vaccinated. Mawr commonly, but a czar whole Onley. About half of people are getting vaccinated. So if we were vaccinating MAWR people, we could prevent MAWR cases. And that's why you're seeing a big push from state Department of Public Health and other groups like the Centers for Disease Control to increase influence the vaccine. This year, of course, there's barriers to vaccination, especially some that air new in the era of Cove in 19 I, for example, I'm seeing more than half of my patients over Zoom these days that can't give a vaccine over Zoom. Uh, they need to come in for a separate visit or to go to a local pharmacy thes air barriers to vaccination that make it more difficult. There's also the baseline problems of certain people having fear of vaccines or not having the right information on which to base their decision making. And then we're all busy. We're doing a million things. How do we remember to bring up in influenza vaccine every visit? So there have been some studies to address these various barriers on the patient side. I think it's important to know that the adverse reactions are very rare. When we look at the inactivated vaccine, we can see local reactions like a bursitis, but those air rare that's happening eight times for every million people that are vaccinated. Other, more feared complications, like the neurologic syndrome Jeon Beret, are happening 1 to 2 out of every million vaccinated individuals for the other variety of of vaccine live attenuated. When they studied 2.5 million vaccine administrations, they saw eight asthma exacerbations seven cases of anaphylaxis. In one case of bills policy, it's hard to know what these numbers, if these air, all directly attributable to the vaccine anyway. So these air kind of serious adverse reactions, and they're all very rare, You know, the more common thing is what I had when I had it a few weeks ago, where my arm was a little bit sore for 24 hours and then you're fine, so I think it's helpful. Toe. Have some of these statistics in your back pocket as you're talking to people about vaccination. There are studies that I've looked at about increasing vaccination rates in different clinic populations. So this was a report out of the American Academy of Family Physicians from a group in Atlanta that was trying to increase their vaccination rates. And they came up with kind of, ah, a five pronged approach. Thio increase vaccination rates and they found that it was successful and dramatically increasing the number of people in the practice that got vaccinated. They suggest that you find someone in the group who is going to be the champion. Who's going to take this on is their issue because of the fact that we're all busy and we can forget to ask people about vaccination, it's better to make standing order so you don't have to opt in tow. Having the vaccine. It's something that they can opt out of. Reducing the burden of documentation is one barrier that we can address and trying to make it easier to vaccinated people and then providing feedback telling people how often they're forgetting to vaccinate or what their outcomes are. This isn't a crucial piece of quality improvement to making sure that people understand what they're missing and what population there capturing. There was, Ah Cochran review that looked at the same question about how to different things work in terms of increasing vaccination rates. And they found that there were a few strategies reminder calls or pamphlets thes were patient facing things that could increase demand for a vaccine. You could also go to the where patients are doing home visits, group clinic visits, free vaccine drives, things to increase access, especially in vulnerable populations that might not have a clinician and might not be making it to the doctor and then on the physician side or the clinician side. You could have incentives to remind people and incentivize them to give the vaccine. Okay, so that kind of summarize here, you know, concurrent outbreaks of influence and Kobe, 19, could be problematic for a number of reasons. They could overwhelm health systems. They could make us run out of supplies, and they could lead to co infection. We have good evidence that influence of vaccination reduces the risk of infection and reduces the risk of serious illness amongst those who are infected. And we know that there is some evidence based strategies for improving vaccination rates in your population, like having a clinic champion making vaccination orders, auto releasable, reminding patients and reminding clinicians and giving them feedback. Another thing to do is Thio. Ensure that you have outreach to vulnerable populations or people who don't otherwise have access to vaccination. So vaccination is one strategy for preventing disease. But what about masks? That's something that we already have and we're starting to have more and more evidence is effective. So this was a report from over the summer looking at how likely how easily researchers could detect virus amongst people who are infected based on whether or not they were wearing a mask. So here on the left column, we can see that subjects without a surgical facemask with coronavirus, flu or rhinovirus, you could detect virus when they were coughing viral particles and about a third of the patients when they wore masks among those with coronavirus that dropped to zero flu, it dropped to just 4%. 1 patient rhinovirus. It also dropped somewhat. These numbers, they're small. So the statistical significance here we have to kind of think about an aggregate. But this is some evidence that masks reduce the risk of generating viral particles that one could easily detect. And we also have epidemiologic evidence that mask they're doing something. So this is an interesting report. I took this slide from the Economist looking at flu, which, of course, in the summer happens in our winter, but in the Southern Hemisphere happens during our summer. So here we are in 2020 in this bold ID Red Line looking at the year of Kobe 19, and from Argentina and Australia, you can see that influenza was on its way up in January February March as the flu season would normally take off in the Southern Hemisphere. Then, as people started using social distancing, masking and other measures to reduce the risk of Kobe, 19 flew was essentially wiped out, and you can see this in Argentina and Australia. Compared to the five prior years, thes air the number of flu cases each week, we saw almost no flu transmission in the Southern Hemisphere. This was also replicated in other countries like Chile and New Zealand. There's actually a report from the California Department Public Health to start giving an early hint that this might be happening here is well, so the Department of Public Health puts out a weekly report on respiratory viruses and influenza in particular. So I pulled some data from that earlier today, and here's what it shows. So this is a graph showing over the last several years that each winter there's an increase in influenza like illness. That's what I ally stands for, and you can see that the gray is kind of the five. Your average, the dash line and the solid line is two standard deviations above that. So some years we've had worse outbreaks like in 28 17, 18 other years. That has not been is dramatic this year. You can see that on average, we should be following this dashed line, and we should already be on our way up as faras influenza cases here in November. You could see that the lines so far is not a steep, and it's been delayed suggesting that we might be delaying or averting influenza Kaiser, which of course, is a large system in California also provides data on this. And if we look over the last several years at the number of cases of influenza in the Kaiser system, you can see that 2020 here in these red dots has yet to increase, so it's still early. But this will be another mechanism for tracking whether the percentage of influenza admissions across the Kaiser system rises this year, as it has in priority years. And I'm hopeful that we'll see what they saw in the summer a Southern Hemisphere, which is that it will not. So that was all talking about masks and other forms of social distancing. Reducing the risk of disease transmission. Can't find it When we do laboratory studies, we basically averted the influenza pen pen season in the Southern Hemisphere. But do masks do something else beyond reducing the risk of transmitting infection? So we all know the and 95 it's named that because it reduces by 95% the amount of small particles that you're releasing that would potentially contain virus. Turns out surgical mass aren't as effective, but they're pretty good. They reduce it by about three quarters, so if every time you're wearing a mask, you disperse fewer viral particles. And if on the other end, a vulnerable person who is susceptible, infection is also wearing a mask receiving fewer viral viral particles, then that means that the in Oculus um, the dose of infection that they're receiving is lower. So there's, Ah, a couple of investigators at UCSF who have written a really compelling piece in The New England Journal and also recapitulated elsewhere as well, thinking about masks as one way. While we're waiting for the vaccines, which now seem like they're gonna be available soon, Mass might be one way that people are getting infected but having less severe illness. And this is another answer for the pattern that I hinted to earlier for reduced severity of disease over time as the pandemic has matured, so there's longstanding evidence that the infectious dose is related to the severity of illness. So this is a famous description of very elation, where cowpox was used to infect people and protect them from smallpox as a means of having cross immunity and kind of the first demonstration that we could do something similar to what we now do with vaccines. So The idea here is that if we know that the severity of diseases related to the viral an Oculus, um, and this is born out with Cove in 19 by the number of health care workers who developed severe illness and very high burden settings like Italy and China, then maybe having people wear masks will make it more likely that if you do become infected, you're less ill. And so here's some experimental evidence looking in mice at mice in black who were given no virus blue, who were given a low dose, and red who were given ah higher dose and looking at their C T scans over time to see the severity of infection. You could see that when animals got higher dose virus, they were more sick. And then a related study said Okay, what if we give high dose virus? But we protect those mice with masks? Turns out that that attenuate the degree of disease back towards more mild illness, like that scene in people who were given lower doses of virus. So all this to say that viral an Oculus is likely lower if you're wearing masks, So not on Lee do masks reduce the rate of disease transmission. But they might mean that even if you do become sick, you're less likely tohave severe illness. So a couple of times I referred to the changes in outcomes over time of Copan 19. So I wanted to come back to that one more time here. So this is data that was just published this month from N. Y. U, looking at 5000 admissions to the hospital over time for patients with Cove in 19. So the gray bars are the number of admissions that they had each month. So this was New York, which was part of that first wave. So most of their admissions came in March, April, and if you were admitted to the hospital in March or April with Cove in 19 in their cohort, you had between 20 and 25% mortality rate. Now, over time, that mortality rate has decreased substantially to more like 5% which is similar to the rate that we've been seeing here in San Francisco. And this holds true both in the unadjusted analyses, meaning not correcting for severity of illness. But in this blue line, when you look at factors like age, sex and co morbidity ease, even after adjusting for those who has been a decrease in the mortality over time. So for all the reasons that we've discussed, maybe the burden of infections and hospitals being overwhelmed may be masking, meaning that people are having less severe illness and then increased clinical experience, treating patients with Kobe 19 and having more treatments available. Some combination of these factors explains this observes decrease in mortality rate for hospitalized patients with Copa 19. So let me summarize here again about masks. Um, so we know mass reduce disease spread. We know that the mortality rate of covert 19 is declining, and we have a sense that masks in addition, in addition to reducing disease spread, might be contributing to the reduction of mortality rate by lowering the viral in Oculus, um, that people are being exposed thio. So until vaccines become available, mass might be one way to do what Jenner was doing with the cowpox and vary elation, which is to say, allow people to naturally develop immunity by getting an infection that's less severe now. Of course, that's not what we want. We want the mask to prevent infection. But if they're also resulting in mawr asymptomatic or less severe infections, that would be something that certainly better than the alternative of having more severe infections with the higher mortality rate. So, of course, um, there is also I'm gonna jump ahead to one slide. I just added today about vaccinations because this is kind of the late breaking news, which is that we're not. We're hopefully not gonna be talking about strategies like masking forever. Now, I don't know how long it's gonna be with us. And it could be that this experience with covert 19 actually changes the culture either in public or at least in the hospital with infectious illnesses going forward. It's too soon to say, but as far as covert 19, amid all of the information about the rampant pandemic and it's spread at this time there has been some silver lining, which is that science is continuing to march forward, and we have to promising vaccines that have been described in the last couple of weeks. So one from Pfizer which we got preliminary results about last week and then mawr definitive results today suggests that it reduces the risk of infection or severe disease by about 95%. So in a study of 44,000 people, they found 170 cases of Copan 19 and 162 of those were in the placebo arm. Those who did not get the vaccination. This protective effect was protection both against severe illness and any form of illness. And it seemed also to be effective in older adults and regardless of race or ethnicity, suggesting that those who are most vulnerable to the infection based on our historical experience are likely to also enjoy the benefit of this vaccination. Now, one downside of the Pfizer vaccine is that it is going to be complicated to distribute, so it's going to need two doses, so you'll need twice as many doses is the number of people you want to vaccinate and it also turns out that it is Onley stable in very cold temperatures like a minus 80 freezer, so it can last a few days in a standard freezer. But the distribution is going to be complicated because it's going to need to have what people call a cold chain of delivery so that we can assure that the dose arrives in a manner that it's still effective now. Madonna Pharmaceuticals has also developed a vaccine based on M R N a technology where your own cells see the Mara and then use that to make viral spike protein, which your body can then respond. Thio. They haven't yet released results of a advanced stage trial like Pfizer, but their early data, which they did release last week, is similar, showing 95% efficacy in reducing the rate of infection. And first of all, it's important that we have as many possible options because we want to make sure that thes pan out, and there's gonna need to be a massive upscaling of production and distribution to get his many doses to as many people as possible. So right there, there's a great it's great news toe have to companies that have so far had success, and there's many more in development. The other thing that's promising about Moderna is their products seems to be stable. Atmore standard temperatures, meaning it would be easier to distribute because you wouldn't have toe have such a stringent cold chain side effects of vaccination so far. The data that Pfizer has released Um suggested they're not substantial. There's some fatigue, some headache. But these happen in a small minority of people. It will be important to see the longer term data. This is just a couple of months of data so far, and this is all from press release. So we need to see the full release of data to Nome or about side effects. But there were not. It was not a substantial rate of serious adverse effects that was reported. So let me kind of give one last summary here, touching on our learning objectives, and then I'll stop for some final questions. So we wanted to talk about risk factors for Severe Cove in 19 disease, and we describe them in a few different categories. You talked about patient level risk factors, which your items that you might have been familiar with before. We also talked about hospital level risk factors, looking at the burden of covert 19 admissions to a specific hospital and also that hospitals, number of I C. U beds and then more at the end there. We talked about the timing in the pandemic when people fell sick with some evidence that earlier stage of the pandemic, the mortality rate was higher. Our second learning objective was to talk about strategies for reducing the spread of Cove in 19. And so here we talked about influenza vaccination as a way toe mitigate the risks of a dual pandemic, and we talked about masking as a means of reducing the risk of disease transmission and then thinking about masking again. We talked about the fact that mass, not Onley, seem to reduce the likelihood of becoming SEC, but they might also lead to a lower degree of illness. And then, of course, there's that late breaking information from the last two weeks about vaccinations for Cova 19 think the signal that we're having is that doses for Frontline healthcare workers might become available in the next 1 to 2 months, which is hard to imagine. That's moving this quickly on at the same time that these products will be available more broadly over the course of the spring. So that's starting to give me some hope that we might be getting over the midpoint here in terms of this pandemic, which at this point has stretched on for eight months, and if we're gonna have a substantial rollout of vaccinations over the next eight months. I'm hopeful that we'll start to see the spread curtailed. Mhm.