Welcome to the Medical Center Occupational Health course coming to you for the first time in four years. Thank you, COVID. And we are so darn happy to be back. I'll tell you, the faculty in this course who've become near and dear friends to me over the years of doing this work together are my personal heroes. And we share the sacred honor of caring for and protecting those frontline healthcare workers who have pulled us all from the depths of the pandemic into the light of day. It is we who take regulation and policy and confusion and go to that frontline worker, interpret, explain, calm, and care for. It is our job to protect them, not to castigate them for their non-compliance. The faculty in this course whom you will meet and who are listed on the back of your agenda are part of that network because you're not going to learn everything that you need to know today. What you are going to learn is that you're not alone. And there's no more powerful lesson. So welcome to this community and join us in this noble work. So this morning, your agenda will consist of the things on the screen, which I won't read to you, and you have printed in front of you. One final word before I introduce our first speaker is that many of you in the audience also work not only with healthcare workers, but with biomedical researchers. And for that group of people and those hazards, we have a new resource, freshly minted, of which one of the editors is the esteemed Dr. Rusci on the stage here, along with Phil Harbour and Beth Baker. And many of us on the panel were contributors to this book, Occupational Health for Higher Education and Research Institutions. If you'd like to peruse this on the break, I have a copy here, and you can order it from OEM Press. It comes out this summer. It's really hard to get a compendium of information on all these topics. So with that, I would like to introduce our next speaker. I'm going to get Dr. Rusci's slides up. Dr. Rusci is the director of everything, occupational health, employee wellness at Yale New Haven. And Dr. Rusci is the most riveting speaker I believe I've ever heard, and has given me so much passion for this work. So I'm very, very pleased and honored to introduce him this morning. Dr. Rusci. I don't know if I can live up to that, but I'll do my best not to disappoint. So I'm going to start with a discussion of outbreaks. And we thought that would be a good idea since all of us have been living through one for the last couple of years. And there are lots of lessons. And what I'd like first is to spend just a few minutes on the horrible and great outbreaks of history. Because before people understood a lot about disease or transmission, I think it's interesting to see the observations that were made and the interventions that came from those observations. So I'll start with the plague of Athens. This actually happened during the second year of the Peloponnesian War, which went on for about 27 years between Athens and Sparta. And part of the Athenian strategy was to fight a naval battle and then to gather its people within the walls of Athens. So the overcrowding predisposed to disease. Nobody knows what actually caused the plague of Athens. It might have been typhus, typhoid, measles, smallpox. We actually don't know. There's a description here from Thucydides. Obviously, it was quite horrible. But I think the lesson is this. And this was at a time when people thought disease was caused by an imbalance of black and yellow bile, blood, and phlegm. But the observation, for at first, neither were the physicians able to cure it through ignorance of what it was, but died fastest themselves as being the men that most approached the sick. So 2,500 years ago, people understood that the closer you got to people, the more likely you were to contract disease from them. So fast forward 1,000 years. Justinian was doing his best to re-establish the Western Roman Empire. You can see where the Byzantine Empire had expanded to. And this was really the first huge Yersinia pestis plague, 541 AD. And it followed a period of substantial change in the climate. There had been a couple of large volcanic eruptions. And there are descriptions of just months and months and you didn't see the sun at all. The crops failed. There were famines. There was a tremendous amount of movement of people. And all of these things, of course, predispose to Yersinia pestis. And they are many of the same things we recognize today as predisposing to the emergence of infectious diseases. And we live in a world, of course, where what we have gone through over the last two years is only going to become more common because of what we're doing to the earth. Think about it. Climate change changes the ranges of vectors like mosquitoes. So think about dengue and malaria and yellow fever. We're encroaching on the rainforest. We are causing human beings to come into contact with previously remote populations of animals and the microbes they harbor. And so these things are going to become more frequent features of our work. So fast forward another thousand years and Peter Broglie, the elder, painted this painting. It's called The Triumph of Death. And I would suggest that if you're feeling a little down or depressed today that you not look at it too closely. It's pretty horrible. I mean, when you look, get close to it in the details. I mean, there's a dog eating the face of a child. There's a pond that's choked with corpses and dead fish. Everything is burning in the background. There are skeletons sort of hauling corpses into this gate of hell. But the Black Death and the worst of these outbreaks was 1346 to 1353. 75 to 200 million people dead. I mean, you know, the Monty Python movie, Bring Out Your Dead. I mean, it was probably like that. And we have things from the Black Death that we still use today. Quarantine is derived from quaranta giorni, which means 40 days. When the ships were anchored off of the Italian ports, they had to remain at anchor for 40 days before anyone was permitted to come to port. They learned that that was an effective intervention. And it's one, of course, that we still use today. And look at this. Look how sensible this is. I mean, from the bottom up, the boots went all the way up to the knees. The gown was on a waxed canvas, so it was resistant to water. The gloves were leather, and they overlapped the gown partway up the forearm. The stick. Physicians were very popular during the Black Death, and people were clamoring all over them. It was handy to have a stick. But importantly, it also allowed the physician to take the stick and lift up the gown of the individual to inspect the bubos without having to get too close to the individuals. And then the beak, which could have been made out of plaster. And then there were holes in the end. This was at the time that the miasmic theory of disease, it preceded germ theory, but people had the notion that sort of these foul vapors transmitted diseases. Makes sense, right? Well, those vapors would have passed through the two holes and then through all of these herbs that were there, so it made it smell better. But it also probably filtered a fair amount. There were glass eyes to protect from splashes. I can't explain the hat. It's the flamboyance of our profession. This is the fall of 2014, a colleague of mine, and I think many of us remember the donning and doffing challenges of personal protective equipment during Ebola. So, 1918, 675,000 dead in the United States. We have, of course, unfortunately already surpassed that. We're at 995,000 right now. But 20 to 80 million across the world. I think we are at around six and a quarter of a million dead so far from COVID-19. The 1918 epidemic occurred in three waves. People imposed hygienic interventions. Then there were spitting ordinances. You can see here right above the putting a stop to the use of slingshots in the city, that in Rapid City, this is a little account of hauling some poor man named J. Mulcahy into court because he was seen spitting in public. The other poster is one you've probably seen, careless spitting, coughing, sneezing spreads, influenza, and tuberculosis. This got a lot of attention, right? This is what we did early on, and we did it because of the observations that were made here, those graphs on the right. The two right side graphs are without shutting things down. And the trouble with that is not only that the area under those curves is a little bit more than the two graphs on the left, but the real trouble is those peaks are the things where we overwhelm the capacity of healthcare. And so you begin to get morbidity and mortality that's the result of not having adequate healthcare for people, not just the result of the disease itself. So this is really the basis of the lockdowns that were imposed during COVID. So people didn't know that flu was caused by a virus in 1918. Everyone was looking for this Pfeiffer's bacillus that no one ever found. But the flu virus was first isolated, actually, in 1933. But you can see this guy is wearing a mask. Everyone sort of understood, hey, that makes sense. People understood that barriers made sense, and those things were imposed. I think, you know, so many take potshots at the CDC, but I do think one of the big errors was that period of many weeks when folks were saying, oh, the masks don't help. I mean, there's a basic sort of common sense here, I think, that people were forgetting and they had worked before. So I illustrated those things just because, you know, we learned a lot from those epidemics before we actually understood exactly what was causing them or exactly how diseases were transmitted. So I'm going to switch gears a little bit now and talk about some modern outbreaks and tell those stories, but specifically because those outbreaks, by and large, demonstrate things that were not supposed to have happened. So the picture in the upper left, of course, is New York City on 9-11. And shortly after that was when many of us went about arming our hospitals and medical centers against the threat of bioterrorism, and a bioterrorist threat followed closely, right? I mean, the anthrax exposures and other things in New Jersey. And so we began stockpiling antidotes and developing protocols and stockpiling personal protective equipment. And not long after, there sort of began this litany of emerging infectious diseases. 2002 were the first cases of SARS. 2003 was monkey pox, you know, imported from Gambian rats that mixed with Midwestern prairie dogs that gave it to people. 2004 were actually the first human-to-human transmissions of H5N1 avian influenza in Vietnam. 2009, of course, many of us were at the ACOM conference in San Diego when those first cases of novel H1N1 influenza were discovered in California and Texas and come up from Mexico. 2012 was MERS. 2013 was H7N9, first human case. And that was actually the virus that had been regarded as having the most potential to cause a pandemic before COVID-19 came along. It's probably too deadly to be successful enough to do that. And of course, 2014 was the horrible West African Ebola outbreak. And we know what happened in 2019. So I'm going to tell some stories here. And the first one actually happened in New Haven early in my career. But before we launch into those, I'm just going to remind you that these are the notions of airborne and droplet transmission. And as the story goes, droplets are those things that you can see sort of arcing their way toward the floor. So if you have a surgical mask on and the surgical mask blocks those big droplets, that's great. It's prevented it from happening. And then airborne transmission are the smaller particles that you can see beginning to kind of float away from that individual. And of course, the three infections that we regard as reliably airborne transmitted are tuberculosis and measles and varicella. And then there are lots of things that we regard as droplet transmitted. There's been a lot of dialogue about that. We're actually going to talk about that a fair amount. And I'll mention also, and some of you were at the MCOH meeting, but we are beginning afresh with this. The isolation guidelines are being rewritten at CDC after 15 years. And I won't say we're starting with a blank slate, but it may not look like this. Okay, New Haven, just above, just below the sports final, deadly virus at Yale. So here's the story. We had a visiting scientist from France and he was working in one of our labs, which was actually on the top floor of the School of Public Health. It was in the Arbo Viral Research Center. And on his way back from Boston, he began developing kind of virally symptoms, which persisted. And he decided to go and see Dr. Michelle Berry, who is now at Stanford as the Dean of International Health, because he thought that it was a recurrence of his plasmodium vivax that was never quite adequately treated. No history of tick bugs, hadn't traveled, said he hadn't had any spills in his lab. He looked a little sick. His pulse was 90. He had low-grade fever, but had been taking ibuprofen. There was no rash. There was no conjunctival injection. Some shoddy anterior cervical nodes. Lungs were fine. Heart was fine. No hepatosplenomegaly. No peripheral edema. His white count was a little bit low. Crit was normal. His platelets were 138,000. He was spilling a little bit of protein in his urine. Importantly, the malaria smear was actually negative. No ehrlichial inclusions either. ALT was slightly up. So Michelle kind of leaned forward and said, are you sure nothing happened in the lab? And he said, well, there was this one thing. And he was spinning concentrate of the virus he was working on. And when he went to, he opened up the centrifuge. And you can see the little black thing there. And he kind of opened up the lid. And he started to pull a tube out. And it stuck to the bottom. And he realized it had cracked. And what he had in there was something called Sabia virus. There's an accent on the last A. So he grabbed the thing. And he walked over to the hood. And he kind of took some Clorox and washed it out. And then he threw the stuff away. And he washed around. And he had on a surgical mask and a gown and gloves. And he sort of kept on working. He didn't think it was a big deal. And he didn't tell anybody about it. That's where it took place. So obviously some biosafety issues here. That thing shouldn't have been opened outside of a biosafety hood. He should have left the room. He just sort of cleaned it up with bleach. He really did not go and don a respirator for any of this. And of course he didn't tell anyone about it. So at this point, 1994, there had been two cases in the world of this hemorrhagic fever. One of them had lived. And one of them had died. So potentially he was dealing with a virus here with a mortality of 50%. So on a Friday evening, he was wheeled across the street to Yale-New Haven Hospital. This was what our emergency room used to look like, Yale-New Haven Hospital. Not so different from that. But we'll come back to that. And of course it's full of people. And you don't spend very much time there before your blood gets drawn and it gets put into these little missile things that go through the tube system. You can imagine the consequence of one of those blowing up. And they go to the laboratory. And of course they don't just go into a machine in the laboratory. It gets opened up and the tubes are potentially opened up. Lots of people are there in an open room. So suffice to say, in the span of just a few hours, a lot of people had been exposed. I happened to be attending in medicine on a Saturday morning. We were about halfway through work rounds. And one of the interns came bounding down the hallway, and it actually happened to be the little brother of my college roommate. And he said, Mark, I've just been assigned a patient with hemorrhagic fever. What should I do? So I had like, I don't know, maybe three months before that or something, been given the job of director of occupational health for the people who worked in the hospital. I had nothing to do with the biosafety stuff with that lab. But anyhow. So I'm going to ask you for a moment to put yourself in my position. What are the issues that need to be addressed here? What's the work you need to begin doing right now? Anybody? Contact tracing is one of them, right? This guy's been in Boston. He's come down. There are people in his lab. There were folks in the emergency room. there were people in the laboratories of the hospital. So we need to get busy on contact tracing, right? So what do we want to do with those contacts? This is the third case in the world, potentially. Quarantine them? Did you have a diagnosis? Not yet. So suffice to say, you could quarantine them. You could not do anything. You could monitor them. You could have them keep a log, check their temperature twice a day, monitor for symptoms. That's what we decided to do. We set up a 24-hour-a-day hotline for them to call, because if they began to have symptoms, you don't want them riding the bus to their doctor's office and sitting in the waiting room, right? So we had a central phone number for that. What about if they came to the ED? So we set up a protocol for that, for getting them directly into isolation, right? OK, good. So what are other issues we need to deal with? The comment is, take a really good occupational history. Find out exactly what the guy's been working with, and develop a hypothesis of what you're dealing with, and move forward with that. So he's working with Sabia virus. There was a lab error. He's exposed himself. And for the time being, we should probably assume that he has this illness. So how do we want to take care of him? How do we want to protect health care workers? What are the standards for hemorrhagic fevers? I'll tell you that at the time, the standards per CDC, whether it was Ebola or loss of fever, were sort of barriered and droplet precautions. It was not airborne precautions. What would you do? Then or now? Then. Airborne, droplet, contact. And we've got plenty of money, and we've got plenty of supplies and it's one patient. So we decided to err on the side of caution. And this is when sort of HEPA masks were just sort of coming in. So we had to think about everyone who might take care of this individual. And we went around and we fit tested all of them and made sure they understood exactly how to use it freshly. And we also decided we wanted to cone down the number of people who actually took care of them, so that the ones who did knew what they were doing, and they weren't going to make a bunch of mistakes. Where do you want to take care of him? He's sitting in a regular room in the hospital right now. Let's get him out of there. So we decided to put him in negative pressure. We actually put him into a negative pressure suite, a negative pressure room, an adjacent room that was also at negative pressure. Both of those rooms negative to an anteroom, which was negative to the hallway. We used the other room adjacent to him for supplies that got used before we took them off to be autoclaved or incinerated. The anteroom was used for staging, donning, doffing. Some of the stuff that we eventually did with Ebola. So suffice to say, a lot of stuff needed to happen really quickly. And I would love to tell you, oh, you know, we did all this stuff because we were so familiar with this outbreak that took place in Jost. So I'm going to tell you about this outbreak, and then we'll come back to ours. Jost, Nigeria was actually where loss of fever was first described. And the outbreak I'm going to describe to you now was almost exactly a year after that. And what happened was that in late January, the University of Ibadan in Nigeria received word that there was a cluster that looked an awful lot like loss of fever. And they sent samples to the CDC, and they actually did serological testing, and it was loss of fever. 23 patients. Most of them got sick during January, and then there were just a few in February. And people tried to figure out what's going on here. They had come from different places, so it didn't seem as though they had all kind of come from one spot. Not a lot of common experiences among them. They did notice that one individual got sick before the others did. They eventually caught up with that individual, interviewed her. And she had delivered a child in her native village of Bassa in November, and then on Christmas Day became febrile, and five days later came into the hospital. And that's her right here. And this is the first wave of the epidemic. They were all in the hospital at the time. And you can see, this was horrible. Died, died, died, died, died, died. Just about all these people died of loss of fever. And then there was sort of a second ripple epidemic that followed that. And so they thought, all right, well, what caused this? Bedpans and emesis basins. Turned out this hospital was sort of T-shaped. So kind of three arms of the T. But everybody who got sick got sick in this arm of the T. The bedpans and the emesis basins actually rotated throughout the hospital. Nobody in other areas got sick. Similarly, the personnel moved throughout the hospital. Food supplies tended to be brought in by families. It did not look as though surface contamination played a role. They trapped about 40 animals around the hospital to look for loss. They didn't find it in any of them. And they were left with the explanation they least wanted to embrace, which was that this had actually been airborne spread. Hemorrhagic fevers aren't supposed to do that. So now back to that picture I actually touched on before. She was there on the far right. There's a window next to her. The prevailing breezes during this dry season time of the year were going this way. And essentially, everyone downwind of her got sick. So this is actually a pretty obscure article. And if you're interested in hemorrhagic fever and you look at hemorrhagic fever outbreaks, just about all of them suggest that people have to be quite close to one another for disease to spread. So the old world arena virus, that this new world arena virus, Sabja, is closely related to, is actually Lassa. And so we were essentially imposing airborne precautions. Saturday night, the PCR confirmed Sabja in our patient. And as mentioned, we had moved him into negative pressure isolation. We, by the way, discontinued the lab work until we could figure out there was an enzyme that was used to add to samples that actually neutralized the virus, but didn't interfere with most of the assays that needed to be done. We developed a whole bunch of protocols at a BSL-3 hood, under which we did a lot of testing. As mentioned, we limited health care worker contact. We also had a plan in place if he'd gotten really sick. Our ICU was open, just like the ED, so we wouldn't have wanted to move him into that. And so the plan was to move the ICU to him in this negative pressure suite had we needed to do it. And if he had started bleeding a lot, we would have imposed a yet higher level of protection and had PAPRs ready to go. So CDC was along for the ride. They helped us. We contact traced 162 individuals. They actually changed their guidance for hemorrhagic fevers in the wake of this, and inserted language that said, you know what? Airborne precautions if you anticipate the person may get more sick. And unfortunately, 10 years after that, they departed from this. And they went back in 2005 to the guidance that had been in place for these 10 years that followed this particular outbreak. And it kind of bit them in 2014, because many people said, hey, you should have imposed a higher level of protection initially with Ebola. So I'd love to tell you, we did all this because we just knew exactly what was going on. But we basically did it because we were trying to be safe rather than sorry, or in the words of Charlotte Bronte, look twice before you leap. Or this is my favorite one, because it comes from a guy who liked to fly kites in lightning storms with keys tied onto the strings. Oh, where'd that go? An ounce of prevention is worth a pound of cure, Benjamin Franklin. Stated more formally, and I think this is one of the most important lessons out there, and this actually comes from the world environmental law, that decision makers anticipate harm before it occurs. Within this element lies an implicit reversal of the onus of proof. Under the precautionary principle, it's the responsibility of an activity proponent to establish that the proposed activity will not, or is very unlikely to result in significant harm. An obligation, if the level of harm may be high, for action to prevent or minimize such harm, even when the absence of scientific certainty makes it difficult to predict the likelihood of harm occurring, or the level of harm should it occur. The need for control measures increases with both the level of possible harm and the degree of uncertainty. This is the world we've been living in. This is the world we're going to continue to be living in, and this really is the guiding principle that needs to be imposed. Maybe everything we did was overkill. 162 people, nobody got sick. Maybe everything we did was excessive. Maybe we didn't need to, but I think it's instructive to look at this. This was the next arena virus discovered. This is Lou Joe, and long story short, four of the first five contacts died. Next story, Michelle. So I have represented, the college is a liaison member of HICPAC now for about 20 years at CDC's Federal Advisor Committee that develops infection prevention recommendations, and in the wake of 9-11, when we were sitting around trying to figure out how do we protect people for these various bioterrorist agents, and whenever this particular bioterrorist agent came up, which was the one we were probably most worried about, everyone would discuss, oh, here's how it spreads, here's how it spreads, and then somebody at the table would say, yeah, but what about Michette? What about Michette? And everybody would be, yeah, right. So here's Michette, a hospital in West Germany. There was a young German guy, he'd kind of been living on the streets in Karachi, and he started getting sick, and ironically, this takes place at the same time as the Jost outbreak in Nigeria that I just told you about. And he comes back home, and there's fever, and he develops a rash, and he goes to the hospital, and they take one look at that, and as this rash has developed, and say, oh my God, all right, let's look at the people who were close to this person. So they start identifying individuals who had been close to him, and they felt pretty good about that, and then the cases just started coming out of the woodwork. People who were nowhere near where he was. There were three floors of this hospital with separate staffs for each floor. People got, he was on the first floor. People got sick on the second floor. People got sick on the third floor. And the doctors and nurses didn't tend to be caring for patients at floor one to two to three. They were generally separate staffs. There was somebody who walked into the lobby of the hospital, had a conversation with a physician, a physician who never got sick, by the way, for about 15 minutes, way down the hallway from where this man was, and that person got this disease. Any guesses as to what we're talking about? And the hint is this disease had almost disappeared by this time, 1970. Smallpox, right? So, how do I go backwards with this thing? Right click? Yeah, I try to go right click, and then it gives me this thing. Yeah, you do previous. Huh? Second one. Oh, I can't even read that. Yeah, I'm sorry. But just tell me and I'll back click for you. Can you back click for me? Yeah. So, a couple months later, they did smoke testing, right? And they put the smoke in this room, and then they followed where the smoke went. And where the smoke went is where the cases were. So, the smallpox actually moved through the HVAC system. At least that was the most compelling explanation for what had happened here. So, you can see why people said, yeah, but what about Meshed? So, under certain circumstances, under these circumstances, this was a good study. It seemed that the smallpox was actually spreading over longer distances. All right, darn, I did it again. Sorry. So, when we, the guidance, the decision was made to essentially impose airborne precautions for smallpox. And it wasn't based on the middle of the bell curve. It was based on a single study. It was based on Meshed. But it was the right thing to do. Hong Kong. All right, what disease is this? SARS, right? And mortality of about 10%. A lot of healthcare workers, right? Because before anybody knew what was going on, the thing that happened, that it's all of our goals to never let happen, is that it's sort of a sacrificial row of healthcare workers who get sick. Because people didn't, you know, these attack rates among healthcare workers were really, really high before people understood what was going on. The weird thing about SARS was these super-spreading events. You know, many people who got SARS didn't even transmit it to anyone. And then you would have these super-spreading events. And the most famous one was the one that happened at the Metropole Hotel. There was a guy who was staying, ironically, in room 911. And everyone on his floor got SARS. And it was an international crowd. And all those folks went off to sort of spark the epidemics in places like Canada and Singapore and Vietnam. And interestingly, also here, the Moy Gardens apartment complex, there was an outbreak here which just exploded. And it exploded vertically on building E, up 33 floors. And it wasn't so, you know, these people got sick and three days later those people got sick. It was like everyone got sick at the same time. So what on earth was going on there? And there was this really good article that was published in the New England Journal. And you sort of look at it and say, oh, come on, really? And this eventually was the most compelling explanation for what had happened there. Anybody know what a U-trap is, right? Like in your sink, keep the sewer gases from coming. So all the bathrooms in the Moy Gardens apartment complex had a drain in the middle of the bathroom. So imagine if for months and months, nobody overflows the tub, nobody spills water, and it eventually does U-traps dry, right? A lot of people in this outbreak happened to have diarrhea. And so the thinking was that liquid waste passes from this toilet into the sewage stack. Aerosol from that is drawn up into this bathroom that has a dry U-trap by the negative pressure from the exhaust fan in the bathroom. Those aerosols then move via that exhaust fan into the exhaust stack where they now have access to essentially all the rest of the bathrooms going up because of the negative pressure generated there. This was regarded as the most compelling, it's probably what happened. So when SARS guidance was put together, again, even though SARS is usually transmitted when people were quite close to one another, the guidance actually called for airborne precautions, at least for short-range aerosol airborne protection. And really, it was based on just a couple of these unusual outbreaks. All right, well, I listed Atlanta here. It didn't really happen in Atlanta, but what are we looking at here? This is what a flu season is supposed to look like, and then this was May of 2009. So this is 2009, novel H1N1 influenza. Here's that big summer peak, and then there was a little bit of a peak that flowed in. By the time we got to December, there was no flu season here between 2009 going into 2010. There were essentially no, there wasn't flu in January, February, March. So we all know how to protect people from flu. We vaccinate them and we give them surgical masks. Any reason not to do that here? Did this kill more people than flu usually kills? It didn't, it didn't. But who did it kill? When I give this lecture to students at Yale, I say it killed you. It killed young, healthy people. 90% of the mortality was actually in people under the age of 65 with novel H1N1, which is, of course, the opposite circumstance to normal influenza. So people approach this a little differently, and they ask, well, gosh, do we really know that this is just droplet transmission? Is there any evidence going back that flu might transmit beyond droplet range? It turns out there is. There aren't very many studies. This is the one that everyone quotes, the Moser study. It was an airplane. It was grounded in Alaska for five hours. For three of those hours, the ventilation system was turned off. There was a young woman who sat in a seat on the plane and did not move, and she was in the throes of coming down with flu, fever of 103, sick, sweaty, awful, right? 72% of the people on this plane got the same influenza that she did within three to five days of their being on the plane. And most people regard this as representing longer-range transmission. There are a couple of other studies that are out there that suggest longer-range transmission of flu. This was one that just essentially showed that the more fresh air you have, the less flu transmission you have. Fresh air doesn't make any difference with droplet transmission, right? You're just right next to each other. Fresh air would make a difference if you have airspace that's potentially infectious. And then this was one from the Hong Kong flu where one building was compared to another. There was upper zone ultraviolet irradiation in one, not in the other. A lot more transmission in the one without the upper zone irradiation. Again, not an intervention that would have any impact on droplet transmission, but one that might impact airborne transmission. So suffice to say, there's a little bit of evidence out there. All right, so then you sort of ask the question, all right, well, let's look at what actually has to go on for there to be airborne transmission. Let's sift through those issues. And is there any evidence for that? Oh, before I go to that, though, I'm gonna put this one up just because this actually happened during a 2009 outbreak. And this was a guy who was just getting sicker and sicker and sicker. I'm trying really hard not to intubate him. And these colors diagram where the airflow went. And all these people downstream of him got sick. These people who were just as close where the airflow didn't go, didn't get sick. And so people looked at that little outbreak and at least sowed a little bit of doubt about whether transmission was truly limited to a short range. This, of course, is much more typical. There's lots of studies like this. When people are close, it transmits. When they're not, it doesn't. All right, so to continue that discussion with flu, we need to start talking about the phenomenon itself rather than the epiphenomenon. And anybody know what this is? It's the Tacoma Narrows Bridge, right? So it's kind of an obtuse reason that I put this up here, but I was having a conversation with one of my sons about the difference between epiphenomena and phenomena. So if you're an epidemiologist, you're the guy who's sitting on the road a mile away, and you notice that the cars have stopped coming by, but you don't really know what's happened, right? So you have to look at the phenomenon itself. Here's the phenomenon. Stokes' Law governs what happens to aerosols. And suffice to say, without going into the other elements here, because the thing that's really changing is the radius of the particle. The smaller the radius of the particle, the floatier the particle becomes. And you get to the point, once you're down below 2, 3, 4, microns, you've essentially got floating particles, because it's not always just still air, right? You have horizontal vectors doing this and mixing things. So when things get small, they get really floaty. So let's go back to that picture we looked at before. So droplet, right? So people would say, oh, yeah, well, 10 microns, that's a droplet. So Stokes' Law tells us that it takes 17 minutes for a 10 micron particle to go from here to the floor. That's not a particle arcing its way beyond the coffer there. For a 20 micron particle, it's four minutes. So that's also not kind of to the floor. So suffice to say that even particles that are in the droplet range spend some time in the air before they make it to the ground. And the other thing to remember, and by the way, some of these outbreaks I just described to you happened during periods when the air was dry. The drier the air, the more rapidly that large droplet desiccates to a droplet nucleus. And the smaller it gets as it's making its way down, the floatier it gets. So some people think that the seasonality of influenza outbreaks has to do with people spending more time in dry indoor heated environments that predispose to the formation of droplet nuclei from droplets. What's the other really important thing about particle size? Well, it determines where the particle gets in the respiratory tract. The bigger the particle, the more likely it is to be intercepted up high and in the ciliated airways. The smaller it is, the more chance it has of actually getting to the alveoli. All right, so let's ask the important questions about flu virus. Can it be detected on particles of aerosol dimension? And it can. Suffice to say, I don't even need to go on. But all of these studies, 42% of the flu RNA in particles are less than 4.1 microns. 64% of the viral genome copies particles smaller than 2 and 1 half microns. 87% of the exhaled particles less than 1 micron in diameter. So yes. But what do we know about PCR, right? I mean, we learned this with COVID-19. It detects RNA that's hanging around remnants. But it doesn't necessarily tell us whether the virus is viable. So this is really the next question. Does it remain viable? And the interesting thing is that this research goes back to the 1960s and 1970s. It would aerosolize influenza, keep it aloft for 24 hours, and then see whether they could infect chick embryos or mice or ferrets. And lo and behold, they could. So come on, more than 10 minutes. Because you had your little introduction. And I've got to get a little bit more than that. OK. OK. OK. OK. Dr. Hodgson exceeds the time here. My dear friend, Dr. Hodgson. So what about animal studies themselves? I think, what experiment would you do, right? You could take a bunch of sick animals, chicken wire. Take a bunch of animals that aren't sick over here on the other side of another piece of chicken wire. And you remember, these guys are only this far off the ground. And if you get transmission over a couple of meters, that's airborne spread of the virus. These studies go back to the 1940s. They knew that influenza could spread over longer distances. And there was one with unidirectional airflow over like 2 and 1 half meters where the flu virus spread. All right, well, what about human beings? So you can put flu on aerosols and deliver it to people. And it will infect them. But that's not really the issue, right? The issue is more, does it spread over longer distances? So some people have cited this observation as being important. Intranasally infected college students had less severe disease than college students who acquired influenza naturally. So how do you get intranasal influenza? You get it from large particles, right? They don't make it down low. So some people have said, well, maybe that implies that full-blown influenza, what we recognize, a fever of 104 and really sick, comes from infections that are actually being transmitted down to the lower part of the respiratory tract, which means it comes from particles that are small enough to get down there. So here's the thing that's kind of interesting. There have been a bunch of studies of masks versus respirators. And it's kind of surprising that we have not seen more difference. Now, there are things that mitigate that. Sometimes it's hard for people to keep a respirator on for the entire time. But suffice to say that there has not been a ringing endorsement from those studies with influenza that respirators have been more protective than masks have been. This was Lou Radanovich's trial here, which may have been too few people. But they also weren't able to show any difference. We can skip that in the interest of time. But suffice to say that there's good evidence that it's really effective to mask the source. It's more effective to mask the source than to mask the recipient. Well, what was the public health guidance that came out of folks thinking about at least the possibility of airborne transmission of flu? We actually switched to airborne transmission for 2009 novel H1N1. And we still have the remnant of that for aerosol generating procedures in influenza where the recommendation is for N95 respirators. Oh, the gnashing of teeth that followed this. And you had sort of OSHA and kind of the occupational medicine folks and the industrial hygienists on one side. You had the ID docs and the hospital epidemiologists kind of on the other side. And to be fair, this was difficult. We had a million dollar stockpile. And we still ran out of small size respirators during 2010. We had to access the state stockpile. So this was really challenging to implement for a lot of smaller hospitals. All right. We touched briefly on H5N1 and H7N9, MERS. Let's just talk a couple of comments on Ebola. The West African outbreak in 2014 dwarfed all prior outbreaks. It was a horrible, horrible event. Many of us here lived through it. And most studies of Ebola have suggested that you have to be pretty close to people. If you're dressing a body, if you've cared for someone, you're likely to be transmitted. This is a typical study. They looked at 27 Ebola cases. They looked at secondary cases and family members, bunch of household contacts. The only people who got sick were the ones who had had direct contact. And that's what most studies show. This study. This one came up at dinner last night. The Rolls study was done. This was the Kikwit outbreak in 1995 is when that outbreak occurred. And suffice to say, there were about 55 people where they just couldn't figure out how they had gotten Ebola. And so they decided to do a case control study. They examined those cases in detail. And had you been in a hospital, had somebody in your house, da-da-da-da-da-da. And in the end, there were 12 cases where they just had no idea. There was no apparent close contact that the individuals had had with Ebola. And some folks have looked at this and said, you know what? We can't rule out the possibility of longer range transmission of Ebola from this. And of course, the measures that we put in place for Ebola in 2014 took that into account. There's also some interesting evidence. This was from an animal lab where they were working with the Zaire strain of Ebola virus. They had a bunch of control animals and a bunch of sick animals. And they were 10 or 12 feet away from each other. And the husbandry workers were careful to do everything first with the control animals before they would work with the sick animals. And then they would leave the room and doff their equipment and everything. Two control monkeys died at 10, 11 days following the death of the last experimental monkey. Now, I have friends at the CDC who have told me, oh, yeah, but you know what monkeys do. They throw a stool at each other across their cages. And I'm like, come on. I guess they do. But this at least suggested the possibility that there was longer transmission, because there really wasn't a better explanation for it. There was a kind of similar outbreak with the Reston virus. This is one that kills non-human primates, but it doesn't give us too much trouble. And there was spread in this facility as well of Reston virus over longer distances. We know that you can deliver Ebola on aerosol range particles. And the pathology it evokes looks exactly like Ebola in the lungs. So in the fall of 2014, we actually had a Yale PhD student who'd been in West Africa helping with the effort there, came back, had a fever of 103, abdominal pain, was really sick. And he called a colleague of mine at the Yale hospital and said, look, I think I might have Ebola. And I don't need to rush into the ED right now, but I need to let you know, because you guys probably need to do preparation. So we had this five, six hour interval to get ready for this. And it was right after the entire country had lost faith in the CDC guidance for Ebola, because it was when the Texas nurses had gotten sick. So there we were, having put into place this plan to provide personal protective equipment consistent with what was out there, and no one had faith in that. So the first night, this is what we did. We put folks in hazmat suits. Ever spend any time in a hazmat suit? Do you know what it feels like after about 20 minutes? Oh god, it's like a, I mean, you have a garbage bag around you, right? It's really, really hot. We also built a negative. We built this wall that night before he got there. This is in one of our ICUs. And so we were able to set up something in an ICU setting, kind of like what we had set up for Sabiavirus. Both of these rooms were negative to this room, and this room was negative to the hallway. The great challenge, of course, with Ebola was teaching people to don and doff this stuff without contaminating themselves. And as you recall, it was a three-person process for each donner and doffer, right? The person who was taking it off, the person who was assisting in taking it off, and the person who was observing to make sure there were no little errors. We all take off contact precaution stuff all the time. We're constantly, probably, exposing ourselves. But this was Ebola, right? All right, COVID. Is it different? I mean, early on in COVID, there were already some indications that it had the potential to spread over longer distances. The choir practice in Skagit County, there were some well-documented outbreaks in restaurants in Asia that suggested longer-range transmission. So, oh, I just updated these last night. We are now, based on antibody surveillance, probably 60% of the US population has been infected at one point or another with COVID-19. And this is what the case rates look like now. I'm going to come back in a moment to the airborne discussion. I thought we should at least take five minutes and talk about COVID-19 since we've all been there. And I imagine that everything I have on this slide is everything that all of you have been doing, setting up our testing enterprises, the transition to telehealth, mass vaccination, as we've never quite seen it before. And, of course, all of us were constantly toggling between containment, when we regard exposures as exceptions, and mitigation, when we regard exposures as the rule, whether we know the specific exposure or not. All of us were paying attention on a daily basis to the guidance, trying to adapt our policies to it. We did our best to exceed the guidance. I mean, we actually never had anybody in anything other than N95s or elastomerics or PAPRs, even if they were not treating people doing aerosol procedures. We were in a position to do that. It was challenging. We were getting N95s from 20 or 30 different sources. A lot of them are really crummy. And we erred on the side of caution with the isolation periods and the travel policies as well. This is what the vaccine statistics look like right now. And, of course, we're living in this time when the virus has departed enough from the original virus that the vaccines are pretty good at keeping people from dying. This shows just how effective. This is just some Connecticut data that showed a 17-fold greater risk of dying if you were unvaccinated. And this is already with Omicron here, and a three-fold lower risk of hospitalization. The boosters, eventually there was pretty decent evidence on the boosters. Came out of Israel, suggesting an 11-fold lower rate of confirmed infection, and severe illness 20-fold lower among older folks who had gotten boosted. And now we're living with Omicron. And it seems to be more infectious. It seems to actually have even more of a predilection for spreading a little further than the droplet range. So what explains that? There's been a fair amount of discussion about that. People observed that it was less of a delta Omicron difference in transmission among the unvaccinated. And so some of this probably was immune escape. People asked, well, is more virus coming out of infected people than with the previous variants? And there's not a lot of evidence for that. Usually, the spread is not kind of like measles, where everyone in a large room potentially gets infected. I mean, measles is just spectacularly contagious. So still more of a gradient, but more potential for longer range spread. The faster incubation period may help enhance spread. And of course, one of the good things about Omicron is it likes the upper respiratory tract a little more than the lower respiratory tract. So people aren't dying as much. Is it possible that they're generating aerosols from the upper respiratory tract, where the size distribution is a little more favorable to longer range spread? We don't really know the answer to that yet. There's a lot that still needs to be learned about the range of sizes of aerosols, the impacts of various factors upon that from the host, as well as in the environment. We don't know whether a lower dose is sufficient. Certainly, a milder disease predisposes to more folks mixing in settings just like this one, not knowing they're infected and potentially spreading it that way. So that may underlie some of this. We've gone from BA1.1 to BA2. Now, 40% of new US cases are the 2.1, 2.1 variant. And I'm sure many of you have read about the BA4 and BA5 variants that now make up 60% of South African cases that appear to spread a little more easily. So I think that we have to regard COVID-19 as a very good example of something that can spread via the airborne route opportunistically. So getting back to this notion of droplet versus aerosol, the trouble, of course, is that our interventions are categorical interventions. And there has been some utility in saying, hey, the epidemiological observation here is that this disease usually requires that people are close to one another in order for spread to take place. Maybe that's due to these really large, efficient packages of virus that are only effective in the short range. But I think it's instructive for a moment to just deny the existence of droplets altogether. For a moment, imagine there's no such thing as a droplet. If that were the case, what would be the epidemiological signature of most diseases? And I would say the signature would be that most studies will show that people have to be close together, because there's lots of concentration of those aerosols. But you're always going to see a few studies that show longer range transmission. And maybe those studies have happened in settings where people are a little more crowded, or in settings where the air was a little drier, or in settings where there was some unidirectional movement of the air currents. And in fact, that's exactly what you see. When you look at this literature, you see that the exceptions, the stuff that's out here on the bell curve, have actually illustrated maybe what's most important, which is that this potential exists with many, many infectious diseases that we regard as quote, unquote, a droplet. And the precautionary principle essentially instructs us when these things come up, and certainly when you have a new infection, that you should impose the maximal level of protection that you're able to. We know from flu. We know from the epidemiology. We know from the studies looking at the phenomenon itself that influenza can do this. So it is possible that both short and longer range transmission actually occurs principally by droplet nuclei. We don't know the answer to that question. Obviously, it's something we need to understand better. And there's a lot of discussion about interventions. Should we be doing more with air circulation? Should we be doing more with regulating humidity, particularly in winter months? Anybody read Troilus and Cressida? Right? I haven't either. Nobody has. It's regarded as Shakespeare's most problematic play. No one knows quite how to classify it. It's a weird play. So there's a scene, act three, scene two. Troilus says, fears make devils of cherubims. They never see truly. And Cressida answers, blind fear that seeing reason leads finds safer footing than blind reason stumbling without fear. To fear the worst oft cures the worst. So on that note, I'm going to thank you. Thank you.

airborne transmission

viruses

influenza

Ebola

COVID-19

outbreaks

precautionary principle

masking

ventilation

vaccination