Update on respiratory infections for the summer: COVID-19, influenza, mpox and more

[00:00] Okay, good afternoon. Welcome to medical grand rounds. This will actually be our last grand rounds of this academic year. So enjoy your time on Thursdays at noon for the next several months and then when we come back in September, we will be on Tuesdays at noon in a room TVD. We still haven't figured out where we are because

[00:20] This building will either be torn down or be in the process of being torn down in the fall, somewhere on campus. And we'll continue to be hybrid. So if folks want to watch virtually, as a majority of our folks do, they will be able to do that. Today it seems appropriate for the last grand rounds of the academic year to.

[00:40] focus on respiratory viruses with a little bit on COVID and what's happening with COVID. Seems like we're in something between an uptick and a surge, and we'll hear from some of our experts about where we are and where we're likely to go and some of the strategies to deal with that.

[01:00] new form of influenza that everyone is talking about and is confusing. So we'll talk about that and we'll also talk about some of the other viral threats that are out there, including measles and empox and a few other things. So to do that, we have a spectacular panel of experts. I will introduce all of them, but the way we'll do it is that we have a new panel.

[01:20] it is the first speaker who is George Rutherford. We'll come up and give his very familiar talk on kind of the state of the pandemics, but on this one it will be COVID and bird flu mostly. And then we'll have George joined by three other experts and we'll spend the rest of our time in a panel discussion, which is

[01:40] I will lead and then we'll open it up for questions in about 10 to 15 minutes before the hour. So briefly, our four speakers are George Rutherford, who's I think familiar to all of you. He is professor in epidemiology, preventive medicine, pediatrics, and history. He's also

[02:00] of the Center for Global Strategic Information, Public Health Practice in our Institute for Global Health Sciences. George is a world expert on epidemiology of infectious disease, and throughout the pandemic was really our go-to person to tell us about the state of the pandemic. And so I look forward to hearing his comments. So George will come up first.

[02:20] And then he will be joined by our three other panelists. First will be Peter Chin-Hang, Peter's professor of medicine and associate dean for regional campuses for the School of Medicine. Peter is an infectious disease expert whose career is focused on the care of patients who are immunocompromised,

[02:40] also became a go-to expert on all things COVID during the pandemic with hundreds or thousands of appearances in the media, somewhere between hundreds and thousands of appearances in the media. Peter's a terrific educator, both of the public and of our trainees. He's one

[03:00] almost every educational award we have to bestow, including the Kaiser Award for Excellence in Teaching, the core teaching awards from several medical school classes, and he was the commencement speaker for the UCSF School of Medicine class of 2015. He was awarded the Carl Sagan Science Popularization Prize for 2022 for his communication during COVID.

[03:20] Next is Debbie O'Coe, who is Professor of Medicine, also in our division of infectious disease based here at UCSF Health. She is the medical director for hospital epidemiology and infection prevention. She also attends on the transplant ID consult services. Deb is not only an ex-nemesis.

[03:40] expert and a go-to leader here for our strategies around combating infectious disease, for which she was essential during COVID. But she also has a number of national leadership roles and recently stepped down as the president for the Society for Health Care Epidemiology of America, the major society of infectious diseases.

[04:00] these epidemiologists in the country. And last and not least is Alison Bond, who is assistant professor of medicine. She's a clinician educator who has a dual life in our division of hospital medicine and also in our division of infectious disease. She's an trained ID doctor who also attends on the medical service. She

[04:20] She is a professionally trained science writer on the side with publications in The New York Times, Boston Globe, The Atlantic, and she continues to write for the popular lay media as well as in medicine. So a really interesting, diverse group of people to help update.

[04:40] us on the state of various infections and so we will start off with George.

[05:00] While it is a reportable disease, it sort of really isn't a reportable disease because everybody tests themselves at home and nobody reports anything. So we're left with other, having to put together other ways to figure out trends in COVID. This is emergency department visits for COVID, RSV, and COVID.

[05:20] V and for influenza in California. What you can see is that we had a lot of activity in the winter of 2022-23, somewhat less so in the winter of 23-24. The top line is the summit of 1.

[05:40] And now there's a drop off with maybe, maybe, maybe, maybe, maybe kind of an uptick, which is predominantly due to COVID. We'll get more to that. The other great system we have, we also look at deaths and hospitalizations, which I'll show you those data. We also do wastewater surveillance.

[06:00] Basewater is very, very, very good surveillance. It was originally put together for polio surveillance and polio eradication areas. But you can see that it is trending upwards in the green with the jump there is in the west.

[06:20] lot of that is in California. This is looking at the concentration of viral particles per whatever of per cubic volume of wastewater. And because this is not a very much of an epizootic disease, although pets can get it, this is largely human waste stream that you're seeing.

[06:40] and it's an early warning sign which is often followed by increases in ER visits and then hospitalization. So something to pay attention to. As you can see, we're reading tea leaves here with sort of a 10% ish of the maximals.

[07:00] peaks. Hospitalizations are here on the left. These are also California data. You can see there has been an increase. And that's largely in Northern California, and a lot of that's in the Bay Area. Why is it going up in the Bay Area? Who knows. But the

[07:20] with the wastewater surveillance, it seems like it is going up, and I'll be interested to hear from the other speakers about what they're seeing in the hospitals. Deaths, however, are very, very low in the state and, in fact, around the country.

[07:40] As you know, COVID loves, as viruses do or want to do, loves to mutate. We're currently dealing primarily with two variants called KP2 and KP3. They're part of the JN1 lineage, which is the darker purple.

[08:00] What the interesting part here is that the FDA panel on what goes into the influenza viruses also is now looking at COVID viruses, and last week they voted to put in the JN1 lineage, which is kind of yesterday's news. But these others are so closely related, it seems that they get a

[08:20] a two-fer or a three-fer out of it. They can revisit it again and put together a bivalent vaccine. But right now the production is gearing up for the MRNA vaccines for a JN1 predominant vaccine. If you're eligible, if you should be getting a second COVID shot, the

[08:40] spring by all means. Get it. Now moving on to flu, influenza A is a disease of water fowl. It spreads by accident into other species, mammals, and other avian species. And chickens seem to be very susceptible.

[09:00] mostly because they don't fly around too much, for those of you who've been around chickens. But we thought this fall started back in 1997, kind of this current outbreak, and it's been a slow-moving, epizootic

[09:20] that spread around the world. What we're seeing here in California is that we're seeing detections in backyard poultry. People have chickens in their backyard, not a good idea, and also in commercial breeding farms, commercial breeding farms.

[09:40] existential threat. Everybody's well one day, everybody's dead the next day in their chicken farms. So this is a big, big deal for commercial chicken farmers. But it also is a marker of how much is being, how much is the spread? So there's the, you see parallel things for wild birds. But it also

[10:00] spread from birds to mammals. What we haven't seen much of is mammal to mammal transmission. What we have seen is a lot of bird to mammal transmission. These are animals like cats and stuff who catch birds who are wounded or dying or

[10:20] down on the ground. But it's a lot of sort of smaller mammals. Yes, yes, there's a polar bear on here, I'll give you that. But there's a lot of smaller mammals that would, that you can imagine as they capture these captured birds, wild birds who are dying of influenza could easily get.

[10:40] pick up the disease. Now, having said that, there are two vicious counter examples to this. One is that there's an outbreak in dairy cattle now, which clearly involves cow to cow transmission. It probably started in Texas. And then because these answers

[11:00] animals get shuffled around a lot, spread across the Midwest and is now in something like nine states. California is not one of them. The other vision is counterexample, and this is something I think that really gives you pause. And this gets to seem utterly exotic and sort of esoteric. And why are we talking about that?

[11:20] talking about this at the hospital, is in elephant seal pups and elephant seals off the coast of Argentina. There's been 96% mortality among newborns, all with, as he coughs, on Q, on 96% mortality.

[11:40] mortality among newborns with H5N1 and it's clearly being transmitted from animal to animal. There's also a parallel outbreak in sea lions that mix with these rookeries. So we do have examples of mammal to mammal transmission. In terms of humans, there have been four

[12:00] cases in the United States, there have been about a thousand cases worldwide going back to 1997 with about a 50% case fatality rate. A lot of these all involve people who are kind of directly in contact with these animals. There may be two cases of human-to-human transmission, very unclear.

[12:20] They're not well investigated. And they've been doing cluster investigations around these cases, these handful of cases of human transmission, erred to human or cow to human transmission, have not found any secondary transmission. So that's good news. Of these four cases, one was an

[12:40] Colorado and it was a guy whose job it was to cull chickens, basically weighed into the flock and kill them. And the other three were people who are very directly involved with dairy cattle. The symptoms are pretty mild.

[13:00] three of them only had conjunctivitis. There was a fourth and also the fourth, most recent case, also had a cough. But okay, so this you can take this for what it's worth, but what we do know is that you know there has been mammal to mammal transmission, right? This is something to worry about.

[13:20] So how to protect your family? Avoid exposure to sick or dead animals, including wild birds, poultry and other domesticated birds and other wild or domesticated animals if possible. Now what does that mean if you have anybody here have chickens in their backyard?

[13:40] I don't have to yell at you. If you have chickens in your backyard and they start to die, don't go out and try and resuscitate them. You know, okay? Let them go. I'm serious. And you know, you want to avoid exposure to littler.

[14:00] Yeah, to Gene Littler, the golfer. Avoid exposure to an animal feces, litter, unpasteurized milk and material, cinnamon, touch fire close to birds or other animals. You could possibly have H5N1. There're very high levels in milk. And the predominant symptom in dairy cows is, as we say in pediatrics, galactopane in

[14:20] decreased milk flow. Avoid drinking raw milk. This is not going to go down well in parts of the country, but this is something, this is yet another reason to pasteurize your milk. Pulch cooked, properly handled and cooked. Pulchery is safe in the US. Handled is about

[14:40] salmonella risk, it's not about influenza risk. And then there are very specific guidance that's going out to people who interact with these animals. So what kind of risk is opposed to human health at the moment? Not a lot, unless you're at occupational risk. Reports of human to human transmission are exceedingly rare.

[15:00] kind of early, the late 1990s. However, there is this concern that a series of mutations, and there's a lot of this stuff circulating now, could make it more tropic for human respiratory cells. There are 100,000 people employed in the dairy cattle industry. We should be vaccinating them in all likelihood.

[15:20] However, 80% of the vaccine is grown in eggs, kills eggs as well as chickens. So you're going to have to use cell culture, which the Chinese have pioneered. We don't have a lot of it in the US. But it's something I think that we'll see more of. You have to do surveillance testing.

[15:40] testing, and then wastewater testing. When it comes off of farms, it's unclear where it all comes from and actually come out of the fields as well. So I'll stop there and look forward to hearing my colleague's insights.

[16:00] We bring everybody up. Thank you. Thank you, Drew. It's time they all know what is out of here. You can be anytime you want. Anytime you want.

[16:20] Why don't we just start with everybody else's reaction to what you just heard? Anything particularly scary or particularly interesting to you as you think about, maybe start with COVID and then we'll turn to influenza. Peter, what strikes you about the current moment in COVID? I think the most striking thing to me in COVID is the low vaccination rate.

[16:40] particularly in seniors. So nationally it's about 40-something percent, but California is actually trailing the country in vaccination of seniors. But the Bay Area may be running about 50 to 60 percent. But when you look at seniors of color, it's even lower like 22 percent Latinx populations.

[17:00] to say that we had a lot of efforts in the beginning of the pandemic for vaccine equity, but it's kind of fallen off. And I was in the hospital for the last few weeks, a few weeks over the last few months, and pretty much I saw a handful of people who were very sick with COVID and not a single one of them had gotten the recent boost.

[17:20] vaccination rate, are you referring to the second six-month one? No, that's the first one. That's the one in the past year. They haven't gotten one in the past year. The fall, yeah, October of 2023. And George recommended that people do, people who are eligible, which I guess is over 65, get the second.

[17:40] Question one, are you on board with that? Yes totally because I think we are going to see a continued increase in COVID in the community, in the Bay Area and California and the country. And if you think about when you, people always ask that question, when should you get the vaccine in the fall? And you don't want to get it too early, you don't want to get it too late.

[18:00] kind of like gully locks. So if the vulnerable populations get that vaccine now for the summer, you can still get it around Halloween, which will be well-timed in general for winter with flu. Dr. Jim Brattyn-Shapirot-W

[18:20] that jump forward not just related to COVID, but also related to the risk of H5N1 is sort of how politicize science and public health recommendations have become and how that does pose an ongoing risk to the public. Not just with regards to COVID vaccines, that's definitely a huge

[18:40] huge issue, but also, you know, George brought up the pasteurized milk and how that's now a hot button topic. So I think that's really dangerous. And there's a big question about sort of where we where we go from here to serve the public's best interests. So that was the big thing that jumped out. Can you, this is sort of the first I've heard of the polypene.

[19:00] politics of unpasteurized milk. What are the politics of unpasteurized milk? Well, from what I understand, I mean, certainly from an infectious disease standpoint, we would recommend against drinking unpasteurized milk just because it can carry a number of types of infections, including the one that we were just talking about.

[19:20] But in certain circles, I think it's become sort of a hot button topic because it represents, you know, to some people, government overreach in terms of like, telling people what to do and not letting people have freedom of choice. And unfortunately, you know, that becomes

[19:40] public health issues sometimes. And I also worry, and this kind of gets back to media coverage of infectious diseases and things like that, sort of if the understanding is necessarily there among some people who choose to drink unpasteurized milk, you know, where they're getting their information in terms of if it's from.

[20:00] TikTok or Instagram saying this is actually pretty safe to drink and so I just want to emphasize that some of the, I think many of the people who are maybe doing some of these practices are actually vulnerable themselves and one of the questions is sort of like how to get the right information to them in a way that they're receptive to.

[20:20] either any of you on this, not quite sure I heard, George, has there been a case of a person getting influenza from unpasteurized milk or it's just a theoretical concern? So theoretical concern. Okay. Yeah, go ahead. You want to anything you want to add to that? Or just that's right now it's a theoretical concern. But and why would

[20:40] Why would it be a concern when, at least I always thought influenza was a respiratory virus and you wouldn't be able to get it from drinking something? It's not a respiratory virus in birch. It's transmitted. It's fecal-oral transmission. And we do know that the

[21:00] The udders are an end organ in cattle because it does cause decreased milk production and not beyond the possibility that that's because there's virus there. Now, they don't kill these guys. These are expensive cattle. But this is a real concern.

[21:20] concern. A lot of the infection from, so in, I don't really want to get into this. In California there are probably about seven raw militaries. Six of them are for goats and they have the names of the goats over their stalls. You know, they have six goats here and there. Then there's one in Riverside County with 50,000 or so cattle in it.

[21:40] And that's for milk, cow milk. And the cows walk in the wintertime, they're utter deep in mud and stuff. So a lot of this is external as well as internal. And the big concern here is Salmonella doublinae, which will kill you if you're a

[22:00] of a certain vintage and that's actually excreted in the milk and when this stuff's not pasteurized, this is mass produced, it's distributed widely. So it sounds like you think, unpasteurized milk is just a bad idea in general and this is a good time to warn people about it. It's not necessarily that people are going to catch it for a long time.

[22:20] from, catch the new influenza from the milk? Is that, you're not sure yet. I can add one nugget to that and people might have seen the investigation that found molecular fragments of H5N1 in one of five samples in US in milk, and that's pasteurized milk. So it's just a statistical game, I think.

[22:40] At some point, you may encounter admixed milk, although the raw milk purveyors say they come from single farms, etc., but you still may get accidentally a sick cow's milk with the others and in the right host you can get serious. But like George said, I think from an idea,

[23:00] perspective, the biggest threat is salmonella and like Alison said, listeria and E. coli because salmonella lives in the gut of birds and dairy as well and that can just get into the wrong person in the wrong place. And just to be clear, one in five samples of pasteurized most fine fragments

[23:20] But it still should be safe. Yeah, it's safe because they actually took those fragments and injected it into, they tried to culture it out and they were dead. Got it. They weren't alive. Got it. Debbie, how are you seeing all of this maybe with a particular spin on how it's affecting your thinking about our policies here? Sure. First of all, I'd like to thank you for your time. Thank you.

[23:40] I want to say that I agree with everything that George and Peter and Allison said. The fact that so many aspects of infectious disease is public health and now politicized, it's been very, very challenging. I also wanted to emphasize the importance of vaccination that Peter brought up.

[24:00] It's one of the major layers of protection that we have against a variety of different infectious diseases. So certainly true for COVID-19 and important to get immunized and be up to date on your immunizations. There's a lot of data that shows that our immunity wanes every time.

[24:20] after getting immunized and after natural infection. So it's really important to be up to date. Also true for M-POCs, which George didn't talk a lot about, but just there was a lot of uptake of the Jynneos vaccine back in 2022, and we're seeing many cases.

[24:40] cases, but that's really fallen off a lot. And although the number of cases has fallen off, it's never gone to zero in the US. We keep seeing clusters of MPOCs infections are really important to make sure that your patients who are at risk for MPOCs are getting the full two-dose

[25:00] And patients who are at risk are who? Patients are at risk according to the ACIP recommendation. And hold the mic a little closer. Yeah, patients who are at risk according to the ACIP recommendations are cis, gender, bi, gender, transgender men or other men who have sex with men.

[25:20] and have at least one of a variety of risk factors within the past six months that include at least one sexually transmitted infection, multiple sexual partners, and some other risk factors, or people who have sex with those individuals.

[25:40] It's actually included now in the ACIP routine adult immunization schedule. So in addition to being recommended, it's paid for by Medicare, Medicaid, and will probably be paid for by commercial health insurance as well. Let's turn back to COVID for a sec.

[26:00] Part of your role is to think about the policies that we have in an organization. And if, you know, in the last year, we've gone away from universal masking requirements, we've gone away from routine testing of people, all of our vaccine sites have gone away. So as we look at that,

[26:20] Georgia's curve where there is at least an uptick in COVID, should we be rethinking any of those decisions now or do you think they're still the correct decisions for now? Dr. Halena Gazelka So great questions. I think COVID is with us for the foreseeable future along with all of these other respiratory infections.

[26:40] we've been talking about. So whatever strategies we come up with have to be sustainable over time. And so it's always a balance of benefits and downsides to any strategies that we put into place. I think it makes sense to make the changes that we have made recently, but also be thinking forward.

[27:00] and knowing that we will see these surges appear periodically over time. So around COVID and masking, Michelle Morad, who's in the audience, and others have been working hard to create a UCSF health-wide community.

[27:20] policy to think about the benefits and the downsides, but also be proactive. And so that policy will include mandatory masking during respiratory viral season. So thinking not only about COVID-19, but also influenza and RSV and other

[27:40] community respiratory viruses. So mandatory masking probably between November and April of each year, plus mandatory masking potentially during other time periods reversing unusually high viral activity in the community. And we're trying

[28:00] We've worked hard to come up with some parameters that are reasonable. So it'll probably be based on the percentage of influenza-like illness visits in outpatient settings. That's all data that's collected through a large network of outpatient providers and available on the CDC website.

[28:20] So and we can look specifically at our region of the country So we'll be setting our parameters based on higher than anticipated levels So we will always so in the winter and flu season We can expect that it will be mandatory masking and in other parts of the year. It will be dependent on the

[28:40] level of influenza-like activity that we're seeing largely in outpatient settings. That's exactly right. That's the proposal. And how close or far are we from that now given the uptick in COVID that we're seeing? We're still under the baseline. So the premise that we had said was about if we exceeded

[29:00] one and a half standard deviations above that baseline for a sustained period of time. And I think we said two consecutive weeks. That's when we would consider reinstituting masking. So we're certainly below that now. Okay. All right, let's come back the other way. Allison, it strikes me that over the time that we're in the space of

[29:20] last however many decades, there is an infectious threat that pops up every couple years and there's a little bit of sort of some people a lot of complacency, some people a little bit of panic. And I'd say for most of them, they have not lived up to their advanced billing, maybe except for COVID, certainly, certainly except for COVID. How do you think

[29:40] sort of looking at the way we are reacting to the new, the bird flu outbreak. How different is that than what would have happened if that outbreak had happened in 2019? And do you think the fact that we're paying more attention to it now maybe is appropriate, that we were under

[30:00] We were under-emphasizing these things in the past, because it's always the risk that we're going to over-emphasize them. People are going to say, you cried wolf again, and it didn't turn out to be a big deal. Yeah, I think that coverage definitely of H5N1 is different than infectious disease coverage.

[30:20] coverage before COVID. For one thing, I think there's generally more of a widespread interest in sort of the intricacies of how we monitor infectious disease, how we're testing. And I think there's more attention as well, like in the media with regards to showing the public kind of every step of

[30:40] the way, for example, all the examples that we've talked about between, you know, animal to animal transmission, for example. You know, I don't know that in that level of detail, it would have been so widely publicized. I think we would have been talking about it probably in the infectious disease and public health world, but maybe not so much

[31:00] public interest. And certainly there is, you know, COVID fatigue and in terms of people, as you mentioned, saying, well, there's always something, you know, why should I be worried? And I think at the same time, people have seen how much of an effect a pandemic can have on your life.

[31:20] people have seen the real world impacts of needing to wear a mask, but bigger than that, the widespread mortality. Millions of people have had some symptoms of long COVID. So I think that COVID has made the threat of infections very real to people.

[31:40] that that's, there's, people are paying a little more attention with that regard. Okay, Peter, let's talk about long COVID for a second. It hasn't come up yet. We know more about it now than we did a year or two ago. And what do you, how do you see the current state of long COVID? Are there any treatments available now that we've learned?

[32:00] more about it? What do we know about the pathophysiology? Well, I think the biggest news about long COVID in the last week or so has been disappointing news from the Stanford study still called stop COVID where they tried to see if people with long COVID and the whole host of symptoms would benefit from 15 days of Pax Libid. So they did like a

[32:20] two to one randomization of people with long COVID symptoms and people with not with who weren't going to get Paxilovid and it was a small study so like 100 in one group and 15 in the other but it showed no benefit of Paxilovid for 15 days you know when looked at it a few

[32:40] weeks later. And a lot of people are disappointed because there have been anecdotal reports of success with Paxilovid. So that's kind of where we are with Longcovid. No good diagnostic tests still yet, but just a few days ago, the National Association of Medicine and

[33:00] several people at UCSF foreign debt organization, made a definition of long COVID, which is meant to be more expansive and more equitable because the whole, what was observed was that people who didn't get a diagnostic test in the beginning weren't able to call

[33:20] what they had long COVID so they weren't eligible for benefits. So right now they made it much more umbrella-like with a whole host of 2,200 symptoms. Didn't give a time when it starts, but it lasts, you know, beyond three months and it's meant to be

[33:40] the beginning of a conversation. So I think we're still in the infancy of LongCovid and probably why the Stanford study didn't work is because LongCovid is probably a bunch of different things in that syndrome and maybe some of it is viral persistence but some of it might be an overactive immune system. So I think LongCovid is going to be

[34:00] the legacy of COVID. Even today, people are still getting chronic symptoms, although there's some thought that the symptom duration for chronic symptoms is shorter. People are still getting it. Probably, I think the most recent estimates are about 7.5% right now.

[34:20] After making progress, it's kind of stalled in that number. And most people get better within a year, but it still represents a whole host of lost earning potential and disruptions to life. So when people call you, as I'm sure they do all the time and say, I have long COVID, what should I do?

[34:40] What do you tell? Well, I think it's really tough. If you live close to a center that has a multimodal, like UCSF, multidisciplinary approach, or if you're in a study, there are two things that happen. One is that you, like Lakshmi, you know, spearheads an up-and-down

[35:00] Center here at UCSF. You can get very specialized here based on your symptoms. It's very symptom management. Or you can be part of a study like recover, but those studies are pretty much mainly saturated now.

[35:20] want to have symptom management, the other thing is community. So a lot of long COVID started off because people got together online and they said, you know, I have these symptoms and it's long COVID. In fact, the National Association of Medicine purposely didn't call it PASC or something biologic sounding and they called it long COVID in

[35:40] homage to the patients who had these symptoms. So a lot of it is community support and symptom management and not a lot of therapy except you know physical therapy, lung pulmonary management, etc. So when people press you on it there's no drug

[36:00] do you recommend that they take and you think the Paxovid study is convincing enough that you would not recommend that someone take a long course at Paxovid? Yes. At this point, I probably wouldn't recommend that they do Paxovid for 15 and 8 courses. They are still ongoing studies with Paxovid for longer durations. And as we get a better

[36:20] sense of the subgroups of long COVID, I think some of these therapies might end up being beneficial but right now it's a whole hodgepodge of people and unfortunately, you know, before COVID and the ID clinic, we saw people with chronic symptoms after things like giardia and then you'll get a

[36:40] irritable, bowel-like symptoms or some random viral infection and they would have very similar symptoms and at that point you know at UCSF we'd refer them to OSHIR for symptom management or just validate their symptoms. So I think you know as clinicians and in health

[37:00] care, validation is probably a really important thing and bearing witness to it even if you do not have very specific therapy for people. Maybe one more question for you about the current state of Paxilvit in general for COVID. Do we know any more? Are you recommending it differently to people now than you would have a year or two ago? Yes, I think that

[37:20] We're evolved from recommending it to pretty much everyone who's diagnosed as positive to picking the lowest hanging fruit. There have been at least a couple of studies now showing that there's little benefit in the generally well population, mainly because we have so much built-up immunity now that.

[37:40] the additional benefit of Pax Levit is probably not that great. But in the, I think the biggest population is say somebody who's older than 65, who didn't get a recent boost in last year, I would definitely want to recommend that they take Pax Levit with somebody who can't make their own.

[38:00] antibodies to vaccination like say somebody in B-cell depleting agents or somebody with a recent trans on aldo you get into drug interactions. I think packs a little bit in the future is probably going to go you know be supplanted by other alternative antivirals like there's one

[38:20] called encytolvir that's being under FDA FASF right now that's from Japan and it doesn't have the drug interactions of pax livid and it's kind of like a time of flu where it shaves off a day, a day and a half of symptoms. So it's not that it would supplant pax livid where there's great data, but it would be an

[38:40] alternative Asia and then there's at least one other that might be impactful. But suffice it to say that there are still probably people would benefit from Paxilovid. It's not everyone, but the people who would benefit, they're not getting it in a recent VA study looking at the mortality of COVID versus influenza.

[39:00] When I looked at the number of vets who again, post-COVID, who are all eligible, it's only about 5% of the people. Okay, George, turning back to the influenza, you mentioned that people should get vaccinated. Is it the standard flu vaccine? Or does that need to be rejiggered or ragged?

[39:20] around this new, or I guess it's not even a new pathogen, it's been around for a little while, but does the regular flu vaccine work? Probably not. Probably not. But understand there are 36,000 deaths in the United States every year from seasonal influenza, so everybody should be getting flu vaccine, period.

[39:40] don't misunderstand me. So there are two neuraminidases associated with highly pathogenic avian influence. It's H5 and H7. So this is H5N1 and it has, there was a death in Mexico earlier this week from H5N2. They re-assort a lot.

[40:00] If we're going to move into that brave new world of giving people as well as animals an H5 vaccine, we're going to have to do it through cell culture because it kills eggs. 80% of the influenza vaccine in the United States is grown in eggs and they're fertilized eggs.

[40:20] They're not just picking them up at Costco. They have to have fertilized eggs and it's a pretty labor intensive thing. And by the way, you get two doses per egg. That's the other thing to remember. So you want to fix it. You had every chicken in China with eggs with probably a 90% wastage rate.

[40:40] of eggs to get. So they've moved, in China they've moved to cell-based vaccines and I think with MRNA technology we may be able to do something a lot better. We do have some cell-based vaccines, it's about 20% in the US, but if we're going to do it for H5N1 we're going to have to figure out a way to keep the system safe.

[41:00] cells, keep the cell lines alive in order to raise the organisms to then kill them so that we can then inject the antigen. So it's a tricky proposition. People are working on it right now. And the vaccines you're talking about are to inoculate, to vaccinate. The chickens are for the

[41:20] humans. Everybody. Everybody include chickens. I would start with chicken to light. I would start with dairy workers right now. People who work in these industries. This is an industrial problem, occupational health problem right now. That's where you want to start because that's going to be kind of the first line.

[41:40] line. And then you can go from there. You decide it's economically feasible to vaccinate chickens. Okay, fine. But chickens have a half life of, come on, what's the half life of a chicken? So what's the half life? Half life or a life expectancy? Same thing.

[42:00] This is epidemiology. Like 12 weeks. Okay. Chickens live for 12 weeks? Yeah, because they slaughter them. For you. For you. That's not the natural life expectancy of a chicken. It ain't much more than that, believe me. Unless there are layers and then they get coddled.

[42:20] You know, it's a big deal to do this, and it's a big expense. So if we, so the flu vaccine that we'll get in October will not be for this virus, and you don't think that it'll work very well for it. Certainly not to my knowledge. And it's not gonna cross over ruin. Yeah.

[42:40] Do you feel like the surveillance is accurate enough now that we'll know when it's breaking out in humans if there's going to be more transmission to humans, either human to human or other mammals to human? I think that, yeah, I think it could be better. It could be tighter. But I think it's, you know, the

[43:00] getting there, right? And the fact that they do big clusters around these individual cases to look for human-to-human transmission makes me feel better. Does the basic, maybe Deb, you know, someone comes in to the clinic with conjunctivitis, are they getting tested for this? Oh yeah, for sure. They are today. Is that-

[43:20] I'm talking about across the street. I'm not a down the dairy, you know, somebody works downtown and comes in with conjunctivitis. Are we going to figure this out? No, we're not going to, they're not going to get, they're not going to get tested for it. I don't. Yeah, no, no, it's such a great question and a challenging one. I totally agree with George that right now it's really

[43:40] But the folks that have exposures to animals that can be infected with H5N1, so that's mainly dairy farm workers, poultry farm workers. It is, I think, going to be important for clinicians to be thinking about this so that we can appreciate. We should be asking about occupational exposures. Yeah. Especially the

[44:00] summer months when people are coming in with influenza-like illness, people are not seeing a lot of seasonal influenza. Think about asking about animal exposures. And ask them if they keep chickens in their backyard. And chickens. While you guys are sitting there saying, well, who would do that? It's not at all uncommon.

[44:20] through. Yes, I don't have any chickens. They just don't have roosters because they make too much noise, but they're all the heads they lay. And if you suspect then just make sure that you're contacting everybody who needs to know that includes infection control and San Francisco Department of Public Health and the Microbiology Lab.

[44:40] It is an influenza A, so our diagnostic test for influenza should be positive for influenza A. Not all of our platforms do the subtyping, but our respiratory viral panels here do. So they will identify an influenza A as H1 or H3, the two regular, usual seasonal influences.

[45:00] but if typing is not possible on that specimen, and that's a red flag to think about. So it doesn't identify the H5, but it will test positive for flu and then negative for the subtypes that we test for. That's the clue that something funky might be on it. That's right. And our microbiology lab is.

[45:20] going to actively be sending those specimens to the public health laboratory for additional testing. Okay. And does Tamiflu work for this? If they're giving it. What is that? Okay. That's not the question I asked. Do we not know if it works? I think there is evidence that it works.

[45:40] The viral sequences that have been looked at so far don't have any mutations that would suggest neuroventitase inhibitor resistance. And the four cases now in the US, I think they have all been treated with also tammepure. And luckily so far, disease has been mild in those.

[46:00] Yeah. They did a diet conjunctivitis. Yeah, right. Alison, I wanted to ask you, we're talking about general vaccine hesitancy and misinformation and all that kind of stuff. And there are now discussions of other outbreaks of childhood illnesses that went away for decades. And do you have any thoughts about that?

[46:20] what the implications of the public attitudes about vaccines might mean for us. And we'll turn to George also after you're done since he's the only card-carrying pediatrician up here as well. No, it's a major issue. I mean, I think it's been an issue for a while, starting with Andrew Wakefield and this autism pseudo-link, which was later.

[46:40] disproven. But you know, I think we are seeing a resurgence of some vaccine preventable infections, measles, for example, 150 cases already this year, whereas in 2023, there were about 60 cases. And so I think measles, pertussis, other infections that

[47:00] maybe we're not used to thinking about or seeing a whole lot necessarily, at least as an adult doc. So you can let me know what you guys see on the feed side. But I think it's trickling over to the public in terms of vaccine hesitancy for a variety of infections.

[47:20] I think the public's been really lucky before COVID, the threat of infectious diseases to a lot of people was sort of abstract because we're very lucky to live in a time where most kids don't get measles and we're not dying from infectious diseases as well.

[47:40] much. But I think that unfortunately that may be something that we do start to see if enough people don't take their vaccines.

[48:00] big buildup of susceptible people. And for those of us who are old enough, from 1988 to 1990, there were 18,000 cases of measles in California, which was a buildup of this cohort of kids, preschool, preschool kids, who went on to get it.

[48:20] And they also, there's also outbreaks of congenital rubella syndrome buried in that because if you get MMR, if you get measles, mumps of rubella together. But I would like, and so everybody knows about measles. Well, I've seen probably thousands of cases of measles, but everybody knows about measles. It's a nasty thing to have as an adult, by the way.

[48:40] What you may not realize is that pertussis is a real issue. Pertussis fell about threefold during the COVID epidemic, mostly because people weren't mixing as much. And now it's come back up to the pre-epidemic level. So it's three times higher than it's been. It's embedded. You can get

[49:00] But you can also get DTAP, AP means a cellular protussis vaccine, one with many fewer complications. And so as people come, as you see your adult patients, make sure they get a protussis vaccine as well. It's something that's very relevant.

[49:20] preventable, but it's a nasty disease and you know if you want to come up afterwards I can do the pertussis cough for you you know followed by running off to vomit. You know it's good to post-tussive amistice is a huge big part of it. And they should get it if they haven't gotten it since childhood or when what's okay. And anyone who will be in contact with

[49:40] incense, right? Get read back. Right. Let's open it up to any questions or comments you have. Yeah, and say who you are. I think I'll see. Katja says, there are questions for the panel. I'm pretty scared about what the potential of the avian's loop, a potential for an epidemic.

[50:00] if there are enough mutations that it's going to jump, you know, well from cows to humans. But how do you see that as playing out? What do you think you should think it is? I think so. I have others, Chairman. Well, I share your concern that it probably, the

[50:20] writing is on the wall, I think at some point it will become go into humans. The last four, and George will probably correct me with this, but the last four influenza pandemics have all have avian flu origins. But when I compare avian flu and where we are to where we were in COVID, I think we're

[50:40] ahead of the curve in some ways, which is we have a test, we have four drugs, including Tamiflu. We have vaccines and the feds actually deployed 4.8 million vaccines already on the production line, other parts of Europe as well. And they're at least

[51:00] these two candidate real vaccines and then the mRNA, people Pfizer and Moderna said that they can like tinker with it and make something in two months if needed. So we have the elements, the cause for concern right now for me and one HVU comes eventually.

[51:20] So H5N1 comes eventually to humans is that we have so much politics-infusing science now. We have people who are fed up. We have people who are not going to go back to, I think Oklahoma had some law saying they're not going to follow any WHO policies.

[51:40] So that is really the scary part, the fact that, which is beneficial in some sense, that public health is local, but also the CDC doesn't have a, you know, an arm where they can mandate things unless it's an emergency. So I think those are some of the pros and cons of where we're going.

[52:00] I think when it jumped from wild birds to sea lions, I think there were several, like a dozen mutations that happened and I think that will continue. Anybody want to add anything? Yeah sure, I'll just add, you know, looking even beyond H5N1 and sort of like these.

[52:20] immediate future thinking large scale and you know if it's not h5n1 it'll be some other virus that mutates and I think thinking in terms of big picture and problems that are really hard to solve but things like factory farming where you've got a lot of animals and people in close contact it sort of

[52:40] makes it inevitable that you'll get new viruses mutating. And so, certainly a problem that's probably beyond the scope of the clinical environment, but I think just helpful to think about how we can be less reactionary in some ways and moving towards a future where we're not breeding these new infectious.

[53:00] by nature of the foods that we're eating. Georgia, do you want to add something? No, I think Peter captured it. Other, yeah. You went right for the cardiology. So I myself do not have chickens in my backyard, but my neighbor does.

[53:20] And while the clicking and clucking is kind of charming, I know that they raise the zonin in chickens. I've seen them. These are spectacular birds. I think they raise them to mate and reproduce. But lately we've seen flies in our vacuum on them. And I'm a little concerned. Am I at risk?

[53:40] No, I would say you're not. If they start to die and they call you to come and stuff, they take them. I would not do that. You have a nuclear ideology studies on them, I would not do that. So we actually do have cases where for cockfighting, where people put the whole beak in their mouth and suck the blood out of the nostrils. Talk about that.

[54:00] That's a species crossover. I don't care. Don't do that. All right. Great. Any other questions here? Let me see what we have online. All right. A question about other products that come from...

[54:20] from animals, for example, raw meat or other kinds of things. Anything else that might be risky other than unpasteurized milk? I would say not. I mean, we obviously have, we don't like people eating raw eggs. We don't eat like

[54:40] people cutting up chickens on the salad board and then cutting the salad up afterwards. We don't like you under cooking the dressing stuffed in the turkey. But those are all really salmonella more than anything else. But the precautions that are in place should take care of pretty much everything, I would say. And it's specifically, you know, raw

[55:00] I mean, sorry, properly handled in book poultry is said to be safe. Okay, Deb, did you want to add something? Just to add that this is a really good example for what the One Health approach is so important. So it's public health, working with veterinary scientists, working with environmental scientists.

[55:20] USDA has been doing a lot of testing of beef and they have at least their results so far can confirm that if you cook beef enough, it should inactivate any H5N1. So there are plenty of folks thinking about other routes of transmission.

[55:40] of a cow, but it wasn't a cattle. It was like a dairy cow that had a gauge 5N1 in the meat. But again, it was a fragr

[56:00] For H5N1, I mean, one might change it for other reasons. But yeah. And George, you've mentioned that sort of in the cannibals, it's fecal-oral. And I guess I didn't understand that. I sort of thought flu was just respiratory. And you're saying that in some kinds of flu, it's not. And then if it mutates, it cannibals.

[56:20] can become? In aquatic birds, it's transmitted through fecal oral. So they all go, the reason we have it here and it's spread from Asia, is that all the ducks are swans and geese from Asia fly north for the summer to Siberia and Alaska. And on the western flyway, all our

[56:40] ducks and geese flying north to these places. And they land in the same lakes and there is fecal oral transmission in those. That's how those animals get it. So what I'm saying is that that's an established route of transmission. For human to human transmissions,

[57:00] clearly respiratory. Nobody's saying anything else. We don't know what we don't know. Yeah. I mean, is there something about the virus that's different or something about why would a pathogen that in a human needs to find your nasal mucosa? And we always said, for example, you're not going to get COVID from eating something. Why would it

[57:20] be fecal oral in a given species and respiratory in a different one or is that just too hard a question? We just don't know. Should I explain the anatomy of birds to you? No, not in two minutes, but is that it? The anatomy of birds is just different. It's just different. They have different types. There's different tropism for different cell types and it is what it is.

[57:40] Alright, I'll buy that. Peter, there's a question online about metformin and either treating COVID or long COVID. Is there anything new on that? There have been some small studies looking at metformin, but I don't think it's trickled down into practice yet. I mean, that it's beneficial.

[58:00] in COVID actually, but it's low cost, et cetera. But there are other alternatives where I think it hasn't really been put into guidelines or anything like that. So is there anybody today that you recommend Metformin?

[58:20] and if they have acute, if they have a case of COVID. No, I wouldn't at this point, although there's been at least one large study suggesting that it might work. And if they're over 65 and they can't take packs of it because of a drug interaction, let's say, what's your next choice? I would think about three days of remdesivir if they are really going to be susceptible to serious disease.

[58:40] but they would have to have access to an infusion clinic for three once-daily doses. But that is very effective on the same level as Paxiloban. It does not have drug interactions. And you actually have a seven-day window period when the study should have benefit, as opposed to five days for Paxiloban.

[59:00] And maybe last question, anything new that I know the guidelines changed about the period of isolation if you have COVID, either Peter or Debbie or anybody want to take on sort of what the current guidelines say and what you think is correct. Those may not be the same thing. So the guidelines are different for the

[59:20] public at large and for the healthcare setting. I think the thought about in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in the in in the in the in in the in in the in in the in in the in in the in in the in in in the in in in the in in in the in in in in the in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in

[59:40] do people think that now or thought that? Have been thinking that for some time now. The changes to the public recommendations, again, it's the balance of benefits and risks in getting people to be able to go back into public and work earlier than previous recommendations.

[01:00:00] care setting, we are still, for example, isolating patients for at least 10 days, most patients for 10 days. And it could be longer for some immunocompromised patients. And for a healthcare worker who gets COVID, what are the rules for them? So the current rules for that at UCSF Health are

[01:00:20] If it's been at least five days, your symptoms are getting better. You've been afebrile for at least 24 hours without the use of antipyretic agents. And if you do a COVID antigen test at that point and you're negative, you can come back to work. But the recommendation is to mask until you're out to that 10-day time period.

[01:00:40] reasonable. I guess you probably invented that. So I think it's reasonable. And again, everything is a balance. Any other comments before we quit? All right. Thank you all. It's a terrific session. And stay safe for everyone. Enjoy the summer.

[01:01:00] You