Influenza | Podcast

Welcome back to the Ninja Nerd podcast. Today we're talking all about influenza. The flu, the bird flu, the the swine flu. — Yeah. All those different flu. — Scary. — Yeah, it is scary. Honestly, influenza. I mean, I don't know. You ever had the flu? — Oh, yeah. Yeah, definitely. Yep. I get the flu vaccine every year, so I don't know if it does anything. — Well, we're going to talk about it today. All right. But yeah, I think I had the flu once and it was pretty terrible. I mean, obviously the flu can look variable for different people and it could be like a lot more upper respiratory stuff involvement and yeah, sometimes you get those unfortunate individuals who get that lower respiratory tract involvement and that's where I get really scared is the primary like influenza pneumonia. But yeah, influenza is pretty it can be a pretty scary condition. I think it's worth kind of like having a little discussion about. — All right. Well, our approach really starts with understanding the flu's machinery. — Okay. So influenza is an envelope virus from the ortho mixover verid family. Did I get that right? — Yeah, you got it. — Okay. — So what I want to know is a little bit more about maybe the ideology and some underlying things about what makes influenza so scary. — Okay. So influenza like you said it's a part of the orthox verde family and it's an envelope virus like you said which has a like a lipid billayer and then what really is interesting about this is the types of surface glyoproteins it has. So that's something called hemoglutin which is essentially it's a glycoprotein that allows for us it allows the virus to attach to our epithelial cells via what's called scialic acid that they express. And then there's another one called nuramidase and basically whenever the virus gets into the cell replicates and it gets ready to butt off and make a new virus you need the nuramidase to kind of cleave it free to get that virus to come out of that infected epithelial cell and go to the next one to the next one. And so that's kind of the two really big proteins that are really critical to that structure of influenza. Influenza also has it's an RNA. So it's a negative sense RNA strand and it comes with eight different segments on it. And so what's interesting about that is that in people who have influenza infections whenever you get infected by it sometimes what can happen is it can have small little point mutations that occur in the RNA whenever it's getting red to make different types of hemoglutin or amidase proteins to make a new virus. Sometimes those small point mutations that occur in the RNA can lead to a small kind of like substitution or deletion in an amino acid on the hemoglutin and amidase which makes it just a little bit different and that's called antigenic drift. So that's pretty common happens like basically whenever you get small little epidemics or outbreaks in the community of an influenza infection. — Sounds like something out of the Fast and Furious — I don't know antigenic drip. — Yeah. So that that's something I definitely would see epidemics that could be like a little outbreak. It's just kind of like a small outbreak due to the virus just changing a small little piece on its hemoglutin and ramenase which is just a little bit different from the current circulating virus and so it can cause like a small little kind of change in outbreak. The one that you got to be worried about influenza is called antigenic shift and we saw this a lot with co 19 too whenever you kind of change up the different variants but it's the same concept with influenza. In certain scenarios, you have the common influenza A strains, which is H1N1. That's the most common. And there's another one called H3N2. And let's say that a pig, usually this is like the pretty much this the type of let's just say host where viruses, different types of like a bird, like a aven type of a flu and a human flu, let's say H3N2 and a bird flu, H5N1, they both infect a pig epithelial cells. usually their intestines because they have different receptors that can express to bind onto those. We don't necessarily have those like a pig cells would. And so what happens is two virus can get into that pig cell. Then that kind of assortment of different hemoglutininses and differences in RNA can get reassorted and then you can essentially package up a completely new like Frankenstein monster like virus. So it's a new novel influenza and because of that we've never humans have never been exposed to that type of virus before. So you have no immunity against it. You have no way of protection against it. There's no vaccine against that one yet. And so that's like an epidemiologist or microbiologist nightmare because you just created a possible pandemic. And so that's what we saw with like SARS KV2 with COVID 19. So it's a similar concept can happen with you know influenza. That's why you got things like the swine flu, the bird flu, the Spanish flu, things like that. So they're global pandemics that can occur and that's one of the things that makes I'd say influenza pretty dangerous and again in general viruses but especially these is it can undergo that antigenic shifting process and that puts a high risk for pandemic outbreaks. — All right so we know the enemy we've laid down the foundation let's get into some cases. — Okay we have a 68-year-old female with a history of COPD and heart failure. She comes into the clinic with a sudden fever, extreme malaise and muscle aches. What are you thinking here right away? — So it sounds like influenza, right?

Because influenza whenever it causes its particular symptoms, it damages primarily the cells of the upper respiratory tract. It's going to prefer that more. So you can get things like rhinocyusitis, fngitis, you can get things like laryngitis, but you also get systemic inflammation. And so what that means is you get kind of cytoines that cause fever, malaise, and cause myalgas. And so this person has fever, malaise, myalgas. Did it say if they had any upper respiratory tract symptoms? — So far, no. But I think the biggest issue is that like we've talked about, we've had the flu before, right? Yeah. — It's still bad. However, with this 68-year-old female, all right, so there's age and then you have the history of COPD and heart failure. — So now we're talking about that patient highrisisk population. — Exactly. — Yeah. And I think that's one of the big concerns here is that regardless of the way that these patients present, which is if they have upper respiratory tract involvement or lower maybe just a little bit more of the systemic findings, this is a patient population that if they did continue to have this infection occur or if it actually let's say that it did actually cause involvement of the low respiratory tract and individuals who have an impaired immune response and so HIV, AIDS, they're on imunosuppressive medications, they got a recent transplant. They're on transplant, you know, rejection meds. They're pregnant — or they're extremes of age, less than five or greater than equal to 65 years of age, which this one is extreme of age. They have more of an amunosineessence, which is kind of like a they got some sleepy immune system cells. They're not really good at this point of being able to fight off potential infections as easily as maybe young dapper individual like yourself, right? — So, because of that, they just have a little bit more of an impaired response. And then on top of that, co-orbidities puts you at high risk of exacerbations and overall mortality and morbidity. So if a person has someone like COPD, asthma, one of the downsides about that is when you get influenza infection, it can cause an exacerbation of your underlying disease. And so you can get COPD, asthma exacerbations. If you have something like coronary artery disease, CHF, it could cause potentially, especially if you got a really good influenza pneumonia, it can cause hypoxmia, cytoine surges. That can cause a lot of stress on the heart, especially the myioardium. It can probably push you into what's called demand eskemia. So you can get unstable anga. You can even get in stemmies and in certain scenarios you could stress the heart out so much that you could put a person who has underlying heart failure into a decompensated state. And so that's the risk. And so this patient is at risk for an impaired immune response being that they're in extreme of age and on top of that they're at high risk for an exacerbation of their underlying disease because they have CHF. Right. Yes. So because of that, this is a high-risisk population that if they got influenza, they could get really, really sick. They could end up with complications, high risk potentially of mortality. — What's your immediate next step then for this patient? — Oh, with this patient, you know, I would want to confirm first that they have influenza because they're a high-risisk population. So we would do like a nasal fingial swab and then I would send that off to the best test is an RT PCR so reverse transcription PCR and to see if it comes back positive for the particular strain and oftentimes more often than not it's influenza A that's going to be the more common one it can cause more severe cases you're more at risk for antigenic drift and shift from that type less as common as it would be influenza B or C. So that's what I would do first and then from that I don't care how long they've been symptomatic. This is a high-risisk patient and so with that if it comes back positive I'm going to start them regardless on something called well there's two different options. One is bloxave which is kind of like it inhibits the RNA transcription process of that virus or I'll give a nuramodase inhibitor which is called omavir also known as tamlu. a common one that people know and I would give that one regardless as well because what it's going to do is it's going to prevent potentially the virus from replicating as much and causing the possibility of influenza complications where they can get severe influenza and so and cause exacerbations of their underlying chronic diseases. So that's what I would do with this patient. Test them. If they come back positive, I'd start them on antiviral agents. — Okay. Well, she is positive. The influenza PCR comes back positive. But there's one thing I want to add on here. Now, let's say she's positive, but what you're noticing is her breathing is getting much worse. So, she's having increased work of breathing. It just looks like she's using accessory muscles. It's not looking like she's really laboring. — Okay. — How do we differentiate if the flu has just wrecked her lungs directly? Yeah. — Or if there's some sort of bacteria that's joined the party. — That's a good question. So yeah, because patients who have impaired immune responses like extremes of age and on top of that have underlying diseases like CHF, things like that, again, you can get disease exacerbation, but they're at high risk for primary like influenza pneumonia or secondary bacterial pneumonia. The difference is that usually with primary influenza pneumonia, it's a continuous path. So they present and they continue to get worse and worse and usually they have an acute worsening where they end up like hypoxmic sometimes cyanotic

respiratory distress. So they can have their typnic their disnic they're having nasal retraction or nasal flaring intercostal retractions etc. They just don't look great or they could have what's called a bifphasic illness. So they get the virus like they did. They have fever, malaise, myalgasalgas, maybe some congestion, a cough, sore throat and then all of a sudden they get better and then after that they get acutely worse and they start having a productive cough, a high fever again. They have signs of consolidation and abnormal oscultation on their exam. Their white blood cell counts really high. You get a chest X-ray and you would compare the two. So if I looked at a chest X-ray for like a primary influenza pneumonia for the most part it's diffuse infiltrates throughout the lungs because it's almost like ARS. They get sick really quick. It's kind of like COVID like a severe COVID infection. Some same thing severe influenza can cause ARDS. And then secondary bacterial pneumonia would cause more of like a consolidation and like a lobe. So it behaves like a community acquired bacterial pneumonia. So it' be more of a consolidated portion of the lung. Sometimes it can cavitate because they're at high risk. especially post flu you can get MRSA infections and so that can cavitate and get really nasty. So that's what I would expect the differences between the two. This one doesn't seem like a bifphasic one. It seems like they're just continuously progressing. If I had any concerns, I'd get a chest X-ray, compare the two. I already have the influenza PCR and if I had any kind of concern, I could even get a sputum culture on this patient just to confirm. But generally with this one, I'm already probably going to put them on antivirals, maybe send off the sputum culture, get a chest X-ray, keep an eye on them, and then because this patient could turn the corner regardless of each one, which one it is, they can get sick pretty good. — Yeah. And like you said, for this patient, she didn't really have any resolution of symptoms, it's really only gotten worse. — Yeah. Seems like it's more like influen like primary influenza pneumonia more likely. — And then that chest X-ray, like you said, you would just see bilateral infiltrates. It'd be pretty obvious cuz it almost looks like that ARS like picture. — Yep. Yeah. Yeah, it look like the ARS like picture. They get acutely sick. They'd be hypoxmic. So, they probably have like a low PF ratio, diffuse bilateral white out. It'd be an acute onset. And then again, ARDS, you're always supposed to rule out that it's not a cardiogenic source. It could actually be kind of hard in this patient because they have underlying CHF, but either way, I'd say that this given the clinical picture, I'd be concerned about more of an ARDS picture. — Okay. And then the antiviral of choice, you did talk about two in particular. — Yeah. So, olemover would probably be better for this person. Okay. just because it's it's definitely more preferred for those complicated cases hospitalized patients probably higher risk populations as well but that's neurodase inhibitors like oelmavir another one is going to be bloxave and bloxave is it can be given I'd say it's probably less s less of its suggestion is in these complicated patients it's more we prefer the oelmavir in the complicated patients could be considered but I say that probably be one that I'd be more likely to do in an uncomplicated influenza But what's those mechanisms of action? Are they what are they inhibiting those two drugs? — Oh yes. So omavir is inhibiting nuramidase which is basically going to prevent the virus from being released from the epithelial cell because the virus gets into the cell already. It's replicated. It's made a new virus and it's getting ready to butt off of that epithelial cell and go to the next cell. But you what happens is nuramidase is supposed to kind of cut it free. It releases like the leash and then it says okay virus go ahead and you can go off to the next cell and damage the next cell the next cell. In this scenario, you don't allow for that neurodedease to cleave the leash and so you keep it there and so it can't actually spread and cause further tissue damage and that's how you may reduce the severity of the disease. — How about doesn't allow for the RNA. So once the virus gets into the cell, it pushes the RNA into the nucleus and then it uses enzymes like RNA dependent RNA polymerase to make more of those RNA strands and more mRNA to make more proteins and to assemble a new virus that has all this RNA and all these proteins. It inhibits the RNA dependent RNA polymerase and so it won't be able to make new mRNA, make new singlestranded RNA and you can't make like a theoretically a newer virus. And so that sounds like really attractive. And again, I think that that's one of those that we're starting to see some slight resistance in that one. Not as much in ocelover, but again, I think usually your first line is going to be oelmavir as compared to the blox. — And how is that prescribed? Is this a one-time thing? Is it given over multiple days? — Oh, usually oelmover is it's probably like 5 days. Okay. — And that's probably one of the attractions of Bloxer is it's a one-time dose. — Oh, yeah. I would like that. — I can understand why. — Yeah. So that's a one-time dose, but again, I think that we prefer that more in the uncomplicated influenza cases. And then the tamlu or oel tamavir is probably going to be more in the complicated cases. So the se severe infection, hospitalized, high risk for complication — and tamlu is the one I've always heard of. If anyone's taking an antiviral, it's always that one. — Yeah, that's probably the most commonly utilized one. There's less resistance to it and things of that nature. But yeah, that's that's what I would do for this patient for sure.

— Okay. Well, let's do a couple rounds. Oh, also I would send I'd have sorry with ours cases like this. I'd have them admitted. — Yeah, I would hope you don't just say, "Hey, hit the — Yeah, I wouldn't like I just want to preface that. I wouldn't say, "All right, here's some oel tem. Go ahead and get out of here. " I they're getting admitted. They're going to be monitored because they're probably going to need airway support. They may need things like high flow nasal canula. They may need to be intubated. I'm going to need to watch their blood pressure. continuously keep an eye on their overall labs and hemodynamics. And so this is a patient that I'm not going to send home with Taml flu. I'm going to likely admit them to the hospital probably depending upon the severity of the ward or the ICU. — Yeah. It's a very important distinction. — Yeah. Y — Now before we get into some other topics here, I want to go through just some rapid fire complications. I'm going to give you a oneliner and give me an idea of what complication that's happening. Whether it's common or rare, we'll get into that. — Okay. — So here's the first one. We have a 10-year-old. probably already gives it away right there. But you have a 10-year-old that takes aspirin for flu-l like symptoms. — Ry syndrome. — There it is. — He couldn't wait. He couldn't contain himself. But yeah, they take this for the flu-l like symptoms, develops altered mental status and hpatomegally. Yeah. — So talk a little bit about ry syndrome. — Ry syndrome is pretty uncommon. However, in young individuals less than 19, they get a viral infection. It kind of puts a little bit of a hit on the liver and then you give them aspirin. That's the double hit. So, it's kind of like a double hit or a two-h hit kind of like pro problem where the virus may give a little injury to the liver. You give the aspirin and that aspirin basically what it does is it kind of shuts down their mitochondria and so then they can't produce ATP. If you can't produce ATP that leads to possible decreases in function in the liver cells. So, the apatocytes die. If the apatocytes die, they can't perform their functions like making coagulation proteins. They can't convert ammonia into ura. And so ammonia levels rise. The ammonia when it gets into the blood, it loves the brother. It loves the brain. So it can cause cerebral edema that can increase your intraanial pressure. That leads to the altermentation that can lead to seizures. worst case scenario you can even herniate. And then the lack of coagulation proteins. It may cause coagulopathies. But oftent times they have things like a prolonged PT, INR, PTT. And if you check their LFTs, which is the marker of liver injury, they probably have a bump in their A and ALT. So, those would all be things that you would see in something like Ry syndrome. — Okay. We have we now have a 30-year-old that gets the flu and 3 weeks later she develops — GBS. This guy. — Yep. You got it. — So, yes, the this person 3 weeks later develops ascending symmetric flaccid paralysis. — Why is it Gonet syndrome? — Yeah. So, when we talked about the the 3-week is what gave it away, but like post flu, it's not common. Like you said, these are kind of rarities. — Yeah. — I mean, obviously, most parents should know not to give their young individual aspirin if they had a viral infection. Again, not trying to be mean, but that should be something that's very wellnown. Do not give a person who has a viral infection or signs of a viral infection aspirin because of the ry syndrome. Gonra syndrome, it is pretty rare. You see this more with campalobacttor jugeni infections, which is kind of like a gastroenterthitis. You can see that happen. But in certain size scenarios like if you got like a flu shot or if you got influenza, especially if it's a severe case, you can develop molecular mimicry. You produce antibodies against some of the proteins that are on the influenza virus, but it goes and attacks other tissues and it attacks the myelin sheets of your peripheral nerves, demyelinates them. You lose that kind of like sending that signal basically the reduction in action potentials. And so obviously you can't stimulate the muscle as much and that's when you get the ascending kind of like symmetric flaccid paralysis and a reflexive but that's usually happens two to four weeks after flu or vaccines but again rare. — All right last one. Let me let me finish this one. — Okay. — We got a patient with massive muscle pain and they're pissing Coca-Cola. — Yeah. That so that sounds like a rabdo case. The severe muscle pain. So, I'll preface this. Influenza does have myot like tropic kind of activities where it can attack muscle tissue like skeletal muscle tissue. — Just like our patient, she had a lot of muscle aches. — Yeah. And so, you can get skeletal muscle damage and you can get cardiac muscle damage. I'd say it's not as common to cause like as severe of a degree of like myocarditis or, you know, myioitis of your skeletal muscles, but it can happen. The other thing that probably contributes to it beside it being a myotropic is it also is inflammatory cytoines. When that infection occurs in influenza you get a cytoine surge interlucan one interlucan 6 but the big one is TNF alpha and TNF alpha really helps to attack the muscle sometimes and put into a catabolic state. It can cause meioitis and sometimes if you get enough inflammation of the muscle it could pop open if you wanted the muscle cells they could burst open that's the lis part and then start spilling out certain types of intracellular contents the destruction

of the tissue is the rabdo portion the rabdomiolyis and that's going to cause pain usually that pain is not like my it's not like oh my muscles hurt it's like ah my muscles really hurt yeah — it's pain out of proportion and so that would be one thing but if they start peeing Coca-Cola, then I'm concerned that they destroyed so much of their muscle that the myoglobin is leaking into their urine. And then on top of that, the downside about that is that when it damages the kidney tubules, it can cause acute kidney injuries. And so they could actually end up with an AKI. So yeah, Rabbdo, you would see pain out of proportion, increased CK, and potentially dark urine due to the myoglobin in the urine. And they're at high risk of acute kidney injury in those scenarios. Again, less common. I'd see that in other kinds of conditions like more like trauma or certain other types of drugs or seizures then I'd probably see that more in like a viral case but — yeah and honestly I hit the exam pearls there just the pretty rare ones but questions you'll see — yeah we talked about treatment already so I'm going to move past that but prevention is key so talk to me a little bit about the flu vaccine why it's so important and then I want to know about the three types which are an in an inactivated vaccine a live attenuated ated vaccine and re combinant vaccine. — Okay. So, yeah, in people who have, you know, we get obviously there's everybody gets a flu shot for the most part annually, right? And when you get this, it's obviously supposed to help you to generate a passive immunity. It's not active. It's a passive immunity, which is essentially you're kind of trying to get your immune system to you're coaxing it a little bit to produce maybe antibodies and memory cells like memory B cells, memory T cells, so that if you ever get exposed to that virus or pathogen in the future, you have some immunity to be able to act against it. And so there's different ways that you can do that. You can give basically dead versions of it. So all you're really giving them is a dead virus with the antigens. So the in inactivated one — inactivated and even recombinant. So the recombinant vaccine is just a little bit special. So and I'll explain the difference between that. So the inactivated version, the recombinant version, they're basically giving them a dead virus with just the antigens, the hemoglutin, the namidase, stuff like that. That's what you're really trying to target with your antibodies and immune cells. And so those are both injections. Usually whenever you get yours, it's IM. All right. So they give you an intramuscular injection. That antigen gets injected into the muscle. lymphocytes, macrofasages all come to that area where the antigens are because it's viewed as foreign. That basically triggers an immune response. That immune response leads to two things. One is you want to be able to remember that antigen in the future. So you pump out some memory cells, memory B cells, memory T cells, particularly the T- helpper type. And then on top of that, you want to trigger plasma cells to make antibodies so that they could also recognize that antigen ever in the future. And so you make some IGG antibodies. So that's going to happen in both of them. The difference between the two is that inactivated we make it in like it's I think it's chicken eggs. I think we use like chicken eggs or something like that to basically make them. And whenever you do that within these eggs they the there's always the chances of chance of mutations. So mutations just occur naturally as this is replicating inside of the chicken egg. And so what happens is in the inactivated version you can get small little changes in the hemoglutin and the nuraminadase that let's say that the current strain that you're trying to protect and make a vaccine is it's against this very specific type of circulating strain right now that it has this hemoglutin and this nuramidase on its surface. You then want that to be replicated in this chicken egg. But along the process is getting replicated in the chicken egg, it gets a small little mutation. That mutation may cause you to make certain types of antigens that are a tiny just a little bit different than the original strain that's circulating. The downside about that is that now when you give them the antigens to that person, that patient, they're going to make antibodies against that. And if it's just a tiny bit different, it may reduce the efficacy of that vaccine. So that's why inactivated influenza vaccines technically can have especially in like really bad years, they might only be like 30 to 40% effective. And it's because of that concept. Whereas the re combinant, we don't make it in like the chicken eggs. We make it I don't know what kind of insect, but I think it's like use insect cells. — And so they they replicate it in the insect cell and there's almost no mutations. — Wow. So you get like a 100% genetic match whereas in the inactivated version in a bad year you may only get like a 30 to 40% genetic match. So the recumbent it's a 100% match whereas the an inactivated influenza vaccine is more of like a it it's kind of depends on the actual year. — Now for the inactivated vaccine the standard dose is for anyone greater than or equal to 6 months old. But yeah if they're greater than or equal to 65 they're not getting the standard dose. Correct. — No because they're high risk. So what are they getting then? — You could do two you could do three

things. You could give them the 100% genetic match, the re combinant vaccine. You can give them a super high dose of the inactivated vaccine. It's usually four times higher than the standard dose. — Oh wow. — Or you can give them it's like there's something called an adgiant. I don't know what exactly what the adgiant is in it, but basically think about an adgivant as it binds to the inactivated vaccine like antigens and it makes it a little bit more immunogenic. So you get a more enhanced immune response against it. So there's three options. One is you can give them four times the standard inactivated dose. You can add an adgiant onto that inactivated dose or you can give them re combinant vac recombination vaccine. — But you would not give the live attenuated vaccine. — No, not not to these patients. — Granny will be killed, — right? She'd be it's probably it might be harder. she might not generate the best response against it. — Just like someone that maybe has underlying COPD, asthma, immuno compromised, right? — That's what I would say is that this the reason why I wouldn't ever give a live attent because a live attenuated one, what's different about that one is that one is you're giving them it's actually a virus. It's not just the antigens. You're giving them the actual virus — that has the envelope. It has the nuclear machinery. It has the proteins. You just weakened it. You crippled it a little bit. So, it's not going to be able to cause significant damage unless — yeah, — you give it to a person who doesn't have that immune vigor, that response that's capable. And so, I would never give this to a pregnant patient. I'd an imuno compromised patient. And the only reason we don't give it to COPD and asthma patients is because it's inhaled. And there's something inside of that. I don't know exactly what it is, but it can cause bronco spasm. — Oh, wow. — Actually, you know what it might be? It might just be because it's a virus. it can actually cause a little bit of destruction of the epithelial cells and it might be enough to kind of put them into an exacerbation to cause bronco spasm. So I just know that that's one thing we don't give it in those because they're higher risk for bronco spasm because this is inhaled. — Sure. — So that's the difference between the inactivated and the recombinant. Those are IM. The live attenuated one is inhaled. And so we don't want to give to someone who doesn't have the immune response or capable of generating the immune response. And we don't want to give something to somebody who if I give it to them and it causes bronco spasm it can exacerbate their underlying disease condition. The benefit of this drug if you did give it is it gives you not just the memory B cells and the memory T cells and the IGG antibbody response but you actually it's I don't know I think this is cool the concept behind is when you inhale it you have to generate mucosal immunity and so you actually generate IgA antibodies against it that get that stay in the mucosa. So whenever influenza is taken in, it's usually by respiratory droplets. And if it gets into that area of the tissue in the respiratory tract, you're going to have IgA antibodies to attack it. If it gets past that through the tissue cells, you have IGG antibodies against it. You have memory T- cells and B cells against it. And then one other thing is it's a live virus. So it infects your cells. When you infect a cell, infected cells and cancer cells express that piece of the antigen on their MHC1 complex and that brings in cytotoxic tea cells. So now you got a mucosal immunity with the IgA. You break through, you got IGG antibodies, you got memory T- cells and B cells. And then on top of that, I get cytotoxic tea cells to help me. So theoretically, it could be a more profound immune response to protect you. But you should have an immune system that's capable of it. And then on top of that, don't have any underlying bronospastic or airway reactive diseases that predispose you to it. — All right. I have one more thing for you until we wrap this episode up. We have part five here. It's talking about the granny chemilaxis scenario. — Ah, — all right. So, let's say granny is 85 years old. — She lives in a nursing home. — Okay. — The patient in the bed next to her just tested positive for the flu. No, — Granny got her highd dose vaccine. Let's say she did the four times the normal dose. — Okay, — but she literally just got the shot five days ago. — Is Granny going to make it? — Granny may not make it. You never know, right? But one of the downsides about — this scenario is this is called an in it's I think they call it the institutional outbreak rule. So when you have someone who's high-risisk like a nursing home, the residents like this one, — maybe she has underlying diseases. She's already in a high-risisk population. — Yep. — She got vaccinated. But it often times, if I remember correctly, it may take you at least around two weeks. — Yeah. — For the vaccine to actually give you that immunity. — Yeah. It's been too soon. And so theoretically you have a high-risisk patient and you may not have the capable immunity if they get exposed which she has been. — Yeah. — So in that scenario I will preface this chemoprilaxis is not routinely recommended according to up-to-date. However it can be considered in scenarios like this. If I have an

institutional outbreak, I have one person high risk and an entire population is high risk and especially if they either haven't gotten vaccinated or they got vaccinated less than two weeks ago, I'm probably going to do chemopilaxis for the entire nursing facility. — Oh wow. — Yeah. So that's one because again you take a chance of it being it's it can be spread by respiratory droplets and by fomite. So if they go and touch something and they touch some part of the respiratory tract. — So the whole nursing home is getting tamlu. Yeah. Yeah. And you usually do it probably until you like it might be up until you get to that two week mark where the vaccine and again I this is kind of like it's controversial. Uh it's not routinely recommended according to some guidelines but in certain scenarios like this — you might do it. — So essentially you're really just bridging the gap until you get that appropriate immune response from the vaccine. — Yeah. That's really all it is. It's theoretically it's the bridge. Yeah. That's cool. — Yeah. Because at that point if they have been in infected you're giving them an antiviral agent to reduce the actual further damage. reduce the symptom duration, reduce the overall risk of it causing a severe influenza infection. So, — see, Granny's going to be just fine. — Granny might be okay. — She's going to be good. That's all I had. — All right. Well, hey, man. I hope you guys like this podcast on influenza. It was fun to make. And I hope that out of this you feel, I don't know, confident. I think that's the overall goal of these is just to help you to build up a thought process, how to analyze things, how to be able to think about things about a given disease. And so, I hope that you feel good about it. confident and if you guys do hit the like button, comment down in the comment section, subscribe. Those of you who guys are listening on all of our audio platforms, again, help us, you know, let other people know. I hope that we're helping you. Maybe bless someone else and help them if possible. All right, I love you guys. I thank you guys. And as always, until next time.