WEBVTT - Ep 110 Influenza, Take 2: Fowl Play 0:00:02.320 --> 0:00:05.960 H five N one is an interloper, an unrefined newcomer, 0:00:06.280 --> 0:00:10.080 all fury without the seasoning of age in human cells. 0:00:10.080 --> 0:00:13.080 It has discovered a fresh target, and it pursues its 0:00:13.119 --> 0:00:17.680 prey deep into the body, penetrating much farther than ordinary flu. 0:00:18.400 --> 0:00:22.200 This novel virus advances on the lungs themselves, attacking the 0:00:22.200 --> 0:00:25.079 branches of the bronchial tree and the myriad little buds 0:00:25.120 --> 0:00:28.600 on their tips called alveoli, where the life sustaining task 0:00:28.720 --> 0:00:33.320 of exchanging carbon dioxide for oxygen occurs. The pathogen infects 0:00:33.320 --> 0:00:36.320 the coating of mucus that protects the membranes of the lungs. 0:00:36.720 --> 0:00:41.240 This newcomer penetrates into the tissue itself. It spreads farther, 0:00:41.640 --> 0:00:45.760 often infecting both lungs at nearly the same time. As 0:00:45.760 --> 0:00:49.000 the pathogen relentlessly erodes the cells of the deep lung, 0:00:49.360 --> 0:00:53.080 you find yourself increasingly short of breath. Your cough is 0:00:53.159 --> 0:00:55.800 often bloody, and you may bleed from your nose and 0:00:55.920 --> 0:00:59.760 even gums. The human body, which has never encountered anything 0:00:59.800 --> 0:01:02.800 like it, has no ready arsenal of antibodies to choke 0:01:02.840 --> 0:01:06.240 off the process. The body can still marshal its innate 0:01:06.360 --> 0:01:09.920 all purpose defenses, but in doing so, it mounts a 0:01:09.959 --> 0:01:14.000 counter attack so furious that some scientists believe it's more 0:01:14.120 --> 0:01:17.959 lethal than the virus itself. The body throws everything it 0:01:18.040 --> 0:01:21.920 has at the intruder, without regard to the tremendous collateral damage. 0:01:21.959 --> 0:01:25.960 This causes the lungs themselves ever more. Immune cells are 0:01:26.000 --> 0:01:29.240 summoned to the front and continue to blast away. The 0:01:29.319 --> 0:01:33.680 carnage mounts. The lung cavities fill with dead and damaged tissue, 0:01:34.000 --> 0:01:38.360 mutilated mucous cells, and other cellular wreckage. The lungs become 0:01:38.440 --> 0:01:40.720 rigid as the cells that make the liquid to keep 0:01:40.760 --> 0:01:44.880 the lungs flexible are annihilated. The seal between the bloodstream 0:01:44.920 --> 0:01:48.520 and the air passages ruptures, red blood cells and plasma 0:01:48.680 --> 0:01:52.280 leak into the lungs. The alveoli sacs are swamped with 0:01:52.360 --> 0:01:55.320 fluid and debris and are no longer able to exchange 0:01:55.360 --> 0:01:59.640 carbon dioxide for oxygen. If you listen closely, you can 0:01:59.640 --> 0:02:04.600 hear the liquid crackling. Your breathing accelerates. You desperately press 0:02:04.680 --> 0:02:08.200 all your chest muscles into helping you suck down precious oxygen. 0:02:08.520 --> 0:02:12.120 You're gasping for air. You're drowning. But the virus is 0:02:12.160 --> 0:02:16.359 not content to remain a solely respiratory disease. It invades 0:02:16.360 --> 0:02:20.840 the digestive tract, often causing diarrhea and sometimes vomiting. It 0:02:20.840 --> 0:02:24.480 can assault the liver in kidneys, it can provoke heart failure. 0:02:25.120 --> 0:02:27.800 It can attack the eyes. It can even breach the 0:02:27.800 --> 0:02:31.400 brain and spine. Yet, in the end, the lungs are 0:02:31.440 --> 0:02:35.000 where this microbe concentrates its energies and takes its heaviest toll. 0:02:35.680 --> 0:02:38.080 The lungs are also the means by which it casts 0:02:38.080 --> 0:02:41.200 its net for further prey. In this one regard, it 0:02:41.240 --> 0:02:44.240 is much like its seasonal cousin. They both spread their 0:02:44.280 --> 0:02:47.920 sickness through contaminated droplets coughed or sneezed into the air, 0:02:48.560 --> 0:02:59.800 one of the most efficient forms of transmission known. 0:03:40.480 --> 0:03:42.960 It is so terrifying. 0:03:43.760 --> 0:03:47.800 Is it somehow scarier because of covid or just scarier 0:03:47.880 --> 0:03:52.000 because we've read more about other pathogens and finally have 0:03:52.120 --> 0:03:54.920 a like more of a respect or appreciation for flu 0:03:55.480 --> 0:03:56.320 I think both. 0:03:56.480 --> 0:03:56.760 I think. 0:03:57.080 --> 0:03:59.240 I think in large part it's probably COVID. I think 0:03:59.280 --> 0:04:03.280 it's living something that is in many ways so similar 0:04:03.440 --> 0:04:09.080 and so terrifying, and knowing that it not just has 0:04:09.160 --> 0:04:13.120 happened again historically, but like it just happened, and now 0:04:13.120 --> 0:04:15.520 we're going to talk about how it can happen again 0:04:15.680 --> 0:04:17.159 and potentially be much worse. 0:04:17.560 --> 0:04:21.919 Yeah, And by can happen again, likely will happen again. Yeah, 0:04:21.960 --> 0:04:27.720 it's yeah. So that first hand account was from a 0:04:27.760 --> 0:04:31.520 book titled The Fatal Strain on the Trail of Avian 0:04:31.560 --> 0:04:34.600 Flu and the Coming Pandemic, and that was written by 0:04:34.640 --> 0:04:37.560 Alan Cipres and it was published in two thousand and nine. 0:04:38.240 --> 0:04:41.440 I think I read that for our first influenza episode. 0:04:41.520 --> 0:04:46.560 I think you did. I think it's on our sources. Yeah. Hi, 0:04:46.800 --> 0:04:50.000 I'm Aaron Welsh and I'm Erin Alman Updyke, and this 0:04:50.160 --> 0:04:52.280 is this podcast will Kill You, And. 0:04:52.200 --> 0:04:57.560 Today we're revisiting our very first ever topic, influenza. 0:04:57.920 --> 0:04:58.440 We are. 0:04:59.120 --> 0:05:05.440 It's our season finale celebration. Yeah, kind of a somber celebration. 0:05:06.400 --> 0:05:11.119 But I think that, you know, given the news about 0:05:11.160 --> 0:05:16.400 Avian influenza this year and the timeliness of this, we 0:05:16.520 --> 0:05:19.480 really wanted the opportunity to kind of go back and 0:05:20.000 --> 0:05:24.160 redo re explore this pathogen that is is so utterly 0:05:24.279 --> 0:05:27.760 terrifying and there's so much information out there about it 0:05:27.800 --> 0:05:30.920 that it really deserves not only like just a second episode, 0:05:30.960 --> 0:05:34.000 but also an entire series. 0:05:34.279 --> 0:05:36.359 Yes, one could certainly argue that. 0:05:37.839 --> 0:05:42.000 Yeah, yeah, so that's what we're doing this episode, kind 0:05:42.000 --> 0:05:44.360 of like talking about all of the different bits that 0:05:44.400 --> 0:05:48.000 we didn't cover in our first episode, which is quite 0:05:48.040 --> 0:05:50.960 a lot. And I think also one of our aims 0:05:51.000 --> 0:05:53.760 is to bring us up to speed more about today 0:05:54.120 --> 0:05:56.919 with a particular focus on Avian influenza. 0:05:57.240 --> 0:06:00.960 Yeah, a lot has changed since Tantine and we've learned 0:06:00.960 --> 0:06:04.560 a lot more, so it's going to be exciting to 0:06:04.839 --> 0:06:06.640 kind of bring it all back together. 0:06:07.080 --> 0:06:10.520 Well, should we start off with quarantiny time? 0:06:10.680 --> 0:06:11.200 We should? 0:06:11.240 --> 0:06:12.400 We certainly should. 0:06:14.120 --> 0:06:15.440 What are we drinking this week? 0:06:15.560 --> 0:06:18.400 Well, we're drinking none other than H one Drink Too. 0:06:21.640 --> 0:06:22.240 I love it. 0:06:22.400 --> 0:06:26.160 So for those of you who haven't listened to our 0:06:26.240 --> 0:06:28.800 very first Influenza episode, we can't blame you. 0:06:29.160 --> 0:06:34.160 First of all necessarily recommending it, Nope, But it is 0:06:34.600 --> 0:06:37.600 maybe pertinent to this part of the episode to know 0:06:37.800 --> 0:06:41.400 that our very first Quarantini was called H one Drink one. 0:06:41.839 --> 0:06:45.560 So this time stage one drink two. Yeah, and what 0:06:45.720 --> 0:06:47.159 is in H one drink too? 0:06:47.279 --> 0:06:51.680 Erin it is kind of a play on the Corpse Survivor, 0:06:52.040 --> 0:06:55.040 So we did the corp Survivor number two for our 0:06:55.240 --> 0:06:58.000 H one Drink one, our very first quarantini, and this 0:06:58.040 --> 0:07:01.320 one we're kind of just doing a variation includes Apricot Liquor, 0:07:01.839 --> 0:07:05.560 light rum, Lemon juice, and lil Itt Blanc and we 0:07:05.640 --> 0:07:08.440 will post the full recipe on our website. This podcast 0:07:08.440 --> 0:07:10.480 will kill You dot Com as well as on all 0:07:10.520 --> 0:07:13.160 of our social media channels, so check it out. 0:07:13.560 --> 0:07:17.400 And as a reminder, this is our season finale, so 0:07:18.000 --> 0:07:22.040 do make sure that you are subscribed to whatever podcast 0:07:22.080 --> 0:07:24.720 app you're listening to this on and to our social 0:07:24.720 --> 0:07:26.880 media so that you don't miss when we drop our 0:07:26.960 --> 0:07:27.760 next season. 0:07:29.200 --> 0:07:31.800 We don't have an exact date for you yet. We're sorry, 0:07:32.440 --> 0:07:34.880 but don't be worried. It won't be too It won't 0:07:34.880 --> 0:07:35.400 be too long. 0:07:35.640 --> 0:07:37.800 Yeah, any other business here? 0:07:38.440 --> 0:07:40.480 I feel like there should be, but I don't think 0:07:40.520 --> 0:07:42.720 there is. So let's just get started. 0:07:42.840 --> 0:07:43.840 We've got a lot to cover. 0:07:44.000 --> 0:08:14.480 Let's take a break and get started. So today we're 0:08:14.480 --> 0:08:18.880 not going to repeat everything that you may have learned 0:08:18.960 --> 0:08:23.320 in our very first episode, which covered influenza. But what 0:08:23.360 --> 0:08:25.800 I do want to do in this biology section is 0:08:25.960 --> 0:08:30.120 take what we learned in that episode and then expand 0:08:30.200 --> 0:08:33.240 on it, but also realizing that that was five years ago, 0:08:33.280 --> 0:08:36.480 and so most of us have probably forgotten or maybe. 0:08:36.200 --> 0:08:38.040 Skipped over the first episode. 0:08:38.559 --> 0:08:40.440 So what I'm going to do in this section is 0:08:40.480 --> 0:08:45.960 talk about influenza viruses in general and then focus primarily 0:08:46.040 --> 0:08:50.960 on bird flu or highly pathogenic avian influenza strains. 0:08:51.760 --> 0:08:54.560 So it's going to be a lot of fun and 0:08:54.640 --> 0:08:55.520 fun meaning. 0:08:55.480 --> 0:09:02.680 Terrifying, okay, as we usually mean, but fascinating all right. So, 0:09:03.520 --> 0:09:07.640 as a perhaps recap for many of us influenza viruses, 0:09:08.320 --> 0:09:14.800 these are RNA viruses, not retroviruses, as I called them 0:09:15.000 --> 0:09:19.040 in our very first ever episode. One of the most 0:09:19.320 --> 0:09:22.280 biggest embarrassments of my life. 0:09:23.520 --> 0:09:24.200 To this day. 0:09:26.480 --> 0:09:28.280 Is it like one of those things that pops into 0:09:28.280 --> 0:09:29.680 your head as you're trying to fall asleep. 0:09:30.120 --> 0:09:31.280 Yeah, sometimes. 0:09:32.600 --> 0:09:34.800 I called it a retrovirus on the internet. 0:09:34.880 --> 0:09:38.400 Forever is tscript. 0:09:38.480 --> 0:09:40.360 I did see the transcript that I was like in 0:09:40.440 --> 0:09:43.000 the transcript, I like made jokes about it, like I 0:09:43.240 --> 0:09:45.760 full on like went hard. 0:09:46.000 --> 0:09:49.760 Okay, it's not a retrovirus, but it is. 0:09:49.880 --> 0:09:55.160 They are RNA viruses in the family Orthomixoviridae, and RNA 0:09:55.240 --> 0:10:00.480 viruses in general not always, but is true for influenza 0:10:00.559 --> 0:10:05.000 viruses tend to mutate much more rapidly than, for example, 0:10:05.120 --> 0:10:10.160 DNA viruses, in large part because they lack good proofreading mechanisms. 0:10:10.920 --> 0:10:14.200 So what happens very commonly with influenza viruses is that 0:10:14.360 --> 0:10:19.120 small mutations can accumulate over time. And if these mutations 0:10:19.440 --> 0:10:22.680 happen to be in regions of the genome that encode 0:10:22.920 --> 0:10:26.680 the major surface proteins of influenza we'll talk about those 0:10:26.720 --> 0:10:31.280 more in a second, aka the antigens, then that can 0:10:31.280 --> 0:10:34.640 make it harder for our immune system to recognize those 0:10:34.679 --> 0:10:39.040 antigens or recognize that virus, and this process is known 0:10:39.080 --> 0:10:40.560 as antigenic drift. 0:10:41.720 --> 0:10:45.120 This is one of the ways that influenza. 0:10:44.600 --> 0:10:49.360 Viruses are particularly adept at evading our immune system and 0:10:49.440 --> 0:10:53.560 why they're so tricky to target and interesting. But on 0:10:53.640 --> 0:10:57.160 top of that, influenza virus genomes are made up of 0:10:57.280 --> 0:11:01.360 multiple short strands of RNA rather than one big long strand. 0:11:02.080 --> 0:11:04.560 And because as we'll talk in a lot of detail about, 0:11:04.600 --> 0:11:08.839 there are so many different strains of influenza viruses. If 0:11:08.880 --> 0:11:14.400 an animal like say a bird, is coinfected with multiple strains, 0:11:14.640 --> 0:11:18.320 which is not at all uncommon. These segments of RNA 0:11:18.480 --> 0:11:22.520 can mix and match inside of their cells and recombine 0:11:22.800 --> 0:11:27.600 to form essentially brand new versions, brand new, unrecognizable strains 0:11:27.600 --> 0:11:29.359 of influenza. 0:11:29.440 --> 0:11:30.360 This is the. 0:11:30.280 --> 0:11:36.840 Process of antigenic shift, and this amazing amount of variation 0:11:36.960 --> 0:11:40.880 in viral strains is why influenza remains such a challenging 0:11:40.960 --> 0:11:46.360 virus to combat in the form of vaccines, etc. But 0:11:46.440 --> 0:11:49.200 let me actually back up even further for a second, 0:11:49.360 --> 0:11:52.360 because when we say influenza virus, we're not talking about 0:11:52.400 --> 0:11:56.360 a single influenza virus. There's actually four major classes of 0:11:56.400 --> 0:12:01.880 influenza viruses ABC and also D, and when we talk 0:12:01.920 --> 0:12:06.520 about influenza viruses in humans, we mostly mean influenza A 0:12:07.320 --> 0:12:11.959 and to a lesser extent, influenza B. Influenza C does 0:12:12.000 --> 0:12:15.040 circulate and causes disease in humans, but it's more like 0:12:15.080 --> 0:12:17.480 a mild cold rather than what we think of as 0:12:17.679 --> 0:12:22.080 the flu, and influenza D is mostly in cattle. Okay, 0:12:22.559 --> 0:12:27.440 So influenza B has two major lineages that circulate only 0:12:27.480 --> 0:12:31.640 among humans. It's not a zoonotic virus, and while it 0:12:31.679 --> 0:12:36.040 can cause a decent amount of disease in epidemics, seasonally 0:12:36.720 --> 0:12:39.320 it's not a zoonotic virus, and it's not like the 0:12:39.480 --> 0:12:43.240 major player in general when we think about influenza. 0:12:43.240 --> 0:12:46.240 SO, I have a question about influenza B. So, from 0:12:46.280 --> 0:12:52.600 my understanding, the vaccines that target you know, seasonal influenza A, 0:12:52.960 --> 0:12:55.959 the influenza A strain that's in there might change from 0:12:56.040 --> 0:12:58.280 year to year depending on what is predicted. But B 0:12:58.440 --> 0:13:02.240 doesn't really seem to change. Why doesn't really change that much? 0:13:02.600 --> 0:13:03.360 That's a good question. 0:13:03.480 --> 0:13:07.320 There's only two major lineages of influenza B, so I 0:13:07.360 --> 0:13:11.440 don't know as much detail because I didn't dig hardcore. 0:13:11.040 --> 0:13:11.920 Into influenza B. 0:13:12.040 --> 0:13:14.160 But it's likely just that there simply isn't as much 0:13:14.240 --> 0:13:16.600 variation as what we see with influenza A. 0:13:16.920 --> 0:13:21.319 Okay, so like fewer opportunities for combination are exactly gotcha. 0:13:21.120 --> 0:13:26.120 Because it's not a zoonotic virus, it's only circulating among humans. Right. Interesting, 0:13:27.360 --> 0:13:30.000 But let us now focus for pretty much the rest 0:13:30.000 --> 0:13:32.960 of this episode on the biggest player, and that is 0:13:33.440 --> 0:13:39.640 influenza A. So most people are probably familiar with classifications 0:13:39.679 --> 0:13:43.160 of influenza A viruses, and those are H one N 0:13:43.200 --> 0:13:46.680 one or H three N two. You've probably heard those 0:13:46.720 --> 0:13:50.000 circulating around every time that there's a new strain that 0:13:50.040 --> 0:13:54.920 causes an epidemic. Right, So those letters H and N 0:13:55.080 --> 0:14:00.120 refer to two specific antigens on the influenza virus surface itself, 0:14:00.440 --> 0:14:05.880 the H antigen hemaglutinin and the N antigen neuraminidase. You 0:14:05.880 --> 0:14:08.280 don't have to remember those names, you could just remember HNN. 0:14:09.360 --> 0:14:12.839 So the H proteins, you can think of these as 0:14:12.880 --> 0:14:16.840 the proteins that bind to our cells and allow influenza 0:14:16.880 --> 0:14:20.560 virus to actually enter our cells. Remember, of course, that 0:14:20.760 --> 0:14:24.360 all viruses have to get into our cells in order 0:14:24.400 --> 0:14:27.240 to be able to replicate. They rely on our machinery 0:14:27.400 --> 0:14:33.800 to finish that process of replication. Influenza viruses are respiratory viruses, right, 0:14:34.200 --> 0:14:37.760 so they predominantly are infecting the cells that line our 0:14:37.880 --> 0:14:42.000 upper and lower respiratory tract. These H proteins on their 0:14:42.040 --> 0:14:45.720 surface are what allow them to bind to these cells 0:14:45.720 --> 0:14:50.320 in particular and enter those cells, Which means that these 0:14:50.800 --> 0:14:54.440 H antigens especially are the ones that in theory and 0:14:54.480 --> 0:14:58.560 in practice our immune system recognizes and if we are 0:14:58.640 --> 0:15:01.760 able to block it, we can stop this virus from 0:15:01.880 --> 0:15:03.120 entering our cells entirely. 0:15:03.920 --> 0:15:10.200 Question. Okay, so the difference between upper and lower respiratory 0:15:10.280 --> 0:15:16.520 tract and the differences in the HS, and are some 0:15:16.680 --> 0:15:21.360 more adept at invading both the upper and lower or just. 0:15:21.360 --> 0:15:24.240 The upper or yeah, a thousand percent? 0:15:24.360 --> 0:15:25.920 Yes, okay? Which ones? 0:15:26.160 --> 0:15:26.520 Okay? 0:15:26.640 --> 0:15:29.840 I can't give you an easy answer on that because 0:15:29.840 --> 0:15:34.000 it varies. The answer to all of these questions of 0:15:34.120 --> 0:15:38.840 detail are probably going to be it depends because let 0:15:38.880 --> 0:15:42.560 me keep going, and we'll see not just how much 0:15:42.680 --> 0:15:46.720 variation there is, but like how terrifyingly much variation is Okay, 0:15:47.160 --> 0:15:51.200 love it? So we can't also forget about the n antigens. 0:15:51.720 --> 0:15:55.520 These are involved in the process of once that virus 0:15:55.560 --> 0:15:58.320 has replicated in our cells and is all packaged up 0:15:58.320 --> 0:16:01.120 and ready to burst forth to go infect more cells, 0:16:01.640 --> 0:16:04.880 the n antigens are what help influence a virus actually 0:16:04.920 --> 0:16:08.680 release from inside of ourselves. That's what the n antigens 0:16:08.720 --> 0:16:13.520 are doing. So another potential target, but a harder one 0:16:13.600 --> 0:16:15.960 given that it's an intracellular site of action. 0:16:16.120 --> 0:16:17.040 So it's really this. 0:16:17.240 --> 0:16:20.000 H antigen that is the one that when we think 0:16:20.040 --> 0:16:24.440 of vaccines, we're predominantly potentially targeting. And we'll get to 0:16:24.480 --> 0:16:26.400 all of that much later in the episode. 0:16:27.040 --> 0:16:29.880 It's interesting to think about from an evolutionary perspective, because 0:16:29.920 --> 0:16:35.000 it seems clear why there would be variation in H 0:16:35.640 --> 0:16:38.880 in the hema glutenants, right, but the neuromidida is like, 0:16:39.040 --> 0:16:41.960 what is the variation in that functionality? 0:16:42.320 --> 0:16:47.000 Ooh, that's a really good question. Yeah, I don't know, Okay, Yeah, 0:16:47.200 --> 0:16:50.200 it's really interesting though, Like what's the benefit of like 0:16:50.520 --> 0:16:53.240 having different receptors to do the binding and releasing? 0:16:53.520 --> 0:16:53.680 Right? 0:16:53.800 --> 0:16:56.520 What is N one versus N two? Is there a 0:16:56.560 --> 0:17:00.760 functional difference or is it just these are different enough different? 0:17:00.920 --> 0:17:01.160 Right? 0:17:01.280 --> 0:17:03.280 Yeah, yeah, it's a good question. 0:17:05.000 --> 0:17:13.200 So there are eighteen different major h antigens sixteen if 0:17:13.200 --> 0:17:15.400 you don't count the ones that are mostly only found 0:17:15.440 --> 0:17:19.719 in bats, and there are eleven or again nine if 0:17:19.760 --> 0:17:21.520 you don't count the ones that are mostly only in 0:17:21.560 --> 0:17:26.240 bats major n antigens. Knowing that you can combine h's 0:17:26.280 --> 0:17:30.280 and ns in pretty much any configuration, that alone is 0:17:30.320 --> 0:17:33.720 a huge amount of potential for recombination and change, right, 0:17:33.840 --> 0:17:36.679 eighteen and eleven or even sixteen and nine, that's a 0:17:36.800 --> 0:17:37.840 ton of variation. 0:17:38.160 --> 0:17:38.760 I can't do that. 0:17:38.840 --> 0:17:44.320 Math no air and math, no air and math this episode. 0:17:45.320 --> 0:17:48.280 But on top of that, you asked, like, what are 0:17:48.320 --> 0:17:51.760 the differences between the different H andigens. Yeah, there is 0:17:51.880 --> 0:17:55.520 not just a difference between say H one and H two, 0:17:56.040 --> 0:17:59.280 but because of the buildup of changes to these H 0:17:59.359 --> 0:18:05.120 and antigen via that antigenic drift, via those small point mutations. 0:18:05.560 --> 0:18:08.520 What that means is that not every version of H 0:18:08.640 --> 0:18:13.520 three and two is exactly the same. There are parts 0:18:13.640 --> 0:18:17.480 of the H antigen and parts of the end antigen 0:18:17.800 --> 0:18:20.639 that are more conserved, and there are other parts that 0:18:20.680 --> 0:18:24.480 are much more variable even within like say H one 0:18:24.680 --> 0:18:30.360 or H five. Interesting, it's fascinating, and yes, absolutely, these 0:18:30.359 --> 0:18:33.520 different H antigens are going to have different affinities for 0:18:33.720 --> 0:18:37.720 specific receptors on our epithelial cells, and that is going 0:18:37.800 --> 0:18:42.080 to determine which cells they invade and how readily. So 0:18:42.359 --> 0:18:46.520 as we see with particular strains like H five N 0:18:46.600 --> 0:18:49.119 one in our first hand account that are able to 0:18:49.240 --> 0:18:54.040 invade lower respiratory tract very rapidly and even invade beyond 0:18:54.119 --> 0:18:58.480 our respiratory tract, that's likely something that's largely mediated by 0:18:58.800 --> 0:19:02.639 particular changes to H or possibly N antigen, allowing it 0:19:02.680 --> 0:19:06.280 to release more readily from certain cells than others. 0:19:07.280 --> 0:19:09.560 So that's all of this variation. 0:19:10.400 --> 0:19:12.679 Let's get into more details of what we know about 0:19:12.680 --> 0:19:15.800 influenza as a as an illness. 0:19:15.960 --> 0:19:17.480 Okay, yeah, So. 0:19:17.560 --> 0:19:21.240 Influenza viruses, of course are respiratory viruses, which means that 0:19:21.280 --> 0:19:27.000 they're transmitted by droplets or aerosols when we cough, sneeze, talk, laugh, 0:19:27.119 --> 0:19:30.840 et cetera. There is also a lot of indirect transmission 0:19:30.920 --> 0:19:35.959 via fomites like door handles, shared coffee cups, whatever you like, 0:19:36.160 --> 0:19:40.280 lick your hand and then touch, and this route of transmission, 0:19:40.320 --> 0:19:45.880 in particular fomtes or like in more indirect transmission seems 0:19:45.880 --> 0:19:47.879 to be and is thought to be a pretty important 0:19:47.920 --> 0:19:51.000 route of transmission, although because I figured you were going 0:19:51.080 --> 0:19:54.200 to ask aarin, I did not get a sense. And 0:19:54.359 --> 0:19:57.439 the papers that I read actually suggested that influenza is 0:19:57.480 --> 0:20:02.840 not actually a very environmentally stable virus. And despite how 0:20:02.920 --> 0:20:06.400 much we know about influenza, we still don't know enough 0:20:06.400 --> 0:20:09.120 to be able to say, like the relative contribution of 0:20:09.400 --> 0:20:12.080 this transmission rate versus that transmission route. 0:20:12.119 --> 0:20:13.240 Does that make sense? Yeah? 0:20:13.320 --> 0:20:15.360 You know me so well. These were literally the two 0:20:15.440 --> 0:20:18.400 questions that was brimming like on the top of my touch. 0:20:18.560 --> 0:20:20.080 Yeah, preem to do you this time? 0:20:20.359 --> 0:20:20.760 You did? 0:20:21.240 --> 0:20:24.359 But in any case, you're breathing and sneezing this stuff 0:20:24.359 --> 0:20:28.200 out because this is a virus that's primarily infecting our 0:20:28.400 --> 0:20:34.639 respiratory cells, the respiratory epithelium, and in general, the incubation 0:20:34.800 --> 0:20:39.600 period for influenza is remarkably short. People are often symptomatic 0:20:39.640 --> 0:20:43.800 by day two after inoculation, sometimes by day one, and 0:20:43.920 --> 0:20:48.320 almost always by day four, So like very short incubation period, 0:20:48.440 --> 0:20:50.640 especially compared to a lot of things we've covered recently, 0:20:51.600 --> 0:20:55.720 and people are generally infectious that is, high viral tiders 0:20:55.960 --> 0:21:00.680 in their nasal epithelium up to twenty four hours before 0:21:00.800 --> 0:21:01.960 symptoms begin. 0:21:02.160 --> 0:21:03.920 Which is where the trouble starts. 0:21:04.040 --> 0:21:06.720 It sure is, And if you think about it too, 0:21:06.800 --> 0:21:11.520 that's like incredibly rapid how quickly this virus gets into ourselves, 0:21:11.760 --> 0:21:15.439 starts replicating, bursts out, and is ready to spread. In 0:21:15.560 --> 0:21:20.560 terms of who gets infected, everybody gets infected with influenza. 0:21:21.119 --> 0:21:24.080 Some data suggests that it's actually children who are the 0:21:24.160 --> 0:21:27.640 most likely to become infected, and the older you are, 0:21:27.800 --> 0:21:30.639 the less likely you are to become infected. But when 0:21:30.680 --> 0:21:34.720 it comes to severe infection and mortality, it's both children 0:21:34.880 --> 0:21:37.560 and older adults over age sixty five that are at 0:21:37.680 --> 0:21:40.359 highest risk of severe infection and death. 0:21:40.760 --> 0:21:43.360 It's that classic U shaped mortality. 0:21:43.600 --> 0:21:47.160 Yeah, yeah, in all but the nineteen eighteen pandemic. 0:21:47.040 --> 0:21:48.119 And of a few others. 0:21:48.119 --> 0:21:53.200 But yeah, other people who are at particularly high risk 0:21:53.320 --> 0:21:56.880 of severe infection include people who are pregnant, and then 0:21:57.000 --> 0:22:02.000 a lot of other comorbidities like heart failailiar pulmonary disease 0:22:02.160 --> 0:22:07.080 of various kinds, cigarette smoking, immunal compromising conditions. All of 0:22:07.119 --> 0:22:10.359 these things essentially just make it harder for our bodies 0:22:10.359 --> 0:22:13.760 to fight off this infection or easier for us to 0:22:13.760 --> 0:22:16.880 get infected with it in the first place. And I 0:22:16.960 --> 0:22:20.399 think we're all probably familiar with the symptoms of the flu, 0:22:20.920 --> 0:22:23.199 although I think a lot of people might confuse it 0:22:23.240 --> 0:22:26.400 with any of another million viruses that we just call 0:22:26.440 --> 0:22:31.440 the common cold, because influenza is not the common cold. No, 0:22:32.040 --> 0:22:37.800 with influenza, you are sick. You are if you are symptomatic, 0:22:37.880 --> 0:22:39.240 which not everyone. 0:22:38.960 --> 0:22:42.120 Is, right, Okay, question real quick, well how many? Yeah, 0:22:42.200 --> 0:22:42.520 thank you? 0:22:43.720 --> 0:22:44.239 I don't know. 0:22:44.359 --> 0:22:47.200 I actually didn't see that number reported very commonly. 0:22:47.840 --> 0:22:49.760 That's so interesting because I feel like we know that 0:22:49.880 --> 0:22:51.880 so well now for things like COVID. 0:22:52.280 --> 0:22:54.439 Yeah, like we should know that, and I just somehow 0:22:54.480 --> 0:22:56.639 missed it, but I didn't see it. 0:22:57.440 --> 0:23:00.280 I mean, I mean, but presumably there are there's a 0:23:00.320 --> 0:23:02.760 subset of people who are asymptomatic. 0:23:02.200 --> 0:23:05.919 Absolutely, and asymptomatic carriers can still shed for even up 0:23:05.920 --> 0:23:08.680 to six days, which is generally how long people shed. 0:23:09.000 --> 0:23:10.960 Okay, but yeah, you're sick. 0:23:12.080 --> 0:23:16.880 You have a fever, you have muscle aches, full body, 0:23:16.920 --> 0:23:21.480 like your entire body is aching. Your throat is sore 0:23:21.720 --> 0:23:26.240 and it's red. Your nose is probably runny. You're coughing. 0:23:26.640 --> 0:23:30.240 You're possibly coughing so hard that you're hurting your ribs. 0:23:30.440 --> 0:23:34.200 You feel like you're coughing your brains out. And this 0:23:34.520 --> 0:23:37.600 is if you have a mild infection. In this case, 0:23:37.720 --> 0:23:41.840 symptoms last seven to ten days, so it's not just 0:23:42.040 --> 0:23:44.760 a few days that you're feeling creuddy. You're feeling bad 0:23:44.800 --> 0:23:45.919 for a long time. 0:23:46.160 --> 0:23:48.520 Yeah, And if. 0:23:48.760 --> 0:23:52.040 Or when this virus makes its way into your lower 0:23:52.040 --> 0:23:56.439 respiratory tract, it can then cause a viral pneumonia. It 0:23:56.480 --> 0:24:01.120 can progress to an acute respiratory distress, which can then 0:24:01.320 --> 0:24:06.359 progress to shock and potentially death. One of the primary 0:24:06.440 --> 0:24:09.199 drivers that determines if someone is going to have a 0:24:09.280 --> 0:24:13.560 severe infection versus a less severe infection Besides just what 0:24:13.760 --> 0:24:17.760 strain of the virus is, it is how far down 0:24:17.880 --> 0:24:21.880 into that respiratory tract did the virus invade? And this 0:24:22.080 --> 0:24:25.000 is probably determined by a whole number of factors, like 0:24:25.119 --> 0:24:29.800 our individual immune response, largely how well did we tolerate 0:24:29.960 --> 0:24:33.200 versus resist that virus in the upper respiratory tract before 0:24:33.280 --> 0:24:36.600 it tried to travel down, What strategies did our immune 0:24:36.600 --> 0:24:37.640 system employ. 0:24:37.440 --> 0:24:38.680 Like and how effective were they? 0:24:39.440 --> 0:24:42.639 But then also likely some degree of infectious dose, like 0:24:42.720 --> 0:24:45.680 how much of the virus were we exposed to, how big. 0:24:45.440 --> 0:24:46.880 Of a load did we have to fight off? 0:24:47.320 --> 0:24:49.800 And then of course the strain of the virus itself, 0:24:49.920 --> 0:24:52.680 like how virulent is it, how big of an affinity 0:24:52.680 --> 0:24:55.560 does it have for those lower cells versus our upper cells. 0:24:56.960 --> 0:25:01.000 And on top of that, because this virus and our 0:25:01.000 --> 0:25:03.639 immune response to it can cause so much damage to 0:25:03.680 --> 0:25:08.800 our lungs, Influenza virus, especially viral pneumonia, can put people 0:25:08.840 --> 0:25:13.679 at significantly higher risk of a superimposed bacterial pneumonia, especially 0:25:13.680 --> 0:25:17.080 from a Staph aureus or a Streptococcus pneumonia. 0:25:17.560 --> 0:25:23.800