WEBVTT - COVID-19 Chapter 1: Virology 0:00:01.040 --> 0:00:04.360 My name is Titiano. I'm from the northeast of Italy. 0:00:05.080 --> 0:00:08.480 I live in a small town in the northeast. I'm 0:00:08.520 --> 0:00:13.119 a school teacher. I teach English in a secondary school here. 0:00:14.080 --> 0:00:18.800 In February there was all the attention was on a 0:00:18.840 --> 0:00:23.720 couple of tourists going around and so on. Then on 0:00:23.800 --> 0:00:28.880 the twenty first, we got our first cases here in Italy. 0:00:31.240 --> 0:00:35.120 They were limited to a small number of towns in 0:00:35.159 --> 0:00:41.879 the north. What happened was that following week it was 0:00:42.159 --> 0:00:46.720 a short Tuesday, so schools were already closed for a 0:00:46.760 --> 0:00:52.440 couple of days. So over the course of that weekend, 0:00:53.479 --> 0:00:58.000 the first ten or so towns were quarantined and all 0:00:58.040 --> 0:01:02.840 the schools in the north were closed. What happened next 0:01:04.319 --> 0:01:09.880 is that the regions asked for and got an extension 0:01:10.080 --> 0:01:14.280 of the closure of the schools. So it's been three 0:01:14.400 --> 0:01:20.800 full weeks now since schools have closed, and there's another 0:01:20.920 --> 0:01:25.760 three weeks planned ahead of us. At least I'm at 0:01:25.800 --> 0:01:31.160 school teacher, so it's been not easy to cope with 0:01:31.200 --> 0:01:36.480 all of this. So the thing is, the schools stopped, 0:01:36.560 --> 0:01:41.720 but the rest of the country went on. But things 0:01:41.760 --> 0:01:48.360 started moving fast. So we are now under this lockdown 0:01:49.640 --> 0:01:55.760 which means that we cannot leave our homes unless it's 0:01:55.800 --> 0:02:01.320 for either work reasons or basic needs. Kind of a 0:02:01.440 --> 0:02:05.040 soft lockdown, because we can actually move, but we have 0:02:05.160 --> 0:02:11.239 to provide some sort of declaration of written statement for 0:02:11.440 --> 0:02:18.560 the reason why we are out of our homes. Until 0:02:18.720 --> 0:02:23.600 the government came out with the lockdown, I think people 0:02:23.639 --> 0:02:28.080 didn't really appreciate what that meant. And so it was 0:02:28.280 --> 0:02:32.600 just a few days before that that there were still 0:02:33.360 --> 0:02:39.080 parties going on and restaurants and so on for the 0:02:40.480 --> 0:02:45.720 let's say, for the lockdown we are under now. So 0:02:45.919 --> 0:02:50.200 if I was to you know, go out small without 0:02:50.240 --> 0:02:56.560 a good reason, So if police is going to stop 0:02:56.600 --> 0:03:00.359 you and check your statement, so if it's for worksons, 0:03:00.400 --> 0:03:05.480 they are going to call your workplace and that so 0:03:05.520 --> 0:03:13.480 there is a fine or you could face charges. You 0:03:13.520 --> 0:03:16.840 could go to jail, but that's only for extreme cases 0:03:17.520 --> 0:03:25.320 after the last regulations. So this past week, I think 0:03:25.360 --> 0:03:31.880 that people are taking the thing more seriously and from 0:03:31.960 --> 0:03:36.040 what I see from my immediate vicinity and people I know, 0:03:37.520 --> 0:03:41.880 we are starting to embrace the social distancing and so 0:03:42.040 --> 0:03:47.960 we are moving to skype calls with friends and we're 0:03:48.520 --> 0:03:51.880 you know, the indoors life as much as you can, 0:03:52.600 --> 0:03:57.160 and as a school teacher I maybe have a slightly 0:03:57.240 --> 0:04:02.600 different perspective than most other people because we started from 0:04:02.640 --> 0:04:08.920 the very beginning to find ways to still keep doing 0:04:09.080 --> 0:04:13.520 school in some form, but there wasn't really a plan 0:04:13.680 --> 0:04:15.800 for that, so a lot of it was left to 0:04:16.279 --> 0:04:22.200 our own you know, creativity and good will to do things. 0:04:23.000 --> 0:04:26.799 There are there are still issues with that. The first 0:04:26.839 --> 0:04:32.640 one is that it's very hard to keep in touch 0:04:32.760 --> 0:04:37.599 with all our students because of course not everybody is available, 0:04:37.680 --> 0:04:42.600 not everybody has the same resources, and it's hard and 0:04:42.640 --> 0:04:47.359 it's impact families, especially families where the parents are still 0:04:47.400 --> 0:04:52.159 working and so they need to take care of the children. 0:04:53.520 --> 0:04:59.960 Traditionally here families are very close knit and this was 0:05:00.120 --> 0:05:05.080 something that often grandparents did. But parents are of course 0:05:05.120 --> 0:05:13.480 one of the most impacted categories for the yeah for 0:05:13.640 --> 0:05:19.279 the virus, so that that has raised some issues. We 0:05:19.480 --> 0:05:23.200 have one of those flash mobs on the balconies every 0:05:23.279 --> 0:05:27.480 day basically, you know, I mean a small town, so 0:05:27.560 --> 0:05:30.920 there's not a lot of houses around here. Every day 0:05:31.040 --> 0:05:35.200 there's someone either playing songs or the other day they 0:05:35.240 --> 0:05:39.599 were tapping for the people in the medical professions, which 0:05:39.600 --> 0:05:44.480 are doing a great job and taking Dublin gifts to 0:05:44.680 --> 0:05:49.920 cover every everything. So that's that's good. There's this other 0:05:50.040 --> 0:05:53.920 thing that's going on now, which is the kids are 0:05:54.080 --> 0:05:59.920 making these rainbow paintings and with an action that is basic, 0:06:00.240 --> 0:06:04.279 everything will be fine in Italian and they are, you know, 0:06:04.400 --> 0:06:10.040 sharing those pictures on the social media. This is bringing 0:06:10.040 --> 0:06:16.320 out a lot of you know, good things. I see 0:06:16.360 --> 0:06:20.279 that really people care, people care about their neighborhoods, people 0:06:20.320 --> 0:06:32.120 care about what's going on. That's a big thing. H 0:06:44.240 --> 0:06:58.920 h yah m m m hm hm h. 0:07:09.120 --> 0:07:13.520 You just heard from Tiziano, who was kind enough to 0:07:13.560 --> 0:07:16.760 spare us a few minutes to chat about his experiences 0:07:16.800 --> 0:07:21.720 while under lockdown in Italy. Thanks so much for chatting 0:07:21.720 --> 0:07:22.120 with us. 0:07:22.400 --> 0:07:23.880 Yeah, we really appreciate it. 0:07:24.400 --> 0:07:24.600 Hi. 0:07:24.760 --> 0:07:27.600 I'm Aaron Welsh and I'm Erin alman Updyke and. 0:07:27.520 --> 0:07:30.040 You're listening to this podcast will kill you? 0:07:30.600 --> 0:07:30.800 Oh? 0:07:30.920 --> 0:07:32.200 Yes you are? 0:07:32.640 --> 0:07:33.040 You are? 0:07:34.120 --> 0:07:38.840 Yes, Welcome to our first ever minisode series, which we're 0:07:38.880 --> 0:07:42.320 calling Anatomy of a Pandemic, and which is shaping up 0:07:42.360 --> 0:07:45.440 to be less of minisodes and more like full length ones. 0:07:45.520 --> 0:07:47.280 So yeah, it's Maxiodes. 0:07:47.320 --> 0:07:48.640 Sorry, not sorry, I don't know. 0:07:48.680 --> 0:07:50.640 It's long strap in. 0:07:51.280 --> 0:07:53.960 There's a lot of information out there, and there's a 0:07:53.960 --> 0:07:56.560 lot of ground to be covered, so you know, we're 0:07:56.560 --> 0:07:59.200 gonna do the best we can. And this is this 0:07:59.280 --> 0:08:02.280 is the first ep episode of six that we're dropping 0:08:02.320 --> 0:08:05.480 all at once, but throughout this pandemic, as it progresses, 0:08:05.480 --> 0:08:08.760 we're going to keep revisiting different topics or visiting new 0:08:08.800 --> 0:08:11.720 topics to get you all the information that you could 0:08:11.800 --> 0:08:17.960 ever want about COVID nineteen yep. So we asked everyone 0:08:18.040 --> 0:08:22.400 out there for questions, and hundreds of you submitted your questions. 0:08:22.400 --> 0:08:25.080 So first of all, thank you so very much because 0:08:25.080 --> 0:08:27.800 that really helped us to figure out what you wanted 0:08:27.800 --> 0:08:31.320 to know and how to organize these episodes, and so 0:08:31.360 --> 0:08:34.440 we are so excited to bring you not one, but 0:08:35.320 --> 0:08:38.760 six of these episodes where we ask the experts to 0:08:38.800 --> 0:08:39.839 answer your questions. 0:08:40.760 --> 0:08:45.319 So today we're starting with chapter one, the virus itself, 0:08:46.760 --> 0:08:48.719 and that's what we're going to cover in this episode. 0:08:48.760 --> 0:08:52.720 But before we get started, we have to report, of 0:08:52.760 --> 0:08:57.000 course that if ever it was quarantin any time, right 0:08:57.040 --> 0:09:00.199 now is most definitely quarantine time. 0:09:00.520 --> 0:09:01.960 Most definitely. 0:09:03.440 --> 0:09:06.559 Quarantinies have been making the rounds in social media, and 0:09:06.800 --> 0:09:10.840 first of all, we appreciate everyone shouting us out in that, 0:09:11.920 --> 0:09:14.360 yeah we do. So what are we drinking today? 0:09:14.480 --> 0:09:18.200 Erin, we are drinking what we're just calling Quarantini one, 0:09:18.280 --> 0:09:20.600 because you know, let's keep it simple. 0:09:20.760 --> 0:09:24.280 We'll keep it simple. Disclaimer, if you're going to listen 0:09:24.320 --> 0:09:27.280 to all six of these episodes in one sitting, you 0:09:27.360 --> 0:09:29.599 don't need to make all six Quarantinies. 0:09:29.800 --> 0:09:33.400 That's probably a bad idea, I personally, So I'm recording this. 0:09:33.559 --> 0:09:37.520 It's eight my time, and I'm drinking coffee. 0:09:37.679 --> 0:09:40.679 It's ten am my time. I'm drinking water. But I 0:09:40.720 --> 0:09:43.280 did drink at Quarantini last night while researching. 0:09:43.920 --> 0:09:47.480 I drank a couple while taking the pictures of them all. 0:09:48.520 --> 0:09:50.440 It's important you gotta taste us. 0:09:50.760 --> 0:09:52.240 So what is Quarantini number one? 0:09:52.360 --> 0:09:52.520 Erin? 0:09:52.920 --> 0:09:58.280 Quarantine number one has rum, it has coconut cream, it 0:09:58.320 --> 0:10:01.240 has lime juice, and and you know, we wanted to 0:10:01.320 --> 0:10:03.520 make these so that hopefully they are things that you 0:10:03.679 --> 0:10:06.720 might have lying around the house, more simple ingredients and 0:10:06.760 --> 0:10:10.400 so on. But I will suggest if you happen to 0:10:10.480 --> 0:10:14.199 have Apricot licour pop, some of that in there as well. 0:10:14.840 --> 0:10:17.840 If your bar card is as well stocked as Aaron Welshit. 0:10:19.800 --> 0:10:23.040 Apricot licour is really good in tiki drinks. Yeah, that's 0:10:23.040 --> 0:10:23.800 all I would say. 0:10:24.559 --> 0:10:25.120 I believe you. 0:10:25.640 --> 0:10:30.040 We will post the recipe for that quarantini Quarantini one, 0:10:30.160 --> 0:10:33.839 as well as the non alcoholic Placy burrita on all 0:10:33.840 --> 0:10:38.400 of our social media pages and our website. Excellent. 0:10:39.600 --> 0:10:40.120 All right. 0:10:40.320 --> 0:10:46.320 So, so, way back in February, which feels honestly like 0:10:46.360 --> 0:10:49.640 an entire lifetime ago, we did a whole episode about 0:10:49.679 --> 0:10:52.560 coronaviruses in general, and so we wanted to give you 0:10:52.559 --> 0:10:56.040 a really quick recap on that. All right, So, coronaviruses 0:10:56.240 --> 0:10:59.200 are not brand new alien viruses. There are large family 0:10:59.280 --> 0:11:03.560 viruses that infect a number of different animals. SARS COVID two, 0:11:03.920 --> 0:11:08.160 which stands for Severe Acute Respiratory syndrome coronavirus number two, 0:11:08.559 --> 0:11:11.240 which is a little bit of a mouthful. This is 0:11:11.280 --> 0:11:13.920 the official name for the virus that causes the disease, 0:11:14.040 --> 0:11:17.160 COVID nineteen. You can break that down to see where 0:11:17.160 --> 0:11:22.480 that comes from. It's coronavirus disease nineteen COVID nineteen. And 0:11:22.520 --> 0:11:25.320 so this is a virus that is new to humans 0:11:25.960 --> 0:11:29.240 and it emerged, as it turns out, or as it 0:11:29.360 --> 0:11:34.840 likely turns out, in November twenty nineteen. Obviously, this is 0:11:35.000 --> 0:11:39.120 now a pandemic, and so we are going to talk 0:11:39.200 --> 0:11:42.679 in this episode about the biology of this new virus 0:11:42.679 --> 0:11:45.480 and some of the characteristics that have allowed it or 0:11:45.679 --> 0:11:49.880 facilitated it to reach pandemic proportions exactly. 0:11:50.559 --> 0:11:53.800 So let's do a quick primer about viruses in general, 0:11:54.120 --> 0:11:56.960 especially for any new listeners who haven't heard all of 0:11:56.960 --> 0:12:02.439 my many virus spiels many times over. So, viruses are 0:12:02.559 --> 0:12:06.520 essentially just packets of genetic material. They're made of either 0:12:06.640 --> 0:12:11.280 DNA or RNA along with protein. Viruses can't replicate on 0:12:11.400 --> 0:12:15.400 their own, so unlike most bacteria, for example, which can 0:12:15.480 --> 0:12:19.280 multiply just by replicating their DNA and then dividing into two, 0:12:20.120 --> 0:12:23.360 viruses have to infect a cell of some kind, a 0:12:23.440 --> 0:12:28.360 host cell, and use that host cellular machinery to actually 0:12:28.480 --> 0:12:32.559 replicate their genetic material. So, in the case of SARS 0:12:32.640 --> 0:12:37.360 covy two, this is an RNA virus. It's a positive 0:12:37.400 --> 0:12:41.120 strand RNA virus. So that means that once it gets 0:12:41.200 --> 0:12:45.480 into your cells, that viral RNA is released into our 0:12:45.840 --> 0:12:49.440 human cells, and then our cells do two things with 0:12:49.520 --> 0:12:53.640 this RNA number One, they start copying it directly as 0:12:53.679 --> 0:12:57.960 if it was our own RNA. And number two, what 0:12:58.160 --> 0:13:01.880 RNA does in normal cell is it codes for protein. 0:13:02.520 --> 0:13:06.320 So our cells start to use this viral RNA to 0:13:06.520 --> 0:13:11.000 make the proteins that that viral RNA codes for, and 0:13:11.080 --> 0:13:16.480 then the replicated RNA plus those proteins get assembled into 0:13:16.640 --> 0:13:21.520 new little virus packets, okay, and those new viruses can 0:13:21.559 --> 0:13:24.600 then burst forth from the cell and go on to 0:13:24.720 --> 0:13:29.040 infect another cell, either in your body or in another host. 0:13:29.880 --> 0:13:34.439 So that's how RNA viruses work. DNA viruses do essentially 0:13:34.480 --> 0:13:37.800 the same thing, except that in order to make protein 0:13:37.840 --> 0:13:41.480 from DNA, your cells have to first translate it into 0:13:41.520 --> 0:13:45.320 that RNA. So RNA viruses sort of skip that step, 0:13:45.840 --> 0:13:49.200 and as you'll hear our expert talk more about, they 0:13:49.280 --> 0:13:53.199 also tend to make more mistakes in that process of replication. 0:13:54.360 --> 0:13:58.400 But either way, viruses are using your host machinery to 0:13:58.600 --> 0:14:01.960 do this. They can't replicate outside of host cells. 0:14:02.640 --> 0:14:02.960 Cool. 0:14:03.840 --> 0:14:04.160 Cool. 0:14:05.480 --> 0:14:09.600 So in this episode, we talk to a virologist, doctor 0:14:09.640 --> 0:14:14.120 Angela Rasmussen from Columbia University, to answer your questions about 0:14:14.120 --> 0:14:17.320 the biology of this virus, how it works, how it 0:14:17.360 --> 0:14:20.160 infects your cells, and what markers it uses to get 0:14:20.160 --> 0:14:23.120 into our cells, and then we also chat about its 0:14:23.240 --> 0:14:26.200 mutation rate and what that means for disease severity, to 0:14:26.280 --> 0:14:29.880 its longevity on surfaces, and whether the existence of multiple 0:14:29.920 --> 0:14:31.240 strains is a concern. 0:14:32.720 --> 0:14:35.800 So she'll introduce herself to you right after this break. 0:15:08.600 --> 0:15:11.560 I'm doctor Angela Rasmussen. I'm on the faculty at the 0:15:11.600 --> 0:15:14.880 Center for Infection and Immunity at the Columbia Mailman School 0:15:14.880 --> 0:15:19.520 of Public Health. I'm a virologist who studies I specialize 0:15:19.520 --> 0:15:22.680 in studying the host response to infection. So when you 0:15:22.720 --> 0:15:26.120 get infected with a virus, your body responds to that 0:15:26.160 --> 0:15:29.800 there's an immune response, an inflammatory response. Sometimes there can 0:15:29.800 --> 0:15:34.960 be metabolic responses and I study those and sometimes those responses, 0:15:35.000 --> 0:15:38.160 depending on what they are, can mean the difference between 0:15:38.440 --> 0:15:43.160 getting rid of an infection and having a mild short 0:15:43.200 --> 0:15:47.360 illness versus having a chronic illness or a more severe disease. 0:15:48.000 --> 0:15:51.920 So the viruses that I've been studying lately are ebolavirus, 0:15:52.080 --> 0:15:57.480 MERSED coronavirus, influenza virus, other hemorrhagic fever viruses, and of course, 0:15:57.600 --> 0:16:00.800 now like many of my colleagues, I'm also studying SARS 0:16:00.840 --> 0:16:02.840 coronavirus two our COVID nineteen. 0:16:03.680 --> 0:16:05.920 That is the reason that we've brought you on today. 0:16:06.120 --> 0:16:09.760 So thank you so much, first of all for agreeing 0:16:09.800 --> 0:16:14.120 to be on the podcast. And yeah, so jumping right 0:16:14.200 --> 0:16:18.760 into the sarskov two, what are the origins of this virus? 0:16:18.800 --> 0:16:19.800 Where did it come from? 0:16:20.560 --> 0:16:23.760 So we don't know for sure, and I suspect that 0:16:23.760 --> 0:16:26.440 that's going to be my answer to almost every single 0:16:26.480 --> 0:16:30.440 one of your questions today. But we do know that 0:16:30.480 --> 0:16:33.960 there was a very very similar virus found in a 0:16:34.040 --> 0:16:39.480 bat in a cave in China in twenty seventeen. And 0:16:39.560 --> 0:16:44.480 this virus is a member of the same genus as 0:16:44.880 --> 0:16:49.760 Stars coronavirus or SARS classic and SARS coronavirus to this 0:16:49.920 --> 0:16:53.560 novel coronavirus that we're all dealing with now. There are 0:16:53.560 --> 0:16:55.760 a number of these viruses that have been discovered. They're 0:16:55.800 --> 0:17:01.760 called bat sars like coronaviruses, very clever original name because 0:17:01.800 --> 0:17:05.840 they are very much genetically like SARS coronavirus and now 0:17:05.920 --> 0:17:10.480 SARS coronavirus too. We do know that this virus, probably 0:17:10.680 --> 0:17:15.240 based on our analysis of the genome, evolved from a 0:17:15.480 --> 0:17:19.240 rus one of these batsars like coronaviruses. We don't know 0:17:19.320 --> 0:17:22.719 if there was another animal involved in the spread of 0:17:22.760 --> 0:17:26.840 this virus from its wildlife reservoir the animal that had 0:17:26.880 --> 0:17:30.239 it in the wild to humans. What we do know 0:17:30.400 --> 0:17:34.440 is that this spillover, which is the transmission of a 0:17:34.520 --> 0:17:39.280 virus from its wildlife reservoir into humans, was probably a 0:17:39.320 --> 0:17:44.960 single event, meaning that there weren't multiple instances of animals 0:17:45.000 --> 0:17:49.360 infecting people. After the first patient or patients weren't infected 0:17:49.359 --> 0:17:52.360 with this from whatever animal it came from, it's been 0:17:52.520 --> 0:17:56.600 transmitted human to human ever since. The reason why it's 0:17:56.640 --> 0:18:00.879 important to understand eventually if this came directly from a 0:18:00.880 --> 0:18:03.520 bat or if it came from a different animal is 0:18:03.560 --> 0:18:09.199 that both STARS classic and MERS coronaviruses were amplified in 0:18:09.280 --> 0:18:13.240 an intermediate species, so both stars and mers are thought 0:18:13.280 --> 0:18:18.840 to have also originated in bats. However, SARS classic was 0:18:18.880 --> 0:18:22.320 transmitted into humans most likely from an animal called a civet, 0:18:22.920 --> 0:18:26.639 and murrs. Coronavirus is known to be transmitted primarily from 0:18:26.760 --> 0:18:31.200 dromedary camels to humans, so we don't know if there 0:18:31.240 --> 0:18:34.240 was another animal in between the bat and the human 0:18:34.640 --> 0:18:39.040 that also was involved in the spillover from its wildlife reservoir. 0:18:40.119 --> 0:18:43.439 To follow up on that, So you mentioned that this 0:18:43.680 --> 0:18:48.560 likely came from one spillover event, So from one infected animal, 0:18:48.560 --> 0:18:51.159 whether it was a bat or a different intermediate host 0:18:51.240 --> 0:18:53.960 into a human. How can we tell whether it's one 0:18:53.960 --> 0:18:55.440 spillover event or multiple. 0:18:56.160 --> 0:18:59.400 Yeah, so you can tell that by looking at the genome. 0:18:59.480 --> 0:19:03.400 And one thing that's been really incredible and also really 0:19:03.400 --> 0:19:06.600 hard to keep up with about this particular epidemic is 0:19:06.640 --> 0:19:09.560 that this is really the first time that we've had 0:19:09.680 --> 0:19:15.280 sequence data from the virus genome really really soon after 0:19:15.359 --> 0:19:19.480 the first patients were reported, So the first viral sequences 0:19:19.520 --> 0:19:23.600 were uploaded and shared with the international scientific community in 0:19:23.640 --> 0:19:27.679 early January. So we've been able to analyze the genome 0:19:27.720 --> 0:19:30.159 of this virus since before we actually were able to 0:19:30.200 --> 0:19:33.239 even isolate the virus. So we can look at the 0:19:33.240 --> 0:19:36.199 genome of this virus, and we can look at the 0:19:36.240 --> 0:19:42.000 specific individual changes in one isolate of the virus versus another, 0:19:42.520 --> 0:19:46.880 and by looking at those changes, we can deduce how 0:19:46.920 --> 0:19:50.080 many different viruses came out of the bats versus went 0:19:50.119 --> 0:19:54.080 from person to person. There are specific genetic signatures that 0:19:54.119 --> 0:19:59.720 are associated in many cases with bat coronaviruses and coronaviruses 0:19:59.800 --> 0:20:04.520 that are transmitted with in bats, including some sequences that 0:20:04.600 --> 0:20:08.919 are part of the envelope glycoprotein which is called spike, 0:20:09.040 --> 0:20:12.480 and that molecule is on the surface of the virus 0:20:12.760 --> 0:20:15.359 and it allows the virus to enter a cell that 0:20:15.359 --> 0:20:20.480 it's going to infect. That protein spike has changes sometimes 0:20:20.480 --> 0:20:24.439 that are specific to bats versus specific to humans, and 0:20:24.480 --> 0:20:27.200 we can look at that as well to determine how 0:20:27.240 --> 0:20:31.840 recently the virus emerged from a bat versus emerged from 0:20:31.880 --> 0:20:32.280 a human. 0:20:33.440 --> 0:20:34.480 Awesome, thank you? 0:20:34.800 --> 0:20:38.840 Did that make sense? Okay? Yes, absolutely, okay, good. 0:20:39.600 --> 0:20:42.439 So kind of along those lines of the proteins on 0:20:42.480 --> 0:20:46.480 the surface, are those related to how the virus gets 0:20:46.480 --> 0:20:49.000 in and actually causes disease. What do we know about 0:20:49.000 --> 0:20:52.400 the mechanism of how this virus causes disease in humans? 0:20:52.760 --> 0:20:55.919 So that's a very excellent question because it gets into 0:20:56.119 --> 0:20:59.840 what I study the host response. So there are two 0:21:00.160 --> 0:21:03.280 things to any virus infection. To keep in mind, the 0:21:03.359 --> 0:21:07.080 virus can infect cells, and that determines whether it can 0:21:07.160 --> 0:21:12.399 establish an infection get inside, versus the viruses what we 0:21:12.440 --> 0:21:17.439 call pathogenicity, or ability to cause disease. Not all viruses 0:21:17.600 --> 0:21:22.919 cause severe disease. Some viruses, most viruses that can cause disease, 0:21:22.960 --> 0:21:27.480 which we call pathogens. Those pathogens in some people will 0:21:27.520 --> 0:21:30.200 cause very mild disease and in some will cause very 0:21:30.240 --> 0:21:33.399 severe disease, and we're seeing that in terms of the 0:21:34.200 --> 0:21:40.280 fairly broad range of disease presentations of COVID nineteen. So 0:21:40.680 --> 0:21:43.480 the ability to get into the cell is just one part. 0:21:43.560 --> 0:21:46.320 And of course, in order to cause disease, a virus 0:21:46.400 --> 0:21:48.920 has to be able to infect the cell. So those 0:21:48.960 --> 0:21:51.159 proteins on the surface of the cell or on the 0:21:51.200 --> 0:21:54.639 surface of the virus particle called spike. Spike binds the 0:21:54.680 --> 0:21:59.479 host cellular receptor, which is in humans. The molecule we 0:21:59.520 --> 0:22:03.040 know about anyways is called ACE two, and ACE two 0:22:03.080 --> 0:22:06.159 is on a variety of different tissues, but there's a 0:22:06.160 --> 0:22:08.239 lot of it in your lungs, which is why this 0:22:08.359 --> 0:22:12.040 causes a pulmonary disease. So certainly in that sense, the 0:22:12.119 --> 0:22:16.760 virus spike protein is involved in determining that this is 0:22:16.800 --> 0:22:21.159 going to be a pulmonary disease. Similarly, we know that 0:22:21.200 --> 0:22:24.400 ACE two is expressed in the gastrointestinal tract, and there 0:22:24.400 --> 0:22:27.520 have been reports that infectious virus has been found in 0:22:27.520 --> 0:22:31.439 the stool of some patients. Also, people have reported diarrhea, 0:22:31.800 --> 0:22:34.879 which may again suggest that the ability to infect the 0:22:34.920 --> 0:22:39.199 intestine because of that receptor binding the spike protein on 0:22:39.240 --> 0:22:42.639 the surface of the virus particle allows this virus to 0:22:42.640 --> 0:22:46.879 cause a gastrointestinal disease. But when you're talking about what 0:22:47.400 --> 0:22:50.679 is the difference between a virus in two different people, 0:22:51.280 --> 0:22:54.680 causing a mild cold like illness in one person versus 0:22:54.680 --> 0:22:59.879 causing severe pneumonia in another, that difference is often related 0:22:59.880 --> 0:23:02.440 to to the host response, and that can be determined 0:23:02.440 --> 0:23:04.320 by a lot of different things. It can be determined 0:23:04.359 --> 0:23:08.399 by genetics, It can be determined by the health state 0:23:08.480 --> 0:23:11.080 of that individual, which we again already know as a 0:23:11.160 --> 0:23:14.800 risk factor because people with pre existing medical conditions are 0:23:14.840 --> 0:23:18.879 more susceptible to severe disease. So really a lot of 0:23:18.920 --> 0:23:21.560 the disease is likely caused by a sort of out 0:23:21.560 --> 0:23:27.440 of control inflammatory response in infected tissues, and that largely 0:23:27.480 --> 0:23:31.960 depends on the person who's infected, as well as their 0:23:32.160 --> 0:23:36.240 overall health condition and sometimes the circumstances in which they're infected. 0:23:37.520 --> 0:23:38.320 That was so. 0:23:38.240 --> 0:23:40.439 Beautiful, such a great answer. 0:23:40.520 --> 0:23:44.000 Yeah, thank you. I get passionate about the host response. 0:23:46.800 --> 0:23:50.680 So recently, there was a paper that was published that 0:23:50.880 --> 0:23:53.800 found that there were two strains of the virus, and 0:23:53.840 --> 0:23:57.120 they named these strains L and S. And these strains, 0:23:57.119 --> 0:24:00.399 according to this paper, seem to differ in their very life, 0:24:00.560 --> 0:24:03.400 one being more aggressive than the other. And this finding 0:24:03.520 --> 0:24:06.520 has seemed to be a little bit controversial. So can 0:24:06.560 --> 0:24:10.399 you talk about why it is controversial and whether the 0:24:10.480 --> 0:24:13.959 possibility of multiple strains is a real concern and maybe 0:24:14.000 --> 0:24:17.879 whether this finding is actually valid. Are there multiple strains 0:24:17.920 --> 0:24:19.320 of stars kov two? 0:24:20.040 --> 0:24:25.320 Right? So this definitely gets down into the an inherent 0:24:25.400 --> 0:24:29.840 property of RNA viruses like coronaviruses, and that is that 0:24:30.040 --> 0:24:33.320 every time the virus copies its own genome in order 0:24:33.400 --> 0:24:37.160 to replicate or make more viruses, the virus makes mistakes. 0:24:37.359 --> 0:24:41.119 The enzyme that copies the genome does not have proofreading 0:24:41.160 --> 0:24:45.240 capability the way that the analogous enzymes that we have 0:24:45.280 --> 0:24:48.960 that copy our DNA genomes do, so that means that 0:24:49.000 --> 0:24:52.720 the virus makes mistakes. We call these mutations. Many of 0:24:52.760 --> 0:24:57.280 these mutations are silent, they don't have any effect on 0:24:57.440 --> 0:25:00.560 the way the virus works. Many more of them will 0:25:00.680 --> 0:25:02.879 have a negative effect on the way the virus works 0:25:02.920 --> 0:25:05.320 and make it so that the virus can't work essentially, 0:25:05.960 --> 0:25:10.840 and some of them will confer an advantage. These mutations 0:25:10.880 --> 0:25:15.480 occur randomly, so there has to be a selection pressure 0:25:15.600 --> 0:25:20.040 to maintain mutations from generation to generation. And some of 0:25:20.080 --> 0:25:25.520 these advantages can be an enhancedability to replicate in various 0:25:25.520 --> 0:25:28.919 host cells. It can be the ability to evade the 0:25:28.960 --> 0:25:33.280 host immune response. It can be something that would make 0:25:33.320 --> 0:25:38.399 the virus more capable of infecting cells or capable of 0:25:38.440 --> 0:25:41.680 inducing a response that would lead to more severe disease. 0:25:42.440 --> 0:25:45.320 So right now we don't know what a lot of 0:25:45.359 --> 0:25:48.800 those theoretical mutations would be that could make the virus 0:25:48.880 --> 0:25:54.400 more virulent, capable of infecting more cells, or more pathogenic, 0:25:54.520 --> 0:25:59.080 capable of causing more intense disease. The paper that you 0:25:59.160 --> 0:26:04.600 mentioned is controversial because essentially it's grouping these two viruses 0:26:04.640 --> 0:26:09.240 into what they're calling strains. But what are normal groupings 0:26:09.440 --> 0:26:14.000 of RNA viruses that have replicated in multiple hosts. What 0:26:14.160 --> 0:26:19.040 makes a virus a strain a different strain often depends 0:26:19.080 --> 0:26:23.479 a lot on which virus you're talking about. In this case, 0:26:24.080 --> 0:26:28.960 if we're talking about two different genotypes or virus genomes 0:26:29.000 --> 0:26:35.120 that encode virus genes that result in differential disease or 0:26:35.400 --> 0:26:38.080 more severe disease in one person versus less in another. 0:26:39.040 --> 0:26:42.320 Whether that's a strain or not is sort of up 0:26:42.320 --> 0:26:45.640 for debate. What I think is controversial about this paper 0:26:46.680 --> 0:26:49.720 is that essentially they were just grouping a variety of 0:26:49.800 --> 0:26:53.520 different clinical isolates of the virus and then going back 0:26:53.600 --> 0:26:56.800 to the clinical data that have been recorded about those 0:26:56.840 --> 0:27:00.639 patients and making assumptions that these genetic changes is that 0:27:00.760 --> 0:27:05.600 distinguished these two groups were responsible for any differences they 0:27:05.680 --> 0:27:12.320 found in the patient's conditions. That is, it's really hard 0:27:12.359 --> 0:27:15.359 to say, first of all, the group the viruses and 0:27:15.400 --> 0:27:17.159 the L group versus I think, what is it the 0:27:17.320 --> 0:27:22.199 S group. Yeah, the differences between those viruses, they're not 0:27:22.359 --> 0:27:26.640 all it's not just two viruses. They're groups of viruses 0:27:26.760 --> 0:27:29.760 that cluster together when you look at their genomes and 0:27:29.800 --> 0:27:33.960 compare them. So it's really difficult to say that any 0:27:34.040 --> 0:27:39.439 one of the specific genomic changes that are characteristic of 0:27:39.480 --> 0:27:45.960 either group are directly responsible for causing increased or decreased disease. 0:27:46.000 --> 0:27:48.120 Severity gotcha. 0:27:48.320 --> 0:27:52.640 So it's possible or likely that there might be multiple 0:27:53.400 --> 0:27:56.439 quote unquote strains of this virus, but whether or not 0:27:56.480 --> 0:28:00.280 that translates into any manifestations in terms of disease. Disease 0:28:00.359 --> 0:28:03.040 severity is not yet clear and we probably won't know 0:28:03.119 --> 0:28:04.080 it for a while. 0:28:04.600 --> 0:28:07.639 Yeah, that's fair to say. And this is really also 0:28:07.960 --> 0:28:11.240