WEBVTT - This is How the Virus Kills 0:00:05.519 --> 0:00:10.479 Welcome to Prognosis. I'm Laura Carlson. It's day twenties. Since 0:00:10.520 --> 0:00:14.880 coronavirus was declared a global pandemic, cases around the world 0:00:14.920 --> 0:00:18.880 have soared past seven hundred and forty five thousand today, 0:00:19.440 --> 0:00:23.640 the deadly tipping point that determines when COVID nineteen kills. 0:00:25.720 --> 0:00:38.199 But first the day's main stories. President Donald Trump extended 0:00:38.240 --> 0:00:41.800 guidelines for Americans to practice social distancing until at least 0:00:41.880 --> 0:00:44.760 the end of April. Last week, he had said he 0:00:44.840 --> 0:00:48.720 hoped to see life returned to normal by Easter. Anthony Fauci, 0:00:49.000 --> 0:00:52.639 the director of the National Institute of Allergy and Infectious Diseases, 0:00:52.920 --> 0:00:56.400 as well as Deborah Burke's, the State Department immunologist advising 0:00:56.560 --> 0:00:59.880 Vice President Mike Pence, were able to change the president's 0:01:00.040 --> 0:01:04.000 lined about a swift economic restart by showing him projections 0:01:04.160 --> 0:01:09.559 that millions of Americans may wind up infected. President Trump 0:01:09.560 --> 0:01:14.040 said Sunday that one hundred thousand people or more may die. 0:01:14.400 --> 0:01:18.400 Only a few weeks ago, the President repeatedly downplayed concerns 0:01:18.440 --> 0:01:21.399 about the virus, saying it would go away and he 0:01:21.600 --> 0:01:26.080 was not concerned at all. A former FDA commissioner proposed 0:01:26.080 --> 0:01:29.000 a roadmap for eventually getting people back to work and 0:01:29.080 --> 0:01:33.760 lifting restrictions on movement. Scott Gottleib is a physician and 0:01:33.800 --> 0:01:36.760 one of the co authors of the paper released Sunday 0:01:36.760 --> 0:01:41.959 by conservative think tank American Enterprise Institute. The paper spells 0:01:41.959 --> 0:01:45.800 out a four phase plan for navigating the COVID nineteen pandemic. 0:01:46.520 --> 0:01:50.840 The paper recommends continuing with aggressive social distancing measures until 0:01:50.880 --> 0:01:54.240 there has been a sustained reduction in cases for fourteen days. 0:01:55.320 --> 0:01:58.440 At that point, Gottleiep and his colleagues say governments could 0:01:58.480 --> 0:02:03.880 start lifting restrictions verry gradually, but the plan requires widespread 0:02:03.920 --> 0:02:07.200 testing that's not currently in place in the US, and 0:02:07.280 --> 0:02:09.880 we seem far from reaching that two week period of 0:02:09.919 --> 0:02:13.840 reduction in cases. The infection rate in the US continues 0:02:13.880 --> 0:02:16.640 to escalate, and the number of deaths grew to more 0:02:16.680 --> 0:02:21.400 than undred over the past two days. All around the world, 0:02:21.639 --> 0:02:25.280 the number of places enacting strict isolation measures is going up. 0:02:26.240 --> 0:02:29.760 The tie tourist hotspot of Poquette went on lockdown, and 0:02:29.880 --> 0:02:33.560 Moscow's nearly thirteen million residents were ordered to stay home. 0:02:34.960 --> 0:02:38.720 In the US, Maryland Governor Larry Hogan issued a stay 0:02:38.720 --> 0:02:43.200 at home order saying voluntary measures weren't working, and on 0:02:43.320 --> 0:02:47.720 Monday afternoon, Governor Ralph Northam echoed the decision. In Virginia, 0:02:47.919 --> 0:02:51.120 Virginians were ordered to remain in their homes except for 0:02:51.240 --> 0:03:00.320 central services and now today's main story, the deadly tipping point. 0:03:03.280 --> 0:03:06.839 The new coronavirus has sickened hundreds of millions and will 0:03:06.880 --> 0:03:10.120 infect many more, but only a small fraction of the 0:03:10.120 --> 0:03:13.120 people who get the virus dye. The virus acts in 0:03:13.160 --> 0:03:15.680 a way that scientists are still trying to figure out. 0:03:16.560 --> 0:03:19.920 In some people who are infected, symptoms are mild, like 0:03:19.960 --> 0:03:24.720 a common cold. Some don't have symptoms at all. In others, though, 0:03:24.960 --> 0:03:28.760 symptoms are severe and even fatal, with the infections stopping 0:03:28.760 --> 0:03:31.720 the lungs from functioning and causing the body to shut down. 0:03:33.000 --> 0:03:35.920 So why are symptoms so mild in some people and 0:03:36.040 --> 0:03:39.960 deadly in others. It turns out there's a tipping point, 0:03:40.520 --> 0:03:42.960 a moment where the virus moves from one part of 0:03:42.960 --> 0:03:46.440 the body to another that can determine whether the virus 0:03:46.520 --> 0:03:50.920 is manageable or fatal. Jason Gale spoke to experts to 0:03:51.000 --> 0:03:53.760 understand what the virus does to us once it's in 0:03:53.760 --> 0:04:01.920 our bodies. As of nineteen, the disease caused by the 0:04:01.960 --> 0:04:06.120 new coronavirus spreads around the world. Scientists are beginning to 0:04:06.200 --> 0:04:09.800 understand more about how it maims and kills. A picture 0:04:09.920 --> 0:04:14.160 is emerging of an enigmatic pathogen whose effects are mainly mild, 0:04:14.560 --> 0:04:18.960 but which occasionally and unpredictably becomes serious. In the second 0:04:19.040 --> 0:04:22.760 or third week in a fraction of patients. Bodily systems 0:04:22.760 --> 0:04:26.279 start to fall apart in a cascade. But what causes 0:04:26.320 --> 0:04:38.600 this deadly tipping point. Other diseases like SARS or severe 0:04:38.600 --> 0:04:43.640 acute respiratory syndrome and influenza offer important clues about what's 0:04:43.640 --> 0:04:46.760 going on inside the body when someone has COVID nineteen. 0:04:46.920 --> 0:04:50.839 The clinical picture suggests a pattern of disease that's not 0:04:51.040 --> 0:04:53.360 dissimilar to what we might see in influenza, with a 0:04:53.480 --> 0:04:57.000 range of outcomes. Dr Jeffrey Taubenberger is a pathologist who 0:04:57.080 --> 0:05:01.080 studied the infection in victims of the Spanish flu pandemic, 0:05:01.560 --> 0:05:04.440 including one exam to more than twenty years ago from 0:05:04.480 --> 0:05:09.200 perma frost in northwestern Alaska. Jeffrey heads the Viral Pathogenesis 0:05:09.200 --> 0:05:12.440 and Evolution section of the National Institute of Allergy and 0:05:12.440 --> 0:05:16.480 Infectious diseases in Bethesda, Maryland. In his spare time, he's 0:05:16.520 --> 0:05:20.360 a musician and composes symphonies and operas, but COVID nineteen 0:05:20.600 --> 0:05:24.039 is his current focus. The answer to what the pathogenesis 0:05:24.040 --> 0:05:26.560 is and why certain people are having more severe disease 0:05:26.600 --> 0:05:29.640 and others having mild disease is not fully understood. But 0:05:29.680 --> 0:05:32.679 I think that in relation to other diseases sours twenty 0:05:32.720 --> 0:05:36.359 years ago almost and influenza now for hundred years, we 0:05:36.440 --> 0:05:40.760 have information where it's at least analogous. COVID nineteen causes 0:05:41.000 --> 0:05:43.240 a little more than a cough if it stays in 0:05:43.279 --> 0:05:45.960 the nose and throat, which it does for most people 0:05:46.000 --> 0:05:48.400 a unlucky enough to be infected. The vast majority of 0:05:48.400 --> 0:05:50.240 people who are exposed to a virus to which they 0:05:50.240 --> 0:05:53.479 probably don't have protective immunity get infected, and most of 0:05:53.520 --> 0:05:56.720 them clear their virus and get better with varying illness. 0:05:56.720 --> 0:05:59.479 A report from China and February showed that one in 0:05:59.600 --> 0:06:05.120 seven patients develops difficulty breathing, and six of cases are critical. 0:06:05.720 --> 0:06:10.080 It's why hospitals worldwide are either experiencing or bracing for 0:06:10.600 --> 0:06:15.120 scores of patients requiring mechanical ventilation. For days two weeks. 0:06:15.960 --> 0:06:19.360 Jeffrey says infection is like a dance between the host 0:06:19.760 --> 0:06:23.960 that's us and the pathogen, in this case, the new coronavirus. 0:06:24.240 --> 0:06:27.679 What causes disease and how quickly it can escalate comes 0:06:27.680 --> 0:06:30.880 down to an interplay of three factors, how nasty the 0:06:30.960 --> 0:06:34.359 virus is, the body's immune response to it, and the 0:06:34.480 --> 0:06:38.599 role of secondary infections. What generally happens is that you 0:06:38.720 --> 0:06:41.600 get an infection of a virus that sets up an 0:06:41.600 --> 0:06:44.400 infection along cells that line your respiratory tracts, starting at 0:06:44.400 --> 0:06:47.839 your nose, maybe migrating downwards into your trachea and the bronchos, 0:06:47.880 --> 0:06:50.839 and then maybe eventually into lungs. If your infection is 0:06:50.920 --> 0:06:53.600 limited to the upper respiratory tract more like a call. 0:06:53.880 --> 0:06:56.880 Even with influenza, you're mostly likely to get a cold 0:06:57.000 --> 0:07:01.080 virus like disease mild. You sort of throat in a 0:07:01.120 --> 0:07:04.760 cough and sniffles and sneeze, maybe fever, but you otherwise 0:07:04.800 --> 0:07:18.400 don't get severely. Danger starts when the virus reaches the lungs. 0:07:18.600 --> 0:07:21.680 Pathogenic viruses that induce a lot of direct sell death 0:07:21.720 --> 0:07:25.600 along the restaur attract induce a very strong inflammatory response. 0:07:25.720 --> 0:07:28.120 The kind of a so called pro inflammatory response that 0:07:28.240 --> 0:07:36.400 itself is actually damaging to bystander cells. The inflammatory responses 0:07:36.440 --> 0:07:40.080 an initial warning system, like a fire alarm. The body's 0:07:40.120 --> 0:07:43.520 first respond is different types of white blood cells, known 0:07:43.560 --> 0:07:47.080 as neutrophils and macrofages are sent out to destroy and 0:07:47.320 --> 0:07:51.240 dispose of infected cells and repair damage tissue. Let's say 0:07:51.280 --> 0:07:54.040 in an analogy, you don't necessarily know where the fire is, 0:07:54.080 --> 0:07:55.920 but there's a fire, and so you should do something. 0:07:55.960 --> 0:07:58.280 We should shun on sprinklers, which you call the fire department. 0:07:58.440 --> 0:08:00.600 We should turn on the water host. So this initial 0:08:00.600 --> 0:08:03.560 inflammatory response is that initial response. There's something wrong, we 0:08:03.640 --> 0:08:06.200 need to do something. Normally, if this goes well, the 0:08:06.240 --> 0:08:09.400 infection is cleared up in just a few days. The 0:08:09.440 --> 0:08:14.120 inflammation tamps down viral replication, enabling the body to recover. 0:08:14.680 --> 0:08:18.880 But in rare instances, this inflammatory response goes overboard and 0:08:18.920 --> 0:08:21.600 becomes damaging. Jeffrey says, cells that may not even be 0:08:21.640 --> 0:08:25.080 infected with the virus can be targeted and damaged by 0:08:25.120 --> 0:08:29.040 these inflammatory cells. Your body is immediately trying to repair 0:08:29.080 --> 0:08:31.440 the damage in the lung as soon as it's happening. Uh. 0:08:31.480 --> 0:08:34.000 And then it's a question of does the inflammatory in 0:08:34.040 --> 0:08:37.800 the virus win or does your reparative and immune responses win? 0:08:37.880 --> 0:08:40.160 And most of the time evene responses win because most 0:08:40.160 --> 0:08:42.280 people will get infective with these viruses survive, but in 0:08:42.320 --> 0:08:45.680 some people they don't. The destruction of cells can release 0:08:45.720 --> 0:08:49.560 toxins into the bloodstream, attracting more neutrophils to clean up 0:08:49.600 --> 0:08:52.200 the dead material, and that can itself kind of create 0:08:52.280 --> 0:08:55.840 kind of a perfect storm of augmenting the inflammatory response. 0:08:56.000 --> 0:08:59.680 Further studies of fatal COVID nineteen patients have confirmed this 0:08:59.760 --> 0:09:03.760 kind of bi standard damage along the respiratory tract. The 0:09:03.800 --> 0:09:07.880 coronavirus targets distinctly shaped protein receptors, and these are found 0:09:07.880 --> 0:09:12.160 on many organs and tissues, including epithelial cells. When an 0:09:12.160 --> 0:09:16.000 infection harms the epithelium lining the trachea and bronchi, it 0:09:16.040 --> 0:09:19.160 can result in the loss of protective mucus producing cells, 0:09:19.520 --> 0:09:22.280 as well as the tiny hairs or cilia that sweep 0:09:22.320 --> 0:09:26.160 dirt and respiratory secretions out of the lungs. It's part 0:09:26.160 --> 0:09:28.560 of the interplay between the initial damage caused by the 0:09:28.640 --> 0:09:32.199 virus and the secondary damage caused by the body's own 0:09:32.200 --> 0:09:36.440 inflammatory response, and that combination can lead you to have 0:09:36.520 --> 0:09:39.240 more severe disease that can set you up for the 0:09:39.320 --> 0:09:42.439 third piece of this puzzle, which is that if you 0:09:42.720 --> 0:09:46.520 damage especially the lower respiratory tract epithelium and all the 0:09:46.559 --> 0:09:49.360 barriers that you have in your lungs from keeping bacteria 0:09:49.400 --> 0:09:52.840 and other pathogens from getting down into the lung, meaning 0:09:52.880 --> 0:09:55.560 that you've damaged the lining of the trichy bronchial trees 0:09:55.600 --> 0:09:58.000 and that the cilia that can constantly move all this 0:09:58.120 --> 0:10:02.200 material upward or lost, you lose mucous secretion, you have 0:10:02.280 --> 0:10:05.160 no ability to keep stuff out of the lower respiratory track. 0:10:05.320 --> 0:10:08.640 You can set yourself up for in an evasive secondary 0:10:08.640 --> 0:10:12.040 bacterial infection. In the case of Spanish flu, autopsies and 0:10:12.160 --> 0:10:16.320 experimental studies performed in the Torbenberger Lab show that almost 0:10:16.400 --> 0:10:19.720 everyone who died from the nine eighteen pandemic succumbed to 0:10:19.760 --> 0:10:24.120 a secondary bacterial pneumonia. Jeffrey says it's too early to 0:10:24.160 --> 0:10:28.520 save something similar as happening with COVID nineteen. The coronavirus 0:10:28.600 --> 0:10:32.040 has some features that set it apart from flu. One 0:10:32.120 --> 0:10:34.480 is that it's capable of replicating not just in the 0:10:34.520 --> 0:10:38.040 cells of the respiratory system, but also in other parts 0:10:38.080 --> 0:10:41.520 of the body, including the gastro intestinal tract, and that's 0:10:41.520 --> 0:10:45.720 probably why some patients experience diarrhea and why the virus 0:10:45.760 --> 0:10:48.720 has been found in stool. But it's the damage to 0:10:48.760 --> 0:10:52.480 the lungs that's feeling intensive care unipeds many I see 0:10:52.520 --> 0:10:56.600 you patients require mechanical ventilation to counter low blood oxygen, 0:10:57.000 --> 0:11:02.000 a condition doctors referred to as hypoxia in terms of 0:11:02.080 --> 0:11:05.600 end stage disease. If the lung ist damaged knowledge from 0:11:05.600 --> 0:11:08.560 a primary of ouril infection and or secondary of bacterial infection, 0:11:08.640 --> 0:11:12.000 both in flu or in coronavirus, but consequence of that 0:11:12.200 --> 0:11:16.600 is um decreased lung functions, You have decreased oxygen exchange, 0:11:17.160 --> 0:11:21.640 and if you have less oxygen available then is needed 0:11:21.800 --> 0:11:25.480 you start damaging other end stage organs. Of course, your kidneys, 0:11:25.480 --> 0:11:28.360 your livering, your brain, your heart as vague get damaged 0:11:28.480 --> 0:11:31.760 and as your kidneys stop being able to clear toxins 0:11:31.800 --> 0:11:34.160 that in self induces more disease. You can see that 0:11:34.200 --> 0:11:37.840 you can have this multi organ failure as an end 0:11:37.880 --> 0:11:42.560 stage of disease, although it's really primarily related to the 0:11:42.600 --> 0:11:46.800 loss of pulmonary function in hypoxia. During my interview, one 0:11:46.800 --> 0:11:50.720 of Jeffrey's main collaborators join the conversation. I'm pretty sure 0:11:50.760 --> 0:11:53.320 I don't know anything more. Dr David Morrens is a 0:11:53.400 --> 0:11:57.400 senior scientific advisor to Tony Fauci, the director of the 0:11:57.480 --> 0:12:01.720 National Institute of Allergy and Infectious Disease IS. David graduated 0:12:01.720 --> 0:12:05.199 from medical school in nine three and joined the Sentence 0:12:05.240 --> 0:12:08.959 for Disease Control and Preventions Epidemic Intelligence Service a few 0:12:09.040 --> 0:12:12.040 years later. He's been at the institute for more than 0:12:12.080 --> 0:12:14.800 twenty years and was wearing a navy uniform of the 0:12:14.880 --> 0:12:19.240 United States Public Health Service. David's been studying emerging infectious diseases, 0:12:19.360 --> 0:12:24.199 including the ways viruses cause disease, for more than forty years. 0:12:24.400 --> 0:12:27.840 He says patterns and COVID nineteen patients are pretty familiar. 0:12:28.040 --> 0:12:30.320 I sometimes think of it as when you get a bad, 0:12:30.400 --> 0:12:33.960 overwhelming infection, everything starts to fall apart. In the cascade. 0:12:34.080 --> 0:12:37.080 It's like dominoes falling over. You know, the oxygen gets 0:12:37.080 --> 0:12:39.480 a lot of the tissue gets more damaged, the immune 0:12:39.520 --> 0:12:44.400 responses more effective, the oxygen radicles come up, and you 0:12:44.760 --> 0:12:47.640 pass the tipping point where everything's going downhill and at 0:12:47.640 --> 0:12:49.880 some point you can't get it back. Both David and 0:12:49.960 --> 0:12:54.440 Jeffrey agree that chronic conditions like hypertension, diabetes, and cancer 0:12:54.440 --> 0:12:59.080 treatment impair the body's ability to fight the coronavirus. These 0:12:59.080 --> 0:13:02.480 elements are more common in older people, which is one 0:13:02.480 --> 0:13:05.040 of the reasons why age is the biggest risk factor 0:13:05.160 --> 0:13:09.160 for dying from COVID nineteen, but that risk overall remains 0:13:09.200 --> 0:13:13.840 relatively low. The experience doctors are gaining from managing patients 0:13:14.360 --> 0:13:18.960 and the evidence flowing from clinical trials are informing treatment guidelines, 0:13:19.520 --> 0:13:36.680 and that should lead to better care for patients. That's 0:13:36.720 --> 0:13:39.480 it for the Prognosis Daily Edition. For more on the 0:13:39.520 --> 0:13:42.720 coronavirus crisis from a hundred and twenty bureaus around the world, 0:13:43.160 --> 0:13:48.479 visit Bloomberg dot com slash coronavirus. If you appreciate the podcast, 0:13:48.720 --> 0:13:50.920 please take a moment to read us and leave us 0:13:50.920 --> 0:13:54.240 a review on Apple Podcasts or Spotify to help more 0:13:54.280 --> 0:13:59.240 listeners find our global reporting. The Prognosis Daily Edition is 0:13:59.280 --> 0:14:02.600 hosted by me Laura Carlson. The show is produced by 0:14:02.640 --> 0:14:08.199 Me Tob Foreheads, Jordan Gospore, and Magnus Hendriksson. Reporting by 0:14:08.280 --> 0:14:13.240 Jason Gale, Original music by Leo Sigrid. Our editors are 0:14:13.280 --> 0:14:18.080 Francesca Leavie and Rick Shine. Francesca Levy is Bloomberg's head 0:14:18.080 --> 0:14:20.240 of podcasts. Thanks for listening.