WEBVTT - Breakthrough, Part Two: How the Dead Are Helping the Living 0:00:01.040 --> 0:00:04.560 It's the early days of the pandemic in and doctor 0:00:04.640 --> 0:00:08.479 Daniel Cherto has a new patient, a twenty six year 0:00:08.480 --> 0:00:11.400 old male who was hospitalized with chance pain. He did 0:00:11.440 --> 0:00:14.640 not present with the typical COVID symptoms, you know, the 0:00:14.680 --> 0:00:17.120 shortness of breath, for fever and all this other stuff. 0:00:17.160 --> 0:00:20.639 It was justice comfort and he tested negative on on 0:00:20.720 --> 0:00:24.919 multiple occasions. Dan runs the Emerging Pathogen Section at the 0:00:25.000 --> 0:00:28.920 National Institutes of Health in Bethesda, Maryland, and if you're 0:00:28.960 --> 0:00:32.199 a COVID case his lab, you're not there for treatment, 0:00:32.640 --> 0:00:36.520 you're the subject of an autopsy. Dan and his team 0:00:36.520 --> 0:00:38.440 are studying this young man as part of a big 0:00:38.440 --> 0:00:41.519 emission to figure out where in the body the coronavirus goes. 0:00:42.040 --> 0:00:45.240 He thinks that by tracing the virus's path and seeing 0:00:45.280 --> 0:00:48.720 what it does, it can understand why it's causing disease 0:00:49.120 --> 0:00:52.560 and how to stop it. Think of it like he's detective, 0:00:52.680 --> 0:00:55.200 trying to collect evidence and looking for the m O 0:00:55.280 --> 0:00:59.000 of a killer before it can strike again. Primary questions 0:00:59.160 --> 0:01:03.520 that were I to address the initial questions are really 0:01:03.920 --> 0:01:09.520 the cellular distribution of the virus across the body and 0:01:09.640 --> 0:01:13.520 the brain. So, in other words, exactly where does the 0:01:13.600 --> 0:01:17.480 virus go, what cell types does it back and really, 0:01:17.520 --> 0:01:27.520 really importantly, how long does the virus stay there. Dan 0:01:27.600 --> 0:01:30.280 and his technique to work fast to get participants like 0:01:30.440 --> 0:01:33.520 his new patient. They have about twenty four hours after 0:01:33.560 --> 0:01:36.640 someone has dyed to study them certain tissues to grate 0:01:36.720 --> 0:01:40.959 quickly after death, destroying the evidence. Getting these patients in 0:01:41.040 --> 0:01:45.319 that time has become a massive logistical undertaking. They first 0:01:45.319 --> 0:01:48.520 talked to the family to get their approval. From there, 0:01:48.560 --> 0:01:51.760 they make arrangements with a funeral home to transport the 0:01:51.800 --> 0:01:55.040 remains to the NIH Clinical Center and Bethesda at least 0:01:55.080 --> 0:01:58.760 set up a call schedule where I might hear about 0:01:58.760 --> 0:02:00.920 these cases. At two o'clock in the morning, communicate with 0:02:00.960 --> 0:02:04.880 our amazing, amazing admissions department, who would facilitate our contract 0:02:04.880 --> 0:02:06.320 funel home and going out in the middle of the 0:02:06.480 --> 0:02:08.480 night bringing bodies here so that my team would be 0:02:08.520 --> 0:02:10.880 suited up. At nine o'clock in the morning on this 0:02:11.040 --> 0:02:14.160 spring day in twenty Dan and his team are in 0:02:14.200 --> 0:02:18.079 a secure along chamber wearing astronaut and spied protective gear 0:02:18.560 --> 0:02:22.320 as they examine their new patient. The man died at 0:02:22.360 --> 0:02:26.200 the hospital and tests were negative for the coronavirus, so 0:02:26.320 --> 0:02:30.560 he doesn't fit the definition of a COVID related fatality. Instead, 0:02:30.760 --> 0:02:34.680 he died of something called viral myokiditis or inflammation of 0:02:34.720 --> 0:02:37.360 the heart muscle. But dances there was a reason he 0:02:37.520 --> 0:02:40.240 still wanted to study him. And at that time you 0:02:40.320 --> 0:02:43.160 probably remembered there were a number of reports in the literature, 0:02:43.280 --> 0:02:46.560 and there were some articles coming out and of imaging 0:02:46.600 --> 0:02:50.200 of the hard and some autopsies, you know, and but 0:02:50.360 --> 0:02:55.440 case reports of viral mild cardiitis being an unusual but 0:02:55.440 --> 0:02:59.960 but present complication of COVID. As they examine his body 0:03:00.000 --> 0:03:04.000 and heart, Dan says there's good evidence COVID is the culprit. 0:03:04.560 --> 0:03:07.680 Not only that the patient offers clues about another condition 0:03:07.760 --> 0:03:11.760 link to the coronavirus. It's called multi system inflammatory syndrome. 0:03:12.200 --> 0:03:15.480 It occurs mostly in children after a saska v TO infection, 0:03:15.840 --> 0:03:19.240 but it's been reported in adults as well. Dan says 0:03:19.360 --> 0:03:23.040 it's a condition that can arise unexpectedly after a mild 0:03:23.120 --> 0:03:27.360 case of COVID. They show up later with sometimes life 0:03:27.360 --> 0:03:30.480 threatening inflammation in different oregans. So in a way he 0:03:30.520 --> 0:03:34.200 fits into that category. And so well, what's driving and 0:03:34.280 --> 0:03:37.480 that is the point of Dan's work performing these autopsies 0:03:37.600 --> 0:03:40.640 is like recreating police sketches and more and more detail. 0:03:41.120 --> 0:03:44.440 With every autopsy, the picture gets clearer of what COVID 0:03:44.520 --> 0:03:47.760 is capable of doing across our bodies and what impact 0:03:47.800 --> 0:03:50.080 it may have on them in the long run. Is 0:03:50.080 --> 0:03:53.000 there going to be, you know, some low level or 0:03:53.080 --> 0:03:57.600 subclinical injury to your heart that then may manifest differently 0:03:57.920 --> 0:04:01.280 later in life. I don't know. Is there going to 0:04:01.360 --> 0:04:05.920 be some subclinical effect on your brain that are going 0:04:05.960 --> 0:04:10.040 to cause nerve cognitive issues later in life that perhaps 0:04:10.080 --> 0:04:15.160 are not immediately noticeable or detectable. If you're going to 0:04:15.320 --> 0:04:22.960 begin to conceive of ways to prevent or treat those manifestations, 0:04:23.800 --> 0:04:26.560 either in the group that the next group that might 0:04:26.600 --> 0:04:29.680 be exposed or among the group that are suffering, you, 0:04:29.680 --> 0:04:32.159 you need to understand mechanism. You need to understand what 0:04:32.279 --> 0:04:34.760 the drivers are. But this work has a long way 0:04:34.760 --> 0:04:38.000 to go. Scientists like Dan are just starting to learn 0:04:38.040 --> 0:04:41.200 the biological means by which siskov two managers to affect 0:04:41.480 --> 0:04:45.440 virtually every organ system in the body. Those infected and 0:04:45.600 --> 0:04:51.000 experience symptoms lasting months and potentially years. The condition is 0:04:51.040 --> 0:04:54.960 called long covid, and Dan's research could help us understand 0:04:54.960 --> 0:05:00.599 how to better combat it. But science is an iterative process. 0:05:01.040 --> 0:05:05.000 New information or clues have to be checked and validated 0:05:05.040 --> 0:05:08.719 before they're accepted as proof, and right now there's a 0:05:08.720 --> 0:05:12.400 ton of information but not a lot of admissible evidence. 0:05:13.160 --> 0:05:15.920 Conflicting theories have popped up over the last year and 0:05:15.960 --> 0:05:19.360 a half, which only shows how much more fact gathering 0:05:19.520 --> 0:05:23.200 needs to be done and resources for critical research like 0:05:23.360 --> 0:05:27.560 autopsies that help us understand new diseases have been stretched 0:05:27.600 --> 0:05:31.400 in It means disease detectives have fewer tools to use 0:05:31.440 --> 0:05:34.400 in that pursuit of the killer. I'm not here to 0:05:34.480 --> 0:05:37.040 service of fear manger. I mean that's not that's not much. 0:05:37.320 --> 0:05:45.920 It's just that these are some under answered questions. I'm 0:05:46.000 --> 0:05:49.800 Jason Gale, chief biosecurity correspondent and a senior editor at 0:05:49.800 --> 0:06:08.680 Bloomberg News. From the Prognosis podcast. This is breakthrough. Pathology 0:06:08.680 --> 0:06:11.000 is one of the sort of fundamental building blocks of medicine. 0:06:11.440 --> 0:06:14.039 This is Dr Linda Isles. She's the head of Forensic 0:06:14.040 --> 0:06:18.200 Pathology Services at the Victorian Institute of Forensic Medicine. It's 0:06:18.240 --> 0:06:21.080 like a medical examiner's office, but this one in Melbourne 0:06:21.200 --> 0:06:24.240 is the largest of its kind in Australia. Linda is 0:06:24.279 --> 0:06:27.880 as heat bespectacled woman with short, salt and pepper hair. 0:06:28.400 --> 0:06:31.680 She finished medical school at the University of Tasmania more 0:06:31.720 --> 0:06:34.480 than twenty years ago and then went on to train 0:06:34.520 --> 0:06:39.080 in anatomical pathology. She estimates she probably did two hundred 0:06:39.480 --> 0:06:43.640 three d autopsies during her training, which if you compare 0:06:43.680 --> 0:06:46.919 that to kind of really old school back in the day, 0:06:47.279 --> 0:06:50.120 then that might not seem like very many. But if 0:06:50.160 --> 0:06:53.880 you compare that to anaton called pathology trainees now, then 0:06:53.920 --> 0:06:58.680 that is a very large amount. These days, pathology trainees 0:06:58.720 --> 0:07:03.680 aren't even required to do autopsies. Fundamentally, autopsies are expensive procedures. 0:07:03.920 --> 0:07:07.960 I think autopsies have been slightly undervalued by clinicians over 0:07:08.040 --> 0:07:12.800 a number of years, even decades perhaps, and as less 0:07:12.840 --> 0:07:17.960 autopsies are requested, less pathologists have experience with autopsies. This 0:07:18.080 --> 0:07:22.160 points to a big problem happening in modern medicine. Autopsies 0:07:22.280 --> 0:07:25.480 have been the bedrock of medical science since at least 0:07:25.480 --> 0:07:30.120 the fifteen hundreds, but today sophisticated imaging and other modern 0:07:30.120 --> 0:07:33.720 diagnostic tools and hospital cost cutting have turned them into 0:07:33.760 --> 0:07:37.640 a dying science. Linda says there are a few reasons 0:07:37.640 --> 0:07:40.680 why autopsies have started to go out of style. One 0:07:40.720 --> 0:07:43.880 of them is that facilities are expensive to maintain at 0:07:43.880 --> 0:07:49.640 a safe standard. So it's this spiral of decreased experience 0:07:49.760 --> 0:07:53.440 and therefore decreasing confidence and then under utilization of the 0:07:53.480 --> 0:07:58.160 facilities to some of the facilities essentially being mothballed, and 0:07:58.200 --> 0:08:00.840 then when you want to reinstat to them, then they're 0:08:00.840 --> 0:08:03.360 no longer really safe for modern practice. So it's sort 0:08:03.360 --> 0:08:06.600 of like this catch twenty two, and now we really 0:08:06.680 --> 0:08:10.040 left with the generation of pathologists that have really quite 0:08:10.120 --> 0:08:14.720 limited autopsy experience, and therefore their confidence in performing autopsies 0:08:15.080 --> 0:08:25.239 safely is significantly diminished. This lack of expertise was only 0:08:25.320 --> 0:08:28.440 exacerbated during the pandemic. In the first few months of 0:08:28.480 --> 0:08:32.160 the outbreak, health authorities warned that doctors would become infected 0:08:32.160 --> 0:08:36.800 while performing autopsies and handling virus laden tissues. That led 0:08:36.840 --> 0:08:39.160 to half of these units shutting down. In the US, 0:08:39.760 --> 0:08:42.720 the same sort of scenario played out across the world. 0:08:43.320 --> 0:08:46.200 In Germany, initially it was like, no, we will definitely 0:08:46.280 --> 0:08:49.120 not autopsy these COVID patients, and then a bunch of 0:08:49.160 --> 0:08:51.200 pathologist said no, we have to do this. Because this 0:08:51.280 --> 0:08:54.160 is a new disease process. And then they just did 0:08:54.160 --> 0:08:57.160 a complete switchero and funded the autopsy program, which is 0:08:57.440 --> 0:08:59.800 where a lot of the really valuable data has actually 0:08:59.840 --> 0:09:02.959 come out of Among the first four million fatal COVID 0:09:03.000 --> 0:09:08.080 cases worldwide, only several hundred were autopsied and the findings 0:09:08.160 --> 0:09:11.720 reported in medical journals. That delayed getting answers to some 0:09:11.800 --> 0:09:15.240 crucial questions about COVID nineteen and its effects in the body. 0:09:15.960 --> 0:09:19.760 The good news is that detailed post mortem investigations are 0:09:19.800 --> 0:09:23.080 picking up now. Linda says this could also bring greater 0:09:23.160 --> 0:09:27.040 awareness the value of autopsy research, whether it's just going 0:09:27.040 --> 0:09:28.640 to be a sort of short term thing or whether 0:09:28.679 --> 0:09:31.160 it's going to translate into something kind of more meaningful. 0:09:31.200 --> 0:09:32.640 I mean, I can only hope that it's going to 0:09:32.679 --> 0:09:35.679 be the ladder. But you know this, the idea that 0:09:35.960 --> 0:09:38.400 novel infectious diseases are a thing of the past is 0:09:38.840 --> 0:09:40.640 you know. I think this has kind of brought this 0:09:41.040 --> 0:09:44.400 certainly front and center for people. Not all doctors waited 0:09:44.480 --> 0:09:48.920 so long before returning to autopsies. Disease detectives like Dancerto 0:09:49.280 --> 0:09:52.000 accepted the risk early on in the pursuit of answers. 0:10:03.480 --> 0:10:06.640 Most of the SHOTS team he's made up of trainees, 0:10:07.320 --> 0:10:09.320 and at the start of the pandemic, he wanted to 0:10:09.320 --> 0:10:12.240 give them the chance to contribute from home if they 0:10:12.240 --> 0:10:15.200 felt more comfortable working that way. I said, we're an 0:10:15.200 --> 0:10:18.240 emerging pathoge in his lab, like there's a pandemic. If 0:10:18.280 --> 0:10:20.480 you want to work remotely, that's okay. But for those 0:10:20.520 --> 0:10:22.920 of you that want to be present on SAITE, these 0:10:22.920 --> 0:10:25.199 are the things we're going to be focusing on. Selectives 0:10:25.280 --> 0:10:29.040 stick around and with rare exception, you know, everybody's like 0:10:29.640 --> 0:10:32.560 we're on deck. Dan himself is used to working in 0:10:32.640 --> 0:10:38.400 dangerous environments. He was in Liberia during the Ebola crisis, 0:10:38.720 --> 0:10:43.040 caring for patients and later studying the virus. Before that, 0:10:43.120 --> 0:10:46.360 he worked on the nineteen eighteen Spanish flu pandemic virus. 0:10:47.120 --> 0:10:50.920 His experience provided a grounding in bio safety that's carried 0:10:50.920 --> 0:10:54.840 through to his personal life. Dan says he takes precautions 0:10:54.880 --> 0:10:57.600 like wearing a face mask when he can't physically distance 0:10:57.920 --> 0:11:01.880 to prevent getting SANSKOVI two. I'm not a risk averse person. 0:11:02.000 --> 0:11:06.160 I'm a believer in calculated and controlled risk, right, but 0:11:06.360 --> 0:11:11.400 I know that my absolute preference for myself, my family, 0:11:11.480 --> 0:11:13.840 my loved ones, my colleagues, my kids. I got an 0:11:13.840 --> 0:11:16.160 eight year old and a twelve year old, my preferences 0:11:16.200 --> 0:11:19.280 for them not to be infected. Dan says he applied 0:11:19.320 --> 0:11:22.120 one hey and I was learned from the Ebola outbreak 0:11:22.400 --> 0:11:27.040 to understanding kinvid nineteen. It started with this idea that 0:11:27.480 --> 0:11:29.920 first we gotta go find where this virus is going, 0:11:30.400 --> 0:11:32.480 what it's doing in those places, and then we got 0:11:32.520 --> 0:11:34.560 to try to link it back to what we're seeing 0:11:34.600 --> 0:11:39.200 clinically and what is coming out with volumes and volumes 0:11:39.200 --> 0:11:43.880 of evidence that we're all struggling to assimilate and trying 0:11:43.920 --> 0:11:47.839 to put those pieces together to to tell a cohesive 0:11:48.040 --> 0:11:53.080 story about the mechanisms that are contributing to severe acute illness, 0:11:53.120 --> 0:11:57.760 to some mild or asymptomatic disease and others, and in 0:11:58.200 --> 0:12:01.480 a reasonable portion of the popular sation of survivors long 0:12:01.600 --> 0:12:05.880 term symptoms that are really distressing. Dan and his group 0:12:05.960 --> 0:12:08.640 are also trying to figure out how the virus and 0:12:08.679 --> 0:12:12.040 the body interact, which is another way of saying, in 0:12:12.320 --> 0:12:16.000 all those locations that you found evidence of RUS, what 0:12:16.160 --> 0:12:19.920 was the body's response. Is there an infiltration of immune 0:12:19.920 --> 0:12:23.000 cells even in the absence of immune cells, is their 0:12:23.040 --> 0:12:27.240 evidence of damage within those tissues or organs, etcetera, etcetera. 0:12:27.360 --> 0:12:31.120 To begin to better understand that relationship between the virus 0:12:31.160 --> 0:12:33.720 and the host the host response. The more you understand 0:12:33.800 --> 0:12:37.000 that relationship, theoretically, the better equip you will be to 0:12:37.559 --> 0:12:41.680 design therapies and interventions that might mitigate aspects of the 0:12:41.720 --> 0:12:46.360 disease course. These postmoneum exams do carry risk, but the 0:12:46.480 --> 0:12:51.079 pathologists from the National Cancer Institute actually performing the autopsies 0:12:51.320 --> 0:12:55.480 have decades of experience. These are the gentlemen of physicians 0:12:55.840 --> 0:12:59.040 and their trainees that that we're here doing autopsies during 0:12:59.040 --> 0:13:01.440 the AIDS era, and these guys were in there doing 0:13:01.480 --> 0:13:04.640 autopsies on hundreds of patients with this new disease, HIV AIDS. 0:13:05.280 --> 0:13:07.440 So we have now the benefit of working with that 0:13:07.480 --> 0:13:12.720 group here now decades later, lots of experience. These aren't 0:13:12.760 --> 0:13:16.720 typical autopsies though they're done over three hours in a 0:13:16.800 --> 0:13:20.640 secure facility. That's required for work involving microbes that can 0:13:20.679 --> 0:13:25.800 cause serious and potentially lethal disease. So our group, the 0:13:25.840 --> 0:13:30.240 pathologists they design home design a grain box, which is 0:13:30.320 --> 0:13:33.520 basically plexiglass with a glove it's like a glove box. 0:13:34.000 --> 0:13:37.920 Bio Engineers on the NIH campus custom build an enclosure 0:13:38.000 --> 0:13:40.360 that fits over the head and shoulders of the deceased 0:13:40.640 --> 0:13:44.120 to contain aerosols when the brain is removed, to cut 0:13:44.160 --> 0:13:48.080 through the skulls. A little bit morbid, but there's aerosolization, right, 0:13:48.120 --> 0:13:51.280 So you don't want to overly contaminate the environment. So 0:13:51.440 --> 0:13:54.720 implementing this thing and working, and this takes some time. 0:13:55.400 --> 0:13:58.840 The seven also doctors, scientists, and technicians working inside the 0:13:58.880 --> 0:14:03.920 autopsy suite, where multiple layers of personal protective equipment, usually 0:14:04.040 --> 0:14:08.839 a plastic apron over a surgical gown, over an impermeable cover, 0:14:08.960 --> 0:14:13.439 all over surgical scrubs. Sometimes arm sleeve protectors are worn. 0:14:14.000 --> 0:14:16.640 They also donned three pairs of gloves and two pairs 0:14:16.679 --> 0:14:20.200 of shoe coverings, and instead of ninety five masks. They're 0:14:20.240 --> 0:14:25.040 breathing through controlled air purifying respirators, which provide heaper filtered 0:14:25.080 --> 0:14:28.120 air under a hood that fits over the head and shoulders. 0:14:28.760 --> 0:14:31.960 It's cumbersome, but it's not the only aspect of these 0:14:31.960 --> 0:14:37.040 COVID autopsies that makes the work painstaking. We're sampling way 0:14:37.080 --> 0:14:38.600 above in the yard. What has done in any sort 0:14:38.640 --> 0:14:43.120 of diffical We sampled almost a hundred different regions within 0:14:43.160 --> 0:14:45.800 the body across the whole body and brings a hundred 0:14:45.840 --> 0:14:49.120 different areas. And for each one of those areas, we 0:14:49.280 --> 0:14:53.400 collected and preserved adjacent pieces of tissue in different ways 0:14:53.560 --> 0:14:57.360 that are amenable to various down stream analysis that preserve 0:14:57.440 --> 0:15:00.760 the tissues in a better way. It's a ton of 0:15:00.800 --> 0:15:04.520 time and energy to analyze these samples, but time is important. 0:15:05.040 --> 0:15:07.520 The first cases of long COVID happened over a year 0:15:07.520 --> 0:15:11.280 and a half ago, and only more developing. The sooner 0:15:11.320 --> 0:15:14.600 we get results from autopsies like Dan's, the Sinner will 0:15:14.640 --> 0:15:17.480 begin to address the long term effects of COVID nineteen. 0:15:18.160 --> 0:15:20.600 Dan's are research will not only help us understand what 0:15:20.640 --> 0:15:33.120 the courses are, but how to counter them. There are 0:15:33.120 --> 0:15:35.480 many theories on white people continue to suffer from a 0:15:35.560 --> 0:15:39.880 multitude of symptoms long after a coronavirus infection. Some are 0:15:40.000 --> 0:15:44.400 easy to explain, others are a mystery. For example, it's 0:15:44.440 --> 0:15:46.800 known that if COVID gave you a severe case of pneumonia, 0:15:47.160 --> 0:15:50.119 your lungs could have scarring that might reduce lung capacity. 0:15:50.720 --> 0:15:54.680 That's an unfortunate consequence of acute respiratory distress syndrome that 0:15:54.760 --> 0:15:57.960 can also occur with the flu. If you were unlucky 0:15:58.040 --> 0:16:01.360 enough to need intensive care, that slinked to muscle weakness, 0:16:01.520 --> 0:16:04.840 memory problems, and a raft of other conditions referred to 0:16:04.880 --> 0:16:08.400 as post intensive care syndrome. And if you were really 0:16:08.480 --> 0:16:13.400 unfortunate and needed mechanical ventilation that's long been associated with 0:16:13.480 --> 0:16:17.720 post traumatic stress disorder. But these aren't the problems baffling 0:16:17.760 --> 0:16:22.360 doctors and researchers. The biggest surprise of COVID is that 0:16:22.920 --> 0:16:26.640 people who are not in the intensive care unit, people 0:16:26.760 --> 0:16:30.040 actually who are never needed to be hospitalized, are still 0:16:30.080 --> 0:16:34.560 having persistent symptoms. This is Dr Walter Kaschatz, who we 0:16:34.680 --> 0:16:37.640 heard from in our last episode. He heads the National 0:16:37.720 --> 0:16:41.600 Institute of Neurological Disorders and Stroke and Bethesda. Walter says 0:16:41.760 --> 0:16:45.320 it's this group of patients, the ones with unexplained fatigue, 0:16:45.600 --> 0:16:49.240 brain fog, weird heart palpitations, and body aches and pains, 0:16:49.320 --> 0:16:52.720 who also represent the largest pool of patients who are 0:16:52.760 --> 0:16:57.040 persistently unwell as a result of the pandemic. The long 0:16:57.160 --> 0:17:02.680 COVID have fatigue. That's the primary, very complaining factor. That's 0:17:02.680 --> 0:17:05.680 true about the post ice use cases, as well, fatigue 0:17:06.000 --> 0:17:10.440 is a major problem, but the long COVID symptom complex 0:17:10.680 --> 0:17:15.800 of fatigue, trouble with memory, travel with thinking quickly, executive function, 0:17:16.760 --> 0:17:23.960 trouble as sleep pain syndromes sometimes, and exercise and tolerance. 0:17:24.720 --> 0:17:28.920 Those are the features of this syndrome that we don't 0:17:28.960 --> 0:17:33.600 have good explanations for at this point. In some ways, 0:17:33.680 --> 0:17:37.160 the disease pattern many long COVID suffers experience resembles mono 0:17:37.680 --> 0:17:41.880 or infectious mononucleosis. It's called glandular fever where I am 0:17:41.920 --> 0:17:44.600 in Australia, and some people refer to it as the 0:17:44.680 --> 0:17:48.240 kissing disease, possibly because it's spread through saliva and often 0:17:48.240 --> 0:17:52.880 occurs in teenagers. The culprit is usually the epstein bea virus. 0:17:53.080 --> 0:17:56.080 It can cause fever, swollen glands in the neck and armpits, 0:17:56.280 --> 0:17:59.359 and a sore throat. Most cases of mono were mild 0:17:59.400 --> 0:18:01.800 and resol of in their own in one to two months, 0:18:01.840 --> 0:18:06.000 but Waltera says that's not always the case with infectious 0:18:06.000 --> 0:18:10.040 mono nucleosis. There is another syndrome which you've probably heard 0:18:10.040 --> 0:18:15.160 about well, realogic can cephalomi elitis chronic critique syndrome and 0:18:15.560 --> 0:18:20.080 symptoms are very overlapping between what long COVID folks are 0:18:20.119 --> 0:18:24.400 complaining of and what happens in NBCFS. It's just that 0:18:25.080 --> 0:18:28.960 MBCFS has a six month period. You have to had 0:18:28.960 --> 0:18:32.160 those symptoms for six months, But it looks like people 0:18:32.200 --> 0:18:36.399 are moving into that space. Waltera says. Researchers have been 0:18:36.440 --> 0:18:39.320 trying for years to figure out the causative driver of 0:18:39.400 --> 0:18:42.879 that longer term illness after infectious morning. Now with the 0:18:42.960 --> 0:18:47.480 thirty four million people with COVID, it's a tremendous challenge 0:18:47.560 --> 0:18:49.359 now that we have to take up to try to 0:18:49.440 --> 0:18:53.280 figure that out. There is now a greater chance that 0:18:53.320 --> 0:18:57.199 we're going to figure it out now because we have 0:18:57.320 --> 0:19:00.920 this opportunity to study so many people and to try 0:19:00.920 --> 0:19:05.960 and understand what differentiates those who get better quickly versus 0:19:05.960 --> 0:19:10.080 those who have these persistent symptoms. So the hope is that, 0:19:10.240 --> 0:19:13.639 you know, we can get some answers that would allow 0:19:13.760 --> 0:19:17.960 us to try different treatments to see what helps and 0:19:18.000 --> 0:19:24.600 then potentially also learns something about what causes NBCFS as well. 0:19:25.119 --> 0:19:28.200 Congress is giving the National Institutes of Health one point 0:19:28.280 --> 0:19:32.080 one five billion dollars over four years to find answers 0:19:32.920 --> 0:19:36.160 Ault along with Dr Anthony Felchi from the National Institute 0:19:36.160 --> 0:19:39.479 of Allergy and Infectious Diseases and Dr Gary Gimmons from 0:19:39.520 --> 0:19:43.600 the National Heart Institute are co directing the research. There's 0:19:43.600 --> 0:19:46.240 a clinical team, that's an autopsy team, that the electronic 0:19:46.320 --> 0:19:50.960 health record team, I know, there's a big data team, 0:19:51.000 --> 0:19:53.600 and there's probably a couple of others, So there's I 0:19:53.640 --> 0:19:56.919 think the estimate was three hundred people have been working 0:19:56.960 --> 0:20:01.320 on this project since November. The amount of money Congress 0:20:01.320 --> 0:20:04.200 has set aside to study long COVID seems a lot, 0:20:04.400 --> 0:20:06.919 but it pales compared with the trillions of dollars the 0:20:06.960 --> 0:20:10.600 pandemic has cost already and the economic toller will have 0:20:10.720 --> 0:20:14.240 decades into the future. Some estimates suggest that more than 0:20:14.359 --> 0:20:17.119 one billion people around the world have been infected with 0:20:17.119 --> 0:20:20.720 the coronavirus. We don't know yet what proportion of them 0:20:20.720 --> 0:20:23.920 will develop long COVID or the duration of their symptoms. 0:20:24.600 --> 0:20:27.439 My gut feeling is that you're probably close to a 0:20:27.520 --> 0:20:30.480 ten percent figuring out about six months out. This is 0:20:30.600 --> 0:20:33.960 Dr RV. Nath He's the clinical director at the National 0:20:34.000 --> 0:20:38.480 Institute of Neurological Disorders and Stroke. The one waterheads people 0:20:38.520 --> 0:20:41.119 do recover or a period of flame on spontaneous people. 0:20:41.400 --> 0:20:43.800 But most often if you're not better by six months, 0:20:43.960 --> 0:20:48.120 then the chances of getting better are become really less. Obviously, 0:20:48.119 --> 0:20:53.280 says the impact on individuals, families, and societies will be 0:20:54.960 --> 0:20:56.840 I mean, nobody's gonna do with the calculations for you, 0:20:58.240 --> 0:21:01.080 but it's a dream on society to get every single level. 0:21:01.119 --> 0:21:03.800 I mean, it affects women more than then. It affects 0:21:03.920 --> 0:21:07.240 people and their average ages forty that's the most productive 0:21:07.320 --> 0:21:10.600 years of your life. And so you can see that 0:21:11.040 --> 0:21:15.600 the impact worldwide impact of this is unbelievable. You couldn't 0:21:15.640 --> 0:21:20.760 translate it to money. The impact is I mean the 0:21:20.800 --> 0:21:25.200 economic toll, the psychological toll. Every aspect of society is 0:21:25.240 --> 0:21:29.679 kind of touched. It's why figuring out the cause and 0:21:29.760 --> 0:21:34.360 waste to treat and prevent long COVID are so critically important. Obviously, 0:21:34.600 --> 0:21:38.320 there could be two main driving forces behind the clinical manifestations. 0:21:38.800 --> 0:21:41.560 One is that the coronavirus manages to persist in the 0:21:41.600 --> 0:21:46.200 body somewhere somehow, and that it's lingering presence is damaging 0:21:46.200 --> 0:21:50.200 the body directly, or it's triggering an immune response that's 0:21:50.240 --> 0:21:54.800 causing the damage. Another hypothesis is that the coronavirus has 0:21:54.800 --> 0:21:58.920 sent the immune system haywire, and it's this disregulated immune 0:21:58.920 --> 0:22:03.640 response that's drive long COVID. I think they're all reasonable hypotheses, 0:22:03.720 --> 0:22:07.600 but they're not exclusive. They could be interrelated. Have He's 0:22:07.680 --> 0:22:11.640 been researching chronic fatigue for years and now he's also 0:22:11.680 --> 0:22:15.000 trying to understand it as well as other elements in 0:22:15.080 --> 0:22:18.960 long COVID patients. One of the interesting features about this 0:22:19.080 --> 0:22:21.600 illness is that if you look at it, the people 0:22:21.600 --> 0:22:24.479 who had were these long haul symptoms are often not 0:22:24.560 --> 0:22:27.200 the individuals who are hospitalized and we're sicking on and 0:22:27.280 --> 0:22:30.560 went later and stuff like that. These are individuals who actually, 0:22:30.640 --> 0:22:33.120 most often they never went to the hospital. They were 0:22:33.160 --> 0:22:37.200 at home and during that time they had relatively mild 0:22:37.240 --> 0:22:41.280 illness in the acute phase and they recovered from it. Obviously, 0:22:41.280 --> 0:22:43.480 says that the people who were sick enough to require 0:22:43.560 --> 0:22:47.840 hospitalization probably mounted a strong immune response that helped them 0:22:47.880 --> 0:22:52.280 to eventually recover and importantly get rid of the virus. 0:22:52.520 --> 0:22:55.840 But if you had a mild illness, perhaps you never 0:22:55.920 --> 0:22:59.439 mounted a strong enough immune response. You thought, oh, you know, 0:22:59.520 --> 0:23:02.280 I escaped, but in reality you've never got rid of 0:23:02.280 --> 0:23:06.159 the virus. Viruses can remain in their infectious form and 0:23:06.200 --> 0:23:09.359 a range of diseases from AIDS to chicken box to 0:23:09.480 --> 0:23:13.160 a bowler. Some sortists say that the coronavirus may cause 0:23:13.200 --> 0:23:15.640 a persistent infection in places like the gas and wind, 0:23:15.680 --> 0:23:19.920 testinal tract, and the nose, but there's no consensus among 0:23:20.000 --> 0:23:25.040 scientists that that's the case, obviously, says Another possibility is 0:23:25.080 --> 0:23:28.600 that what's persisting are viral particles. They may not be 0:23:28.600 --> 0:23:32.840 completely replicating, butter instead expressing some features of the virus. 0:23:34.040 --> 0:23:36.320 Now what the body is going to see it as 0:23:36.359 --> 0:23:38.119 a foreign object, is going to try to mount an 0:23:38.119 --> 0:23:42.320 immune response against. So you've got this conic immune activation 0:23:42.400 --> 0:23:44.960 that persists in these individuals, but it's never good enough 0:23:45.000 --> 0:23:46.480 to get rid of it because they never got river 0:23:46.520 --> 0:23:48.840 in the first place, but it's enough to start causing 0:23:48.840 --> 0:23:53.199 collateral damage. Obviously, the same pattern of immune activation and 0:23:53.200 --> 0:23:57.520 exhaustion in chronic fatigue or m ec effast patients. They 0:23:57.560 --> 0:24:00.639 look very much like these long hold COVID patients, and 0:24:00.720 --> 0:24:02.800 they had the similar problems. They usually start off with 0:24:02.960 --> 0:24:05.760 some violent infection, then they had cover from it, and 0:24:05.760 --> 0:24:09.560 then this thing persists. Whatever. The field of researchers working 0:24:09.560 --> 0:24:13.520 to unravel COVID's mysteries is growing, and it's bringing in 0:24:13.640 --> 0:24:19.919 expertise from all kinds of areas neurology, cardiology, horminology, and 0:24:20.040 --> 0:24:31.680 infectious diseases that includes HIV. Medicine Professor Steve Deetz has 0:24:31.720 --> 0:24:35.560 been researching a cure for HIV for almost thirty years 0:24:35.600 --> 0:24:40.120 at the University of California, San Francisco. When the pandemic hit, 0:24:40.520 --> 0:24:43.520 Steve took notice. We had no idea what was going 0:24:43.560 --> 0:24:45.280 to go on with Sariskoby too, but we knew it 0:24:45.280 --> 0:24:47.440 was a big deal, and we had a good sense 0:24:47.480 --> 0:24:50.800 that they're probably going to be some long term content places. 0:24:50.840 --> 0:24:54.840 Everybody was focused on short term. Steve began enrolling patients 0:24:54.960 --> 0:24:58.879 in a study aimed at identifying how saskov two affects 0:24:59.040 --> 0:25:03.000 long term health. Subset have long COVID and some don't, 0:25:03.560 --> 0:25:06.040 and we're beginning to do the biology. And one of 0:25:06.040 --> 0:25:10.000 our leading hypotheses is that the virus does persist in 0:25:10.080 --> 0:25:14.400 some people for some reason, and that that persistent virus 0:25:14.480 --> 0:25:17.960 initiates an inflammatory process. At the heart of all this 0:25:18.040 --> 0:25:22.320 has always been the concern that there is something that 0:25:22.440 --> 0:25:27.480 persists and stimulates that a normal response. Steve thinks the 0:25:27.520 --> 0:25:31.920 coronavirus might be leaving traces behind. It could be viral protein, 0:25:32.440 --> 0:25:36.320 strands of its genetic material, or even bits of antigen 0:25:36.480 --> 0:25:40.000 that the immune system responds to. We don't think it's 0:25:40.080 --> 0:25:42.680 virus replication, but I guess it could be virus that's 0:25:42.720 --> 0:25:46.360 replicating in target cells and tissues. We always thought that 0:25:46.359 --> 0:25:50.000