SCRIPT:
Hi I’m Wendy Zukerman and you’re listening to Science Vs from Gimlet. Today on the show. What’s going on with young people and the coronavirus? Is it now coming for us?
From the early days of this coronavirus, we were hearing that older people were the ones who were getting really sick … and dying.[1] But in the past few weeks, it seems like there have been more and more stories of younger folk getting hit really hard[2].
So we’ve started to wonder, is this virus scarier for younger people than we thought? And for today’s episode, we’re thinking about young people as those who are under 60 … basically: boomers and up - we’re calling you older[3]. And that’s because a lot of the data we have divides people up like this.
OK, so we're going to begin with a story about a guy, a younger guy, who’s gone through all this ..
Ring ring
WZ Hi this is Wendy
DS: Hi Wendy, How are you going?
WZ I’m good. How are you going is the question?
DS Yeah yeah It’s been aah harrowing week
Meet Dani Schuchman[4] [SCHUCK-MAN]. He’s 40. And before all this hit him .. he was a healthy guy. In fact, a very healthy guy. This is Dani’s usual Sunday morning.
I get up at 5:30 in the morning, I go out for a cycle for two hours that’s usually about 30 miles
WZ Oh wow
And then I come home and start the day off with the kids
Dani’s a father of four, from Florida, but now lives with his family in London.
WZ When did you start realizing something was off?
DS I think it was about 2 weeks ago, so I think it was a friday morning, um, I woke up, wasn't 100% feeling the best, a little bit more tired than normal, I didn’t really think that much of it. But then a few days later on Sunday night is when I really started feeling that something wasn't right.
He started coughing, got a fever. And his muscles were aching.
DS My body was just starting to burn up a bit and getting very hot
Over the next few days - it didn’t let up.
DS It feels painful, it feels pounding and it feels draining, as if my body was just weighted down as well
And then he started having trouble breathing… he was sitting in the living room … and tried to get up to go to the bathroom … and realized he couldn’t walk …
DS And it was as if someone was choking me, and that’s kind of really when it started to get scary was then. Y’know I wasn’t even catching my breath
WZ What do you mean you weren’t able to catch your breath?
DS Imagine that every time you take a breath you're grasping for, you are, you feel that the oxygen is in the distance, and you're grabbing and trying to get it but you can’t get it…
DS And already by Wednesday morning I was completely out of it. Didn’t really know where I was. I think at one point my wife Anna found me on the couch hallucinating a bit and I think I had just completely blanked out
AS: He sort of mumbled something and I said, what? What? What?
That’s Anna, Dani’s wife.
AS He took about 30 seconds and he was back, and I said what was that - he would say I don't know, I don't know, he just didn’t know where he was! he was so confused… he was scared at that point, he was really scared.
She took him to the hospital and parked the car, he could barely walk to the entrance.
And thankfully they had a wheelchair that I could sit down in, so I wouldn’t have to really walk anymore
WZ What did that feel like for you - a guy who’s riding 30 miles on a Sunday and now you’re in a wheelchair?
DS It was scary, it really was because here, a few days early, I'm going about my daily life, like everything I would normally do - going to work, exercising, doing things with the family … and all of a sudden here I am in the hospital in a wheelchair not being able to breathe
Dani was wheeled into triage, and they sent Anna home. From there, things got worse. Dani’s lungs were so messed up that he couldn’t get enough oxygen into his body… he was given an oxygen mask, kind of like the ones you’re told about on planes - assist yourself before you assist the kids? That kind of thing. But meanwhile at home… Anna had no idea what was going on… and the next few days for her were a wreck…
AS I kept calling… You know, every hour reports were changing, so I’d have one report - ‘He’s ok, he's stable, we’ve not had to increase his oxygen…’ and another report going, ‘We're looking at putting him on a ventilator… and you know people would be texting me and I’d say he’s stable and then an hour later everything would change and it was just so terrifying.
Saturday morning I called the hospital, and... there was panic… and you heard in the background a lot of panic, and then the nurses couldn’t talk… they said, he's being moved, he’s being moved, at the same time the newspaper come through my door - and on the second page, it said the hospital he was in ‘at capacity’… It was just it was just I don’t even know… I can’t even… My head went to some very dark places…
WZ Did you think you might lose him?
AS Absolutely. And although we had all statistics on our side, and that he was young and healthy. But he also shouldn't have got it this seriously. And you know, in my head, I’m thinking yes it's all very well everyone’s saying he's young and healthy, but he wasn't supposed to get it, so who’s to say.
While Anna was frantic… no idea what was going on, Dani would soon make a turn around. A few days later, a moment came when he realised. Oh I’m going to be ok.
DS I had a nurse who in a way was quite pushy, but pushy in a good way, and she said, ‘You know what? Today we’re getting up.’ She opened the window in the room, let some fresh air in, I sat down in the chair next to the bed, I ate my breakfast sitting up as well in the chair vs being in the bed, and she said after you eat your lunch, we’re getting you out of that chair, and you’re going to take a shower, and you’re going to change your clothes, and today is going to be that day. I still needed to have the oxygen with me, I couldn’t do it on my own as of yet. But that’s exactly what we did. That was the turning point.
WZ Wow, gotta love nurses don’t you, that she just knew
DS She knew. Yeah.
He was weaned off the oxygen to see if he could breathe on his own. After a week in the hospital … he was well enough to be taken home … a hospital van dropped him off
DS Having the family waiting by the door for me, it’s really emotional, it was, it was that sense of relief that I’m home
Dani’s doctors told him that he should make a full recovery. But the thing is... he never expected the virus to hit him so hard. And it felt like it was touch and go for a few days there. So. On today’s show - what does this virus do to make someone so sick? And when it comes to young people… is Dani an outlier here… or is this virus even scarier than we thought?
To help wrap our mind around all this, we called up an old pal … who we spoke to a few episodes ago…
WZ I guess we don’t need the pleasantries, we’re friends by now
VR Hahaha
WZ Just so we have it can you please introduce yourself,
VR My name is Vincent Racaniello, I have been doing research and teaching about viruses for over 38 years
Vincent is a professor of Columbia University.[5] And the first question we asked Vincent is how does this virus make us so sick? And he says it all starts when the virus gets into our body, and starts infecting our cells. If the virus makes its way into our lungs[6] it can be really bad[7][8][9].. That's because -- it can go after these tiny clusters of air sacs in our lungs...they look a bit like a bunch of grapes… except they’re microscopic[10]… and they help us breathe. [11][12][13][14] They’re called alveoli…
VR So the virus is destroying the cells that are lining the alveoli[15][16][17][18]
When these little air sacs … when they get damaged … stuff can sneak inside. Like fluids from our body - and that’s bad[19]. You don’t want fluids in your lung!
WZ So I’m imagining if your if you think of these little cells in your lungs like balloons in a swimming pool, and then the virus is popping these balloons and letting all this water flow in. Is that kind of what’s happening?
VR except they’re not popping, there’s very tiny holes poked in them so they still look like a balloon but they’re slowly filling with water until they’re full and the balloon looks still like a balloon except all the air is replaced with water now
WZ What would it feel like for someone experiencing that
VR It would feel like you can’t breathe.[20] You’d feel like ‘I can’t catch my breath’
But it’s important to know that during all this - the virus itself isn’t the only thing attacking our little air sacs. Something else is happening too… to battle off these nasty viruses our body starts recruiting a bunch of immune cells. And Vincent says, sometimes the body overdoes it[21][22][23] [24]… it sends too many of these fighters. And then these fighters start to damage good cells too.[25][26]
WZ So if we think about the way this virus is killing people, it's like two punches? One the virus itself is attacking our cells and then two, it’s our immune system going after those viruses, overshooting and injuring ourselves?
VR Perfect analogy. I think few people appreciate that it's not just virus hurting you, it’s actually your own immune defenses, as you said it’s a two punch thing.
So this is what can happen to people like Dani when they get really sick from this coronavirus. It’s a double punch --- the virus is infecting your lungs … and causing your immune system to freak out and then do more damage.
Our next question: How many Danis are out there? How many young people are getting so sick that they need to go to the hospital? The best data on this comes from the CDC - which found that out of 500 patients who were hospitalised - 1 in 5 were between 20 to 44 years old[27]. That’s actually quite a lot of Gen Z’s, Millennials and Gen X’s in the hospital. 20% A report out of Spain showed similar numbers. [28][29] And this idea that all these young folks are landing in hospital -- feels different to what we’ve been hearing right? Has something changed?
VR It’s not that it’s different,[30][31] it’s nothing different, I see no reason to think that at all.
It’s just that we know more now. In the early reporting of this pandemic -- a lot of the numbers we were getting were about deaths not people going to hospital.
But as this virus has spread to more places and more people -- we have gotten more information about hospitalizations. And that new data is showing -- as you just heard - that younger people are being hospitalized at fairly high rates.
Despite this though, even with the new data, we’re still seeing[32] that very few young people die from this virus. So for example recent data from Italy looking at about 5000 deaths[33] found that less than 5% of those who died were under 60. Less than 5%.
And Vincent says it's easy to understand why this is hitting older people harder…
VR So I think the virus is not doing anything special with old people, it’s just that their lungs are already problematic[34][35][36] As you age, the elastic nature of the lung goes away… Your chest muscles become weaker, and so that makes it very difficult for them
Older people often have a harder time handling respiratory viruses, like coronaviruses,[37] that’s because their lungs tend to be less resilient,[38] and their immune systems can’t get rid of the virus so easily [39][40][41][42] . Plus, they’re more likely to have other risk factors too like heart disease and diabetes.[43][44] Whereas with young people -- recovery just tends to be easier…[45]
VR They can be on oxygen for a week or two and eventually their lungs will heal and they’ll recover
And for those who don't recover ... in a lot of cases so far, it looks like they have other health problems[46][47] - like heart disease, lung disease, cancer or diabetes.[48][49][50] [51] The data we have from New York City, so far shows that around 95% of the people who are under 65 who have died … they had something else going on with their health[52] 95%.
But even though it is still very, very rare for young people with no underlying health issues to die, as more and more people get infected in the US… it will keep happening. And we might see some of those stories on the front pages[53]. But it won’t change the bigger picture.
VR The serious infections of young people are a fraction of the total, and as you get more and more infections, you get more of those.
WZ Right so it’s like, if we think of all the serious viral infections as a mountain, and young people are the tip of the mountain, it’s just now in the US, the whole mountain has gotten bigger so the tip is bigger too, is that fair?
VR That's right, that’s right, the whole mountain is getting bigger, yeah
And there is a part of that mountain that won’t get headlines… We talked to other young people who had confirmed cases of coronavirus but never had to go to hospital…
Extreme like fatigue, try to make some food, but get back in bed, don’t get me wrong, it sounds quite bad, but I’ve had much worse illnesses in the past
Just exhausted, my head was pounding, it kind of felt like an intense flu, I just figured it would have been way worse than it was
A little bit of nausea, mild scratchy throat, very much allergy symptoms, I developed a bit of chest tightness, a mild cough and that was it, it was so mild
Ok so that’s the story for young-ish folks, people who have owned Cold Play albums --- but what if -- you don’t even know who Chris Martin is? After the break -- what does this disease look like in the under 20 crowd?
BREAK
Welcome back… We’re now looking at what this disease does to people under 20 …[54] [55] While there have been some really young kids dying,[56] it’s very rare. In that Italian report of 5000 deaths, no one under 20 died[57].
And scientists are still trying to understand why --- one theory[58] -- that Vincent Racienello - our professor from Columbia - is most convinced by is that kids have baby immune systems that are actually working to their advantage…. They’re not fully matured[59] - and so their immune system isn’t reacting to the virus with that huge, dangerous inflammatory response. In other words, they might not get sick because they have a crappy immune system.
VR Well I think that kids don't actually have a crappy immune system. I think parts of it are pretty good and well developed, I think other parts are underdeveloped.[60] I think it's just the right combination to be able to escape disease
VR Now I still see very few deaths under 10 years old, it’s a good time to be young I guess.
WZ Always
VR Always is good to be young, that’s right
WZ 26 And it’s possible that kids with their weird immune system, their developing immune system I’m sorry, can do the one, can control the virus, maybe, but they don't have to worry about the second punch, maybe that’s the theory?
VR Yeah, and let me take it even further for you, let’s let’s talk just briefly about bats[61] because bats have more virus infections than probably[62] anything else on the planet and yet they’re pretty healthy[63][64][65]
Yes, bats. Our infamous little buddies who are giant reservoirs of coronaviruses.[66] Not a lot of research has been done on this, but one theory about why bats don’t get so sick, suggests that the immune system of bats doesn’t go nutso when they’re exposed to these viruses -- so they’re not getting that second dose of damage from the disease.[67][68]
VR So that’s why bats remain healthy with all these virus infections
WZ So like kids are like bats. VR That’s really obscure isn’t it? WZ That’s so obscure, I know, but I love it.
So here’s what we’ve learned from all this - is that when it comes to this coronavirus - young people can get seriously ill from it. And in very rare cases. They can die. Which means we’ve all got to take care. And one thing is for sure…
WZ No coronavirus parties. Remember chicken pox parties?
VR those can be very serious, those viruses!! That’s crazy to send your kids to a party, so no coronavirus parties, absolutely not
So… what a coronavirus party pooper. So no coronavirus parties… no parties at all in fact…
OK, now, let’s take a break from the coronavirus and go up...Waaaaaay up … 22000 feet up - that’s more than 6700 meters, We’re in the Andes mountain range.[69] And up there... just hanging out... is the yellow-rumped leaf-eared mouse… it’s a mouse that as you might expect, has a yellowish bum and ears that look a bit like a leaf. Recently, a researcher from the University of Nebraska-Lincoln spotted this little mouse - up on this mountain...and he was like hang on...what are YOU doing here? 22,000 feet up. Mammals don't usually live that high… it turned out... this little mouse was setting a WORLD RECORD!! No other mammal has been found to make its home so high up.[70] This little mouse smoked other animals known to live way up in the mountains[71][72].. like the large eared pika[73], the shrew opossum[74][75][76][77], So yeah, all of you ... Eat dust. Long live the yellow-rumped leaf-eared mouse.
That’s Science Vs
RINGING
Hello!
Hey Michelle - producer of Science Vs
AHHHH
How many citations are in this week’s episode
I still have to add one! There are 77 cites in this episode.
77 cites, that’s pretty good...ok bye
Bye!! Wait. Michelle!
Oh yeah!
Where should people go to get these citations?
Check out the link in our shownotes, or go to sciencevs.show
Thanks, Michelle
That’s Wendy bye
If you want to get more on the coronavirus, you should listen to Vincent’s Podcast, it’s called This Week in Virology. This episode was produced by Michelle Dang, Wendy Zukerman, Rose Rimler, Meryl Horn, Laura Morris, Meg Driscoll and Sinduja Srinivasan. We’re edited by Blythe Terrell and Caitlin Kenney. Fact checking by Lexi Krupp. Mix and sound design by Haley Shaw. Music written by Peter Leonard, Emma Munger, and Bobby Lord. A big thanks to all the researchers that we got in touch with for this episode, including Dr. Helen Petousis-Harris. Thanks to all the people we spoke with Anna and Daniel Schuchman, Lauren Dulay, Maggie Kaltwasser, Adria Mallett, Holly Ryan, and Ash Tilbury. And special thanks to the Zukerman family and Joseph Lavelle Wilson.
I’m Wendy Zukerman, fact you next time..
[1] BBC (Feb 18, 2020), Science Alert (Feb 19, 2020), US News (Feb 28, 2020), Time (Mar 4, 2020), Vox (Mar 12, 2020), Buzzfeed (Mar 13, 2020), AARP (Mar 14, 2020), The Conversation (Mar 17, 2020),
[2] https://www.thesun.co.uk/news/11223668/doctor-italy-intensive-care-65-young-patients/ The Sun: NOT JUST ELDERLY Doctor says HALF of coronavirus patients in Italy intensive care are under 65 with some as young as 20
“As Italy records its highest number of deaths in one day, new study shows the majority of in the 19 – 50 age group.”
Wash Post: French health ministry official Jérome Salomon said half of the 300 to 400 coronavirus patients treated in intensive care units in Paris were younger than 65; half the ICU patients in the Netherlands were younger than 50
Buzzfeed (Mar 24, 2020)
[3] The Baby Boom Cohort in the United States: 2012 to 2060: The term “baby boomer” refers to individuals born in the United States between mid-1946 and mid-1964. .. which would make the youngest boomer 56...
[6] Fifty-three patients with confirmed COVID-19 infection underwent thin-section CT examination. Forty-seven cases (88.7%) had findings of COVID-19 infection, and the other six (11.3%) were normal. Among the 47 cases, 78.7% involved both lungs
[7] Italy Characteristics of Death report: Respiratory failure was the most commonly observed complication in this sample ( 96.5% of cases), followed by acute renal injury (29.2%), acute myocardial injury (10.4%) and superinfection (8.5%). Original Italian report found here.
[8] [Note this cite is for SARS-CoV-1 -MD] Early phase disease (<11 days) is most commonly associated with acute diffuse alveolar damage. Later phase disease demonstrates a combination of diffuse alveolar damage ) and acute fibrinous and organizing pneumonia.
[9] SARS-CoV-2 was reported to utilize angiotensin-converting enzyme-2 (ACE2) as the cell receptor into humans [14], and firstly causing pulmonary interstitial damages and subsequent with parenchymal changes.
[10] The mean size of a single alveolus was rather constant with 4.2 x 10(6) microm3 (range: 3.3-4.8 x 10(6) microm3; coefficient of variation: 10%), irrespective of the lung size.
[11] In SARS: The pathological changes include thickening of the basement membrane of the alveoli capillary, edema of the alveoli septum, hyperplasia of the interstitium, apoptosis and desquamation of the alveolar epithelium cells, formation of the pulmonary hyaline membrane by exudate and other cellular components in the alveoli, hyperemia and edema of the bronchioles, infiltration of inflammatory cells and inflammatory edema, red blood cells in the alveoli, and microthrombosis formation in the blood vessels
[12] Viruses that infect endothelium may induce more significant lung injury particularly to the alveolar epithelium as a result of increased vascular permeability, edema, and spatial proximity to alveolar cells.
Release of proinflammatory cytokines, NO, and ROS from epithelium and leukocytes can enhance endothelial permeability and disrupt the integrity of the endothelial-epithelial barrier [35]. Damage to alveolar epithelium can expose and increase the susceptibility of localized endothelium to injury. Increased vascular permeability and pulmonary edema impairs efficient gas exchange between the airways and blood, resulting in respiratory distress. Thus, endothelium damage caused directly by virus or indirectly by inflammatory processes can play a significant role in pulmonary injury in response to respiratory infection.
[13] Based on the pulmonary infection of SARS-CoV-2 and SARS-CoV (811), GGOs may be due to mild edema of the alveolar septi, hyperplasia of the interstitium, partial filling of airspaces, or a combination of these features.
[14]“High ACE2 expression was identified in type II alveolar cells (AT2) of lung, esophagus upper and stratified epithelial cells, absorptive enterocytes from ileum and colon12, cholangiocytes13, myocardial cells, kidney proximal tubule cells, and bladder urothelial cells10. These findings indicated that those organs with high ACE2-expressing cells should be considered as potential high risk for 2019-nCoV infection10”
[15] Pre-print: Two lung lobectomy patients in China found to have COVID-19 at time of surgery. CASE 1 showed “ revealed evident alveolar damage, including alveolar edema”; CASE 2 “g varying degrees of proliferative phase of diffuse alveolar damage”
[16] Multifocal, patchy, or segmental consolidation, distributed in subpleural areas or along bronchovascular bundles, is usually presented in COVID-19 patients (Fig. 1b) with occurrence rate of 2~64%. NB: Consolidation is “alveolar air being replaced by pathological fluids, cells, or tissues,”
[17] One patient over 60 - Alveolar cavity congestion was prominent, and contained mucus, edema fluid, desquamated epithelial cells, and inflammatory cells… Enlarged and ruptured alveolar septum, massive pulmonary hemorrhage in alveolar cavity were found
[18] When SARS-CoV-2 infects most of the ciliated cells in the alveoli, these cells stop carrying out their normal activity, which consists of clearing the airways, with a consequent progressive accumulation of debris and fluids in the lungs and acute respiratory distress syndrome (ARDS).
[19] noncardiogenic pulmonary edema is caused by an increase in the vascular permeability of the lung, resulting in an increased flux of fluid and protein into the lung interstitium and air spaces
[20] In one study of 138 patients hospitalized in Wuhan for pneumonia due to SARS-CoV-2, dyspnea (difficult or labored breathing) developed after a median of five days since the onset of symptoms
[21] Increased levels of serum CRP, PCT, IL-6 were also found. It indicated the obvious inflammatory response among these patients… Gradually decreased lymphocytes and increased inflammation biomarkers were found in these patients, and need to be monitored in the routine treatment.
[22] Case reports from autopsies of covid-19 patients: https://www.jto.org/article/S1556-0864(20)30132-5/pdf - 2 patients
Pathologic examinations revealed that apart from the tumors, the lungs of both patients exhibited edema, proteinaceous exudate, focal reactive hyperplasia of pneumocytes with patchy inflammatory cellular infiltration, and multinucleated giant cells… these changes likely represent an early phase of the lung pathology of COVID-19 pneumonia.
[23]Non-heart-related (noncardiogenic) pulmonary edema: Fluid may leak from the capillaries in your lungs' air sacs because the capillaries themselves become more permeable or leaky, even without the buildup of back pressure from your heart. Some factors that can cause noncardiogenic pulmonary edema include: Acute respiratory distress syndrome (ARDS). This serious disorder occurs when your lungs suddenly fill with fluid and inflammatory white blood cells.
[24] Lancet letter: Accumulating evidence suggests that a subgroup of patients with severe COVID-19 might have a cytokine storm syndrome.
[25] Pre-print: Respiratory failure in severe COVID-19 is generally associated with hyperinflammation. A cytokine storm syndrome probably may be the reason for hyper inflammation in severe SARSCoV-2 disease (Huang et al. 2020; Mehta et al., 2020).
[26] Collectively, the virus particles invade the respiratory mucosa firstly and infect other cells, triggering a series of immune responses and the production of cytokine storm in the body, which may be associated with the critical condition of COVID-19 patients.
[27] CDC report from the first wave of Covid-19 patients, up to March 16 Among 508 (12%) patients known to have been hospitalized, 9% were aged ≥85 years, 36% were aged 65–84 years, 17% were aged 55–64 years, 18% were 45–54 years, and 20% were aged 20–44 years. Less than 1% of hospitalizations were among persons aged ≤19 years [55% of hospitalizations under 65yo]
[30] See graph: JAMA Paper comparing Italy’s epidemiology report to China’s “The overall case-fatality rate in Italy (7.2%) is substantially higher than in China (2.3%). When data were stratified by age group, the case-fatality rate in Italy and China appear very similar for age groups 0 to 69 years, but rates are higher in Italy among individuals aged 70 years or older, and in particular among those aged 80 years or older.”
[31] CDC Report: fatality was highest in persons aged ≥85, ranging from 10% to 27%, followed by 3% to 11% among persons aged 65–84 years
[34] The aging lung The elderly population has less pulmonary reserve, and cough strength is decreased in the elderly population due to anatomic changes and muscle atrophy.
[35] For acute respiratory failure in general: Although the survival rate among patients 70 years of age or older was high, these patients were twice as likely to die of acute lung injury compared with their younger counterparts, even after adjustment for covariates. … older patients...had delayed liberation from the ventilator even after adjustment for survival status.
[36] Acute lung injury in the medical ICU: comorbid conditions, age, etiology, and hospital outcome. With univariate analysis, age > 65 yr, organ transplantation, human immunodeficiency virus (HIV) infection, active malignancy, chronic steroid use, and a septic or aspiration-related etiology of ALI were associated with a > or = 1.2-fold greater relative risk (RR) of hospital mortality. With multiple logistic regression, independent predictors of hospital death were age > 65 yr, organ transplantation, HIV infection, cirrhosis, active malignancy, and sepsis. Full paper found here.
[37] SARS: https://www.nature.com/articles/nrmicro3143 Disease outcomes seem to be more severe in aged macaques86, which reflects human disease outcomes. As in humans, increased virus replication and increased lung pathology are noted in primates that are infected with wild-type SARS-CoV...Of particular importance is the protection of the elderly, as they might be disproportionately susceptible to severe disease from both SARS-CoV and MERS-CoV infections.
[38] https://www.journalofinfection.com/article/S0163-4453(20)30116-X/fulltext The ARDS [Acute respiratory distress syndrome] in the elderly group (4 of 18 patients [22.22%]) was higher than that in the young and middle-aged group...The proportion of multiple lobe involvement in the elderly group was higher than that in the young and middle-aged group (P < 0.001),... It may be due to changes in the elderly’s lung anatomy and muscle atrophy leading to changes in the physiological functions of the respiratory system, reduced airway clearance,7 reduced lung reserve,8 and reduced defense barrier function,
[39] The age-dependent defects in T-cell and B-cell function and the excess production of type 2 cytokines could lead to a deficiency in control of viral replication and more prolonged proinflammatory responses, potentially leading to poor outcome.
[40] Reduction and Functional Exhaustion of T Cells in Patients with Coronavirus Disease 2019 (COVID-19) The number of total T cells, CD4 + and CD8 + T cells were dramatically reduced in COVID-19 patients, especially among elderly patients (≥60 years of age) and in patients requiring Intensive Care Unit (ICU) care. .. Since an effective immune response against viral infections depends on the activation of
cytotoxic T cells that can clear infection by killing virus-infected cells, 8 boosting the numbers and function of T cells in COVID-19 patients is critical for successful recovery. A
[41] The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak – an update on the status: Collectively, the virus particles invade the respiratory mucosa firstly and infect other cells, triggering a series of immune responses and the production of cytokine storm in the body, which may be associated with the critical condition of COVID-19 patients…. “The elderly and people with underlying diseases are susceptible to infection and prone to serious outcomes, which may be associated with acute respiratory distress syndrome (ARDS) and cytokine storm.”
[42] Advances in the research of cytokine storm mechanism induced by Corona Virus Disease 2019 and the corresponding immunotherapies (Abstract in English, Article in Chinese). Translation: When the virus infects, the body quickly initiates immune defense mechanisms including specific and non-specific immune responses. Unlike specific immune responses, non-specific immune responses can occur immediately after infection and participate in viral clearance throughout the process. Nonspecific responses cause secondary damage to tissues by secreting a large number of active mediators to infected cells and nearby normal cells. It is suggested that the elderly and patients with basic diseases can not complete or need long-term induction to develop an effective specific immune response due to the degradation of their immune function. Therefore, a longer period of time after infection can only rely on a continuously increasing non-specific inflammatory response to resist the invasion and spread of the virus, leading to a greater risk of triggering a cytokine storm, an earlier onset of severe illness, and a higher mortality rate.
[43]The prevalence of chronic conditions increased with age, with four in five (80.0%) people [Australians] aged 65 years and over having one or more chronic conditions.
[44] the severe patients were older and had a more significant number of comorbid conditions than those Non-severe. These results suggest that age and comorbidities may be risk factors for critical patients
[45]Acute Lung Injury & SARS: Older patients needed the respirator longer, were more likely to require reinstitution of respirator therapy after initial improvement, and stayed in the intensive care unit longer than younger patients. At 28 days after initiation of respirator use, the survival rate was lower with each decade of advancing age.
[46]https://www.sciencemag.org/news/2020/03/how-sick-will-coronavirus-make-you-answer-may-be-your-genes#
[47] For example, this study is looking into whether the number of white blood cells people have might affect infection
[48] For patients with underlying CVD, including hypertension, coronary heart disease, and cardiomyopathy, viral illness can further damage myocardial cells through several mechanisms including direct damage by the virus, systemic inflammatory responses, destabilized coronary plaque, and aggravated hypoxia
[49] See Table 1 under comorbidity E..g About 90% of inpatients with pneumonia had increased coagulation activity, marked by increased d-dimer concentrations
[50] Italy Report on deaths: Number of positive deaths for Covid-19 who have one or more pre-existing diseases remains high. The average number of pathologies observed in this population is 2.7. Report says 9 fatalities under 40yo, 2 w/no clinical info available. The other 7 had serious pre-existing pathologies. Original report available here.
[51] CFR (case fatality rate) was elevated among those with preexisting comorbid conditions —10.5% for cardiovascular disease, 7.3% for diabetes, 6.3% for chronic respiratory disease, 6.0% for hypertension, and 5.6% for cancer.
[52] NYC Covid-19 Deaths - As if March 30, 10 am, NYC COVID-19 Deaths in age groups under 65:
Of those w/confirmed health history, 176 /184 deaths had an underlying condition
Underlying illnesses include Diabetes, Lung Disease, Cancer, Immunodeficiency, Heart Disease, Hypertension, Asthma, Kidney Disease, and GI/Liver Disease. (176/184 = 95.6)
[54] CDC March 16: 1.6% hospitalizations; NYC March 29: 11% of hospitalizations; China JAMA report: 2% of cases; Italy - See Tabella 1: 1.4% of cases
[55] China Pediatrics Data n=2143, 1/3rd confirmed cases: Clinical manifestations of pediatric patients were generally less severe; most cases were mild, with much fewer severe and critical cases (5.9% n= 125) than adult patients (18.5%)
[56] Public Health Officials Announce the First Death of an Infant with Coronavirus Disease: The Illinois Department of Public Health (IDPH) today reported the death of an infant younger than one year in Chicago who tested positive for coronavirus disease (COVID-19)
[58] Why don't children seem to get very ill from the coronavirus?: Because children’s immune systems are still developing, one suggestion is that they are shielded from this type of dangerous immune response – called a cytokine storm – when they get covid-19 or similar diseases.
[59] “children’s immune system is still developing, and may respond to pathogens differently to adults.”
[60] The immune system gradually matures during infancy. Critical early protection against many infectious diseases previously experienced by the mother is given by the passive IgG antibody transferred from the mother transplacentally and in milk. Once that fades away, young children become more vulnerable to infections, though by then better armed with the maturing innate and adaptive immune systems.; more explanation of innate and adaptive immune system maturity in text
[61] “It's no coincidence that some of the worst viral disease outbreaks in recent years -- SARS, MERS, Ebola, Marburg and likely the newly arrived 2019-nCoV virus -- originated in bats.”
[62] Bats and Coronaviruses: "Although bats harbor more zoonotic viruses per species, rodents harbor a larger total number of zoonotic viruses [102]."
[63] We inoculated 10 Jamaican fruit bats with MERS-CoV. Although all bats showed evidence of infection, none of the bats showed clinical signs of disease. Virus shedding was detected in the respiratory and intestinal tract for up to 9 days.
[64] “Understanding what immune mechanisms enable bats to coexist with RNA viruses may provide critical fundamental insights into how to achieve greater resilience in humans.”
[65] The evolution of flight in bats seem to have selected for a unique set of antiviral immune responses that control virus propagation, while limiting self-damaging inflammatory responses.
[66] To date, over 200 novel coronaviruses have been identified in bats and approximately 35% of the bat virome sequenced to date is composed of coronaviruses [20].
[67] it is unknown how bats, while naturally maintaining a high burden of viruses and the oxidative stressors of flight, are able to regulate the response against stimulatory sensing of cytosolic DNA to avoid overactivation of innate immune pro-inflammatory pathways…we hypothesized that cytosolic DNA, whether it is flight-induced or infection-derived, imposes strong selective pressures on the bat DNA sensors, resulting in a functionally dampened sensing mechanism and downstream IFN (inflammasome activation and type I interferon) production to avoid overactivation on a regular basis during normal flight and/or co-existence with viruses
[68] Bats have a suite of antiviral defenses that keep the amount of virus in check. For example, some bats have an antiviral immune response called the interferon pathway perpetually switched on. In most other mammals, having such a hyper-vigilant immune response would cause harmful inflammation. Bats, however, have adapted anti-inflammatory traits that protect them from such harm, include the loss of certain genes that normally promote inflammation.
[69] Mighty mouse: Storz discovers world’s highest-elevation mammal: World-class mountaineer Mario Pérez Mamani had guided the pair to the summit of Llullaillaco (zhoo-zhuh-ZHEYE’-koh), a dormant volcano on the western edge of the Andes Mountains and the southern fringe of the Atacama Desert.
[70] This summit specimen represents an altitudinal world record for mammals, far surpassing all specimen-based records from the Himalayas and elsewhere in the Andes
… we captured a specimen of the yellow-rumped leaf-eared mouse (Phyllotis xanthopygus rupestris) on the very summit of Llullaillaco at 6739 m
[71] A total of 125 Chinese cashmere goats were used for Sanger sequencing and covered the entire genomic region of DSG3 (44 kbp) consisting of 16 exons. Isolated genomic DNA used from Ritu (RT, 4700 m)
[72] The Tibetan cashmere goat (Capra hircus), one of the most ancient breeds in China, has historically been a critical source of meat and cashmere production for local farmers. To adapt to the high-altitude area, extremely harsh climate, and hypoxic environment that the Tibetan cashmere goat lives in, this goat has developed distinct phenotypic traits compared to lowland breeds...Tibetan Plateau, which is at an elevation above 5,000 m
[73] Large eared pikas were observed from elevation of 3560m (Thadepati) to 5000m (Lirung Glacier).
[74] In South America, several marsupials of the families Caenolestidae, Microbiotheriidae and Didelphidae inhabit high latitudes and/or altitudes with seasonally cold conditions
[75] You never really hear much about shrew-opossums or rat-opossums, the small group of living, South American marsupials properly called caenolestids or caenolestoids … inhabiting cool highlands
[76] Caenolestidae - shrew opossums - found in the Andes Mountain
[77] Among New World marsupials, the behavior and ecology of shrew-opossums of the family Caenolestidae (order Paucituberculata) are poorly known