7 ms·

1. this is a preprint, so take their results with a massive grain of salt. 2. the sample size for this is quite low. They cite number of cells in the thousands,

1. this is a preprint, so take their results with a massive grain of salt. 2. the sample size for this is quite low. They cite number of cells in the thousands, but when you look at the number of people in the study the sample size is 3 live people undergoing surgery (line 193) and 8 autopsies (line 439). 3. technical replicates in RT-qPCR are not the same as biological replicates (i.e. more people) 4. Single cell RNAseq is trendy, but again, without more biological replicates it's very much in the realm of extrapolation when considering sample size of patients vs the whole human population.

andy_ppp 5y ago
I think we should be more positive about such research (it helps us to further our understanding of COVID-19), there are many other studies that show bad outcomes for those who are obese and this paper suggests a mechanism for the poor outcomes. https://www.thelancet.com/journals/landia/article/PIIS2213-8587(21)00089-9/fulltext https://www.thelancet.com/journals/landia/article/PIIS2213-8... That paper shows nearly 3x the hazard ratio for ICU admission and death for the most obese people which is terrifying!
- FeepingCreature 5y ago
  Um. Is high hazard and death ratio for obese people something that needed explaining?
  - chiefalchemist 5y ago
    Agreed. But apparently we're on the wrong side of the narrative. The simple fact is, we don't have leadership able to tell consumers that they've done too good job (to the point of ruining their own health), that the (over) consumption economy has failed them. This is why (in the USA) we hear very little about areas not overrun (e.g., many African countries). I am by no means a Covid denier, but the bottom line is: Covid is more of a symptom (of broader health and healthcare issues) than it is a Black Plague-esque disease. Since the majoriry rules, and illness has been normalized there will be few in power willing to speak truth.
    - hdjjhhvvhga 5y ago
      It's an interesting take but you are only partly correct, because only some of these problems are self-inflicted, so to say. There are only as many ways you can influence your blood pressure levels for example. At some point no matter what you do - you run an hour a day, eat veggies mainly, eat zero salt (which is not recommended btw) - and still have higher blood pressure than your older colleague with BMI above average. So you can't just claim COVID-19 is punishing the people who don't take care of themselves.
      - nradov 5y ago
        The impact of salt on blood pressure is based on concentration (osmolality), not quantity. Consuming excess fructose can also cause hypertension due to the biochemical mechanisms in humans and other primates that cause higher uric acid production. https://peterattiamd.com/rickjohnson/ https://peterattiamd.com/rickjohnson/
      - chiefalchemist 5y ago
        I agree 100%, and should have said so in my OP, there are some who have conditions that are difficult to treat. However, there are a significant number that are legitimately preventable. Rare is rhe case where a doctor's prescription is "consume more sugar." The science, which we're all in favor of, is pretty clear on this. It's not logical that we (in the USA) continue to side step a serious discussion about the value of prevention (and how that relates to the level of unhealthines we are on average.)
    - gelert 5y ago
      Congratulations on realising that successful diseases reflect their environments and times in human history. Were you alive during the Black Death I imagine you'd be talking about how, though you're no denier, it's the fault of people using ships to trade.
      - techbio 5y ago
        Since GP refers to ubiquitous systemic issues, not xenophobia, not technological ventures, "ships to trade" seems to be a red herring. Also worth noting: "congratulations" reads more than a bit disingenuously.
  - andy_ppp 5y ago
    Obesity being a risk factor was well known. Why obesity causes more chance of death hadn't been studied well, which I believe is why the paper is appearing here. Pre-print might lead to it being rejected or outcomes changed or tweaked, and it clearly needs replication in a larger study to see if the findings hold up. But equally I think being healthy and reducing your weight is likely to increase your odds of not becoming severely ill.
    - FeepingCreature 5y ago
      Sure, but I didn't think that obesity deaths needed a factor unique to Covid 19 to explain. I'd expect, as a layman, that what causes obese people to die more from Coronavirus is probably the same thing that causes them to die more from everything else that stresses the body. (Whatever that is.)
      - hwbehrens 5y ago
        > probably the same thing These things, which are usually things like diabetes, blood sugar problems, high blood pressure, elevated cortisol and so on, do correlate with poorer COVID outcomes. My understanding is that, even when you control for these factors, outcomes for obese patients are still below what we would expect to see. This means that there is still a contributing factor that we haven't considered yet, and the parent study hypothesizes one possible reason.
      - justinator 5y ago
        > is probably the same thing that causes them to die more from everything else that stresses the body. (Whatever that is.) There's a good chance that whatever that is, isn't actually a thing, and that people unfairly find fat people repulsive for no reason except that they are fat, https://podcasts.apple.com/us/podcast/is-being-fat-bad-for-you/id1535408667?i=1000542081632 https://podcasts.apple.com/us/podcast/is-being-fat-bad-for-y...
      - Villeinesse 5y ago
        Severe D deficiencies is the 'why', while this paper deals with part of the 'how'. Since D is fat soluble, all D goes into the fat cells first, but so much fat cannot be easily filled, so while leaving the free-floating blood & organs completely unprotected, even many fat cells are still largely empty & unprotected too! D is the critical immune hormone traditional Equatorial tribes, like the Maasai, continue to make naturally in their skin, outside under their year-round UVB. With little exercise, they stay thin, healthy & happy their whole lives with D maintained at 45-55ng/ml! Obese suffer much higher rates of most modern diseases because of ever lower D, becoming diabetic, cancerous, heart-diseased, and/or auto-immune. But cheap & safe supplementation to evolutionary repletion >50ng/ml, (though requiring much higher dosing for obese), is just as protective for the obese as for any healthy or other CovidComorbid person. A recent PubMed peer-reviewed Meta-Analysis showed the complete inversality of D & Covid. They surmised that 50ng/(or 125nmol) would have ZERO CovidMortality!
  - Brave-Steak 5y ago
    > something that needed explaining This is like asking why we need science at all. We might know that obesity is a significant risk factor, but we don't know why and what we could do about it. So yes, it does need explaining. This is a possible explanation and might inspire further research into the topic, in particular preventative or curative treatments.
  - techbio 5y ago
    If something is so obvious as to need no explanation, it just might be worth understanding what about it is causal. What can be done given the predisposition to obesity in a time of abundant necessities? It seems your conclusion is to let it go to the joint processes of sin and natural selection, which would tend to call into question your moral certainty. EDIT: Another post today titled "Causal Information Affects Decisions" seems relevant here: https://news.ycombinator.com/item?id=29509236 https://news.ycombinator.com/item?id=29509236
    - FeepingCreature 5y ago
      I don't care about the moral aspect, I just thought it was established that obesity causes the body to be less able to handle ~any kind of stress. Is that actually incorrect? Like, my confusion is that I didn't think we needed to go look for a new mechanism unique to Covid here.
      - andy_ppp 5y ago
        Yes but the point is your point is added onto buy the possibility (likliyhood given the study) that being fat has a particular mechanism for it being worse than all the other co-morbidities we're talking about. That's what the paper is studying!
  - _pmf_ 5y ago
    > Um. Is high hazard and death ratio for obese people something that needed explaining? Some people might argue that convincing people to not get fat is much lower hanging fruit than transforming every democracy into an authoritarian apartheid state for effects that are well below any statistical significance threshold.
    - FeepingCreature 5y ago
      Well, to be fair, I don't even think that's obviously true even given your unsourced claims.
    - xapata 5y ago
      I think you left that under-explained.
    - hippie_queen 5y ago
      It seems that the "convincing people to not get fat" project has been a massive failure so far.
    - Klinky 5y ago
      If it has no statistical significance why would you run a campaign at all?
- peteradio 5y ago
  I think in general the advice is "preprints are not yet holy gospel". Don't start preaching on it, don't start basing your life on it.
  - andy_ppp 5y ago
    Neither are published papers in peer reviewed journals, we need to always treat everything with healthy skepticism. That obesity and bad covid outcomes happen is beyond any doubt, the interesting part for me in this paper is that they try to explain the mechanism for obesity itself being a problem, rather than say diabetes or atherosclerosis.
    - rbartelme 5y ago
      I guess my whole point was if they're trying to explain a mechanism, their sample size doesn't generalize to the population; even limiting it to the obese population. If anything they've shown, in their small cohort, that the hypothesis is worth further study. Having spent a lot of time in academia before moving into biotech, I think this is a pilot study and they're fishing for more research funding. The way those funding mechanisms work, I tend to view manuscripts like this with a critical eye.
  - evandrofisico 5y ago
    Look, even peer reviewed papers are not supposed to be treated as any kind of unquestionable truth, especially in medical sciences. It is unfortunately very common to have papers with repeatability issues or even outright wrong. Peer review just means that experienced scientists read a paper and concluded that nothing they saw was outright wrong.
- lamontcg 5y ago
  This method suggests a possible mechanism for poorer outcomes in the obese, but that does not mean that the mechanism is correct. The mechanism also involves a way for SARS-CoV-2 to infect lymphocytes in fat tissue that doesn't involve ACE2, which the authors leave completely unexplained, which is whole lot of highly surprising results. There's also simpler explanations for why the obese are at higher risk, because systemically they're in poorer shape to begin with (metabolic syndrome, etc), and mechanically they have more trouble breathing when they get sick. The title explanation is so simplistically attractive while the biological mechanism is unexpected and unexplained, which I'd say adds up to requiring a large amount of skepticism, until it gets validated by real experts in the field (not just someone with an MD or PhD on twitter, but someone who is active in exactly this kind of research). It might be an emotionally satisfying result, but it smells like bad science to me.
  - andy_ppp 5y ago
    I agree with your analysis you are correct to put these ideas forward, it does not mean the paper is incorrect. I personally think we should think of this paper as really useful datapoint rather than a set in stone conclusion either way. For me it's really interesting rather than to be dismissed as being completely not probable. Let's see and wait for other research, but I think it's a great theory that needs a lot for it to be fact (as close as we have to one). What is a fact (again, as close as we can get to one...) is that obese people die a lot more readily from COVID and anyone over say 30 BMI (because of fat) should undoubtedly assess the risk of any vaccine as being massively in their favour!
    - lamontcg 5y ago
      Hard disagree. There's so much junk science that articles need to be treated skeptically, particularly if they have strong headline claims that reinforce some common belief combined with details which are hazy and unexplained. Being totally open minded is actually not a virtue, you can be so open minded that you'll start to believe any sort of drivel you pour into your head because it sounds persuasive rather than being correct. I will happily flip my impression of this paper on a dime if someone who is actually qualified to review the actual lab methods and procedures (and if adequate controls were used, etc) pops up to defend it and to explain how cells that don't express ACE2 could possibly be important in COVID-19 pathogenesis, but until then my default setting is to be critical since the paper "smells" bad. It is not a particularly "great" theory, its a very fishy smelling theory.
- jessriedel 5y ago
  > I think we should be more positive about such research (it helps us to further our understanding of COVID-19) Listing important limitations of a study is not being negative. It is contributing to understanding the paper. The comment you are replying to is the most substantive comment in the thread. One does not need to encourage authors with compliments, nor does one need to balance criticism with praise.
NoblePublius 5y ago
Morbid obesity is the number one comorbity of Covid death.
- fdjsafdsjl 5y ago
  At least in the UK, dementia is the number one comorbidity of Covid death.

andy_ppp 5y ago

I think we should be more positive about such research (it helps us to further our understanding of COVID-19), there are many other studies that show bad outcomes for those who are obese and this paper suggests a mechanism for the poor outcomes. https://www.thelancet.com/journals/landia/article/PIIS2213-8587(21)00089-9/fulltext https://www.thelancet.com/journals/landia/article/PIIS2213-8... That paper shows nearly 3x the hazard ratio for ICU admission and death for the most obese people which is terrifying!

FeepingCreature 5y ago
Um. Is high hazard and death ratio for obese people something that needed explaining?
- chiefalchemist 5y ago
  Agreed. But apparently we're on the wrong side of the narrative. The simple fact is, we don't have leadership able to tell consumers that they've done too good job (to the point of ruining their own health), that the (over) consumption economy has failed them. This is why (in the USA) we hear very little about areas not overrun (e.g., many African countries). I am by no means a Covid denier, but the bottom line is: Covid is more of a symptom (of broader health and healthcare issues) than it is a Black Plague-esque disease. Since the majoriry rules, and illness has been normalized there will be few in power willing to speak truth.
  - hdjjhhvvhga 5y ago
    It's an interesting take but you are only partly correct, because only some of these problems are self-inflicted, so to say. There are only as many ways you can influence your blood pressure levels for example. At some point no matter what you do - you run an hour a day, eat veggies mainly, eat zero salt (which is not recommended btw) - and still have higher blood pressure than your older colleague with BMI above average. So you can't just claim COVID-19 is punishing the people who don't take care of themselves.
    - nradov 5y ago
      The impact of salt on blood pressure is based on concentration (osmolality), not quantity. Consuming excess fructose can also cause hypertension due to the biochemical mechanisms in humans and other primates that cause higher uric acid production. https://peterattiamd.com/rickjohnson/ https://peterattiamd.com/rickjohnson/
    - chiefalchemist 5y ago
      I agree 100%, and should have said so in my OP, there are some who have conditions that are difficult to treat. However, there are a significant number that are legitimately preventable. Rare is rhe case where a doctor's prescription is "consume more sugar." The science, which we're all in favor of, is pretty clear on this. It's not logical that we (in the USA) continue to side step a serious discussion about the value of prevention (and how that relates to the level of unhealthines we are on average.)
  - gelert 5y ago
    Congratulations on realising that successful diseases reflect their environments and times in human history. Were you alive during the Black Death I imagine you'd be talking about how, though you're no denier, it's the fault of people using ships to trade.
    - techbio 5y ago
      Since GP refers to ubiquitous systemic issues, not xenophobia, not technological ventures, "ships to trade" seems to be a red herring. Also worth noting: "congratulations" reads more than a bit disingenuously.
- andy_ppp 5y ago
  Obesity being a risk factor was well known. Why obesity causes more chance of death hadn't been studied well, which I believe is why the paper is appearing here. Pre-print might lead to it being rejected or outcomes changed or tweaked, and it clearly needs replication in a larger study to see if the findings hold up. But equally I think being healthy and reducing your weight is likely to increase your odds of not becoming severely ill.
  - FeepingCreature 5y ago
    Sure, but I didn't think that obesity deaths needed a factor unique to Covid 19 to explain. I'd expect, as a layman, that what causes obese people to die more from Coronavirus is probably the same thing that causes them to die more from everything else that stresses the body. (Whatever that is.)
    - hwbehrens 5y ago
      > probably the same thing These things, which are usually things like diabetes, blood sugar problems, high blood pressure, elevated cortisol and so on, do correlate with poorer COVID outcomes. My understanding is that, even when you control for these factors, outcomes for obese patients are still below what we would expect to see. This means that there is still a contributing factor that we haven't considered yet, and the parent study hypothesizes one possible reason.
    - justinator 5y ago
      > is probably the same thing that causes them to die more from everything else that stresses the body. (Whatever that is.) There's a good chance that whatever that is, isn't actually a thing, and that people unfairly find fat people repulsive for no reason except that they are fat, https://podcasts.apple.com/us/podcast/is-being-fat-bad-for-you/id1535408667?i=1000542081632 https://podcasts.apple.com/us/podcast/is-being-fat-bad-for-y...
    - Villeinesse 5y ago
      Severe D deficiencies is the 'why', while this paper deals with part of the 'how'. Since D is fat soluble, all D goes into the fat cells first, but so much fat cannot be easily filled, so while leaving the free-floating blood & organs completely unprotected, even many fat cells are still largely empty & unprotected too! D is the critical immune hormone traditional Equatorial tribes, like the Maasai, continue to make naturally in their skin, outside under their year-round UVB. With little exercise, they stay thin, healthy & happy their whole lives with D maintained at 45-55ng/ml! Obese suffer much higher rates of most modern diseases because of ever lower D, becoming diabetic, cancerous, heart-diseased, and/or auto-immune. But cheap & safe supplementation to evolutionary repletion >50ng/ml, (though requiring much higher dosing for obese), is just as protective for the obese as for any healthy or other CovidComorbid person. A recent PubMed peer-reviewed Meta-Analysis showed the complete inversality of D & Covid. They surmised that 50ng/(or 125nmol) would have ZERO CovidMortality!
- Brave-Steak 5y ago
  > something that needed explaining This is like asking why we need science at all. We might know that obesity is a significant risk factor, but we don't know why and what we could do about it. So yes, it does need explaining. This is a possible explanation and might inspire further research into the topic, in particular preventative or curative treatments.
- techbio 5y ago
  If something is so obvious as to need no explanation, it just might be worth understanding what about it is causal. What can be done given the predisposition to obesity in a time of abundant necessities? It seems your conclusion is to let it go to the joint processes of sin and natural selection, which would tend to call into question your moral certainty. EDIT: Another post today titled "Causal Information Affects Decisions" seems relevant here: https://news.ycombinator.com/item?id=29509236 https://news.ycombinator.com/item?id=29509236
  - FeepingCreature 5y ago
    I don't care about the moral aspect, I just thought it was established that obesity causes the body to be less able to handle ~any kind of stress. Is that actually incorrect? Like, my confusion is that I didn't think we needed to go look for a new mechanism unique to Covid here.
    - andy_ppp 5y ago
      Yes but the point is your point is added onto buy the possibility (likliyhood given the study) that being fat has a particular mechanism for it being worse than all the other co-morbidities we're talking about. That's what the paper is studying!
- _pmf_ 5y ago
  > Um. Is high hazard and death ratio for obese people something that needed explaining? Some people might argue that convincing people to not get fat is much lower hanging fruit than transforming every democracy into an authoritarian apartheid state for effects that are well below any statistical significance threshold.
  - FeepingCreature 5y ago
    Well, to be fair, I don't even think that's obviously true even given your unsourced claims.
  - xapata 5y ago
    I think you left that under-explained.
  - hippie_queen 5y ago
    It seems that the "convincing people to not get fat" project has been a massive failure so far.
  - Klinky 5y ago
    If it has no statistical significance why would you run a campaign at all?
peteradio 5y ago
I think in general the advice is "preprints are not yet holy gospel". Don't start preaching on it, don't start basing your life on it.
- andy_ppp 5y ago
  Neither are published papers in peer reviewed journals, we need to always treat everything with healthy skepticism. That obesity and bad covid outcomes happen is beyond any doubt, the interesting part for me in this paper is that they try to explain the mechanism for obesity itself being a problem, rather than say diabetes or atherosclerosis.
  - rbartelme 5y ago
    I guess my whole point was if they're trying to explain a mechanism, their sample size doesn't generalize to the population; even limiting it to the obese population. If anything they've shown, in their small cohort, that the hypothesis is worth further study. Having spent a lot of time in academia before moving into biotech, I think this is a pilot study and they're fishing for more research funding. The way those funding mechanisms work, I tend to view manuscripts like this with a critical eye.
- evandrofisico 5y ago
  Look, even peer reviewed papers are not supposed to be treated as any kind of unquestionable truth, especially in medical sciences. It is unfortunately very common to have papers with repeatability issues or even outright wrong. Peer review just means that experienced scientists read a paper and concluded that nothing they saw was outright wrong.
lamontcg 5y ago
This method suggests a possible mechanism for poorer outcomes in the obese, but that does not mean that the mechanism is correct. The mechanism also involves a way for SARS-CoV-2 to infect lymphocytes in fat tissue that doesn't involve ACE2, which the authors leave completely unexplained, which is whole lot of highly surprising results. There's also simpler explanations for why the obese are at higher risk, because systemically they're in poorer shape to begin with (metabolic syndrome, etc), and mechanically they have more trouble breathing when they get sick. The title explanation is so simplistically attractive while the biological mechanism is unexpected and unexplained, which I'd say adds up to requiring a large amount of skepticism, until it gets validated by real experts in the field (not just someone with an MD or PhD on twitter, but someone who is active in exactly this kind of research). It might be an emotionally satisfying result, but it smells like bad science to me.
- andy_ppp 5y ago
  I agree with your analysis you are correct to put these ideas forward, it does not mean the paper is incorrect. I personally think we should think of this paper as really useful datapoint rather than a set in stone conclusion either way. For me it's really interesting rather than to be dismissed as being completely not probable. Let's see and wait for other research, but I think it's a great theory that needs a lot for it to be fact (as close as we have to one). What is a fact (again, as close as we can get to one...) is that obese people die a lot more readily from COVID and anyone over say 30 BMI (because of fat) should undoubtedly assess the risk of any vaccine as being massively in their favour!
  - lamontcg 5y ago
    Hard disagree. There's so much junk science that articles need to be treated skeptically, particularly if they have strong headline claims that reinforce some common belief combined with details which are hazy and unexplained. Being totally open minded is actually not a virtue, you can be so open minded that you'll start to believe any sort of drivel you pour into your head because it sounds persuasive rather than being correct. I will happily flip my impression of this paper on a dime if someone who is actually qualified to review the actual lab methods and procedures (and if adequate controls were used, etc) pops up to defend it and to explain how cells that don't express ACE2 could possibly be important in COVID-19 pathogenesis, but until then my default setting is to be critical since the paper "smells" bad. It is not a particularly "great" theory, its a very fishy smelling theory.
jessriedel 5y ago
> I think we should be more positive about such research (it helps us to further our understanding of COVID-19) Listing important limitations of a study is not being negative. It is contributing to understanding the paper. The comment you are replying to is the most substantive comment in the thread. One does not need to encourage authors with compliments, nor does one need to balance criticism with praise.

NoblePublius 5y ago

Morbid obesity is the number one comorbity of Covid death.

fdjsafdsjl 5y ago
At least in the UK, dementia is the number one comorbidity of Covid death.