There is a lot of misinformation about COVID-19 lung disease. This article's title is alarming, but most of its content is mainstream. Lung protective ventilation - the standard approach for ARDS (which COVID-19 seems to cause) - avoids high pressure and high volume ventilation.
Further evidence for abnormal iron handling was demonstrated by Decker et al. (2011) who showed that zinc protoporphyrin (Zn-pp) levels are high in patients with PAH (mainly iPAH) indicating deficient iron incorporation to form heme suggestive of iron deficiency; levels were closely related to clinical severity (Decker et al., 2011). Zinc competes with iron for binding sites, therefore when iron levels are diminished zinc replaces iron at these sites. PAH patients also had a high red cell distribution width (RDW), again corresponding to markers of clinical severity, such as higher pulmonary arterial pressures and lower 6MWT. Most recently, using proteome analysis in the plasma of patients with PAH, Rhodes et al. (2017) were able to identify a combination of nine circulating proteins associated with a high risk of mortality, two of which, plasminogen and erythropoietin, are associated with abnormal iron metabolism (Rhodes et al., 2017).
Why would pulmonary hypertension, which increases RV afterload and can contribute to shock, be beneficial?
What evidence do you have that zinc deficiency, rather than an infection causing a global pandemic, is causing hypoxemic respiratory failure right now?
To me, these seem totally irrelevant to COVID, but can you elaborate a direct connection?
I was just using the PAH as an example, but the issue in the lungs results from vasodilation (please correct me anyone if I am wrong). So vasocontriction might slow the leaking of fluid into the intercistal space.
Regarding the zinc deficiency; we see a large variation in outcomes after infection. Part could be viral load, but since we know people with "comorbidities" are more vulnerable to bad outcomes this delta should be an area of interest. Some people are totally asymptomatic!
The comorbidities (let's say heart disease) are caused by environmental or genetic variables. It seems zinc deficiency, to me, might be a common thread to both comorbidity and infection outcomes.
Since ACE2, a zinc metalloprotein which uses zinc as a cofactor, is in the alveoli and is the receptor for the virus, it would make sense to look at this as a serious possibility. ACE2 is a "Therapeutic Target for Heart Failure"
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3944399/
And zinc plays a role in the lung disease as well:
Interleukin-1α (IL-1α) production by alveolar macrophages in patients with acute lung diseases: the influence of zinc supplementation
"These results suggest that zinc can regulate the production of IL-1α from AM in patients with pulmonary tuberculosis or bacterial pneumonia."
Both anecdotally and experimentally there is evidence that zinc inhibits the replication of several virii. So zinc deficiency might make infection more likely and weaken the immune system to make outcome worse.
It's fine to speculate, but there is no real connection between these ideas and COVID beyond pure speculation. Vasodilation is not the issue with the lungs (unless you mean V/Q mismatch for specific vascular beds, in which case this is the accepted dogma and is unrelated to pulmonary hypertension). The other hypotheses are at the level of preclinical evidence. Some (e.g., zinc deficiency being a common cause of causing heart disease) would upend all known clinical data.
Yes, speculation is the fertilizer of hypothesis. All anyone has at this point with COVID is speculation.
How can you say vasodialtion is not a vector in COVID19 outcomes? It is vasodialtion that increases capillary permeability leading to fluid in the intercistal space, am I correct? I may be wrong because I am reading that they are showing signs it appears as HAPE initially.
ACE2 uses Zinc as a cofactor. So a zinc deficiency could mean less ACE2 and a greater risk of HAPE.
Regarding zinc and heart disease, I am not saying it is THE cause, just a part of the cause. It is demonstrated very well that zinc deficiency is common in people with diabetes and heart disease. The clinical data is there, I just showed you part of it.
You were talking in favor of pulmonary hypertension and now you’ve shifted. And you’re pushing vitamin deficiencies as some cause-all. I’m not continuing this discussion with you.
I do not think I will be here long. It is even worse than it has been in academia.
I will share this with you, I do not think hydroxychloroquine is needed, only high dose zinc. It is looking more like lower ACE2 activity is causing the majority of issues. Since ACE2 needs zinc as a cofactor, well...
"Covid-19 enters the lungs via the ACE2 receptor. The virus binds to the receptor, which then pulls it into the lung cell where the virus can multiply. In case of a massive infection, this process makes the ACE2 receptors disappear from the outside of the cell. With that, their function also disappears."
Can you share what's a high dose in this case, how many milligrams of zinc per day ?
Also, with zinc it's important to increase the dose slowly or there might be some adverse effects, like hair loss.
I think it may matter more if you are zinc deficient when you are infected.
But Zinc does not need to be in the cell to help. It will also increase ACE2 activity, which is more important they are finding. When the ACE2 is destroyed, there is a build up of ANGII, which seems to be causing a majority of the issues. They are in a trial giving ACE2 directly to patients.
I've looked at the findings from France (although I'm not a doctor, I can still look at the numbers and try to make sense of them). It does seem that people on ACE inhibitor blood pressure medication have worse outcomes than almost any other group. Which is relevant to me, since I've been taking lisinopril (an ACE inhibitor) for the past 5 years. The "official" medical recommendation is to continue taking it, but I'm pretty certain at this point that the official recommendations are more or less full of shit when it comes to C19. It's not their lungs that are on the line. If I get any symptoms, I'll stop taking it as a precaution, my blood pressure issues weren't that bad to begin with.
Thanks for this comment, this stuff is super confusing. The effect must have been dominated by age distribution then. A lot of the older folks take ACE inhibitors, so it could be that they fared worse just because they're older.
Welcome to HN! I'm not an expert on the subject, nor am I anybody important here, but give it time. Sometimes downvotes are accidental, sometimes it takes a while for a refutation to make it clear what was wrong, sometimes you just never find out. Best to just take it in stride as something random until more information is available.
You can add a blurb about your credentials to help with down votes. For example, lead with "I have a PhD in <subject>" when your creds are applicable to the case you're trying to make.
Also, votes are just fake internet points. No need to worry about them too much :)
The drive by downvoting is out of control. I wish they changed it from a threshold of 500 to a threshold of 500 and you’re only allowed to downvote accounts that came after you until you get to like 2000 points or something like that.
Basically we need a mechanism to mitigate the impact of eternal September. There are too many new people with downvote ability changing the culture here for the worse. What’s insane is the number of times I see people downvoted for simply asking for sources/citations/references/ evidence/etc.
I would suggest that any down or up votes must be accompanied with a reason and reply then, yes? Or maybe just get rid of the voting and let the comments speak for themselves.
Drive-by downvoting of quality or interesting comments usually are offset by upvotes in any marginally popular post. Don't worry about it. Points here mean much less than they do on sites like Stack Overflow and Reddit.
In terms of the type of behaviour that should be encouraged on YC.. celebrating a diversity of understanding, belief and practice should be OK in a community of individuals wanting to build things that are different.
podgaj - have you checked out https://www.reddit.com/r/COVID19/? It a well moderated discussion thread focused solely on the science. You will find it a little saner there.
I did my best to talk about some sort of disruption to the pathway involving oxygen uptake and utilization.
I'm a layman, so I'm maybe not phrasing it the best way. But I'm getting the impression that the reason ventilators are failing so badly is because it's not treating the right problem.
I have this idea that the infection is interfering with the oxygen pathway -- with how red blood cells take on and/or utilize oxygen. If that's the problem, more oxygen won't do much. If the body can't absorb it, extra supplies of oxygen just won't really take.
Can anyone speak to that idea in layman's terms with regards to what is known about the pathology of this class of infection?
Edit: I'm talking about a process similar to anemia or altitude sickness. I'm talking about some barrier to the body adequately using oxygen, in addition to any other challenges like fluid in the lungs blocking oxygen uptake.
The hypoxia issue is more of a physical problem caused by inflammation. Think about trying to push a marble through plastic, that is what the vents are trying to do with the oxygen that is trying to get from the aveoli to the capillary.
Vents are not a treatment, they are support. Treatment would either slow replication or lower the inflammation.
The thing is that if you also have an issue like pneumonia, intervention like ventilation would help with that element. But if that's just one problem and we are overlooking a biochemical pathway issue, it would serve as an invisible bottleneck in the system.
So, say, twenty percent of the problem is pneumonia and you can see gains by addressing that, but it's just one piece.
Lowering demand on the system would help accommodate the low oxygen. One way the body does this is by sleeping. People are reporting they are sleeping a lot.
Anyway, zinc makes sense based on stuff I'm aware of. And it's cheap and the body apparently doesn't store it. You need a daily supply.
So if zinc is a critical factor, dietary differences could be a significant detail. People sucking down sufficient zinc keep breathing. People not eating zinc-rich foods suffocate.
Does anyone know what Coronavirus does with regards to zinc usage in the body?
Apparently this is not presenting in the lungs as either ARDS or pnemonia which has been the problem. There is a doctor in this thread who was saying vents were making O2 levels drop so they just provided low pressure oxygen.
My focus more on nutritional genetics and biochemistry so I am trying to put something I know well with something I can maybe understand. This is why I reached out here.
I have a relatively mild form of cystic fibrosis. I don't have any of the 100 most common alleles and was diagnosed late in life. Insurance denied my pulmonologist's request for a more comprehensive genetic paneling covering the 1400 or so known alleles.
I was just happy to have a better label than "hypochondriac" and was responding well to treatment and was fighting for my life. I shrugged and thought nothing of it, but that detail undermines my credibility in the CF community. (I mean the fact that I don't know my alleles.)
I was diagnosed nearly 19 years ago and I have been steadily getting better using dietary and lifestyle interventions. I know a lot about things like inflammation in the lungs and how to manage it.
At this point, I most likely have the infection and have had it for a while, though that only recently became clear to me because I'm largely asymptomatic.
The most prominent symptom I do have is that my energy levels are low in a way that suggests a bottleneck in the system on energy supply. Impaired oxygen availability would fit with what I'm experiencing.
I have a history of anemia and it is somewhat similar to that.
My lungs are clearer than they have been in weeks. I had a mold exposure earlier this year and spent weeks coughing up a lot of phlegm multiple times per day.
At the moment and in the last couple of weeks, my lungs aren't all gunked up and my chronic inflammation is currently very well controlled.
But we are all three (me and my sons, one of whom also has atypical CF) sucking down zinc-rich foods. And we feel notably better after eating.
So your remarks hit a nerve for me.
I'm not suggesting it's the entire answer. But CF is, itself, a bottleneck in the system at the cellular level. The mechanism causing the condition is a defective channel that handles traffic of certain molecules into and out of the cell.
That's what is known by medical science and it has been enormously helpful information for me. Beyond that, my mental models for what is going on with my body depart from current medical dogma and I get attacked and dismissed a lot as a loon because I'm a former homemaker, not a doctor.
But I'm extremely familiar with what it feels like to have a bottleneck in the system and this feels to me like a bottleneck in the system somewhere. And it's not lung function per se. I'm not having any breathing difficulties at all.
This is why I think Coronavirus is impairing oxygen uptake somehow in terms of some biochemical pathway.
I work from home, part time and when I feel like it. I'm poor, but I have a lot of control over my schedule.
My sons and I are lazing about a lot and struggling to come up with the energy to take care of what few tasks must be done daily. But with pollution levels down and no pressure to perform, we are managing to not end up in serious crisis. We just aren't pushing ourselves.
With a bottleneck in the system, you can't readily recover from stress events. You don't have the capacity.
For normal people who are used to being able to push themselves to do something when they don't feel well, a bottleneck in the system would create a potentially deadly problem where pushing themselves could be a cataclysmic event from which they cannot recover.
If there is a bottleneck, you have to slow down, take it easy, don't push. You have to take pressure off the system by lowering demand.
You have to max out support of all other areas that might impinge on the system in a way that would further narrow the bottleneck. I'm still doing lung clearance multiple times per day. I'm not bringing up much, but I'm keeping my lungs clear of obstruction because any obstruction further narrows the bottleneck.
So other things, like fluid in the lungs or inflammation, would further narrow the bottleneck. But clearing those additional burdens on the system doesn't, per se, fix the problem. It just lets the body get as much throughput through the bottleneck as possible.
My impression currently is that zinc consumption is easing the bottleneck itself. It's opening up capacity modestly, though it's certainly not a cure. It's just a means to keep energy levels up enough to not be a dire problem.
Please, if you can think of or learn of anything in terms of how Coronavirus impacts cell function that may cast light on interference with oxygen uptake at the biological pathway level (as opposed to mechanically in the lungs, which is what ventilators are trying to address and failing), shoot me an email. My email is in my profile.
I lave Lupus which is what led me to research since my mother had it as well I saw it as genetic, and it is for us.
There of many people with common disease living on on the nature----nurture spectrum. But the nurture part is largely overlooked in the PRACTICE of medicine. MD's have admitted to me that it is just easier to not focus on it.
Back to Coronavirus, it might be that the zinc is not as available to replace the iron in the Porphyrin ring.
I am not yet ready to see the low blood oxygen as totally bad. We used to think fevers were totally bad. It might be a way the body fights coronavirus. See:
I'm not suggesting it's all bad. I'm just suggesting it's potentially an explanation for the high rate of death on ventilators.
Ventilators may be the wrong treatment because the low oxygen levels may be largely due to a process more like anemia rather than primarily due to lung issues. You don't treat anemia by putting people on ventilators.
We can't successfully treat people if our mental models of the problem are entirely wrong.
Current thinking is that CF is relatively common in some populations because it is protective against certain conditions and those conditions swept through Europe a lot for a while. CF is predominantly Caucasian and it's homozygous recessive.
So the current belief is that it's sort of like Sickle Cell Anemia. One copy of the gene improves survival against certain infections without being an egregious burden to live with. Two copies are a terrible problem that kill you at an early age.
About 18 years ago, not long after me and my older son were diagnosed with CF, my younger son -- who is only a carrier -- had Winter Vomiting. It was a very deadly stomach flu.
He spent eight days miserable and barely eating. I told him if he got dehydrated, I was taking him to the ER to get an IV. He had an IV once and didn't want it again. So once a day, he drank 32 ounces of water, had a few crackers or ramen and then immediately projectile vomited it all back up. But it kept him from ending up dehydrated.
Me and my oldest son felt kind of meh for like maybe a day and a half. Our gut doesn't work right. This stomach flu didn't thrive in our system.
So I am abundantly familiar with the concept you are talking. What you are saying is like that X Files scene where she says "The cold is the only thing keeping him alive." when they are trying to treat him for hypothermia.
But ventilators are apparently killing people and apparently not primarily due to antibiotic resistant secondary infection. This is a clue. We need to follow the clues and see where they take us.
The lung issues are the obvious explanation for low oxygen, but treating for lung issues isn't getting the expected result. Ergo the low oxygen most likely is due to a different mechanism. Logically, it's a mechanism more akin to anemia, which is basically a bottleneck on how much oxygen the body can absorb at one time.
I am wondering about how NOS enzymes (like NOS2) might play a role since they are expressed at high altitudes and COVID is looking a lot like high altitude sickness by one doctor in NYC.
I am thinking myself that some people with poor NOS genetics or poor nutrition will have this issue. The result of higher need for NOS2 will lead to polycythemia and to improved oxygen delivery to tissue when accompanied by increased blood volume.
(Yes, I'm aware the last two are trying to sell you something and are probably skeevy.)
So, some general off-the-cuff thoughts:
Glutathione is a big deal with CF. There is too little on the surface of cells and too much inside the cells.
Some people with CF report good results from inhaling NAC (iirc) tro promote glutathione on the surface of the lungs.
I think people with CF have too much inside their cells because we hoard it, along with calcium, to buffer against high acidity and other chemical derangement. As I have been getting healthier, I periodically experience what I think is glutathione dumping. My armpits and bowel movements smell strongly sour, similar to a skunk, and then my baseline function permanently improves afterwards.
I took milk thistle for a while, maybe a couple of years or something. It's a glutathione precursor. You can't supplement glutathione directly. You have to take precursors so the body can manufacture it.
I did it in part as liver support. Glutathione is important to liver function which is important to cleaning the blood. I spent a whole lot of time worried about my circulatory health as that seems to be the key that pulls everything together.
I read up on altitude sickness at one time and it was hugely eye opening. The mechanism involved provides a clear connection between the lung and gut issues in CF via the bloodstream.
I lived at 3000 feet above sea level for 2.75 years. My rib cage size enlarged and has remained enlarged ever since (as evidence by changes in the band size of my bras). I likely had underdeveloped lungs.
From there, I moved to about 100 feet above sea level and was soon bedridden due to pneumonia and this led to my diagnosis just before I turned to 36. It is known that people who live at altitude and then go down in altitude experience a big boost in energy levels. I likely survived being bedridden from pneumonia in part because of my recent time at altitude.
I'm wondering if you know of any research into long-term effects of NO production for having lived at altitude for a time.
I'm thinking my more normal distribution of glutathione these days may be a factor in why I have been largely asymptomatic, in spite of being in a high risk category.
One of those articles indicates that NO deficiency also inhibits glucose and/or NO enhances glucose uptake. This would also lower energy levels.
My impression of what I am experiencing absolutely fits with the idea that poor vasodilation in the lungs, and thus poor trafficking of oxygen into the blood stream, could explain the low oxygen levels, at least in part.
I don't know how to describe it, but I feel like, yes, my lungs are cut off in some way from my body, in spite of not being full of fluid. I breathe fine, but I sometimes feel like my airways aren't really doing their job in some important way. I feel like the tissues are "closed" in some sense, in spite of not being gunked up and covered over.
Insufficient vasodilation impairing oxygen uptake fits with that impression.
I think that's all I had in mind to say.
Edit: I have just spoken with my son (who also has atypical CF) about this discussion and he says lack of vasodilation -- and oxygen thus failing to cross adequately into the blood stream -- also fits with what he is experiencing. None of us has an active cough. We are mostly just really tired.
I have looked into altitude and NOS activity a lot because of the issues I have at altitude as well. This is largely controlled by the genetics of NOS2.
This article says though that in New York 80% of people put on a ventilator die; is that fact refuted by anyone? For a machine that's in short supply and quite invasive, a 20% survival probability seems extremely low.
The figure for the England that I've seen is 50% (vs 20% death rate for viral pneumonia in 2017-2019, see [0]). I think that's for intubated ventilation as opposed to "just" non-invasive ventilation like BiPAP (which IIRC is contra-indicated; maybe because it impairs expectoration???).
But as others have said, if you only use the ventilator for the very sickest people, then the more pressed you are the fewer survivors you'll get because people who have a chance without it will be kept off the ventilator if at all possible. My very limited understanding is that ventilation has major issues around bacterial infection.
>But as others have said, if you only use the ventilator for the very sickest people, then the more pressed you are the fewer survivors you'll get because people who have a chance without it will be kept off the ventilator if at all possible. My very limited understanding is that ventilation has major issues around bacterial infection.
This is why everybody is locking down so you don't have to make a choice between those that will benefit the most from ventilation and those that have little hope left. For most socialized healthcare systems once a resource is in sort supply guidelines for selecting those that will benefit the most are established. So at the end of the day the 80 y.o won't receive the ventilator but the 50 y.o. will( at least that's how it works here).
It's a short report but it's crammed full of information.
Critical care unit outcome Patients receiving advanced respiratory support*
(N=1053) (first and second columns)
Patients receiving only basic respiratory support*
(N=444) (third and forth columns)
Outcome at end of critical care, n (%)
Alive 355 (33.7) 358 (80.6)
Dead 698 (66.3) 86 (19.4)
The ICNARC report is important because it gives us clear information about people who die. It's not just those who are severely ill or those who are very old. Most people who die needed no help with day to day living. There are lots of deaths in the 50 to 80 age range. Comorbidities can be things which are well controlled and otherwise relatively minor.
Yes, this seems to be an extremely morbid disease.
The current protocols became widely agreed upon after clinical trials showed that this approach to mechanical ventilation reduced mortality. It is in physicians' nature to speculate about new approaches to care for sick patients. But it's important (for MDs) to put that speculation into the proper context and understand equipoise.
Okay first of all thank you for that resource. I read through it (not all the references yet but that's next). Clearly written by experts, but something I'll still fully disagree. The mailing list analysis seems far more concerned with trying to determine if this is "ARDS as we define it" or not. It touches on way too many angles and tries to address many random hypothesis (the hemoglobin one is so outrageous to even bother addressing!), That I'm afraid they're losing focus on the fundamental question - should patients with covid-19 be ventilated the moment their pO2 drops below 90?
The author has not convinced me (an amateur) that they should be. They don't address the first primary hypothesis properly, which is that perhaps the pCO2 is actually in acceptable ranges in covid patients for some reason. Clearly the mortality for ventilated patients is higher for covid cases than other sources of past, so it's very intriguing they mix and match findings from 2016 with what we observe in covid.
This is not to question the authority of the authors, clearly they are experts, but personal experience from working with experts in academia is that they can also be very wrong because they're lost in the details, which is my worry here.
We should hope to strive and be great scientists though, so if a doctor or a scientist asks _why_ we should consider that the ARdS is slightly different in covid, they are owed some explanation and some data. Which we should explore together. In the meanwhile though, unless my further reading is going to change my mind, my current working hypothesis is going to be that the ARDS or whatever in covid patients is fundamentally slightly different in some way that means patients should be put on ventilators much later than conventional wisdom would suggest.
That could be the effect of conserving ventilators for the most seriously ill, in a C19 hotspot. That is, selection bias caused by a tight supply of ventilators.
Except that there don't appear to be shortages yet. It appears that doctors who need them are able to get access for patients, but they're still seeing these mortality rates
They've reported this two times in Seattle briefings. I believe the first number reported was 75% die. I can't remember the lastest number. It was lower, but still very high. So, IMO, Seattle's number is within the ballpark of NYC's
Should they be trying experimental antiviral or immune system therapies instead of ventilators? At the very least these therapies are not as invasive (or expensive).
These are not either/or. Whatever treatment is available or given, people get the ventilator if the current experience says they're slightly less likely to die with than without it.
Or maybe looking at the therapy in countries that show low death rates? Could it be that some countries got lucky with the choice of therapy? For example, Russia seem to show surprisingly low death rate so far - 1 per million, as per today's Worldmeter data. As per Reuters/30 Jan, their health ministry recommended "ribavirin, lopinavir/ritonavir and interferon beta-1b".
> Russia seem to show surprisingly low death rate so far - 1 per million
Officially low rate. There could be low rates, just like there are no gays in Chechnya, or actually low. But it would be very surprising if any recommendation from January wasn't verified by now in other countries and used worldwide if it's successful.
Well, how about this, in New York on Apr 14, rate is 552/M. In California it is 19/M. This is 30x factor. Maybe people just do different things in different places. And this results in different numbers. It might be worth to examine what people are doing in different places.
US doctors are using ventialtors because that's how they've always done it.
But China found out months ago they're not working.
The general recommendation now is to use a cannula until you faint, since almost nobody survives the ventilator after a week - it's like major surgery.
This is the sort of stuff ("There is no ‘pneumonia’ nor ARDS.") that Corey Hardin is refuting. Like, literally some of these hypotheses (e.g., that SARS-COV-2 disrupts heme binding - as if that could cause a decreased P:F ratio!) are specifically refuted.
Broadly, I would suggest that interested people read Corey Hardin's response to the cacophony of voices saying that COVID-19 respiratory failure is not ARDS: https://mailchi.mp/e10a89ac5988/tz4idnzryr-4388986?e=96507de...