How does the coronavirus kill? | Hacker News Reader

How does the coronavirus kill?

sciencemag.org

164 pointscar62 comments

Interesting read. My father-in-law died of Covid-19 last week. The thing that got him in the end after a 9 day battle was kidney failure. He had heart problems and diabetes already as underlying conditions.

There’s one thing I take away from all of this and that is to eat and live healthy to reduce the things working against you as you get older. Age is bad enough on its own.

Sorry for your loss. You're right about age being bad enough on its own!

NYT just has an article about kidney failure being a cause of death for COVID patients:

https://www.nytimes.com/2020/04/18/health/kidney-dialysis-co...

Thanks - will read.

wow. How are we supposed to plan for future calamities like this we cannot predict what we are going to need for the next pandemic. Looks like we should overstock everything we could possibly ever need.

https://en.wikipedia.org/wiki/Disease_X

Cameron Kyle-Sidell is a New York ICU doctor that has been trying to help figure out why treatments aren't working as expected. His videos are highly technical but interesting to watch.

Kyle-Sidell believes it's a diffusion hypoxemia problem, leading to pulmonary edema (which is something you see in high-altitude sickness)

https://www.youtube.com/watch?v=NmRlvX3VrAQ&feature=youtu.be

https://twitter.com/cameronks/status/1251259213554335744

The hypothesis suggested in the science article sounds more plausible - these patients are truly oxygen deprived, but potentially because of the vascular Nature of the infection, the typical gasping response is not initiated

Isn't it true that gasping is typically caused by CO2 profusion, not O2 deprivation?

I know nothing about medicine, but is there any way to skip the lungs and give patients oxygenated red blood cells directly?

Yes: https://en.wikipedia.org/wiki/Extracorporeal_membrane_oxygen...

Interesting, thanks. Apparently it's already being used to treat covid-19. But the potential side effects seem to be nasty and the survival rate not great, so I guess it's only really a last resort treatment.

Human bodies are just too damn complex. Even when the problem is clearly identified--a lack of oxygen in the blood--there's no way to just insert more that doesn't cause a hundred new problems :-/ Natural selection seems to be really bad at modular design.

> Natural selection seems to be really bad at modular design.

Or the other way around, modular design does not appear to be a requirement for "success.". We like it for the reduction in complexity but that is ultimately a tradeoff.

Well, it’s successful until it’s not. Nature’s primary approach to debugging seems to be: you die. We clearly weren’t intended to open up the hood and fix things.

Biology doesn't care about individuals. It cares about populations. The main mechanism is exponential growth, capable of quickly filling carrying capacity boundaries of arbitrary size. Individual death is a small setback, as another branch of the exponential growth tree takes over shortly.

Biology is layers and layers of legacy code and technical debt and it never gets refactored.

There's also a concern that the filters in an ECMO machine damage or eliminate the antibodies that are trying to fight the virus.

So putting someone on an oxygenator might condemn the patient to stay on one until the virus kills them.

In case of intubated patients the reflex is irrelevant, no?

Only one thing is clear about our immune system: it's extremely complex and even after a century of prodding it, we still don't know it well enough to prod it in targeted ways and know what to expect.

Especially, suppressing the immune system is always dicey, since its not just one variable you tune up or down. However, there _is_ a magic bullet of sorts out there, Intravenous immunoglobulin (IVIG).

IVIG is just concentrated antibodies made from plasma of thousands of donors. Its original use case was to clear out a patients antobodies to suppress any antibody-mediated autoimmune response, but turns out IVIG can have global immunosuppressive effects through other mechanisms as well. Importantly, it's very "benign" - almost no known side effects, and your general immunity is still left intact. This has led to extensive use of this drug off-label for anything dealing with excessive immune responses.

The more and more I think and look, the more I'm convinced IVIG might help worsening covid patients. Indeed, a case study from China suggests it can be beneficial (3 of 3 very sick patients fully recovered) but of course a proper study is needed (IVIG is quite possibly the worst drug to try and ramp up production). On the other side, a pre-covid trial of IVIG on ARDS patients (already on EMCO) showed no effect, though I personally felt the study was too broad. More studies are also needed, because I'm sure any _new_ IVIG made, since it pools thousands of patients' plasma, is bound to have anti-covid antibodies as well, and this could have some potentially dangerous effects as well (Antibody-Dependent Enhancement). But I'm still cautiously optimistic and am hoping to write to some experts after gathering more data to see what they think.

I read a report on a GBS patient who recovered after getting immunoglobin

Edit: https://www.thelancet.com/journals/laneur/article/PIIS1474-4...

Issue with this report and others from China is that they seemed to treat all patients with a concoction of antivirals, one of which is not even available outside of China and russia. No way we can make fully conclusive inferences from this data :(

Isn't the original use of IGIV as a supportive therapy for people not producing antibodies (for whichever reason)?

In the case of COVID-19, plasma therapy (which transfers antibodies from a survivor to an infected) is one of the more promising short term mitigations.

Yes, that was the original use. But turns out it has other effects as well, one of which is through the increased dosage of a small fraction of antibodies with increased suppresive activity.

You have to be careful with concoctions that have direct antivirus activity though, because it can have a dangerous side effect (ADE). However this is also a very important intervention possibility (probably more important than just IVIG), but it needs to be done in an extremely controlled fashion. But the two approaches are supposed attack in completely opposite angles so I think they should be discussed and tested independently.

Today's news in Austria was also a successful treatment with antibodies out of survivors plasma. Graz.

I don't see how that's going to be meaningfully useful in a pandemic. We don't have anywhere near the infrastructure required to harvest plasma on that scale. It's possible it might be a useful treatment once we get back down to a stable baseline but before a vaccine is available.

I just don't see how the number of lives this will save is going to be significant vs. other more obvious mitigation strategies.

There's a deep temptation among the technical set here to look for magic bullets. There isn't one. Stay home.

Of course stay home. No one's saying we found the cure. We still want to know what can help patients who get sick anyways (given what's happening in the US now, stupid people make stupid choices but doesn't mean they shouldn't be treated).

Of course I flagged that IVIG could be the worst thing we can try to scale up. Doesn't mean we shouldn't find out if it works or not.

I think you'd be surprised at the infrastructure that out there for plasma collection. I was doing due diligence on one of these companies a few years back and was surprised to learn that the pharmaceutical company owns thousands of plasma collection clinics. The IV Ig market is quite large.

That said, you're right, this could never be used with every infected patient, but companies could probably produce enough for the sickest patients.

A statistic that needs to be gathered is correlation between levels of Vitamin D,C,A B12 and deaths

Regarding the oxygen saturation levels that have been so much in focus the last few days (the usual thresholds for starting intubation might be wrong for Covid-19 patients): is this a metric that is measured directly or is it usually derived from proxies? That's what my debugging instincts are shouting whenever I read something about the oxygen saturation mismatch, it would be easy to get misled of the proxies have never been (noticeably) unreliable before.

It's relatively direct:

https://www.lung.org/lung-health-diseases/lung-procedures-an...

Pulse oximeters measure the light absorbed by hemoglobin. So that's pretty much a direct measurement, I don't think it could be wrong.

https://opentextbc.ca/vitalsign/chapter/why-is-pulse-oximetr...

When this first started popping off, I ordered one of them on Amazon. If I get it, it should help give me info on if / when I would need to go to the hospital.

Same here. You can get a fitness band that measures SpO2 among other things for 30 bucks or so

Most recent Samsung Galaxies have one built in. You just need to enable it in the Samsung Health app.

I have a Samsung Galaxy myself but it's less accurate than a real medical device. Readings depend on how you hold your finger against the sensor.

I think you'd only be looking for a significantly low reading anyway. So if you get a low reading try again until it goes up or it's time to go to the hospital.

Couldn't there be a million other things that change light absorption?

Not inside a body, no. These aren't the most accurate tests (the big failure mode has nothing to do with the science, it's that the little clamp falls off the finger), but they are very mature technology with well characterized behavior.

Basically everyone who's been under anaesthesia of any kind (even stuff like wisdom teeth removal) for the past 3-4 decades has had one of these on them. We know how they work.

I read that despite the simple measurement mechanism ("shine a light through a finger"), the accuracy is generally pretty high (+/- 2%). This document from the American Thoracic Society does state some corner cases though [1]. Quote:

"How accurate is the pulse oximeter?

The oxygen level from a pulse oximeter is reasonably accurate. Most oximeters give a reading 2% over or 2% under what your saturation would be if obtained by an arterial blood gas. For example, if your oxygen saturation reads 92% on the pulse oximeter, it may be actually anywhere from 90 to 94%. The oximeter reading may be less accurate if a person is wearing nail polish, artificial nails, has cold hands, or has poor circulation."

[1] https://www.thoracic.org/patients/patient-resources/resource...

One very important thing to note is that the Oxygen - Hemoglobin dissociation curve has a sigmoidal shape. It is not linear. After a certain point, around 90 %, there is a very sharp drop-off.

https://en.m.wikipedia.org/wiki/Oxygen–hemoglobin_dissociati...

I read speculation based on protein protein docking, that it could limit ability of hemoglobin to bind oxygen. On the other hand it can't enter red blood cells so it does not make sense.

But I think you would see high blood oxygenation even in a person with CO poisoning as it just measures whether something is bound to hemoglobin

I'm not a science person nor do I know how a virus kills a human body but this one is for sure something amazing. What we can't see can lead you to an absolute death destroying your whole body, it certainly is quite shocking. It's 2020 and we are still losing so many lives, yet we are still lucky to be alive because of the advancement in medicine and health care.

It's a virus that is completely unadapted to the human body, fresh off the boat from whatever animal it evolved on. It's like an early prototype medication: it already has the desired effect (reproduction in a body part that serves as a launch pad for transmission to other hosts), but it's chock-full off side effects. Unfortunately, it is so good at pre-symptomatic transmission that those side effects impose very little selection pressure.

At this point we have an interesting link to the topic of contact tracing apps: if we shift our countermeasures from wholesale isolation to fast, computerized contact tracing that is fast enough to overtake the infectivity/symptom last, it will increase the evolutionary advantage of less damaging strains (asymptomatic cases don't trigger a contacts cascade)

If you compare it to MERS/SARS it is actually less harmful (at an individual level) than those. But of course this ends up meaning more harmful at a collective level since it takes a while for people to develop symptoms while still being able to infect other people.

I wonder if there is something in your immune system, maybe genetic or your viral experience, that determines how well your body will cope with this new virus. There are reports of really old people (I read a 103 and 99 year old's stories) who recovered from a bout, yet my niece lost a 30 year old friend.

I guess its like debugging an app you have never seen and the source code is in a language you barely know; everything seems like a clue as to what is going wrong, yet much of what you think it's doing is simply a mystery because you don't understand enough.

Even in 2020 there are mysteries in the human body we simply don't understand yet.

This was very true for the H1N1 epidemic but it's not clear something like this is happening with Covid. If anything, the opposite might be happening where prior infection with a related virus makes the current infection much worse.

Do you have any sources for that last sentence?

What kind of source would satisfy you for "the opposite might be happening..."?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102551/

Thank you, that is super interesting.

I wonder how valid this bit still is:

> the discrepancy between the severity of cases observed in the Hubei province of China and those occurring elsewhere in the world

I think at this point we’ve already seen very severe cases in many other countries, no? I don’t have proper sources though, just thinking of misc news articles I’ve read.

Ya inflammation. See my post above.

From my layman understanding the initial viral load is a strong factor in how well you can respond to the infection. Immune response more or less happens in a constant time, while the unchecked virus spreads roughly exponentially. If your initial load was low, then by the time your immune system responds, the infection will be relatively little spread, but if your initial load was high, the virus will have spread much more, which can be challenging for the immune system to handle, event for healthier people.

please read this report by dr sherif sultan based on consultations with frontline doctors and postmortem examinations. it forms a coherent picture of symptoms and medication trials that we keep hearing about.

https://www.facebook.com/ProfSherifSultan/posts/319343963736...

Here is a treatment protocol that is being regularly kept up to date with latest information

https://www.evms.edu/covid-19/medical_information_resources/

i fear that well meaning doctors are killing their patients because they don't have updated treatment protocols: even though so much of this information has been released in chinese treatment protocols many weeks ago, i still keep seeing "news" articles with these "new discoveries".

i fear a tragedy of the commons situation where everybody assumes the next guy already knows. who is responsible for keeping treatment protocols updated and propogating this information to doctors? much of this information is readily testable, why are we not hearing either positive or negative feedback to this data?

please help me get this information out to doctors. even if it is not all accurate, they can make a better informed judgement. please help me understand if my understanding of this reality is correct, or how to get more information about this. thank you for your attention.

The updated protocol to change Ventilators to ECMO was distributed at April 11, yes.

Latest theory is high correlation with air pollution. NOx and tiny dust particles. https://www.sciencedirect.com/science/article/pii/S004896972...

This would explain the extraordinary high death rates in Lombardy, Spain, Styria, Wuhan,... compared to other regions with worse ICU situation and more seniors.

And esp. Belgium. The highest outlier without proper explanation so far.

I am putting this here to help others. Fry me whateveter. I'm no medical or WHO but I also prepared and knew it was coming week 1 of Jan. I have made many accurate predictions weeks or months ahead this while time so time it for what you paid. It's pulmonary edima 'esque yes, but it's an underlying issue that I think is a big determining factor in who lives and who dies. Lung capacity sure is important BUT the lungs strangle themselves by on over immune system response to fight this aka inflammation. And that's it. Most Americans eat tons of sugar and carbs. They are walking around already in a state of heavy gut inflammation unknowingly. Chrone's and IBS are rampant too. I have seen several people who say the 'normally' struggle with lower immune responses get through it ok. Because the start with a lower inflammation baseline. Others are starting already heavily inflamed due to diets, and then when they get COVID it the lugs over inflame as well causing medicinal issues I don't know the specifics of but that I think can be deadly. Over inflammation has a name and it's not good. It can cause all sorts of other issues and being over inflamed in your lungs well we know what happens then. Fast. Do a prolonged fast for a few days. Only black coffee and water. This will create new white blood cells. This will eliminate gut inflammation. It will reset your old immune system with a healthy new one. You go 72hrs you will also get Autophogy and new stem cells. I can go on but if my post Sparks your interest, and you might agree what do you have to lose? A few days without food I do it all the time. If I'm wrong why not try and save your life by giving you a heads start with no already in state inflammation? It will be healthy for you either way. Also look at the curves and national diets.

Proposing intermittent fasting as a cure for COVID-19 with no clinical research is dubious. This is the same as any other quack medicine.

Ironically carb consumption is important to maintain immune function in very active individuals.

The poster did not claim it was a "cure". The way I read it was that if you're gut biome is dysfunctional because you eat too much, that is a factor in the immune response to SARS-CoV-2. That is actually possible. Resetting your gut biome with a 72 hour fast is known to provide significant health benefits. Clearly the poster is not a medical professional and states that fact. But everything stated is reasonable advice. It's certainly not "quack medicine".

That’s an interesting idea. Could you point me at any papers on the subject?

> This will create new white blood cells. This will eliminate gut inflammation. It will reset your old immune system with a healthy new one.

How are you measuring these results?

Short term, calorie deficit will deplete the immune system. But long term getting to a healthy weight and less diabetic will make you less susceptible to SARS2.

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