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Medicine

A Supercomputer Analyzed COVID-19, and an Interesting New Hypothesis Has Emerged (medium.com) 251

Thelasko shares a report from Medium: Earlier this summer, the Summit supercomputer at Oak Ridge National Lab in Tennessee set about crunching data on more than 40,000 genes from 17,000 genetic samples in an effort to better understand Covid-19. Summit is the second-fastest computer in the world, but the process -- which involved analyzing 2.5 billion genetic combinations -- still took more than a week. When Summit was done, researchers analyzed the results. It was, in the words of Dr. Daniel Jacobson, lead researcher and chief scientist for computational systems biology at Oak Ridge, a 'eureka moment.' The computer had revealed a new theory about how Covid-19 impacts the body: the bradykinin hypothesis. The hypothesis provides a model that explains many aspects of Covid-19, including some of its most bizarre symptoms. It also suggests 10-plus potential treatments, many of which are already FDA approved. Jacobson's group published their results in a paper in the journal eLife in early July.

According to the team's findings, a Covid-19 infection generally begins when the virus enters the body through ACE2 receptors in the nose, (The receptors, which the virus is known to target, are abundant there.) The virus then proceeds through the body, entering cells in other places where ACE2 is also present: the intestines, kidneys, and heart. This likely accounts for at least some of the disease's cardiac and GI symptoms. But once Covid-19 has established itself in the body, things start to get really interesting. According to Jacobson's group, the data Summit analyzed shows that Covid-19 isn't content to simply infect cells that already express lots of ACE2 receptors. Instead, it actively hijacks the body's own systems, tricking it into upregulating ACE2 receptors in places where they're usually expressed at low or medium levels, including the lungs.

The renin-angiotensin system (RAS) controls many aspects of the circulatory system, including the body's levels of a chemical called bradykinin, which normally helps to regulate blood pressure. According to the team's analysis, when the virus tweaks the RAS, it causes the body's mechanisms for regulating bradykinin to go haywire. Bradykinin receptors are resensitized, and the body also stops effectively breaking down bradykinin. (ACE normally degrades bradykinin, but when the virus downregulates it, it can't do this as effectively.) The end result, the researchers say, is to release a bradykinin storm -- a massive, runaway buildup of bradykinin in the body. According to the bradykinin hypothesis, it's this storm that is ultimately responsible for many of Covid-19's deadly effects.
Several drugs target aspects of the RAS and are already FDA approved, including danazol, stanozolol, and ecallantide, which reduce bradykinin production and could potentially stop a deadly bradykinin storm.

Interestingly, the researchers suggest vitamin D as a potentially useful Covid-19 drug. "The vitamin is involved in the RAS system and could prove helpful by reducing levels of another compound, known as REN," the report says. "Again, this could stop potentially deadly bradykinin storms from forming." Other compounds could treat symptoms associated with bradykinin storms, such as Hymecromone and timbetasin.
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A Supercomputer Analyzed COVID-19, and an Interesting New Hypothesis Has Emerged

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  • by OMBad ( 6965950 ) on Wednesday September 02, 2020 @08:14AM (#60465278)
    Prevention is the important thing. Once you get it, you might die ot suffer from lung clots or scarring. So wash your hands, wear a mask, and SOCIALLY DISTANCE --- Most important. Do not leave your house unless you must.
    • You missed a massive injection of super computing in your ARM!
    • by bill_mcgonigle ( 4333 ) * on Wednesday September 02, 2020 @08:27AM (#60465310) Homepage Journal

      > Do not leave your house unless you must.

      Sorry, this is deadly advice.

      Get outside, develop a tan before winter comes, and do whatever else is necessary to build up endogenous stores of Vitamin D.

      The virus hasn't yet evolved UV-resistance and there are no documented cases of people outside, who stay six feet apart, transmitting the virus. Wear a mask if you're going to be close, but don't be silly and wear a mask while riding a bike or hiking a mountain, except when other people are nearby. There is only negative impact on reducing airflow in the absence of others - nuance matters.

      Be smart, not afraid.

      • by Immerman ( 2627577 ) on Wednesday September 02, 2020 @08:42AM (#60465344)

        I could be wrong, but I think vitamin D is one of those things that's mostly stored in your blood - which is to say you can't really store more than a few days worth, so you need a steady supply.

        Meanwhile, by blocking sunlight a tan actually reduces the rate at which your body can produce vitamin D - the darker your skin, the longer you have to stay in the sun to produce the same amount of D.

        • by Anonymous Coward on Wednesday September 02, 2020 @10:06AM (#60465676)

          I'm VitD deficient - or more accurately, at risk of - due to side effects of some chronic meds, and take a tablet with 50 000 IU every two weeks. 50 000 IU represents the upper daily tolerable limit in some official recommendations, which in this case means taking that much EVERY DAY may result in toxicity in about 4 months or so. (Obviously general figures, which will differ from person to person. And unfortunately the tablets look similar to purple M&Ms...)

          It wasn't nice when I was VitD deficient, but the upside is that I now undergo blood tests every 3 months to check the levels and get prescription meds (albeit cheap) to keep it in the acceptable range since way before 2020.

          Wikipedia states 5-30 minutes moderate exposure of face, arms, and legs, twice a week, for light-skinned people, as sufficient. But yeah, darker people have to stay longer. Also, not wear sunscreen or sit behind window glass.

          Ergocalciferol (D2 - typically from food and supplements) and Cholecalciferol (D3 - produced in the skin) are not biologically active. These are converted in the liver to 25-hydroxycholecalciferol (calcifediol or 25(OH)D), which is the form that blood tests measure in blood serum. Which however needs to be converted in the kidneys to 1,25-dihydroxycholecalciferol (calcitriol or 1,25(OH)2D) before being biologically active - it binds to a specific protein for transport through the blood to its final sites. So the whole tanning/supplementing thing is only half the issue, you still need adequate liver and kidney health too.

        • The tan also is not healthy, the 50s were wrong about that. Tanning increases the aging effects on skin (wrinkles) and can cause skin cancer. If you are outside in the sun then use suncreen with a high SPF number.

      • by rsilvergun ( 571051 ) on Wednesday September 02, 2020 @09:03AM (#60465434)
        or you could wear a mask and social distance.

        That said, GP isn't entirely wrong. If everybody would just stay home and pick up their groceries for a month or two this would all be under control. One of the things that really, really pisses me off is that I put a ton of effort into containing the virus and made a bunch of sacrifices only to have yahoos blow my work to hell going to the beach and bars and shit...
        • Re: (Score:2, Funny)

          by OMBad ( 6965950 )
          Not only am I not entirely wrong, I am currently marked +5 Insightful! Since there is no +6 mod, I must be entirely right. I cannot get any higher. If only we would work together and do what the government tells us we would be done with the COVID by now.
        • The beach is fine. Part of the problem that we're getting here is mixed messages from the government and the media.

          Go to the beach. The sun will cause you to produce vitamin D (mentioned in the article as a possible partial treatment), and the volume of air and presence of UV light degrading the virus make it *extremely* unlikely that's where you'll catch it.

          But governments are telling people to stay out of parks and off the beach, and allowing hair salons and cafes and bars to open, which is insane. And th

          • Going to the beach isn't the problem per se. Indeed, getting vitamin D from sunlight is helpful.

            It's the complete and utter lack of social distancing which tends to happen at a crowded beach. Yes, the UV and the open air reduces the chance of transmission. It REDUCES it; it doesn't eliminate it. All the screaming and yelling from people running around at the crowded beach increases the chance of transmission. Remember, there was choir practice at a church which turned into a superspreader event. They were
          • by HiThere ( 15173 )

            I think that saying "Outdoor transmission is nearly non-existent," is grossly overstating the case, but it certainly is a lot lower than indoor areas with recirculating air flow. Especially where people are densely packed. Hair salons might be reasonably opened, as the people there are usually not densely packed, and they often have good air circulation. Similarly cafes, though there's a lot of variation in the design of those places. Bars, though, generally encourage close packing of people...and alcoh

        • Uhm, who do you think delivers the groceries? And stocks the stores? And distributes the food to the stores? And makes the food?

          Robots? Maybe in 20 years. What you describe has clear and obvious flaws.
          Note, just because someone is wrong, does not mean the opposing theory is right.

          We are just a bunch of primates throwing crap at each, we can ALL be WRONG together.

        • by smooth wombat ( 796938 ) on Wednesday September 02, 2020 @12:22PM (#60466270) Journal
          If everybody would just stay home and pick up their groceries for a month or two this would all be under control.

          You mean like the 4-6 week quarantine we should have done back in February/March but instead were told by dear leader, who had been warned in January action needed to be taken [nytimes.com], we have it totally under control [cnbc.com], it's only one person from China, it will magically go away [cbsnews.com], then went golfing [snopes.com] before announcing, "The world was blindsided [youtube.com]. No one saw this coming."
    • by mark-t ( 151149 ) <markt AT nerdflat DOT com> on Wednesday September 02, 2020 @08:43AM (#60465350) Journal
      Actually, having a convenient and effective treatment is probably more useful than simple prevention, because if such a thing exists, then the deadliness of the virus is effectively downgraded, becoming no more serious than most other endemic viruses. It is not before then that society can resume business as usual. Millions of people are still unemployed, and employment insurance will not last the time required for the virus to eventually mutate into something less deadly on its own.
      • by OMBad ( 6965950 )
        By the time you receive treatment you might already be dead or your lungs scarred so badly you cannot even swallow the Vitamin D.
        • by mark-t ( 151149 )
          That's why I said both convenient *AND* effective treatment... If the treatment is convenient enough, it can be widely deployed, not even necessarily requiring hospitalization. If it is effective enough, then the deadliness of the virus is effectively reduced.
      • "the time required for the virus to eventually mutate into something less deadly on its own": IIUC, that isn't what happens (at least not in less than millennia). The virus can mutate all it wants, but what that means is that somewhere an individual virus--one out of a trillion individual viruses--has mutated, and maybe that mutation makes it less deadly. That doesn't mean the other 999,999,999,999 viruses share that mutation, so they're still as dangerous as ever. (Of course, many of those other viruses

    • Well, no, they're both important. Prevention is important because it buys time for more effective and less drastic means of prevention (vaccines) and new treatments. But the amount of coordination and stoppage of commerce required from every person and nation on Earth to actually eliminate the virus is so improbable that you may as well treat it as impossible. Therefore, people WILL contract the virus. Probably even some of the ones who are being careful. Knowing that, it's important to understand the

  • Vitamin D (Score:5, Informative)

    by cirby ( 2599 ) on Wednesday September 02, 2020 @08:18AM (#60465288)

    This explains a number of things.

    It's been known for a while now that patients with Vitamin D deficiencies have a harder time with COVID, with much worse outcomes.

    Of course, one way to make sure you have a D deficiency is to spend all of your time indoors.

    So if you're stuck inside, take D3 supplements.

    • by ArchieBunker ( 132337 ) on Wednesday September 02, 2020 @08:22AM (#60465294)

      Well the user base here is certainly doomed.

      • by OMBad ( 6965950 )
        The first thing that happened after I heard about the COVID was I stopped having sex or even kissing.
      • by Ksevio ( 865461 )

        That'd require interacting with someone in person so I think we'll be ok

      • > Well the user base here is certainly doomed.

        Not really. We might be low on vitamin D due to the lack of sunlight, but the fact that we've all been sheltering in place and social distancing for our entire lives will keep us from getting it to begin with.

        People talk about all this "effort" to not go anywhere or do anything, but I've been taking most of the precautions since way before Covid was a thing. Half the time I'd hear of a new idea, I'd laugh because we were already doing it pre-Covid.

    • So if you're stuck inside, take D3 supplements.

      But what if I'm not a JavaScript programmer?

    • by Kokuyo ( 549451 )

      You forgot vitamin K2... It is essential for the absorption of Vitamin D.

      Taking one without the outher makes little sense.

      • Except Vitamin K2 is not something that you should just take lightly and has its own pretty severe issues if you get to toxicity levels...

    • Or just walk out your door or onto your balcony for literally 10 minutes a day in the sunlight. But as winter is coming, definitely stock up on D3 supplements now.

    • by clovis ( 4684 )

      Or we can get some sunlight.
      The body is very good at making vitamin D using sunlight. An exposure at midday of 20-30 minutes 3 times a week while wearing shorts and a t-shirt will meet your needs. Dark skinned people need more exposure.

    • The Vitamin D connection to COVID severity has been known since March. It also explains why dark skinned people suffer more severe effects from COVID. If we had leaders that cared, there would be a huge campaign to encourage Vitamin D supplements, especially for dark skinned people. It would be a lot safer and more effective than hydroxycloroquine.

      It almost looks like our âoeleadersâ donâ(TM)t care ?

  • Silver Lining? (Score:5, Interesting)

    by wulfhere ( 94308 ) <slashdot AT huffmans DOT org> on Wednesday September 02, 2020 @08:19AM (#60465290)

    If there's one bright side to this whole pandemic, it's been fascinating watching the world's scientists start to piece together the puzzle on SARS-CoV2.

  • So your telling me we spent all this time and money just for an "electronic brain" to "hoover up" data and all it came back with was "you're an asshole"?

    Bill .... I don't think there's a future in this Computationalizer nonsense, lets go have a martini and a pack of redwoods

  • Vitamin D advantages (Score:4, Informative)

    by gnasher719 ( 869701 ) on Wednesday September 02, 2020 @08:37AM (#60465336)
    Advantages of vitamin D are: It's cheap. And it's good for you regardless of Covid unless you take excessive amounts. And it won't heart you, again if you don't take excessive amounts. I take 25micrograms / 1000 units every day, that is about reasonable for the average white person. 50 micrograms / 2000 units every day is likely better if you are black or otherwise dark in Europe or the USA / Canada. 100 microgram / 4000 units is the limit that you should not exceed. 1000 microgram / 40000 units will cause damage.

    So if you are black, or otherwise dark skinned, living in the US or Europe, you should definitely take some, especially in the winter.
    • by HiThere ( 15173 )

      Umnh...maybe. I understand that there's some evidence that dark skin color is associated with a different metabolism of vitamin D. So *perhaps* the blood serum value associated with deficiency isn't the same. IIUC, the answer is "we don't know".

      Still, AFAICT, it's reasonable advice until more evidence comes in.

      OTOH, I'm no expert in the field.

  • I predict a shortage of Vitamin D supplements and Milk in 3, 2..
  • How much money and time would it take to get a couple dozen blood samples from diseased victims through a chromotographer?

    • by pjt33 ( 739471 )

      Depends on how many hurdles the ethics committee makes them jump through. And, without looking at their CVs, authors of a simulation paper might not be trained to work in biosafety level 2 labs.

  • Dr. John Campbell has been touting vitamin D since that start of the pandemic. I bought mine months ago: https://www.youtube.com/watch?... [youtube.com]
    • by OMBad ( 6965950 ) on Wednesday September 02, 2020 @09:06AM (#60465442)
      Taking medical advice from Youtube is always a great strategy to stay ahead of the curve and remain healthy.
    • Sorry but there is a lot of evidence that the Vitamin D you stuff into your face isn't available for many benefits. You're going to need a proper UV-B lamp if you can't get into sunlight, which are VERY hard to find now, the companies that made the good ones were forced to nerf their products.

  • Does the phrase "computer model" ring a bell with anyone? As with Imperial clusterfuck, someone wrote a program and loaded a lot of data into it.

    And from this they get all the conclusions described in TFA?

    I would have hoped that, if nothing else, Slashdotters would be alert to the risks of computer models.

    • "The computer had revealed a new theory about how Covid-19 impacts the body: the bradykinin hypothesis".

      So... "the computer... revealed a new theory". Did it wave its arms and talk loudly while chalking up incomprehensible equations on a blackboard?

      Come on. It's just a very fast adding machine.

    • by OMBad ( 6965950 )
      Um, this is a SUPERcomputer, not just a computer! Plus the guy is a Doctor, so he must know what he is talking about. Good enough for me!
    • I don't why you are so pessimistic, its not like they claimed this was the result of AI. Because then you would know it was hogwash.
    • As with Imperial clusterfuck, someone wrote a program and loaded a lot of data into it.

      I have yet to see anybody criticizing that model point out anything substantially wrong with it.

      • PS, I did see the critique of the code quality. But with regards to the predictions themselves, I don't think I've seen anybody complaining about anything except that the predictions for the "if we do nothing" scenario didn't line up with what actually happened when we in fact did a lot more than nothing.
    • That's how most science is done today, dummy. Computer models. All fields.
    • They've developed a hypothesis (and it seems reasonable, afaict). There is an easy way to test if their hypothesis is correct, as mentioned in the summary:

      "Several drugs target aspects of the RAS and are already FDA approved, including danazol, stanozolol, and ecallantide, which reduce bradykinin production and could potentially stop a deadly bradykinin storm."

      So the next step is to have a double-blind test using some of those drugs.

      This is good science here.

    • First of all, it is not a "computer model", it is a computational analysis of gene expression data from Covid-19 patients.

      Second, there is no supercomputer involved in the findings. This appears to be something completely made up by one of the journalists. The medium.com article, which references a Forbes article and an ieee.org article, claims they did a large scale GWAS analysis, but that is not what was published. The actual paper is a rather ordinary gene expression study. They had a cohort of ~50 patie

  • Would be nice to have these findings peer-reviewed.
  • When the whole thing began, death rates were very high. Granted, part of that was a lot of deadly treatment and the culling of the weakes that was likely to happen... but it was also winter.

    Might explain why death rates in Switzerland have been constant and very low (0-2 individuals per day on a pop of 8million) in the last few months. Seems to me now that fall is coming, they might rise again as exposure to sunshine gets rarer.

  • TFS states the virus enters the body mainly through ACE2 receptors in the nose. So, is mouth breathing safer, or might the virus still get up into the nose if it gets into person's mouth?

  • What's the 'interesting new hypothesis'? Everything as reported here was already well known.
  • "the virus enters the body through ACE2 receptors in the nose, "

    That's why the covidiot mouth-breathers don't catch it.

  • by sjames ( 1099 ) on Wednesday September 02, 2020 @02:10PM (#60466668) Homepage Journal

    The entire discussion here has been about the most minor findings about Vit. D. While vit. D may be helpful, the other findings are quite interesting.

    For one, it suggests anyone on an ACE inhibitor should stop taking it if they get COVID. Perhaps that even partially explains why older people are more vulnerable since older people are more likely to have hypertension and so are more likely to be prescribed an ABE inhibitor. Note that hypertension is known to be a risk factor in COVID. Perhaps the prescribed ACE inhibitors is why.

    There are several already approved medications that reduce bradykinin levels that are worth considering for COVID treatment.

    This is not medical advice, I am not a doctor and I have never played one on TV. Discuss any change of medication with your doctor, etc. etc. etc.

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