Blood sugar and COVID-19

    Novel pandemic is very new for science, often it takes years before scientists prove connection of risk factors and replicate their findings in experimental setups, but it is not the case to wait. I have been observing different facts about COVID-19 and propose “Hypothesis for connection between blood sugar levels and infection”. The only reason I do this now with so many controversies is that I genuinely believe it can save lives. Lives of my friends, and their relatives.

    In the article below I summarise my knowledge on infection and immunity, back it up by links to COVID observations of doctors and scientific papers.

    UFO care minute


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    For now we heard a lot about people with chronic diseases having higher mortality rate after COVID-19 and especially people with Diabetes. It is well known that Diabetic patients have very high blood sugar, and over more proteins in the body are glycated — meaning “small bit of sugar attach on the surface of huge protein molecule”. One of the most abundant proteins in blood stream is Haemoglobin (Hb), and to confirm Diabetes often degree of Hb glycation (i.e. sugar coating) is measured, logically as people with Diabetes have higher blood sugar their Hb is more “coated in sugar” then Hb of Healthy people. Remember this for now.

    We should also know that Hb is the protein to transfer Oxygen from small sacks (alveoli) in the lungs to all the cells of the body. To do this Hb contains Iron atom (just a few proteins are like this).

    Any infection be it bacterial or viral is in essence very fast multiplication of infectious agent. Bacterial do this by cell division, i.e. every cycle they multiply by 2. Viruses are bits of information coated in proteins, they enter the cells and “inject” their programme into cellular machinery of our own cells, meaning our own cells produce more and more copies of virus, at certain point ur cell dies and all the copies exit into the body to infect more cells. This can happen much faster than bacterial infection, as virus is much much smaller.

    Now the speed of production depends on availability of resources to build more viruses. Over millions of years Viruses evolved to steal SUGAR from our own cells, our own cells speed up sugar consumption from the blood. If there is more SUGAR in the blood the production is faster.

    To fight the virus our own cells also speed up and use sugar to prepare immune response. Part of that immune response is producing cytokines, it is very well known that if the immune response is to fast it can damage the tissues, while trying to save the body. This is called Cytokine Storm. It can cause bleeding in the tissues where infection is. Doctors even stop the cytokines by drugs (inhibit) to save our body from our own immune response.

    Recently scientists [1] were studying common Flu and shown that patients INFECTED had higher blood SUGAR than normal.

    So far it is already interesting. I was observing few friends on my social networks who had very light symptoms and after that had enough antibodies even to donate their blood to help those who are very sick. I know some of that are on sugar restrictive diet. Makes sense.

    Another group of doctors in US is also observing this connection [2]. New research has found that people with diabetes and poorly managed hyperglycaemia who are hospitalised for COVID-19 have a death rate and longer length of hospital stay that’s four times higher than people without these conditions. Forty-two percent of those without a prior diagnosis of diabetes before being admitted, and who developed hyperglycemia during their time in the hospital, died. Experts say it’s important to limit the amount of time people with diabetes visit hospitals right now to protect themselves and healthcare workers, and to reduce strain on the healthcare system.

    Adam M. Brufsky, professor of medicine in Pittsburgh, is telling even more interesting things on COVID and sugar [3]. He is mentioning that COVID virus uses specific proteins on the surface of our lungs. Protein called ACE. This protein is very common in cells of lungs and pancreas. He is describing that if this protein is coated with sugar — it makes it easier for virus to stick to that. And as virus infects PANCREAS as well (because of ACE protein on the surface), blood has even more sugar. Why so? Infected pancreas produces less insulin, and sugar from blood stream deas not enter the cells, so it is coating even more ACE proteins in lungs and pancreas. This is like a chain reaction.

    Prof. Brufsky hypothesis is built upon observation of SARS (epidemic in 2003 caused by virus similar to COVID-19) patients, where the above mechanism is well know. And now for COVID patients doctors also observe hyperglycaemia, this is supporting the mechanism described for SARS Drug called “hydroxychlorquine” is now used more and more, as it stops sugar from coating proteins, meaning stopping chain reaction.

    Why is sugar coating so important for virus. I imagine this as JAM, the more sugar on surface of both viral proteins and ACE, the easier it is to stick to one another. Like a sugary JAM when it sticks to the table.

    Haemoglobin, lung damage and sugar

    I was talking to my friend, Vardan, brilliant heart surgeon, yesterday — this whole conversation made me think about sugar and accumulate this information. Vardan is fighting COVID since the beginning. First as ER doctor, but for the last 20 days, as a patient. He says, when he saw the CT scan he decided to record a video for family. His precise words were “it is not Pneumonia, they say here it is broken Haemoglobin, but you should know it better.”

    Indeed last grant I was preparing in European Research Institute of Ageing was on protein oxidation and glycation and ageing. We believe that ageing is influenced by high blood sugar, on molecular level inside and outside the cells our perfectly crafted machines of life are influenced by sugar coats. Just as Haemoglobin and ACE from above every protein covers slowly by sugars. Imagine cogwheels inside the clock covered by grease, at certain point clock will stop.

    Coming back to Haemoglobin, main problem with COVID is decrease in functional space in the lungs. You can imagine lungs as an upside down tree, where trachea is trunk and lungs are branches, that become smaller and smaller. The finest branches contain small air sucks — alveoli, they are as small as 0,2 mm, with very thin walls of 0,02 mm serving as divider between them. There are 600 million alveoli. It is in the walls of alveoli, where we have smallest blood capillary, part of the breathing is happening. Haemoglobin is taking the oxygen from air and runs to deliver it across the body. It is the alveoli cells that are infected by virus during COVID.



    Now the high blood sugar causes cytokine storm and immune system attacks the thin walls of alveoli and the blood pours out. When Blood is touching the air, it starts to clot — as proteins (Fibrinogen mainly) are sticking to each other. This is a normal process and this protects us from bleeding when we cut ourselves, the clotted piece of blood is called thrombus. Rings a bell. Diabetics have higher risk of thrombosis, this is when blood clots and thrombi appear in the blood vessels. We actually know a lot about clotting inside large vessels, or when vessel is damaged. It is also very likely that in alveoli haemoglobin is also present as clotting factor when it comes out of broken blood cells. Some research on that was summarised recently [4]. It looks like that exactly the case with complications in COVID.

    The more virus in the lungs, the more chances to get internal bleedings and thrombi. Blood is clotting and less and less space is left of exchange oxygen and patient ultimately will die of low oxygen in the blood. If the proteins are coated with sugar, they stick even better. JAM analogy from above, and a lot of evidence in diabetic patient thrombosis [6] increase. All because of sugar.



    Another recent hypothesis [7] is that Virus of COVID is also attacking the Haemoglobin itself — eating part of it called porphyrin. Porphyrin is a ring inside Haemoglobin which holds Iron, which binds Oxygen. Can you imagine? Virus is breaking our oxygen transport proteins themselves. And our blood with broken Hemoglobins transports less and less oxygen, while blood clots decrease the available space for oxygen exchange in the lungs. I bet, that when haemoglobin is coated with sugar, it is much easier for virus to stick to that and destroy the protein. Viral proteins themselves are covered with sugars, so the JAM analogy is here again.

    Everything comes in order now

    If you have low blood sugar: virus has less substrate to replicate, it is harder to induce cytokine storm and bleedings, pancreas damage will not cause even more blood sugar, even if bleeding starts clots are less stickier. And in addition there is a chance that virus has hard time destroying oxygen carrying Haemoglobin. Great chance that you breathe and have enough time for immunity to fight the alien inside of you.

    If you have high blood sugar: virus has a lot of building blocks to replicate, cytokine storm is easily induced and bleedings start, pancreas damage is even more and insulin is not produced, even more blood sugar and more sticky proteins. When bleeding starts clots are bigger and stickier. And in addition there is a great chance that virus easily destroys oxygen carrying Haemoglobin. Patients like this are know to have a chain reaction speed of few hours when they go from normal to critical and need air supply.

    Questions that you have to think about

    What kind of food they give people in the hospital? Does rise blood sugar? After working inside/with Hospitals in Russia, UK and Netherlands — I know it does. And I know bone broth would be best substitute.

    Recovery

    Survivors are known to have fibrosis. This is the same clots in the lung becoming connective tissue, making those people disabled for the rest of their lives. Now clots can actually dissolve with time, by process called lysis, and again diabetic patients are known to have [8] bad clots, which are harder to dissolve because of … JAM

    Education

    Funny enough we are doing tons of seminars for the kids using the «Tim's adventure in the world of bacteria» book [9] content.



    One of the questions during seminar is «Imagine two kids, one eating sweets, another eating vegetables, both got their feet wet. Who will be the first one to get sore throat?». This is the same principle. We just remove the substrate for disease to spread and take control of our own health.

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    Comments 2

      0
      Hi Dmitry, thank you for the post. Well written, perfect explanations. My comment can be regarded as critical, but I thought that any comment is better than no comments at all. So…
      You've already mentioned that in the introduction, and I agree with you in that: I would also be rather cautious making conclusions from single clinical observations of an association between behavioral patterns (like a healthier diet) or lab test results (e.g., hyperglycemia) and disease outcomes. As wisdom asserts, correlation does not imply causation. A tendency toward higher blood sugar is natural for acute infections, even mild ones. It may sound like truism, but this is the exact reason why, dealing with risks in medicine, people distinguish between risk factors and risk markers. Higher blood sugar in diabetes predicts a worse outcome in many acute conditions, but is it a cause of the bad outcome or just a predictor. Imagine a residential building and the smoke coming out of it. I you see no fuss, it may be a pretty insignificant accident. If you see people running out, there may be a fire. Are those running people the true cause of the smoke accident's terrible outcome or a mere predictor. If plasma glucose is really the villain, to confirm it scientifically is no expense. It would be comparatively cheap to conduct a small randomized trial with low-dose long-acting insulin or sugar-lowering tablets like the newer SGLT2 inhibitors, which make glucose come out with urine (though some believe they make promote ACE2 expression in the kidneys; doi:10.3390/ijms18051083), or any other «gentle» sugar-lowering drugs like tablets with DPP4 inhibitors. The fatality rate is so high that the small sample size won't be statistically an issue, either.
        0
        There are also the info that patients from countries with high COVID-19 mortality rates, such as Italy, Spain and the UK, had lower levels of vitamin D compared to patients in countries that were not as severely affected.

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