This is an article of more guesswork and random brainstorming in isolation.
In a previous article I compared Covid-19 as similar to a Kawasaki disease in adults, but there is really a difference in how it operates. Kawasaki disease is more an autoimmune disease that causes the squamous epithelial cells in various areas of the body that are linked to sensation and surround most organs to become inflamed, but Covid-19 infects these same cells and damages or impairs them rather than inflames. The inflammation is a result rather than an effect. How it transfers and infects around the body may be simply damaged cells that it has previously infected naturally flaking off from the organ that they normally populate to be recycled and it hitching a ride to the next one where through temporary attachment uses a similar ACE2 entry mechanism. The worse the initial infection load the more travel around the system causing problems where they land up.
One of the unusual effects is on a thing called cellular opoptosis, where cells die and like a phoenix are reborn from the ashes. Our other bodies mechanism recycling them. If the recycling is prevented by them being in an unusual form it takes longer to kill them off and recycle them, and in some ways this lingering also leads to cellular deformation when they are reconstructed, causing a surge of repair signals for incorrect formation. The body likes to kill off cells that aren’t absolutely correct. Cytokines are the messngers for cell recycling. Cancer cells tend to get around this by mimicking ‘correct cells’ signals allowing them free reign, but a similar mechanism used with healthy cellas may prevent a storm occurring.
The squamous cells are flat cells that are labelled as type I cells. They surround most areas but being flatter usually act as a dividing semi-permeable membrane. Most of the surface cells are squamous and type I, whereas most of the internal cells are type II. Being flatter they allow better transfers of necessary chemicals to and from the body but are more easily penetrated by destructive agents. Surface skin cells are ‘hardened’ and supported against this, mainly by a virtually dead set of cells on its outer layers. So you could call it in some ways a sort of fire break or back burning. Burning an area in a controlled way to stop transmission of the flames through it.
The cells in the surface of the lungs, epithelial cells called the squamous alveolar cells, are flat cells very similar to those in various other parts of the body such as the liver, kidneys, heart, eyes, intestines and the mouth. These cells are found on surfaces as they are designed by contruction to allow chemical transfers easier than the standard spherical ones. A sphere has a larger surface, but contact between is less ordered, so a flat membrane type construction is preferable. Each performs a particular function in each area but the effects of infection by Covid-19 causes separate symptoms. In the lungs they impair oxygen and carbon dioxide transfer, organ failures in the kidneys, liver and heart, glaucoma in the eyes, diarrhoea in the intestines, and loss of sensations of smell and taste in the mouth. There are probably other effects such as loss of sensation on the soles of the feet and palms of the hands. A large viral load will cause most of the systems to be impaired possibly causing a general system failure.
One of the things that Covid-19 seems to affect is the squamous cells that are usually columnar epithelial cells which are on the surface of a number of organs, especially those that have a higher than normal ACE2 content. These flat cells are slightly different to the ones that are farther in which are more rounded. Covid-19 seems to infect and interfere with them, slowing down the processes that they normally perform. In the lungs they perform gas transfers, impairing them causing a backlog of required gasses both in and out. Oxygen is useful to energise the cells via the lungs, but if the system is impaired in transfer you might get oxygen damage occurring. Oxygen is converted in the lungs into a less harmful form to be use by the body, but as a very active agent it can also do damage if there is too much of it in free form that is not taken up. The lungs basically rust out, and the cytokine storm that many experience is more a large scale attempt to repair a mass of very damaged cells, signalled by the non-squamous cells behind them. In the intestine they act as a membrane to allow digestion to take place and Covid-19 interferes with digestion causing diarrhoea. On the surfaces of the tongue they allow a sense of taste and smell, Covid-19 interfering with this. In the eyes it causes redness similar to early glaucoma or a night out on the tiles. On the hands and feet they interfere with sensation and the quick repair mechanism causing them to become more sensitive. This is very similar to Kawasaki disease in a breakdown of the epithelial barriers.
The oxygen transport from the lungs and the CO2 to them is a very complicated set of chemical processes and are dependent on the PH levels of the blood and the availability of 2,3-diphosphoglycerate, breathing rapidly to acquire more oxygen quite often causing a compensatory form of alkalosis that reduces uptake by unoxygenated haemoglobin. Breathing slower but at slightly raised oxygen levels produces the opposite effect, but everything is a set of checks and balances, so altering that balance too quickly may cause the opposite effect. The body need time to slowly compensate to reach a new equilibrium.
It’s interesting that people have made various claims for the antimalarial drugs hydroxychloroquine and the less tolerated chloroquine as both operate on the parasites manipulation of heme that the malarial parasite plasmodium falciparum produces in the human body. Basically heme is poisonous to the plasmodium parasite and is produced when the parasite digests haemoglobin, where it uses enzymes to convert the heme to crystallized hemazoin. In an advanced stage it can cause a similar effect to Covid-19 resulting in general organ failure due to reduced oxygen transmission. A lot of this is linked to vascular endothelial growth factor that increases the permeability of the endothelial cells. But there is a problem with both drugs as although they interfere with the mechanism, allow the heme to build up, you need exposure to the parasite to produce it.
A much more suitable treatment for malaria could be to increase the amount of heme oxygenase by the use of something like hemin and/or cobalt protoporphyrin IX to resist such parasites as plasmodium, but may have an equal effect on Covid-19, by strengthening the squamous epithelial cells walls, making them less permeable to agents.
In the wild one such heme oxidase inducer has found as a phytochemical in curcumin that is found in turmeric root (Curcuma longa), of the ginger family that forms part of the Indian Ayurvedic medicine, although there is no formal evidence of it’s ability to treat anything. It’s probably in small quantities, but maybe people affected just aren’t eating enough curries to get the benefit?
The controversy is over what level of belief constitutes enough difference to be called different. All viruses evolved are similar and structurally work in similar ways, so to say ‘this one doesn’t work like all the others’ is a bit absurd. This ones trade is in ACE2, as is SARS-Cov1 and MERS, so its specialisation may be its downfall, others simply not getting out and doing similar, and therefore having more than one discovered strain because their characteristics were wrong.
Its characteristics were near exact for the proposed ‘virus x’ that could get past the worlds current virus defence network, but a fraction less fatal, and it was obvious 5 months ago this ‘this was the first,’ not that ‘this was the one.’
Of the common cold, about 20% of them are caused by the coronaviruses 229E, NL63, OC43, and HKU1, mostly mild, and most people will catch something like 20 coronavirus colds in their lifetime, not all of them classed as different, some better, some less. So probably about 5 of each strain on average, classed as the same.
Also a recent study found SARS-CoV-2 reactive cells in about 50% of people tested antibody negative for SARS-Cov2. It didn’t mean that they were immune to SARS-CoV-2, but that there may possibly be some help with the disease provided by their T Cells in previous response to other coronaviruses. You don’t get that if they are completely different and rare.
Well, if you wanted to be more exact you would call it an squamous epithelial disease. ACE2 which it uses, is found around the body, mostly in the lungs and at higher levels in overweight and obese people. There is less of it in younger people, and in older people the system is less flexible and balanced, so prone to upset, because of a increasingly weaker repair system. We are under constant renewal, and a repair is OK, but a repair of a repair of a repair isn’t so good. The older you are the less resources you have, and it’s easier to tip it, allowing faster and more severe dispersion.
Covid-19, a Wolf at the Door
But as all the information for this ‘novel’ virus is based on completely different ones, there isn’t a ‘correct’ way of dealing with it, as very few countries or areas have and are. All countries and areas underplay the disease in some way and most are now busy extolling the size of their fish that weren’t eaten by sharks. Some doing nothing, others restricting into damage, some having local and temporary success and thinking the problem is over and the sharks are gone.
But the signs are that the world is trying to deal with it on a local and personal basis and doesn’t remove the problem, just making sure it is delayed until the politicians have left office with their victories. It then becomes somebody elses problem; it didn’t happen on my watch or when I was in charge, so the viral debts of doing nothing to help others or not cooperating internationally doesn’t count on my political balance sheet.
But cases in the world are increasing, and lately starting to accelerate again. My current worry with how the disease is progressing, is that with all the cases now and happening in the world at an increasing rate, the scenario for a ‘next variant’ developing is becoming more probable. It’s still a statistical problem, and a ‘1918 scenario’ or model is worryingly developing. The world population in 1918 was about 1.8 billion, now 7.8 billion, and the mortality rate appears similar to Covid-19 for the same distribution spread, so the consequences are obvious.
Experts are divided by what happened for so many reasons, mainly because last time this it was in a different world that was 100 years ago, and only known about from what their textbooks and very limited records say. It lasted for just over 2 years with little restriction and little normal mobility, and Covid-19 is roughly 11 months old and restricted in a fairly mobile world to less than 1 percent.
The numbers have come down a lot due to social distancing, facemasks and hygiene, so this is something that needs to continue for a long time, probably at least until the end of the year. But we also need things to start running again with care. For countries and areas where the numbers have currently dropped to a bearable level they need to use the time to put in place pandemic sustainable infrastructures and organisation, ready for low infection rates, for those that aren’t they need to restrict and reduce to lower infection rates.
Countries vary by demographic, and a failure in a large or dense population may in fact turn out to be more of a success that is in small or low-density population.
Countries that are wealthy need to help countries that are not to get things under control. This idea of ‘I’m alright Jack,’ will world right up until the time it arrives back at your door again, and the lack of help then increases the chances of it doing so later. The wolf was at the door and its currently turned to other doors, so we need to help others to help ourselves before its finished feasting elsewhere, and coming back stronger having done so.
This is just waiting for the time the predator says, ‘I missed this one.’
I would agree that most colds are caused by rhinoviruses (40%), but statistically coronaviruses tend to come out next (15%), 50% more than influenza viruses (10%) and 3 times as many as adenoviruses (5%). 30% are unknown. As we catch so many we usually catch more than one at a time, quite often overlapping in effect, and there are hundreds we normally catch. A study recently showed that on average 50% of people had an immune type response to coronaviruses, but it doesn’t necessarily equate to being immune or helping in any way. That is a untested and unverified jump, so far not resulting in any effective treatment. NL63 is one of four that are associated with colds, 229E, NL63, OC43, and HKU1, so we probably catch a particular variant of each type 8 or 9 times with varying results.
If the NL63 coronavirus offered any immune capability it would be easy to cultivate and pre-infect everybody at risk with a suitable strain, but there’s no evidence at the moment it offers any protection whatsoever, above what they already have.
If it stays common in the world then it will probably come around in different forms about 7 times in a normal lifetime now that is has got out, but unless a vaccine or treatment is found it will be a battle of length of effective immunity and familiarity against age and sickness.
Not all children, especially the very young have caught colds, and the numeric exposure grows as you get older, so the same logic dictates that having too many colds has the effect of making you more susceptible. Although a 13 day old baby has died in the UK from it deaths under 1 year are very rare, so their T-Cells would be either not so active or partially inherited from their mother. Babies and small children are normally at greater risk because of this, but not in this case.
I think it more likely to be related to the reason why the varicella zoster virus causes a lesser response in the young, and more severe as you get older when it reactivates. The varicella zoster virus affects the afferent nerves in a dermatome rather than the squamous epithelial cells with Covid-19, but there is a similarity of effect.
As you get older some things become stiffer and some things more limp. Medicine is about trying to swap them.
Turmeric, black pepper and alcohol.
Kudzu and Isatis
Chinese arrowroot and woad
Feverfew and parthenolide.
The use of MACE2 to treat Covid-19
Thinking of the mechanism that Covid-19 uses to enter the body, the use of a sweet tooth by our cells and its adaptation for its own use of the ACE2 enzyme I thought rather than fight the virus, why not give it what it wants, ACE2, but in a form that it can’t take, so effectively poisoning it at source. The best way to do this in normal living cells is to add a methyl component. Methyl components to compounds are usually stronger reactions than ethyl based ones than normal life uses, so an active virus that is searching and planning to use a particular enzyme may prefer it and possibly rendering itself inert in the process. Animal bodies are just not suited to this, so a virus being part of the natural system will be susceptible to the same. A lot of drugs and antibacterials are methyl based, and viruses even given their propensity to spread, are quite fragile in construction so getting them to drink meths would not probably agree with them.
This is where a methyl derivative of ACE2 comes in. I have a picture in my mind of a methyl attachment/replacement to the N-acylethanolamine-hydrolyzing acid amidase. The acylethanolamine being an amide of ethanolamine, but what would it be if it was composed with a N-acylmethanolamine-hydrolyzing acid amidase. Would it be acceptable food?
The area that appears to be affected the worst is the lungs, although any squamous epithelial cells are prone to attack. Most cells affected in this way do not die a natural death and quite often form distorted components in the construction of new cells, so a treatment to kill off severely damaged cells will be needed, possibly in the form of a modified T-Cell.
ACE2 is short for Angiotensin Converting Enzyme 2, and has a structure of of a zinc linked carboxypeptidase. To provide the lungs with MACE2 a modified vaping solution containing glycerine and a low level form of MACE2 is needed, the glycerine being just there for transport. The idea of a low concentration is to allow for lung cell regeneration, but not to poison the subject by too much, so the levels of MACE2 need to be delicately administered.
The problem is a very complicated one and a number of things seem connected, the virus using ACE2 as a mechanism and the ACE/ACE2 balance being the likely thing that is a cause of the problem, and may be linked to such things as Kawasaki disease in children. It is a strange coincidence that such things like Lisinopril also has side effects of a dry cough and allergic inflammation when it tries to control ACE, being an inhibitor of it, and I’m sure they are related as they are symptoms of Covid-19, especially as problems found in younger children with it display the same symptoms as found in Kawasaki.