2 June 2020
You will have your head bashed in with everything written about, claimed about, and talked rubbish about COVID-19. What to believe, what not to believe? Is this some weird virus that kills people in a way never seen before? Why are children developing a strange widespread inflammatory condition that looks like Kawasaki’s disease? And suchlike.
What I am going to tell you here are my thoughts on what I have learned about COVID, incorporating a great deal of previous knowledge from clever people. This is not the Gospel according to Dr Kendrick, but I am going to present what I believe to be a coherent hypothesis about how COVID kills people. Everyone can feel free to attack it from all sides. [This is going to get quite technical at times].
The hypothesis here is that, the way the COVID kills people is, primarily, by damaging the endothelial cells that line all blood vessels, and also the lung endothelium facing the atmosphere.
This endothelial damage then triggers a widespread ‘inflammatory’ response that triggers the development of blood clots – not just in the lungs – but also everywhere else in the body. The endothelial damage is, in effect, the body attacking itself, through an immune response – the so-called ‘cytokine storm’. Some of the resulting clots that result are small, some big. This overall process is known as Disseminated Intravascular Coagulation (DIC).
DIC, by blocking and damaging a high percentage of small blood vessels in the lungs, hampers gas exchange, driving down oxygen levels, and can lead to death through oxygen desaturation.
Other organs can also become seriously damaged, because DIC can block up blood vessels anywhere in the body. Larger blood clots can cause strokes, heart attacks, kidney failure and suchlike. Clots forming in veins, in the legs, can break off and travel into the lungs where they create pulmonary embolism. Venous Thromboembolism (VTE) is a common cause of death.
Essentially, people die as a result of blood clots.
Diabetes and COVID
The probable reason why diabetes has been found to be an important risk factor for dying from COVID is that, in diabetes, hyperglycaemia (excessively high blood sugar level) specifically damages the glycocalyx (a protective glycoprotein layer covering all endothelial cells). This exposes the endothelial cells to greater damage and will lead to a greater and more widespread level of DIC1.
An additional problem with diabetes is that the glycocalyx layer is primarily where nitric oxide (NO) is synthesized. Nitric oxide is a potent anticoagulant factor and helps to protect endothelium from damage by Reactive Oxide Species (ROS) a.k.a. super-oxides.
NO also stimulates the production of endothelial progenitor cells (EPCs) in the bone marrow. EPCs will cover areas of endothelial damage, growing into mature endothelial cells, to form a new layer of endothelium. This can reduce both the inflammatory response and DIC.
COVID-19 does nothing unique – it just does more of it
The idea of a virus causing and inflammatory response, followed by DIC is not new. Influenza A has also been shown to do this. As highlighted in the article ‘Aberrant coagulation causes a hyper-inflammatory response in severe influenza pneumonia.’
‘Influenza A virus (IAV) infects the respiratory tract in humans and causes significant morbidity and mortality worldwide each year. Aggressive inflammation, known as a cytokine storm, is thought to cause most of the damage in the lungs during IAV infection. Dysfunctional coagulation is a common complication in pathogenic influenza, manifested by lung endothelial activation, vascular leak, disseminated intravascular coagulation and pulmonary microembolism. Importantly, emerging evidence shows that an uncontrolled coagulation system, including both the cellular (endothelial cells and platelets) and protein (coagulation factors, anticoagulants and fibrinolysis proteases) components, contributes to the pathogenesis of influenza by augmenting viral replication and immune pathogenesis.’ 2
As you can see, this is much the same sequence of events as happens with COVID infection. The additional, major problem with COVID is that, because it enters cells through the ACE2 receptor, it specifically disables/damages this receptor.
This, in turn, blocks a key pathway pathway to NO synthesis. Instead of NO being synthesized, a ‘super-oxide’ is created, which causes more endothelial damage. In this way COVID has a dual damaging effect. There is less NO being made, with additional ‘super-oxide’ production. This effect was also seen with SARS 3.
Kawasaki’s and COVID
It seems that in the midst of COVID far more children are developing Kawasaki’s than has been seen before – although it remains very rare. This has led to the question, can COVID cause Kawasaki’s. I think this is almost certainly the case, because these conditions have very similar clinical manifestations.
Although the agent, or agents, that can cause Kawasaki’s have never been identified, Kawasaki’s disease is essentially a widespread vasculitis (damage/inflammation in blood vessels). It seems that an infective agent may alter endothelial cells in such a way that the body feels they are ‘alien’ and then decides to attack. A delayed immune response.
‘A new hyper-inflammatory disease seen in children is now thought to be a delayed immune reaction to COVID-19, as experts say there could have been up to 100 cases in the UK so far.
Last week, the president of the Royal College of Paediatrics and Child Health, Professor Russell Viner, said the number of cases across the country stood between ’75 and 100?, and said the evidence pointed to the syndrome being the body’s delayed overreaction to the virus.’4
This delayed reaction is probably why the infective agent(s) causing Kawasaki’s have never been found. The agent causes the problem, then is gone, then the antibodies become active two or three weeks later.
In support of this concept, in Kawasaki’s Anti-Endothelial Cell Antibodies (AECA) can be detected 5. These almost certainly coordinate the immune attack on the endothelium, causing the secondary cytokine storm, and the other forms of organ damage that have also been seen in COVID.
In essence, the parallels between COVID and Kawasaki’s are very close, and both can be related directly to endothelial damage. So, I think it can probably be said that COVID does cause Kawasaki’s.
COVID as a form of viral sepsis?
Another way to look at this is as COVID as a form of viral sepsis. Sepsis is due to a bacterial infection, not viral infection. In sepsis, bacteria get into the bloodstream and multiply.
As they multiply, they secrete (waste product) ‘exotoxins’. These exotoxins strip off the glycocalyx and seriously damage the underlying endothelial cells. This, in turn leads to widespread clotting (DIC). As with COVID you end up with organ failure and death. There can also be loss of fingers, toes, entire limbs, due to the blockage of smaller blood vessels.
‘Deviations from normal endothelial barrier function can lead to or be caused by various internal or external stresses and pathologic conditions. Sepsis and septic shock, as recently redefined, are associated with pulmonary edema caused by increased permeability to proteins across pulmonary endothelial and epithelial barriers, and recovery from septic shock is associated with a reduction in edema, consistent with restoration of vascular function.’6
The treatment regime
Looked at in this way, the treatment regime for COVID (support treatment) should consists of three prongs
1: Anticoagulants – e.g. low molecular weight heparin (to prevent DIC)
2’: Immunosuppression to reduce the assault on the endothelium by the immune system. The most powerful immunosuppressants are corticosteroids (to stop the immune attack on the endothelial cells)
3: Agents to help protect/stabilise the endothelium and/or increase nitric oxide synthesis
COVID kills the endothelium
Many people have been baffled by the manifestation of COVID:
‘In April, blood clots emerged as one of the many mysterious symptoms attributed to COVID-19, a disease that had initially been thought to largely affect the lungs in the form of pneumonia. Quickly after came reports of young people dying due to coronavirus-related strokes. Next it was COVID toes — painful red or purple digits.
What do all of these symptoms have in common? An impairment in blood circulation. Add in the fact that 40% of deaths from COVID-19 are related to cardiovascular complications, and the disease starts to look like a vascular infection instead of a purely respiratory one.’ 7
In fact, COVID is both a respiratory and cardiovascular disease. However, I believe that its many manifestations, and the way that it kills people can be explained by the unifying observation that it damages endothelial cells.
Can Vitamin C be beneficial?
There have been many studies demonstrating the vitamin C can help to support nitric oxide synthesis and reduce super-oxide damage. As described below:
‘Circulating levels of vitamin C (ascorbate) are low in patients with sepsis. Parenteral administration of ascorbate raises plasma and tissue concentrations of the vitamin and may decrease morbidity. In animal models of sepsis, intravenous ascorbate injection increases survival and protects several microvascular functions, namely, capillary blood flow, microvascular permeability barrier, and arteriolar responsiveness to vasoconstrictors and vasodilators. The effects of parenteral ascorbate on microvascular function are both rapid and persistent. Ascorbate quickly accumulates in microvascular endothelial cells, scavenges reactive oxygen species, and acts through tetrahydrobiopterin to stimulate nitric oxide production by endothelial nitric oxide synthase. A major reason for the long duration of the improvement in microvascular function is that cells retain high levels of ascorbate, which alter redox-sensitive signalling pathways to diminish septic induction of NADPH oxidase and inducible nitric oxide synthase. These observations are consistent with the hypothesis that microvascular function in sepsis may be improved by parenteral administration of ascorbate as an adjuvant therapy.’8
I am aware there have been many attacks on the use of Vitamin C in COVID with various experts stating that it does not protect against becoming infected with COVID, nor does it boost the immune system. However, that is completely beside the point, we are looking at endothelial damage here.
If it is true that COVID attacks and damages the endothelium – and the evidence seems strong that it does – we must protect it. Nitric oxide can do this, as can Vitamin C. Even if it does no good, vitamin C certainly does no harm. I would strongly support its use in COVID, even if the mainstream view is to dismiss it as nonsense.
COVID is a virus that, because it forces entry to cells through the ACE2 receptors, which are found in high concentration in both lung and circulatory endothelium, causes specific damage to these cells. Due to the addition, specific action of knocking out ACE2 receptors, NO synthesis is greatly reduced, and ROS/super/oxide compounds are formed. This greatly amplifies the endothelial damage.
This damage, and the resultant ‘cytokine storm’, leads on to DIC. This in turn causes deaths through organ failure and/or large blood clot formation which can block blood supply to the lungs, the heart, the brain, the kidneys etc.
Supportive treatment requires the use of agents that can increase NO/reduce ROS, slow or stop the cytokine storm, and anti-coagulants. Oxygen is required when there is significant lung damage.
That’s it. Attack away.