POST MORTEM RESULTS ARE GRADUALLY REVEALING THE PATHOPHYSIOLOGY OF COVID 19 DISEASES.
Based on observations in USA, Spain, Italy, France and UK, and from postmortem of lungs involvement in COVID 19 , all revealed pulmonary thrombosis which is not typical ARDS , but more alarming that it is patient hypoxemia that is not responding to PEEP but high oxygen flow.
Like methemoglobin, the COVID 19 virus structural protein, sticks to heme - displaces oxygen - which release iron-free ion , that leads to toxicity and causes inflammation of alveolar macrophages- that results in bilateral CT scan changes as it is a systemic response.
There is No benefit of invasive ventilation, but patients May require frequent blood transfusions or plasmapheresis.
The COVID 19 virus attacks beta chain, dissociates heme, removing iron and converting it to porphyrin. The virus can dissociate oxy-Hb, carboxy-Hb and
Lung inflammation results from the inability of both oxygen and CO2 exchange, leading to the ground glass on x rays, it mimics CO2 poisoning as an invisible enemy.
Chloroquine competes for the binding to porphyrin.
Favipiravir binds to the virus envelope protein with very high affinity, prevents entry into the cells as well as binding of the structural protein to porphyrin.
If free radicals scavengers and iron chelating agents are added to the protocol of management, it may lessen the inflammation process.
COVID 19, SARS2 is not 'pneumonia' nor ARDS. Invasive ventilation is not only the wrong solution, but emergency intubation can harm and result in more damage, not to mention complications from tracheal scarring and stiff lung during the duration of intubation.
Furthermore, a new treatment protocol needs to be established, so we stop treating patients for the wrong disease.
COVID-19 causes prolonged and progressive hypoxia by binding to the heme groups in the red blood cells.
People are desaturating due to failure of the blood to carry oxygen.
This will lead to multi-organ failure and high mortality.The lung damage seen on CT scans is due to the oxidative iron released from the haemolysed red blood cells which in turn overwhelm the natural defences against pulmonary oxidative stress and causes what is known as Cytokine storm.
There is always-bilateral ground-glass opacity in the lungs. Recurrent admission for post-hypoxic leukoencephalopathy fortifies our findings that COVID-19 patients are suffering from metabolic hypoxia due to blood capacity failure.
COVID-19 glycoproteins bond to the heme in RBC, and in doing so, the toxic oxidative iron ion is disassociated and released. The freely roaming iron in the blood without any physiological function will culminate into the following;
1) Without the iron ion, haemoglobin can no longer bind to oxygen. Once the haemoglobin is impaired, the red blood cell is essentially none functioning in carrying and delivering oxygen to any tissues.
RBC's Become useless and a burden on the patients as they circulate around with COVID-19 virus attached to its porphyrin. This lead to the destruction of the red blood cells and the patient's oxygen saturation levels drop significantly.
What is happening equates to carbon monoxide poisoning, in which carbon monoxide is bound to the haemoglobin with the failure of gas exchange.
Ventilations will not manage the root cause, which is blood organ failure.
COVID 19 patients, unlike CO poisoning in which eventually the CO can break off, the affected haemoglobin is permanently stripped of its ability to carry oxygen where the body compensates by secreting excess erythropoietin to stimulate the bone marrow to secrete new red blood cells. This is the reason we will find thrombocytosis and decreased blood oxygen saturation as one of the three primary indicators of COVID 19 severity score.
2) The freely floating iron ion are highly reactive and causes oxidative damage. This always happens physiologically and naturally to a limited extent in our bodies and such cleanup is a defence mechanism to keep the balance.
The Three primary Lung defences to maintain "iron homeostasis", 2 of them are in the alveoli.
The first of the two are macrophages that roam around and scavenge up the free radicals of the oxidative iron. The second is a lining on the epithelial surface which has a thin layer of fluid packed with high levels of antioxidant molecules such as ascorbic acid (Vitamin C) among others.
When too much iron is in circulation, it begins to overwhelm the lungs' counter measures begins, the process of pulmonary oxidative stress. This leads to damage and inflammation, which leads to the so-called Cytokine storm; this can be documented on high-resolution CT scans of
In COVID-19 patient lungs, It is a fact that it affects both lungs at the same time and Pneumonia rarely ever does that, but COVID-19 does every single time.
The liver is attempting to do its best to remove the iron and store it in its 'iron vault'. Only its getting overwhelmed too. It is starved for oxygen and fighting a losing battle from all the haemolysis haemoglobin and the freed iron ion. The liver will start releasing alanine aminotransferase (ALT) which is the second of 3 primary COVID 19 severity score indicators.
A patient must be managed on maximum oxygen flow through a hyperbaric chamber on 100% oxygen at double or multiple atmospheres of pressure, for 90 minutes twice per day for five days.
This is in order to give what has left of their functioning haemoglobin a chance to carry enough oxygen to the organs and keep them alive.
We do not have nearly enough of those hyperbaric chambers, and we might use all parked grounded aeroplanes as a ready-made functional hyperbaric chamber with the advantage of providing double atmospheric pressure with an aerosol of prostacyclin as pulmonary hypertension modulator.
Blood transfusion with packed fresh red blood cells to patients after plasmapheresis may ameliorate the cytokine storm.
The main point that patients will require ventilators if they present late with multi-organ system failure to tie them over this life or death scenario. However, intubation is futile unless the patient's immune system modulates the situation. We must address the root of the illness and avoid using traditional teachings to manage a failing system.
3) No longer armchair pseudo-physicians sit in their little ivory towers, proclaiming "Chloroquine use is stupid as malaria is bacteria, COVID-19 is a virus, anti-bacteria drug no work on the virus!". A drug does not need to act on the pathogen to be effective directly. Chloroquine lowers the blood pH and interferes with the replication of the virus.
We advise that if COVID-19 positive patients are conscious, alert, compliant, they must be kept on maximum oxygen and initiate hyperbaric oxygen as early as possible.
If we reach the inevitably to ventilate, it must be done at low pressure but with maximum oxygen flow. We must avoid tearing up the lungs with maximum PEEP as we are doing more harm to the patient because we are managing the wrong organ.
There is a small village in northern Italy where the majority of its population suffers from thalassemia. They had no deaths and no cross-community spread. Moreover, parts of Nepal which are 1km above sea level are COVID-19 free. All points that we are chasing the wrong organ; it is not the lungs; it is a blood problem.
We recommend the following :
1. Inhibit viral growth and replication by the adjuvant use of CHQ+ZPAK+ZINC or other retroviral therapies being studies. The less virus load we have, the less haemoglobin is losing its iron, the less severity and damage with the prevention of cytokine storm.
2. Hyperbaric medicine utilization in any shape or form for anyone with thrombocytosis and elevated ALT can prevent the rapid ascent to the abyss.
3. Plasmapheresis and Blood transfusions will give supportive symptomatic relief.
4. No international Travel until an effective vaccine is available.
5. Cessation of tobacco, vaping and alcohol products.
Stay safe and Self Isolate
Prof Sherif Sultan MD, FRCS, FACS, PhD