2.-Why is there very high DDimer levels disproportionate to the severity of infection?
3.-Why ARDS in those are nearly
unresponsive to high PEEP and Fio2 levels?
4.-Why all CT chest patterns are largely Ground glassing and associated with rapid and marked hypoxemia and is disproportionate to the geographical CT findings size ?
5.- Why Early Chinese protocol for Covid includes high dosing of systemic steroids which is questioned and rejected by WHO ?
6.- Why body immune response aganist Covid is not like other respiratory viruses by lymphocytosis ( Cytotoxic T cells and Natural killer cells) , instead body prefers to react against covid by phagocytosis ( monocytosis ) ?
7.- Why Covid attacks mature red blood cell when it is one of the body cells that does not contain nucleus and DNA ?
8.-Why Critically ill Patients are responding well to anticoagulation , Hydroxycholoquine and novel antiviral Favipiravir ?
The following molecular pathogenesis is the only one for the time being that can answer all these questions .
- COVID -19 may not cause pneumonia either typical or atypical or classical ARDs . It seems like we are dealing with a presumed wrong disease.
- The Key pathogenic molecular step of SARS-Cov2 is to attack the 1-Beta Chain of Hemoglobin and hunting the porphyrins dissociating the iron from it and releasing iron into the circulation.
- Thus Hb loses its capacity to bind with oxygen , so oxygen is not supplied to major organs. That is why we see resistant hypoxia coupled with very rapid multi-organ failures.
- Moreover The free iron released into the circulation is so toxic as it causes a powerful oxidative damage to the lungs .
- Free iron toxicity causes inflammation of alveolar macrophages- leads to CT scan characteristic changes.
- The body tries to compensate this by elevating the rate of Hb synthesis which explains why Hb is high in those patients.
- Other compensatory mechanisms to deal with such iron load is increasing ferritin production ( iron store ) which explains the very high ferritin levels observed in those patients.
- Therefore the cause of monocytosis in the body needs to exceed macrophages to engulf the excess iron load .
- And the cause of Lymphopenia is the WBCs differentiation favored towards monocytes line rather than lymphocytes line.
- This makes ferritin a bad prognostic marker (too much iron means too much Hb loses its O2 carrying capacity) .
- Also this iron load and increased Hb production lead to increased blood viscosity with recurrent and diffuse micro and macro circulatory thrombosis.. that is why there is high levels of DDimer in those patients and this explains the cause of sudden deterioration and death in some sporadic cases
- This disseminated thrombosis is proved by postmortem examinations of ARDS victims ( it is not true ARDS)
- This theory could explain why we are losing patients so rapidly and why mechanical ventilation is not so effective in treatment and using ARDS mechanical ventilation protocol is not causing any benefit. Actually it could be futile and cause more lung damage
- On the other hand this crucially explains the very rapid and good response of those patients to full therapeutic anti coagulation.
- Chloroquine an antimalarial drug works by protecting Hb against invasion by malarial parasites .It is doing the same here but just protecting the Hb against invasion by the virus.
- The chemical components in chloroquine phosphate compete with the porphyrin and bind to the viral protein, thereby inhibiting the viral protein's attack on heme or binding to the porphyrin.
- Favipiravir is the latest anti-novel coronavirus drug with specific therapeutic effects.
- In Favipiravir, the most critical ligand is 1RP, which is 6 - fluoro - 3 - oxo - 4 - (5 - O - phosphono - beta - D - ribofuranosyl ) - 3, 4 - dihydropyrazine - 2 - carboxamide.
- Favipiravir cannot bind to E2 glycoprotein and Nucleocapsid, and its binding energy to viral envelope protein, ORF7a, orf1ab is higher than that of porphyrin.
- It is useful to note that the binding energy of Envelope protein and Favipiravir is more than 2700 times the binding energy of porphyrin.
- The primary function of Envelope protein is to help the virus enter host cells, which shows that Favipiravir can effectively prevent the virus from infecting human cells.
According to these clinical observations ,correlations and understandings :-
1- Hydroxychloquine , Favipiravir and early full anti coagulation therapy should be involved as early as possible in our National Management Protocol of Covid-19 .
* References :-
-Data is collected and interpreted from different clinical observations and reviews of many doctors and intensivists and from the postmortem examination pictures of Covid-19 victims in USA and Europe.
-Wenzhong Liu and Hualan Li2 (2020):
COVID-19: Attacks the 1-Beta Chain of Hemoglobin and Captures the Porphyrin to Inhibit Human Heme Metabolism; School of Computer Science and Engineering, Sichuan University of Science & Engineering, Zigong, 643002, China;
School of Life Science and Food Engineering, Yibin University, Yibin,644000, China; Correspondence: [email protected]