By Charles Adisa MD
It binds to the ACE2 receptor via its S protein(spike protein).
When it gets into the cell cytoplasm usually the type 2 pneumocytes, it releases its Single strand RNA.
Several things can occur at this stage
1. It can utilize the host ribosomes to produce the viral macro proteins in a process called translation.
2. These viral macroproteins are further acted upon by the host proteinases to form the virus component like the nuclear capsids, Spike proteins and viral enzymes etc
3. It can use the host RNA dependent RNA Polymerase enzyme to mass produce more RNA strands of the virus
4. The virus proteins products and the new RNA strands combine to form more virions which overwhelm the type 2 pneumocytes.
5. Type 2 pneumocytes get damaged and release inflammatory mediators that attract the macrophages.
6. Macrophages release cytokines (IL2, IL6, TNF) into the cells.
7. Cytokines attack the vascular endothelium leading to vasodilatation and increase capillary permeability.
8. Increased vascular permeability leads to interstitial edema causing the typical ground glass opacities seen on CT and Xray of the chest.
9. Damage of the type 2 pneumocytes lead to loss of the sulfactants it produces leading to increase alveolar tension and pressure and eventual collapse of the alveoli.
10. This progresses to poor air exchange in the lungs, hypxemia and increased work of breathing.
11. Cytokines invites more wbcs which in an attempt to destroy the virus particles release reactive oxygen and proteases that further damage the type 1 and 2 alveoli leading to pulmonary consolidation.
12. All these eventually lead to ARDS.
13. Cytokines released into the circulation gets into the brain and at the hypothalamus resets the thermostat leading to pyrexia.
14. Systemic effects of the cytokines lead to multiple organ failure.
15. Other organs with abundant ACE2 receptors include the heart and the bowel.
This results in myocarditis, several instances of direct effects on the heart have been reported in the literature.
If bowels are involved, you have enteritis and colitis with GIT symptoms.
16. In some cases, you have cytokines storm which could be severe and lead to multisystemic organ failure. Another word for cytokine storm is hypercytokinemia
17. Another mechanism is it’s ability to bind with great affinity to the heme component of the hemoglobin displacing Fe3+ radicals, and placing its own protein subunits there causing a methemoglibinemia equivalent state, and also allow free Fe radicals to snatch up electrons from tissue molucules from organ systems, the lungs, causing further injury… and also heme rings which can get into circulation can injure tissue. The release of Fe radicals probably explains the high level of ferritin in the blood of COVID 19 patients.
▪ Adisa, a professor of Surgery and Surgical Oncologist, is with the Abia State University.
By Charles Adisa MD