@NoReturn @borsabil @Lichen Bark
It's kind of interesting going over those links to posts in the previous thread. It's basically confirmed by this point that severe COVID-19 is essentially a form of sepsis.
When bacteria are the causative organism, most patients improve with oral antimicrobials, and only a few patients experience sepsis or more severe forms that require aggressive inpatient care. In the case of COVID-19, some patients are asymptomatic; others experience mild symptoms, and only a small fraction progress to severe COVID-19. A key difference between viral sepsis and either bacterial or fungal sepsis is that, for most viral infections, specific therapies are substantially less effective than antibacterial or antifungal agents. Specific to the current pandemic, remdesivir shortens the duration of illness for survivors but does not improve survival. We believe that this inability to alter the infectious burden exogenously results in the necessity for care that is principally supportive. It potentially explains the high mortality rate of patients with severe COVID-19 who required invasive mechanical ventilation in early reports, a lethality higher than expected for severe ARDS related to sepsis of another cause.
COVID-19 can be said to be sepsis with no highly effective antimicrobial therapy. Although we are unlikely to ever see a trial that will compare antibiotics vs no antibiotics in bacterial sepsis, Kumar et al
2
provided the closest evidence to that scenario. The mortality rate of patients with septic shock who received inappropriate antimicrobials bordered 90%; those patients who received appropriate antibiotics had a fivefold mortality rate reduction. The mortality rate of the inappropriate antibiotic group is similar in magnitude to the 88% mortality rate reported in patients with severe COVID-19 on mechanical ventilation. The patients with COVID-19 could not receive appropriate antimicrobials because such therapy for SARS-CoV-2 did not exist.
All COVID-19 patients who are severely ill with COVID-19 have some sort of redox deficiency, either in the form of endothelial dysfunction, or micronutrient deficiency, or both.
Humanity is battling a respiratory pandemic pneumonia named COVID-19 which has resulted in millions of hospitalizations and deaths. COVID-19 exacerbations occur in waves that continually challenge healthcare systems globally. Therefore, there is an urgent need to understand all mechanisms by...
www.mdpi.com
Multi-system involvement and rapid clinical deterioration are hallmarks of coronavirus disease 2019 (COVID-19) related mortality. The unique clinical phenomena in severe COVID-19 can be perplexing, and they include disproportionately severe hypoxemia ...
www.ncbi.nlm.nih.gov
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is involved in a global outbreak affecting millions of people who manifest a variety of s…
www.sciencedirect.com
Sepsis involves redox physiology due to the simple fact that the first-responder cells of the innate immune system, such as neutrophils, use powerful oxygen radicals to try and destroy the lipid membranes of bacteria, fungi, viruses, et cetera. Our cells are made of the exact same stuff as bacteria and are also vulnerable to damage by reactive oxygen species.
Oxidation in this instance is the same exact chemical process as rust, fire, and bleaching, and involves electron exchange and highly reactive molecules. Radicals are referred to as such because they're not in a stable configuration. They are missing a valence electron and want to steal a replacement from molecules in their environment. The process of stealing an electron in this way is referred to as oxidation. It is identical to the process that produces rust, where air in the atmosphere oxidizes iron and makes iron oxide. That's also an oxidation reaction.
The thing is, when we're talking about oxidation in the body due to the presence of ROS like superoxide, hydrogen peroxide, hypochlorous acid, and hydroxyl radicals and the like, we're
not talking about oxidation of metal. We're talking about the oxidation, denaturing, and destruction of fats and DNA. Normally, cells defend themselves from the radicals produced by neutrophils using protective antioxidant enzymes like glutathione peroxidase to destroy the ROS before it becomes a problem.
COVID-19 shuts down those protective antioxidant enzymes.
The result of this is a buildup of DAMPs/OSEs that recursively increase inflammation in a biological feedback loop.
The oxidized lipids activate pattern recognition receptors and summon more neutrophils, which release more destructive enzymes, which make more ROS, which oxidize more lipids, in a loop.
This entire process trends towards sepsis, which damages red blood cells, spills free iron all over the place (COVID-19 patients have pronounced hyperferritinemia; see also acute phase reactants), and promotes blood clotting and hypoxia. The damage to endothelial cells in the small capillaries in the lungs and damage to the glycocalyx leads to pulmonary edema. That's where the pneumonia comes from; from the blood vessels outward and into the lungs.
So, the subject is now blue in the face, their O2 levels tanking, and they're in the ER. What do the doctors do?
They intubate them, which actually makes more oxygen radicals and accelerates lipid peroxidation, due to the simple fact that oxygen is the precursor of every kind of ROS. When hypoxic cells switch from anaerobic back to aerobic metabolism due to the sudden introduction of O2, they spew reactive oxygen species everywhere, partly as a result of breaking down stress metabolites like hypoxanthine.
The ROS attacks glucocorticoid receptors, and the patients become insensitive to steroids like methylprednisolone and dexamethasone.
The Remdesivir that they give them does nothing beneficial at all, because the virus is already long gone and it's all just delayed sepsis.
The blue line on the chart represents the viral load. Every patient who has COVID-19 sepsis is actually near the nadir of their viral load. See the shrinking cone there for "Clinical benefits of antivirals"?
What this means is that all of the studies where they tested antivirals like Ivermectin, HCQ, Kaletra, and Remdesivir on hospitalized patients were 100% bullshit and the treatment was futile. Antivirals work by inhibiting the replication of viruses. What is the point of giving someone an antiviral when the virus is gone?
I believe that the key to preventing COVID-19 sepsis is to improve a subject's antioxidant status before they ever get sepsis. I don't just mean Vitamin D. I mean the whole deal. Vitamin D, selenium, glycine, NAC, Pepcid, Benadryl, avoiding excess iron in the diet, and so on.
Vitamin D helps remove excess calcium from the cells, which slows the replication of the virus (calcium is essential to the life cycle of coronaviruses). People with Vitamin D deficiency are massively overrepresented in those severely ill with COVID-19. The chronic oxidative stress from Vitamin D deficiency promotes endothelial dysfunction and redox issues; the excess superoxide destroys nitric oxide in the blood vessels. This also helps the virus because nitric oxide produced by endothelial nitric oxide synthase is antiviral against SARS.
Selenium and glutathione are crucial for detoxifying ROS. Glutathione peroxidase uses them as substrates to convert hydrogen peroxide into water.
Famotidine and diphenhydramine are not just antihistamines, they're also antioxidants. In fact, famotidine and its related H2 blockers ranitidine and cimetidine were found to inhibit the Fenton reaction in biological systems and scavenge radicals.
This preventive antioxidant cocktail (hell, throw in Ivermectin, while we're at it) has to start at the first sign of symptoms. By the time a patient has sepsis, they're already in big trouble.
The main killer in COVID-19 is delayed treatment.
If they're sending people home who are symptomatic and not telling them to take anything, that's a big mistake.
