There's still no consensus about ventilator settings by the way. It isn't ARDS except when it sometimes is ARDS. It's really not surprising NYC managed to murder so many patients with them.
I started getting a NAC drip set up before I left to go back outpatient and that shit was working great.
N-acetylcysteine, too. Anything to boost levels of Vitamin D, selenium, glutathione, dietary nitrate, and so on. The body's own antioxidant precursors and sustainers, in other words.
SARS-CoV-2's proteins have some very weird tricks, many of which essentially promote a pro-oxidative state in the body by disabling its natural antioxidant pathways. This, in turn, leads to lipid peroxidation.
Viral infections usually cause disease through direct cytopathogenic effects and excessive inflammatory responses. Here, Olagnier et al. show that two NRF2 agonists, 4-OI and DMF, possess broad IFN-independent antiviral activity and decrease host inflammatory response to SARS-CoV-2 infection.
www.nature.com
The current coronavirus disease (COVID-19) outbreak caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV2) has emerged as a threat to g…
www.sciencedirect.com
COVID-19 is often related to hyperinflammation that drives lung or multiorgan injury. The immunopathological mechanisms that cause excessive inflammation are under investigation and constantly updated. Here, a gene network approach was used on recently published data sets to identify possible...
msphere.asm.org
I don't think a lot of people realize that a large portion of what's happening in COVID-19 is neutrophilia. Hell, the average person on the street doesn't even know what neutrophils are, or how extravasation works.
I'm starting to think that neutrophils are one of the main culprits in all this. If glutathione peroxidase is disabled, H2O2 will build up in neutrophils and form hypochlorous acid through the action of the enzyme myeloperoxidase. This hypochlorous acid has the potential to trigger further, runaway oxidative stress by damaging heme and releasing free, unliganded iron, as well as damaging macrophages and causing them to dump their iron, too. Then, you end up with hydroxyl radicals because of the Haber-Weiss and Fenton reactions. If there is a bradykinin storm on top of that, then there will be arachidonic acid release, and the formation of prostaglandins and isoprostanes. Then, you end up with oxidized phospholipids and oxidized LDL all over the place. The oxPL can actually trigger autoimmune reactions, like the formation of antiphospholipid antibodies (a.k.a. Lupus Anticoagulant), as the body sees the damaged, oxidized phospholipids as though they were a foreign object.
In fact, almost everything about COVID-19's coagulopathy can be explained by runaway lipid peroxidation.
Due to the formation of many micro-clots, there may also be ischemia-reperfusion injury and further oxidative stress by the action of xanthine oxidase.
Neutrophils are basically oxidative stress bombs that live for the sole purpose of killing foreign invaders by blasting them with peroxide and bleach. Normally, your cells clean up the mess with enzymes that break hydrogen peroxide down into water, but what if those enzymes stop working? The free radicals start oxidizing the membranes of your body's own healthy cells. Imagine the Neutrophils from Cells at Work, but they go crazy and start killing
everyone.
Neutrophils have another neat trick, too. They can do this:
They can shoot web like fucking Spider-Man to kill bacteria. Yes, this is a thing that happens our bodies all the time. They're called neutrophil extracellular traps.
COVID-19's hyper-inflammation causes neutrophils to flip out and start doing this all over the place.
This is some heavy-duty friendly fire. This is like unloading on a crowd of innocent people with a belt-fed machine gun to kill a few insurgents.
This is why I've been so interested in apocynin for the past few months and its potential in treating COVID-19.
Neutrophils are key players in the pathophysiological process underlying inflammatory conditions not only by release of tissue-damaging cytotoxic enzymes, reactive oxygen species (ROS) but also by secretion of important immunomodulatory chemokines and cytokines. Here, we report the effects of...
link.springer.com
Apocynin essentially defangs neutrophils. They can still phagocytize pathogens successfully, but there's less ROS release.
This pathology is insanely complicated and involves many factors in the immune system going haywire in some very specific and devastating ways. If I'm reading all this correctly, then basically, the reason why COVID-19 is more aggressive in people with Metabolic Syndrome (obesity, diabetes, high blood pressure, etc.) is because of a lack of redox equilibrium and a greater susceptibility to a positive feedback loop of runaway lipid peroxidation.
I think that if this could be dampened somehow in these vulnerable individuals, mortality and morbidity could be greatly reduced.
