COVID-19 is not a viral pneumonia — it is a viral vascular endotheliitis:
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30937-5/fulltext
https://academic.oup.com/eurheartj/article/41/32/3038/5901158
https://www.embopress.org/doi/full/10.15252/embr.202152744
COVID-19 is not just a respiratory disease — it can precipitate multiple organ failure, including hypoxic and inflammatory damage to various vital organs, such as the brain, heart, liver, pancreas, kidneys, and intestines:
https://www.nature.com/articles/d41586-021-01693-6
https://www.health.harvard.edu/blog/the-hidden-long-term-cognitive-effects-of-covid-2020100821133
https://www.nature.com/articles/s41422-020-0390-x
https://www.embopress.org/doi/full/10.15252/embj.2020106230
https://jamanetwork.com/journals/jama/fullarticle/2776538
https://pubmed.ncbi.nlm.nih.gov/32921216/
https://www.nature.com/articles/s41575-021-00426-4
https://pubmed.ncbi.nlm.nih.gov/32553666/
https://www.nature.com/articles/s41467-021-23886-3
https://pubmed.ncbi.nlm.nih.gov/34081912/
https://www.nature.com/articles/s41581-021-00452-0
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438210/
https://www.nature.com/articles/s41598-021-92740-9
Some of the most common laboratory findings in COVID-19:
https://www.uptodate.com/contents/covid-19-clinical-features
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426219/
COVID-19 can present as almost anything:
https://www.nature.com/articles/s41591-020-0968-3
https://www.frontiersin.org/articles/10.3389/fmed.2020.00526/full
COVID-19 is more severe in those with conditions that involve endothelial dysfunction, such as obesity, hypertension, and diabetes:
https://www.dovepress.com/obesity-related-inflammation-and-endothelial-dysfunction-in-covid-19-i-peer-reviewed-fulltext-article-JIR
https://jamanetwork.com/journals/jama/fullarticle/2772071
https://mdpi-res.com/d_attachment/cells/cells-10-00933/article_deploy/cells-10-00933.pdf
The vast majority of COVID-19 cases are mild and do not cause significant disease:
https://www.webmd.com/lung/covid-recovery-overview#1
https://academic.oup.com/ofid/article/7/9/ofaa286/5875595
https://pubmed.ncbi.nlm.nih.gov/33289900/
In those who have critical COVID-19-induced sepsis, hypoxia, coagulopathy, and ARDS, the most common treatments are intubation, injected corticosteroids, and blood thinners like heparin, which often precipitate harmful hemorrhages:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7548860/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448713/
https://www.nejm.org/doi/full/10.1056/NEJMoa2103417
The majority of people who go on a ventilator are dying due to COVID-19 mimicking the physiology of ischemia-reperfusion injury with prolonged transient hypoxia and ischemia, leading directly to the formation of damaging reactive oxygen species:
https://www.journalofsurgicalresearch.com/article/S0022-4804(14)00176-0/fulltext
https://www.nature.com/articles/nature13909
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4625011/
https://www.atsjournals.org/doi/full/10.1164/rccm.201401-0168CP
https://pubmed.ncbi.nlm.nih.gov/18974366/
The end-stage of COVID-19 is severe lipid peroxidation, where fats in the body start to “rust” due to damage by oxidative stress:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768996/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357498/
https://www.liebertpub.com/doi/10.1089/ars.2021.0017
Oxidized lipids appear as foreign objects to the immune system, which recognizes and forms antibodies against OSEs, or oxidation-specific epitopes:
https://ard.bmj.com/content/annrheumdis/early/2020/08/04/annrheumdis-2020-218145.full.pdf
https://ard.bmj.com/content/80/9/1236
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7256550/
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30937-5/fulltext
https://academic.oup.com/eurheartj/article/41/32/3038/5901158
https://www.embopress.org/doi/full/10.15252/embr.202152744
COVID-19 is not just a respiratory disease — it can precipitate multiple organ failure, including hypoxic and inflammatory damage to various vital organs, such as the brain, heart, liver, pancreas, kidneys, and intestines:
https://www.nature.com/articles/d41586-021-01693-6
https://www.health.harvard.edu/blog/the-hidden-long-term-cognitive-effects-of-covid-2020100821133
https://www.nature.com/articles/s41422-020-0390-x
https://www.embopress.org/doi/full/10.15252/embj.2020106230
https://jamanetwork.com/journals/jama/fullarticle/2776538
https://pubmed.ncbi.nlm.nih.gov/32921216/
https://www.nature.com/articles/s41575-021-00426-4
https://pubmed.ncbi.nlm.nih.gov/32553666/
https://www.nature.com/articles/s41467-021-23886-3
https://pubmed.ncbi.nlm.nih.gov/34081912/
https://www.nature.com/articles/s41581-021-00452-0
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438210/
https://www.nature.com/articles/s41598-021-92740-9
Some of the most common laboratory findings in COVID-19:
https://www.uptodate.com/contents/covid-19-clinical-features
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426219/
COVID-19 can present as almost anything:
https://www.nature.com/articles/s41591-020-0968-3
https://www.frontiersin.org/articles/10.3389/fmed.2020.00526/full
COVID-19 is more severe in those with conditions that involve endothelial dysfunction, such as obesity, hypertension, and diabetes:
https://www.dovepress.com/obesity-related-inflammation-and-endothelial-dysfunction-in-covid-19-i-peer-reviewed-fulltext-article-JIR
https://jamanetwork.com/journals/jama/fullarticle/2772071
https://mdpi-res.com/d_attachment/cells/cells-10-00933/article_deploy/cells-10-00933.pdf
The vast majority of COVID-19 cases are mild and do not cause significant disease:
https://www.webmd.com/lung/covid-recovery-overview#1
https://academic.oup.com/ofid/article/7/9/ofaa286/5875595
https://pubmed.ncbi.nlm.nih.gov/33289900/
In those who have critical COVID-19-induced sepsis, hypoxia, coagulopathy, and ARDS, the most common treatments are intubation, injected corticosteroids, and blood thinners like heparin, which often precipitate harmful hemorrhages:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7548860/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448713/
https://www.nejm.org/doi/full/10.1056/NEJMoa2103417
The majority of people who go on a ventilator are dying due to COVID-19 mimicking the physiology of ischemia-reperfusion injury with prolonged transient hypoxia and ischemia, leading directly to the formation of damaging reactive oxygen species:
https://www.journalofsurgicalresearch.com/article/S0022-4804(14)00176-0/fulltext
https://www.nature.com/articles/nature13909
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4625011/
https://www.atsjournals.org/doi/full/10.1164/rccm.201401-0168CP
https://pubmed.ncbi.nlm.nih.gov/18974366/
The end-stage of COVID-19 is severe lipid peroxidation, where fats in the body start to “rust” due to damage by oxidative stress:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768996/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357498/
https://www.liebertpub.com/doi/10.1089/ars.2021.0017
Oxidized lipids appear as foreign objects to the immune system, which recognizes and forms antibodies against OSEs, or oxidation-specific epitopes:
https://ard.bmj.com/content/annrheumdis/early/2020/08/04/annrheumdis-2020-218145.full.pdf
https://ard.bmj.com/content/80/9/1236
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7256550/
OUP Academic
COVID-19 is, in the end, an endothelial disease
Abstract. The vascular endothelium provides the crucial interface between the blood compartment and tissues, and displays a series of remarkable properties
https://www.hss.edu/conditions_top-ten-series-antiphospholipid-syndrome-coronavirus-covid-19.asp
In COVID-19, neutrophil degranulation and NETosis in the bloodstream drives severe oxidative damage; hemoglobin becomes incapable of carrying oxygen due to heme iron being stripped out of heme by hypochlorous acid:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757048/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436665/
https://www.nature.com/articles/s41418-021-00805-z
https://www.sciencedirect.com/science/article/pii/S221249262030052X
SARS-CoV-2 Spike binds to ACE2. Angiotensin Converting Enzyme 2 is an enzyme that is part of the renin-angiotensin-aldosterone system, or RAAS. The RAAS is a hormone control system that moderates fluid volume and blood pressure in the body and in the bloodstream by controlling sodium/potassium retention and excretion and vascular tone:
https://www.ncbi.nlm.nih.gov/books/NBK470410/
https://www.merckmanuals.com/home/multimedia/figure/cvs_regulating_blood_pressure_renin
This protein, ACE2, is ubiquitous in every part of the body that interfaces with the circulatory system, particularly in vascular endothelial cells and pericytes, brain astrocytes, renal tubules and podocytes, pancreatic islet cells, bile duct and intestinal epithelial cells, and the seminiferous ducts of the testis, all of which SARS-CoV-2 can infect:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167720/
https://www.frontiersin.org/articles/10.3389/fmed.2020.594495/full
https://www.frontiersin.org/articles/10.3389/fneur.2020.573095/full
SARS-CoV-2 infects a cell as follows:
https://www.nature.com/articles/s41401-020-0485-4
https://www.science.org/doi/10.1126/science.abb2507
https://www.sciencedirect.com/science/article/abs/pii/S1931312820306211
SARS-CoV-2 Spike proteins embedded in a cell can actually cause adjacent human cells to fuse together, forming syncytia/MGCs:
https://www.nature.com/articles/s41418-021-00782-3
https://pubmed.ncbi.nlm.nih.gov/33051876/
SARS-CoV-2’s viroporins, such as its Envelope protein, act as calcium ion channels, introducing calcium into infected cells:
https://www.nature.com/articles/s41422-021-00519-4
https://virologyj.biomedcentral.com/articles/10.1186/s12985-019-1182-0
The virus suppresses the natural interferon response, resulting in delayed inflammation:
https://www.nature.com/articles/s12276-021-00592-0
https://mdpi-res.com/d_attachment/viruses/viruses-12-01433/article_deploy/viruses-12-01433.pdf
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310780/
SARS-CoV-2 N protein can also directly activate the NLRP3 inflammasome:
https://www.nature.com/articles/s41467-021-25015-6
https://www.frontiersin.org/articles/10.3389/fimmu.2020.01021/full
SARS-CoV-2 suppresses the Nrf2 antioxidant pathway, reducing the body’s own endogenous antioxidant enzyme activity:
https://www.nature.com/articles/s41467-020-18764-3
https://ctajournal.biomedcentral.com/articles/10.1186/s13601-020-00362-7
https://mdpi-res.com/d_attachment/ijms/ijms-22-07963/article_deploy/ijms-22-07963.pdf
The suppression of ACE2 by binding with Spike causes a buildup of bradykinin that would otherwise be broken down by ACE2:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834250/
https://www.the-scientist.com/news-opinion/is-a-bradykinin-storm-brewing-in-covid-19--67876
This constant calcium influx into the cells results in (or is accompanied by) noticeable hypocalcemia, or low blood calcium:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292572/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041474/
https://www.sciencedirect.com/science/article/abs/pii/S1871402121000059
Bradykinin upregulates cAMP, cGMP, COX, and Phospholipase C activity. This results in prostaglandin release and vastly increased intracellular calcium signaling, which promotes highly aggressive ROS release and ATP depletion:
In COVID-19, neutrophil degranulation and NETosis in the bloodstream drives severe oxidative damage; hemoglobin becomes incapable of carrying oxygen due to heme iron being stripped out of heme by hypochlorous acid:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757048/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436665/
https://www.nature.com/articles/s41418-021-00805-z
https://www.sciencedirect.com/science/article/pii/S221249262030052X
SARS-CoV-2 Spike binds to ACE2. Angiotensin Converting Enzyme 2 is an enzyme that is part of the renin-angiotensin-aldosterone system, or RAAS. The RAAS is a hormone control system that moderates fluid volume and blood pressure in the body and in the bloodstream by controlling sodium/potassium retention and excretion and vascular tone:
https://www.ncbi.nlm.nih.gov/books/NBK470410/
https://www.merckmanuals.com/home/multimedia/figure/cvs_regulating_blood_pressure_renin
This protein, ACE2, is ubiquitous in every part of the body that interfaces with the circulatory system, particularly in vascular endothelial cells and pericytes, brain astrocytes, renal tubules and podocytes, pancreatic islet cells, bile duct and intestinal epithelial cells, and the seminiferous ducts of the testis, all of which SARS-CoV-2 can infect:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167720/
https://www.frontiersin.org/articles/10.3389/fmed.2020.594495/full
https://www.frontiersin.org/articles/10.3389/fneur.2020.573095/full
SARS-CoV-2 infects a cell as follows:
https://www.nature.com/articles/s41401-020-0485-4
https://www.science.org/doi/10.1126/science.abb2507
https://www.sciencedirect.com/science/article/abs/pii/S1931312820306211
SARS-CoV-2 Spike proteins embedded in a cell can actually cause adjacent human cells to fuse together, forming syncytia/MGCs:
https://www.nature.com/articles/s41418-021-00782-3
https://pubmed.ncbi.nlm.nih.gov/33051876/
SARS-CoV-2’s viroporins, such as its Envelope protein, act as calcium ion channels, introducing calcium into infected cells:
https://www.nature.com/articles/s41422-021-00519-4
https://virologyj.biomedcentral.com/articles/10.1186/s12985-019-1182-0
The virus suppresses the natural interferon response, resulting in delayed inflammation:
https://www.nature.com/articles/s12276-021-00592-0
https://mdpi-res.com/d_attachment/viruses/viruses-12-01433/article_deploy/viruses-12-01433.pdf
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310780/
SARS-CoV-2 N protein can also directly activate the NLRP3 inflammasome:
https://www.nature.com/articles/s41467-021-25015-6
https://www.frontiersin.org/articles/10.3389/fimmu.2020.01021/full
SARS-CoV-2 suppresses the Nrf2 antioxidant pathway, reducing the body’s own endogenous antioxidant enzyme activity:
https://www.nature.com/articles/s41467-020-18764-3
https://ctajournal.biomedcentral.com/articles/10.1186/s13601-020-00362-7
https://mdpi-res.com/d_attachment/ijms/ijms-22-07963/article_deploy/ijms-22-07963.pdf
The suppression of ACE2 by binding with Spike causes a buildup of bradykinin that would otherwise be broken down by ACE2:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834250/
https://www.the-scientist.com/news-opinion/is-a-bradykinin-storm-brewing-in-covid-19--67876
This constant calcium influx into the cells results in (or is accompanied by) noticeable hypocalcemia, or low blood calcium:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292572/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041474/
https://www.sciencedirect.com/science/article/abs/pii/S1871402121000059
Bradykinin upregulates cAMP, cGMP, COX, and Phospholipase C activity. This results in prostaglandin release and vastly increased intracellular calcium signaling, which promotes highly aggressive ROS release and ATP depletion:
Hospital for Special Surgery
Antiphospholipid Syndrome & COVID-19: What to Know | HSS
Evidence suggests that COVID-19 increases the risk of blood clots. This is dangerous for people who test positive for antiphospholipid antibodies (aPL). | HSS
https://www.sciencedirect.com/science/article/abs/pii/S089158490700319X?via%3Dihub
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1218972/
https://pubmed.ncbi.nlm.nih.gov/2156053/
https://www.sciencedirect.com/topics/medicine-and-dentistry/bradykinin-b2-receptor-agonist
https://www.sciencedirect.com/topics/neuroscience/bradykinin
NADPH oxidase releases superoxide into the extracellular space:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4556774/
https://www.pnas.org/content/110/21/8744
Superoxide radicals react with nitric oxide to form peroxynitrite:
https://pubmed.ncbi.nlm.nih.gov/8944624/
https://www.pnas.org/content/115/23/5839
Peroxynitrite reacts with the tetrahydrobiopterin cofactor needed by endothelial nitric oxide synthase, destroying it and “uncoupling” the eNOS enzymes, causing nitric oxide synthase to synthesize more superoxide instead (this means that every process that upregulates NOS activity now produces superoxide instead of nitric oxide):
https://pubmed.ncbi.nlm.nih.gov/24353182/
https://academic.oup.com/cardiovascres/article/73/1/8/316487
https://pubs.acs.org/doi/10.1021/bi9016632
This proceeds in a positive feedback loop until nitric oxide bioavailability in the circulatory system is depleted:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276137/
Dissolved nitric oxide gas produced constantly by eNOS serves many important functions, but it is also antiviral against SARS-like coronaviruses, preventing the palmitoylation of the viral Spike protein and making it harder for it to bind to host receptors:
https://journal.chestnet.org/article/S0012-3692(20)34397-X/fulltext
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7111989/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754882/
The loss of NO allows the virus to begin replicating with impunity in the body (clearly, the virus has an evolutionary incentive to induce oxidative stress to destroy nitric oxide):
https://scitechdaily.com/nitric-oxide-a-possible-treatment-for-covid-19-only-substance-to-have-a-
direct-effect-on-sars-cov-2/
Those with endothelial dysfunction (i.e. hypertension, diabetes, obesity, old age, African-American race) have redox equilibrium issues to begin with, giving the virus an advantage:
https://www.nature.com/articles/s41392-020-00454-7
https://www.frontiersin.org/articles/10.3389/fphys.2020.605908/full
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430889/
https://pubmed.ncbi.nlm.nih.gov/19004510/
Due to the extreme cytokine release triggered by these processes, the body summons a great deal of neutrophils and monocyte-derived alveolar macrophages to the lungs:
https://www.frontiersin.org/articles/10.3389/fimmu.2021.652470/full
https://www.frontiersin.org/articles/10.3389/fimmu.2021.720109/full
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1218972/
https://pubmed.ncbi.nlm.nih.gov/2156053/
https://www.sciencedirect.com/topics/medicine-and-dentistry/bradykinin-b2-receptor-agonist
https://www.sciencedirect.com/topics/neuroscience/bradykinin
NADPH oxidase releases superoxide into the extracellular space:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4556774/
https://www.pnas.org/content/110/21/8744
Superoxide radicals react with nitric oxide to form peroxynitrite:
https://pubmed.ncbi.nlm.nih.gov/8944624/
https://www.pnas.org/content/115/23/5839
Peroxynitrite reacts with the tetrahydrobiopterin cofactor needed by endothelial nitric oxide synthase, destroying it and “uncoupling” the eNOS enzymes, causing nitric oxide synthase to synthesize more superoxide instead (this means that every process that upregulates NOS activity now produces superoxide instead of nitric oxide):
https://pubmed.ncbi.nlm.nih.gov/24353182/
https://academic.oup.com/cardiovascres/article/73/1/8/316487
https://pubs.acs.org/doi/10.1021/bi9016632
This proceeds in a positive feedback loop until nitric oxide bioavailability in the circulatory system is depleted:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276137/
Dissolved nitric oxide gas produced constantly by eNOS serves many important functions, but it is also antiviral against SARS-like coronaviruses, preventing the palmitoylation of the viral Spike protein and making it harder for it to bind to host receptors:
https://journal.chestnet.org/article/S0012-3692(20)34397-X/fulltext
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7111989/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754882/
The loss of NO allows the virus to begin replicating with impunity in the body (clearly, the virus has an evolutionary incentive to induce oxidative stress to destroy nitric oxide):
https://scitechdaily.com/nitric-oxide-a-possible-treatment-for-covid-19-only-substance-to-have-a-
direct-effect-on-sars-cov-2/
Those with endothelial dysfunction (i.e. hypertension, diabetes, obesity, old age, African-American race) have redox equilibrium issues to begin with, giving the virus an advantage:
https://www.nature.com/articles/s41392-020-00454-7
https://www.frontiersin.org/articles/10.3389/fphys.2020.605908/full
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430889/
https://pubmed.ncbi.nlm.nih.gov/19004510/
Due to the extreme cytokine release triggered by these processes, the body summons a great deal of neutrophils and monocyte-derived alveolar macrophages to the lungs:
https://www.frontiersin.org/articles/10.3389/fimmu.2021.652470/full
https://www.frontiersin.org/articles/10.3389/fimmu.2021.720109/full
Sciencedirect
Bradykinin enhances reactive oxygen species generation, mitochondrial injury, and cell death induced by ATP depletion—A role of…
This study aimed to study the effect of bradykinin on reactive oxygen species (ROS) generation, mitochondrial injury, and cell death induced by ATP de…
Ivermectin shown as approved treatment/under evaluation on #NIH website
https://www.covid19treatmentguidelines.nih.gov/tables/table-2e/
https://archive.is/VNwhF
https://www.covid19treatmentguidelines.nih.gov/tables/table-2e/
https://archive.is/VNwhF
https://covid19criticalcare.com/covid-19-protocols/math-plus-protocol/ MATH+ protocol
#treatmentprotocols #math
#treatmentprotocols #math
Independent Medical Alliance
MATH+ COVID Hospital Treatment - Independent Medical Alliance
MATH+ is the hospital treatment protocol for COVID-19, developed by the healthcare professionals at The FLCCC Alliance.