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.
N-Acetylcysteine, #NAC #earlytreatment #therapeutics
Inhalation of Vapor with Medication (Diclofenac Sodium, Menthol, Methyl Salicylate and N-Acetyl Cysteine) Reduces Oxygen Need and Hospital Stay in COVID-19 Patients – A Case Control Study
N-Acetylcysteine to Combat COVID-19: An Evidence Review
N-acetyl cysteine: A tool to perturb SARS-CoV-2 spike protein conformation
N-Acetylcysteine as Adjuvant Therapy for COVID-19 – A Perspective on the Current State of the Evidence
N-Acetylcysteine to Combat COVID-19: An Evidence Review
Efficacy of N-Acetylcysteine (NAC) in Preventing COVID-19 From Progressing to Severe Disease
The efficacy of N-Acetylcysteine in severe COVID-19 patients: A structured summary of a study protocol for a randomised controlled trial
N-acetylcysteine: A rapid review of the evidence for effectiveness in treating COVID-19
A Study of N-acetylcysteine in Patients with COVID19 Infection
N-acetylcysteine as a potential treatment for COVID-19
N-Acetylcysteine and Hydrogen Sulfide in Coronavirus Disease 2019
Case Report: Use of hydroxychloroquine and N-acetylcysteine for treatment of a COVID-19 patient [version 2; peer review: 2 not approved]
Studies show N-Acetyl Cysteine supplement can possibly protect patients against COVID-19
Bottom-up analysis of emergent properties of N-acetylcysteine as an adjuvant therapy for COVID-19
Application of methylene blue -vitamin C -N-acetyl cysteine for treatment of critically ill COVID-19 patients, report of a phase-I clinical trial
N-acetylcysteine in Severe COVID-19: The Possible Mechanism
Therapeutic potential of N-acetyl cysteine (NAC) in preventing cytokine storm in COVID-19: review of current evidence
Interventions for treatment of COVID-19: Second edition of a living systematic review with meta-analyses and trial sequential analyses (The LIVING Project)
Experience of N-acetylcysteine airway management in the successful treatment of one case of critical condition with COVID-19
Inhalation of Vapor with Medication (Diclofenac Sodium, Menthol, Methyl Salicylate and N-Acetyl Cysteine) Reduces Oxygen Need and Hospital Stay in COVID-19 Patients – A Case Control Study
N-Acetylcysteine to Combat COVID-19: An Evidence Review
N-acetyl cysteine: A tool to perturb SARS-CoV-2 spike protein conformation
N-Acetylcysteine as Adjuvant Therapy for COVID-19 – A Perspective on the Current State of the Evidence
N-Acetylcysteine to Combat COVID-19: An Evidence Review
Efficacy of N-Acetylcysteine (NAC) in Preventing COVID-19 From Progressing to Severe Disease
The efficacy of N-Acetylcysteine in severe COVID-19 patients: A structured summary of a study protocol for a randomised controlled trial
N-acetylcysteine: A rapid review of the evidence for effectiveness in treating COVID-19
A Study of N-acetylcysteine in Patients with COVID19 Infection
N-acetylcysteine as a potential treatment for COVID-19
N-Acetylcysteine and Hydrogen Sulfide in Coronavirus Disease 2019
Case Report: Use of hydroxychloroquine and N-acetylcysteine for treatment of a COVID-19 patient [version 2; peer review: 2 not approved]
Studies show N-Acetyl Cysteine supplement can possibly protect patients against COVID-19
Bottom-up analysis of emergent properties of N-acetylcysteine as an adjuvant therapy for COVID-19
Application of methylene blue -vitamin C -N-acetyl cysteine for treatment of critically ill COVID-19 patients, report of a phase-I clinical trial
N-acetylcysteine in Severe COVID-19: The Possible Mechanism
Therapeutic potential of N-acetyl cysteine (NAC) in preventing cytokine storm in COVID-19: review of current evidence
Interventions for treatment of COVID-19: Second edition of a living systematic review with meta-analyses and trial sequential analyses (The LIVING Project)
Experience of N-acetylcysteine airway management in the successful treatment of one case of critical condition with COVID-19
jmscr.igmpublication.org
Inhalation of Vapor with Medication (Diclofenac Sodium, Menthol, Methyl Salicylate and N-Acetyl Cysteine) Reduces Oxygen Need and…