COVID-19 is not a viral pneumonia — it is a viral vascular endotheliitis: | Endothelial cell infection and endotheliitis in COVID-19
COVID-19 is, in the end, an endothelial disease
Rapid endotheliitis and vascular damage characterize SARS-CoV-2 infection in a human lung-on-chip model | 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:
| COVID and the brain: researchers zero in on how damage occurs
The hidden long-term cognitive effects of COVID-19
SARS-CoV-2 infects human neural progenitor cells and brain organoids
SARS-CoV-2 targets neurons of 3D human brain organoids
Researchers Investigate What COVID-19 Does to the Heart
COVID-19 and cardiac injury: clinical manifestations, biomarkers, mechanisms, diagnosis, treatment, and follow up
COVID-19 and liver disease: mechanistic and clinical perspectives
COVID-19 and the liver
Viral infiltration of pancreatic islets in patients with COVID-19
SARS-CoV-2 infects human pancreatic β cells and elicits β cell impairment
Pathophysiology of COVID-19-associated acute kidney injury
Gastrointestinal symptoms associated with COVID-19: impact on the gut microbiome
Limited intestinal inflammation despite diarrhea, fecal viral RNA and SARS-CoV-2-specific IgA in patients with acute COVID-19
| Some of the most common laboratory findings in COVID-19:
| COVID-19: Clinical features
Laboratory findings in COVID-19 diagnosis and prognosis | COVID-19 can present as almost anything: | Extrapulmonary manifestations of COVID-19
Pulmonary and Extra-Pulmonary Clinical Manifestations of COVID-19 | COVID-19 is
more severe in those with conditions that involve endothelial
dysfunction, such as obesity,hypertension, and diabetes: | Large Meta-analysis Digs Into Obesity’s COVID-19 Risks
https://mdpi-res.com/d_attachment/cells/cells-10-00933/article_deploy/cells-10-00933.pdf
Assessing
the age specificity of infection fatality rates for COVID-19:
systematic review, meta-analysis, and public policy implications | 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: | CORTICOSTEROID TREATMENT IN PATIENTS WITH SEVERE COVID-19 PNEUMONIA
Timing of Intubation and Mortality Among Critically Ill Coronavirus Disease 2019 Patients: A Single-Center Cohort Study
Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19 | 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: | Acute respiratory distress syndrome induction by pulmonary ischemia–reperfusion injury in large animal models
Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS
Reperfusion injury and reactive oxygen species: The evolution of a concept
https://www.atsjournals.org/doi/full/10.1164/rccm.201401-0168CP
Xanthine oxidase contributes to mechanical ventilation-induced diaphragmatic oxidative stress and contractile dysfunction | Oxidized
lipids appear as foreign objects to the immune system, which recognizes
and forms antibodies against OSEs, or oxidation-specific epitopes: | Anticardiolipin and other antiphospholipid antibodies in critically ill COVID-19 positive and negative patients
Clinically significant anticardiolipin antibodies associated with COVID-19
Top 10 points patients should know about the association between antiphospholipid antibodies and COVID-19 | 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: | A
Multiple-Hit Hypothesis Involving Reactive Oxygen Species and
Myeloperoxidase Explains Clinical Deterioration and Fatality in COVID-19
Blood myeloperoxidase‐DNA, a biomarker of early response to SARS‐CoV‐2 infection?
Patients with COVID-19: in the dark-NETs of neutrophils
Devilishly radical NETwork in COVID-19: Oxidative stress, neutrophil extracellular traps (NETs), and T cell suppression | SARS-CoV-2
Spike binds to ACE2. Angiotensin Converting Enzyme 2 is an enzyme that
is part of the reninangiotensin-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 ontrolling sodium/potassium retention and excretion and vascular tone: | Physiology, Renin Angiotensin System
Regulating Blood Pressure: The Renin-Angiotensin-Aldosterone System | |
|  | 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: | Tissu
distribution of ACE2 protein, the functional receptor for SARS
coronavirus. A first step in understanding SARS pathogenesis
Body Localization of ACE-2: On the Trail of the Keyhole of SAR-CoV-2
The Spatial and Cell-Type Distribution of SARS-CoV-2 Receptor ACE2 in Human and Mouse Brains | SARS-CoV-2 infects a cell as follows: | Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19
Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation
Cryo-EM
Structures of SARS-CoV-2 Spike without and with ACE2 Reveal a
pH-Dependent Switch to Mediate Endosomal Positioning of Receptor-Binding
Domains | SARS-CoV-2 Spike proteins embedded in a cell can actually cause adjacent human cells to fuse together, forming syncytia/MGCs:
| SARS-CoV-2 spike protein dictates syncytium-mediated lymphocyte elimination Syncytia formation by SARS-CoV-2-infected cells | SARS-CoV-2’s viroporins, such as its Envelope protein, act as calcium ion channels, introducing calcium into infected cells:
| SARS-CoV-2 envelope protein causes acute respiratory distress syndrome (ARDS)-like pathological damages and constitutes an antiviral target Coronavirus envelope protein: current knowledge
| The virus suppresses the natural interferon response, resulting in delayed inflammation:
| Type I and III interferon responses in SARS-CoV-2 infection Innate immune interferons (IFNs), including type I and III IFNs, constitute critical antiviral mechanisms. (DownLoad)
Immune evasion of SARS-CoV-2 from interferon antiviral system | SARS-CoV-2 N protein can also directly activate the NLRP3 inflammasome:
| SARS-CoV-2 N protein promotes NLRP3 inflammasome activation to induce hyperinflammation Novel Coronavirus-Induced NLRP3 Inflammasome Activation: A Potential Drug Target in the Treatment of COVID-19 | SARS-CoV-2 suppresses the Nrf2 antioxidant pathway, reducing the body’s own endogenous antioxidant enzyme activity:
| Antiviral strategies to inhibit Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) and the pathogenic consequences of COVID-19 are urgently required
There are large between- and within-country variations in COVID-19 death rates
The Good and Bad of nRF2: An Update in Cancer and New Perspectives in COVID-19
| 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:
| 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
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