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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

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:

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

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

Dr Rush Medical Freedom Quote.jpg
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:
This constant calcium influx into the cells results in (or is accompanied by) noticeable hypocalcemia, or low blood calcium:
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:

Association of American Physicians and Doctors