Abstract
The COVID-19 pandemic has caused monumental mortality, and there are still no adequate therapies. Most severely ill COVID-19 patients manifest a hyperactivated immune response, instigated by interleukin 6 (IL6) that triggers a so called "cytokine storm" and coagulopathy. Hypoxia is also associated with COVID-19. So far overlooked is the fact that both IL6 and hypoxia depress the abundance of a key anticoagulant, Protein S. We speculate that the IL6-driven cytokine explosion plus hypoxemia causes a severe drop in Protein S level that exacerbates the thrombotic risk in COVID-19 patients. Here we highlight a mechanism by which the IL6-hypoxia curse causes a deadly hypercoagulable state in COVID-19 patients, and we suggest a path to therapy.
Keywords:
ACE2; COVID-19; IL6; Protein S; coagulopathy; cytokine storm; hypoxia.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Angiotensin-Converting Enzyme 2
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Anticoagulants / metabolism
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Anticoagulants / pharmacology
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Betacoronavirus / physiology
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COVID-19
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Coronavirus Infections* / blood
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Coronavirus Infections* / immunology
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Coronavirus Infections* / therapy
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Cytokine Release Syndrome* / blood
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Cytokine Release Syndrome* / virology
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Disease Management
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Humans
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Hypoxia* / blood
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Hypoxia* / etiology
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Hypoxia* / immunology
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Interleukin-6 / blood
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Pandemics*
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Peptidyl-Dipeptidase A / metabolism
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Pneumonia, Viral* / blood
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Pneumonia, Viral* / immunology
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Pneumonia, Viral* / therapy
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Protein S* / metabolism
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Protein S* / pharmacology
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SARS-CoV-2
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Severity of Illness Index
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Thrombophilia / immunology*
Substances
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Anticoagulants
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Interleukin-6
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Protein S
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Peptidyl-Dipeptidase A
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ACE2 protein, human
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Angiotensin-Converting Enzyme 2