PMC:7293470 / 44-1867 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7293470","sourcedb":"PMC","sourceid":"7293470","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7293470","text":"Although most of the 4.7 million individuals infected to date with COVID-19 (SARS-CoV-2) worldwide remain asymptomatic or have transient symptoms followed by complete recovery, approximately 316 thousand (6.7%) have died [1], most often from acute respiratory distress syndrome (ARDS) leading to organ failure and death. The components that contribute to morbidity include forceful activation of both innate and adaptive immune pathways that release a cytokine storm which causes extensive damage to lung alveolar endothelium, oxygen insufficiency and downstream bystander damage to the heart, liver and kidneys. Recent publications predicted immunological processes anticipated in COVID-19 patients based on previous findings in severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MARS) and sepsis patients [2], [3], [4]. To reiterate, upon binding to the ACE2 (angiotensin-converting enzyme-2) receptor via its spike (S) protein, the SARS-CoV-2 virus infects alveolar epithelial cells, triggering the complement cascade and inducing fibrin deposition leading to platelet aggregation and macrophage activation resulting in metabolic changes in arachidonic acid with release of thromboxane A2 and secretion of IL-1β, IL-6, TNF-α, platelet activating factor \u0026 nitric oxide. In addition infection induces neutrophil activation, aggregation and degranulation with release of O2 radicals and proteases and CCR4+CCR6+Th17 cell activation with secretion of IL-2, IL-7, IFN-γ, G-CSF and chemokines CCL2, CCL3 and CXCl10. This focused collection of highly inflammatory factors in the lungs causes serious endothelial damage and respiratory failure. As well, ACE2 is expressed on heart, liver and kidney cells that may also be infected and gravely damaged by SARS-CoV-2, leading to fatal multi-organ 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