Inflammation Triggered by SARS-CoV-2 and ACE2 Augment Drives Multiple Organ Failure of Severe COVID-19: Molecular Mechanisms and Implications.
Masae IwasakiJunichi SaitoHailin ZhaoAtsuhiro SakamotoKazuyoshi HirotaDaqing MaPublished in: Inflammation (2020)
The widespread occurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a pandemic of coronavirus disease 2019 (COVID-19). The S spike protein of SARS-CoV-2 binds with angiotensin-converting enzyme 2 (ACE2) as a functional "receptor" and then enters into host cells to replicate and damage host cells and organs. ACE2 plays a pivotal role in the inflammation, and its downregulation may aggravate COVID-19 via the renin-angiotensin system, including by promoting pathological changes in lung injury and involving inflammatory responses. Severe patients of COVID-19 often develop acute respiratory distress syndrome and multiple organ dysfunction/failure with high mortality that may be closely related to the hyper-proinflammatory status called the "cytokine storm." Massive cytokines including interleukin-6, nuclear factor kappa B (NFκB), and tumor necrosis factor alpha (TNFα) released from SARS-CoV-2-infected macrophages and monocytes lead inflammation-derived injurious cascades causing multi-organ injury/failure. This review summarizes the current evidence and understanding of the underlying mechanisms of SARS-CoV-2, ACE2 and inflammation co-mediated multi-organ injury or failure in COVID-19 patients.
Keyphrases
- cell death
- sars cov
- cell cycle arrest
- respiratory syndrome coronavirus
- angiotensin converting enzyme
- oxidative stress
- nuclear factor
- coronavirus disease
- angiotensin ii
- induced apoptosis
- acute respiratory distress syndrome
- toll like receptor
- ejection fraction
- rheumatoid arthritis
- early onset
- dendritic cells
- mechanical ventilation
- end stage renal disease
- extracorporeal membrane oxygenation
- newly diagnosed
- intensive care unit
- endoplasmic reticulum stress
- binding protein
- risk factors
- cardiovascular disease
- type diabetes
- cardiovascular events