Inflammation Triggered by SARS-CoV-2 and ACE2 Augment Drives Multiple Organ Failure of Severe COVID-19: Molecular Mechanisms and Implications

• Published in: Inflammation Vol. 44; no. 1; pp. 13 - 34
• Main Authors: Iwasaki, Masae, Saito, Junichi, Zhao, Hailin, Sakamoto, Atsuhiro, Hirota, Kazuyoshi, Ma, Daqing
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.02.2021; Springer Nature B.V
• Subjects: ACE2; Angiotensin; Angiotensin-converting enzyme 2; Angiotensin-Converting Enzyme 2 - metabolism; Biomarkers - metabolism; Biomedical and Life Sciences; Biomedicine; Coronaviridae; Coronaviruses; COVID-19; COVID-19 - metabolism; COVID-19 - physiopathology; Cytokine Release Syndrome - metabolism; Cytokine Release Syndrome - physiopathology; Cytokine Release Syndrome - virology; Cytokine storm; Cytokines - metabolism; Humans; Immunology; Inflammation; Inflammation - metabolism; Inflammation - physiopathology; Inflammation - virology; Interleukin 6; Internal Medicine; Macrophages; Molecular modelling; Monocytes; Multiple Organ Failure - metabolism; Multiple Organ Failure - physiopathology; Multiple Organ Failure - virology; NF-κB protein; Pandemics; Pathology; Peptidyl-dipeptidase A; Pharmacology/Toxicology; Receptors, Coronavirus - metabolism; Renin; Respiratory distress syndrome; Review; Rheumatology; Severe acute respiratory syndrome coronavirus 2; Severity of Illness Index; Spike protein; Tumor necrosis factor-α; COVID-19; multiple organ failure; SARS-CoV-2; angiotensin-converting enzyme 2; cytokine storm; renin-angiotensin system
• ISSN: 0360-3997; 1573-2576; 1573-2576
• DOI: 10.1007/s10753-020-01337-3

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.