Endothelial contribution to COVID-19: an update on mechanisms and therapeutic implications

Zhangjing Ma; Kevin Y Yang; Yu Huang; Kathy O Lui

doi:10.1016/j.yjmcc.2021.11.010

Endothelial contribution to COVID-19: an update on mechanisms and therapeutic implications

J Mol Cell Cardiol. 2022 Mar:164:69-82. doi: 10.1016/j.yjmcc.2021.11.010. Epub 2021 Nov 24.

Authors

Zhangjing Ma¹, Kevin Y Yang¹, Yu Huang², Kathy O Lui³

Affiliations

¹ Department of Chemical Pathology, Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
² Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China.
³ Department of Chemical Pathology, Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; Li Ka Shing Institute of Health Science, Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China. Electronic address: kathyolui@cuhk.edu.hk.

Abstract

The global propagation of SARS-CoV-2 leads to an unprecedented public health emergency. Despite that the lungs are the primary organ targeted by COVID-19, systemic endothelial inflammation and dysfunction is observed particularly in patients with severe COVID-19, manifested by elevated endothelial injury markers, endotheliitis, and coagulopathy. Here, we review the clinical characteristics of COVID-19 associated endothelial dysfunction; and the likely pathological mechanisms underlying the disease including direct cell entry or indirect immune overreactions after SARS-CoV-2 infection. In addition, we discuss potential biomarkers that might indicate the disease severity, particularly related to the abnormal development of thrombosis that is a fatal vascular complication of severe COVID-19. Furthermore, we summarize clinical trials targeting the direct and indirect pathological pathways after SARS-CoV-2 infection to prevent or inhibit the virus induced endothelial disorders.

Keywords: COVID-19; SARS-CoV-2; endothelial dysfunction; immunity; thrombosis.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Adolescent
Adult
Aged
Angiotensin-Converting Enzyme 2 / physiology
Animals
COVID-19 / blood
COVID-19 / complications
COVID-19 / pathology*
COVID-19 / physiopathology
COVID-19 / therapy
Clinical Trials as Topic
Endothelial Cells / pathology
Endothelial Cells / virology
Endothelium, Vascular / immunology
Endothelium, Vascular / pathology*
Endothelium, Vascular / physiopathology
HMGB1 Protein / physiology
Humans
Macaca mulatta
Mice
Neuropilin-1 / physiology
Oxidative Stress
Reactive Oxygen Species
Receptors, Virus / physiology
SARS-CoV-2*
Scavenger Receptors, Class B / physiology
Severity of Illness Index
Signal Transduction
Systemic Inflammatory Response Syndrome / pathology
Systemic Inflammatory Response Syndrome / physiopathology
Thrombophilia / etiology
Thrombophilia / physiopathology
Vascular Endothelial Growth Factor A / physiology
Vasculitis / etiology
Vasculitis / immunology
Vasculitis / physiopathology
Young Adult

Substances

HMGB1 Protein
HMGB1 protein, human
NRP1 protein, human
Reactive Oxygen Species
Receptors, Virus
SCARB1 protein, human
Scavenger Receptors, Class B
VEGFA protein, human
Vascular Endothelial Growth Factor A
Neuropilin-1
ACE2 protein, human
Angiotensin-Converting Enzyme 2

Supplementary concepts

pediatric multisystem inflammatory disease, COVID-19 related