COVID-19 is, in the end, an endothelial disease
- PMID: 32882706
- PMCID: PMC7470753
- DOI: 10.1093/eurheartj/ehaa623
COVID-19 is, in the end, an endothelial disease
Abstract
The vascular endothelium provides the crucial interface between the blood compartment and tissues, and displays a series of remarkable properties that normally maintain homeostasis. This tightly regulated palette of functions includes control of haemostasis, fibrinolysis, vasomotion, inflammation, oxidative stress, vascular permeability, and structure. While these functions participate in the moment-to-moment regulation of the circulation and coordinate many host defence mechanisms, they can also contribute to disease when their usually homeostatic and defensive functions over-reach and turn against the host. SARS-CoV-2, the aetiological agent of COVID-19, causes the current pandemic. It produces protean manifestations ranging from head to toe, wreaking seemingly indiscriminate havoc on multiple organ systems including the lungs, heart, brain, kidney, and vasculature. This essay explores the hypothesis that COVID-19, particularly in the later complicated stages, represents an endothelial disease. Cytokines, protein pro-inflammatory mediators, serve as key danger signals that shift endothelial functions from the homeostatic into the defensive mode. The endgame of COVID-19 usually involves a cytokine storm, a phlogistic phenomenon fed by well-understood positive feedback loops that govern cytokine production and overwhelm counter-regulatory mechanisms. The concept of COVID-19 as an endothelial disease provides a unifying pathophysiological picture of this raging infection, and also provides a framework for a rational treatment strategy at a time when we possess an indeed modest evidence base to guide our therapeutic attempts to confront this novel pandemic.
Keywords: Inflammation; Microvasculature; Thrombosis; Cytokine; Endothelium.
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.
Figures
Comment in
-
Understanding COVID-19: in the end it is the endothelium-what else?Eur Heart J. 2020 Aug 21;41(32):3023-3027. doi: 10.1093/eurheartj/ehaa706. Eur Heart J. 2020. PMID: 33216863 Free PMC article. No abstract available.
Similar articles
-
Endothelial dysfunction contributes to COVID-19-associated vascular inflammation and coagulopathy.Rev Cardiovasc Med. 2020 Sep 30;21(3):315-319. doi: 10.31083/j.rcm.2020.03.126. Rev Cardiovasc Med. 2020. PMID: 33070537 Review.
-
COVID-19 May Predispose to Thrombosis by Affecting Both Vascular Endothelium and Platelets.Clin Appl Thromb Hemost. 2020 Jan-Dec;26:1076029620933945. doi: 10.1177/1076029620933945. Clin Appl Thromb Hemost. 2020. PMID: 32619104 Free PMC article. No abstract available.
-
The vascular endothelium: the cornerstone of organ dysfunction in severe SARS-CoV-2 infection.Crit Care. 2020 Jun 16;24(1):353. doi: 10.1186/s13054-020-03062-7. Crit Care. 2020. PMID: 32546188 Free PMC article. Review.
-
Inflammation resolution: a dual-pronged approach to averting cytokine storms in COVID-19?Cancer Metastasis Rev. 2020 Jun;39(2):337-340. doi: 10.1007/s10555-020-09889-4. Cancer Metastasis Rev. 2020. PMID: 32385712 Free PMC article.
-
Productivity of Young Experts in Hemostasis and Thrombosis before and during the SARS-CoV-2 Pandemic-A Special Issue.Hamostaseologie. 2020 Aug;40(3):255-256. doi: 10.1055/a-1081-6973. Epub 2020 Jul 29. Hamostaseologie. 2020. PMID: 32726820 No abstract available.
Cited by
-
Recovery of Smell and Taste in Patients With Persistent COVID-19-Related Hyposmia and Dysgeusia by Targeting Inflammation and Endothelial Dysfunction.Cureus. 2024 Feb 26;16(2):e54925. doi: 10.7759/cureus.54925. eCollection 2024 Feb. Cureus. 2024. PMID: 38544584 Free PMC article.
-
The S1 subunits of SARS-CoV-2 variants differentially trigger the IL-6 signaling pathway in human brain endothelial cells and downstream impact on microglia activation.NeuroImmune Pharm Ther. 2024 Jan 9;3(1):7-15. doi: 10.1515/nipt-2023-0024. eCollection 2024 Mar. NeuroImmune Pharm Ther. 2024. PMID: 38532784 Free PMC article.
-
Investigating efficacy of colchicine plus phenolic monoterpenes fraction as a potential treatment for patients diagnosed with COVID-19: A randomized controlled parallel clinical trial.Heliyon. 2024 Mar 6;10(6):e27373. doi: 10.1016/j.heliyon.2024.e27373. eCollection 2024 Mar 30. Heliyon. 2024. PMID: 38515718 Free PMC article.
-
Neurovascular coupling impairment as a mechanism for cognitive deficits in COVID-19.Brain Commun. 2024 Mar 7;6(2):fcae080. doi: 10.1093/braincomms/fcae080. eCollection 2024. Brain Commun. 2024. PMID: 38495306 Free PMC article. Review.
-
Risk factors for intubation and mortality in patients treated with high flow nasal cannula due to COVID-19 infection. Survival Analysis Study in a Northern Mexican Population.PLoS One. 2024 Mar 15;19(3):e0296931. doi: 10.1371/journal.pone.0296931. eCollection 2024. PLoS One. 2024. PMID: 38489289 Free PMC article.
References
-
- Aird WC. Endothelium In: Kitchens CS, Kessler CM, Konkle BA, eds. Consultative Hemostasis and Thrombosis, 3rd ed Philadelphia. PA: W.B. Saunders; 2013. p33–41.
-
- Libby P. The vascular biology of atherosclerosis In: Zipes DP, Libby P, Bonow RO, Mann DL, Tomaselli GF, eds. Braunwald’s Heart Disease, 11th ed Philadelphia, PA: Elsevier; 2018. p859–875.
-
- Pober JS, Sessa WC.. Evolving functions of endothelial cells in inflammation. Nat Rev Immunol 2007;7:803–815. - PubMed
-
- Libby P. The active roles of cells of the blood vessel wall in health and disease. Mol Aspects Med 1987;9:499–567. - PubMed
-
- Libby P, d Birinyi LK.. The dynamic nature of vascular endothelial functions In: Zilla P, Fasol R, Deutsch M, eds. Endothelialization of Vascular Grafts. Basel: Karger; 1987. p80–99.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Medical
Miscellaneous
