NIH , Guo J , Zuo M , ten Cate V , Tschudi MR , Varga Z , Posma J National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error. , Li VW The research suggests the potential to therapeutically target activation, rather than infection of the endothelium, as a strategy for resolving coagulation and inflammatory COVID … , Tomelleri A , Palacios-Callender M , Lütgehetmann M , Guerci P Yet Covid-19 can affect … , Campochiaro C This function depends on endothelial surface expression of an ecto-ADPase, CD39, as well as the release of nitric oxide and prostacyclin.8,9 Together, this array of anticoagulant and antithrombotic properties accounts for much of the ability of the endothelial cell to combat intravascular blood clot formation under normal circumstances. , Tanner FC The coagulopathy, endotheliopathy, and vasculitis of COVID-19. , Skepper JN The Specter of Endothelial Injury in COVID-19 Studies signal that damage to the endothelium—cells that cover blood vessels like wallpaper—could underpin the thrombosis and inflammation induced by coronavirus infection. , Bonow RO , Cleman M , van Paridon P , Provenzale I , Lin L , Gogos C Possible Correlations between Atherosclerosis, Acute Coronary Syndromes and COVID-19. , Borczuk A However, when stimulated by proinflammatory cytokines, pathogen-associated molecular patterns such as bacterial endotoxins, or neutrophil extracellular traps (NETs; see below), the endothelial cell can express and in turn exert tissue factor activity.12,13 Tissue factor activates the coagulation system by amplifying many-fold the enzymatic capacity of factors VII and X, triggering thrombin generation and clot formation.14 The endothelial cell also stores pre-formed von Willebrand factor (vWf) in intracellular granules called Weibel–Palade bodies. , Dangas G Here we present an update on ED-relevant vasculopathy in COVID-19. Under normal conditions, the endothelial cells promote tonic vasodilatation through the well-known mechanism of production of the vasodilatory gas nitric oxide from l-arginine via the activity of endothelial nitric oxide synthase.17 The endothelial cell can also elaborate diverse hyperpolarizing factors that promote relaxation of smooth muscle and hence dilatation of muscular arteries. These molecules include intercellular adhesion molecule-1 (ICAM-1, CD54) and vascular cell adhesion molecule-1 (VCAM-1, CD106). As noted in each of the foregoing sections, proinflammatory cytokines conspire to elicit from endothelial cells a change from their homeostatic functions to those that can contribute to thrombosis and local tissue injury. The firm binding of leucocytes to the activated endothelial surface depends upon adhesion molecules of the IgG superfamily. , Landray MJ. Thus, loss of the endothelial protective and unleashing of the mechanisms depicted can lead to multiorgan system failure that characterizes the advanced stages of COVID-19. , Pogue JM. , Zuo Y , Tzankov A , Lüscher TF. , Schmiedel S Epub 2020 Jun 30. To explain these widespread injuries, researchers are studying how the virus affects the vascular system. , Vanstapel A Maiuolo J, Mollace R, Gliozzi M, Musolino V, Carresi C, Paone S, Scicchitano M, Macrì R, Nucera S, Bosco F, Scarano F, Zito MC, Ruga S, Tavernese A, Mollace V. Int J Mol Sci. , Verleden SE , Jeffery K Coronavirus uses the angiotensin converting enzyme 2 (ACE2) endothelium receptor, as an entry cell point. COVID-19 infection is caused by Coronavirus-2 (SARS-CoV-2). , Sacco E , Lauring AS "When the virus damages the inside of the blood vessel and shreds the lining, that's like the ice after a hockey game," noted Dr. Li, a researcher and founder of the Angiogenesis Foundation. Impaired endothelial barrier function can contribute to protein accumulation in the alveolar space and fluid accumulation and impaired oxygenation of the blood. , Ye P , Boffini N , Zhang C , Fegan C , Caligiuri G. Dinarello CA , Yost CC All rights reserved. The novel coronavirus triggers a condition seen in other cardiovascular diseases called endothelial dysfunction. P.L. Thus, the very same cytokines that elicit abnormal endothelial functions can unleash the acute phase response which together with local endothelial disfunction can conspire to cause the clinical complications of COVID-19. , Emberson J , Sperhake J-P 2020 Sep 30;21(3):339-344. doi: 10.31083/j.rcm.2020.03.131. , Vogler TO , Sianos G  |  Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study. , Scotti R , Binder C The endothelial cell is a key target of cytokines, as they induce action of a central proinflammatory transcriptional hub, nuclear factor-κB. , Heinemann A , Brightling C , Elmahi E In small vessels, such as those that embrace alveoli in the lung, this impaired barrier function can lead to capillary leak. , Weber A . , Malik AB. When the endothelial cells undergo the cytopathic effect of a viral infection such as SARS-CoV-2, or encounter pathogen-associated molecular patterns (PAMPs) derived from viruses or bacteria such as lipopolysaccharide, proinflammatory cytokines such as IL-1 or TNF, or damage-associated molecular patterns (DAMPs) derived from dead or dying cells, the endothelial cells become activated. , Cannon JG , Dagna L. Huet T In Figure 1, a transmission electron micrograph of the endothelium from a patient with Covid-19, we show numerous endothelial viruslike particles, ranging in … It produces protean manifestations ranging from head to toe, wreaking seemingly indiscriminate havoc on multiple organ systems, in particular the lungs, heart, brain, kidney, and vasculature. , Orencole SF , Turina M , Nepal S , Wang L , Hanauer DA COVID-19 is, in the end, an endothelial disease The vascular endothelium provides the crucial interface between the blood compartment and tissues, and displays a series of remarkable properties that normally maintain homeostasis. , Mehes G , Heinrich F By comparing with similar patterns of … , Werlein C , Islam N The endothelium is an important target for SARS-CoV-2 infection, and vascular disorders are a major problem in COVID-19. , Kluge S. Barnes BJ NLM , Salvatore S , Huang J The Multifaceted Covid-19 We see all imaginable symptoms with Covid-19, which is supposed to be a pneumonia disease. , Colotta F The endothelial monolayer that lines the intima of arteries, veins, and microvessels measures up to 7000 m 2 in surface area. , Jaki T , Mawson TL , Tsukasaki Y , Linsell L , Dolleman SC SARS-CoV-2, the aetiological agent of COVID-19, causes the current pandemic. , Sun W 4,5. , Karlheinz P , Tantiwong C , She Z-G , Wei H. Somers EC , Jonigk D. Wichmann D Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. , Han M , Sheikhzadeh-Eggers S , Jeney V , Leopold JA Higher levels of acute phase reactants (IL-6, C-reactive protein, and D-dimer) are also associated with SARS-CoV-2 infection. , Angelidis C The endothelial cell usually possesses little procoagulant potential. , Labugger R IL-1 can induce its own gene expression, providing an amplification loop that can instigate a cytokine storm.38–40IL-1 induces not only its own gene expression but also that of other proinflammatory cytokines including TNF-α.41 In addition, IL-1 produced by endothelial cells and invading leucocytes can elicit the production of chemoattractant molecules including the chemokines that mediate the penetration of inflammatory cells into tissues.42IL-1 also potently stimulates the production of another proinflammatory cytokine, IL-6.43,44 This induction of IL-6 production by IL-1 provides another amplification loop that contributes to the cascade of cytokine overproduction that characterizes a cytokine storm. , Wang X In: Kitchens CS , Scarpellini P , Werner A , Bourne JH The endothelialitis hypothesis is compatible with the role of the RAS in COVID-19 because the RAS is a critical regulator of endothelial function. Nutrients. Rev Cardiovasc Med. , Metallidis S SARS-CoV-2, the aetiological agent of COVID-19, causes the current pandemic. , Kolettis T , Gerakari S  |  , Giannopoulos G The endothelium displays a tightly regulated palette of functions that control vasomotion, inflammation, oxidative stress, vascular permeability, and structure.2 The endothelial cells also provide a crucial interface in host defences, forming the front line of encounter with bloodborne pathogens, thus sensing danger threatening the organism in a concerted fashion, sending early warning signals of infection, invasion, or injury.3 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 (Figure 1, middle and right). SARS-CoV-2 infects the host using the angiotensin converting enzyme 2 (ACE2) receptor, which is expressed in several organs, including the lung, heart, kidney, and intestine. , Zhang X , Yang L , Staplin N , Even G The untrammelled production of proinflammatory cytokines contributes to a condition termed a cytokine storm (Figure 2). Concerning the specific interaction of SARS-CoV-2 with the cardiovascular system, we know that this virus enters the body through the receptors for the conversion of angiotensin II (ACE2r) that are present in the lungs, heart, intestinal epithelium and vascular endothelium. Deep venous thrombosis can occur as endothelial disfunction represents an important part of Virchow’s triad, and sets the stage for pulmonary embolism. , Yang Y , Zhou F , Weber C , Lüscher TF Cytokines, protein pro-inflammatory mediators, serve as key danger signals that shift endothelial functions from the homeostatic into the defensive mode. , Zhu L The thrombotic diathesis provoked by endothelial dysfunction can also predispose towards strokes. is an unpaid consultant to, or involved in clinical trials for, Amgen, AstraZeneca, Baim Institute, Beren Therapeutics, Esperion, Therapeutics, Genentech, Kancera, Kowa Pharmaceuticals, Medimmune, Merck, Norvo Nordisk, Merck, Novartis, Pfizer, and Sanofi-Regeneron. , de Heer G , Veninga A This systemic form of COVID‐19 may be due to inflammation and vascular endothelial cell injury. , Dillman NO , Chen M-M Adherent neutrophils can undergo formation of neutrophil extracellular traps that provide an amplifier for endothelial damage mediated in part by IL-1α. , Brown H Positioned at the key interface between the blood and tissues, the endothelium normally resists prolonged contact with the leucocytes that abound in blood that bathes the intimal surface.3,24 Stationed as the sentinel, the endothelium serves as the portal governing the entry of leucocytes into tissues to combat invaders, microbial or viral, and to help repair injury and heal wounds. Further research for ED in COVID-19 patients is warranted to understand therapeutic opportunities. , van Moorsel M , Sukhova G Cytokine storm. , Frings D , Zhang P 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. , Püschel K , Hahalis G Scientists are finding similar blood clots and endothelial issues across the body. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (, EMPEROR-REDUCED reigns while EMPERIAL whimpers, Management of refractory angina: an update, Noise and cardiovascular risk: nighttime aircraft noise acutely triggers cardiovascular death, Time to revisit implantable cardioverter-defibrillator implantation criteria in women, Myocarditis-associated necrotizing coronary vasculitis: incidence, cause, and outcome, The endothelium participates pivotally in thrombosis and fibrinolysis, The endothelial vasodilator/vasoconstrictor balance, Antioxidant/pro-oxidant balance in the endothelium, Cytokine storm: a perfect storm in COVID-19, Endothelial functions as a therapeutic target, https://doi.org/10.1093/eurheartj/ehaa623, https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model, Receive exclusive offers and updates from Oxford Academic, [Study of the functional state of the periodontium in older persons and its correction by means of oral hygiene. , Yang H , Schurgers L , Lim WS , Looney MR , Neagoe RAI , ten Cate-Hoek AJ , Olympios CD These molecules bind antithrombin III, as do heparinoids that we use daily in practice as an anticoagulant. , Salmeron S Evidence Regarding Vitamin D and Risk of COVID-19 and Its Severity. , Castiglioni B , Loscalzo J , Béa ML , Kishimoto T. Wright FL Quillard T , Chatellier G , Moore EE , Morvan M , Renaud S , Wang D The complications of COVID-19 follow very closely the consequences of excessive cytokine actions on endothelial cells outlined above and depicted in Figure 1. Adventures and excursions in bioassay—the stepping stones to prostacyclin, Reduced endothelial nitric oxide synthase expression and production in human atherosclerosis, Mechanisms for oxidative stress in diabetic cardiovascular disease, Enhanced peroxynitrite formation is associated with vascular aging, Linking regulation of nitric oxide to endothelin-1: the Yin and Yang of vascular tone in the atherosclerotic plaque, Oxidized low density lipoproteins induce mRNA expression and release of endothelin from human and porcine endothelium, Endothelial cell dysfunction and the pathobiology of atherosclerosis, Monocyte–endothelial cell interactions in the development of atherosclerosis, Chemokines as therapeutic targets in cardiovascular disease, Glutathione peroxidase-1 deficiency augments proinflammatory cytokine-induced redox signaling and human endothelial cell activation, Red cells, hemoglobin, heme, iron, and atherogenesis, Regulation of human heme oxygenase in endothelial cells by using sense and antisense retroviral constructs, Oxidative stress and endothelial dysfunction in vascular disease, Molecular pathways of aging and hypertension, Adverse epigenetic signatures by histone methyltransferase Set7 contribute to vascular dysfunction in patients with type 2 diabetes mellitus, VE-cadherin and endothelial adherens junctions: active guardians of vascular integrity, Aortic endothelial cell death and replication in normal and lipopolysaccharide-treated rats, Death receptors and their ligands in atherosclerosis, Haemodynamic stress-induced breaches of the arterial intima trigger inflammation and drive atherogenesis, Once more unto the breach: endothelial permeability and atherogenesis, Interleukin-1 induces interleukin-1. , Dauriat G , Zangrillo A , Kanonidis I , Liu M , Adrover JM , Narazaki M The pathophysiological mechanisms of a cytokine storm depend on phenomena described in the 1980s that centre on autoinduction of the primordial proinflammatory cytokine IL-1. , Shi H Alterations in endothelial thrombotic/fibrinolytic balance can predispose to thrombosis not only in the pulmonary circulation but also in peripheral veins and arteries of the cerebral circulation, causing unheralded strokes in apparently healthy young people and doubtless contributing to the local and patchy embarrassment of blood flow in ‘COVID toes’ that probably represent microvascular dysfunction with tissue ischaemia. , Fasol R , Bode C , Cosentino F. Hansson GK , Bredereke-Wiedling H , Ripa M van der Loo B , Moore PK , Ruggeri A , Zhou S , Wohlauer MV , Capretti G , Loda M The vascular endothelium: the cornerstone of organ dysfunction in severe SARS-CoV-2 infection. Peter Libby, Thomas Lüscher, COVID-19 is, in the end, an endothelial disease, European Heart Journal, Volume 41, Issue 32, 21 August 2020, Pages 3038–3044, https://doi.org/10.1093/eurheartj/ehaa623. The hallmark of COVID-19 is respiratory symptoms, but doctors now know that the disease can cause wide-ranging problems throughout the body. He is a member of the scientific advisory board for Amgen, Corvidia Therapeutics, DalCor Pharmaceuticals, Kowa Pharmaceuticals, Olatec Therapeutics, Medimmune, Novartis, and XBiotech, Inc. His laboratory has received research funding in the last 2 years from Novartis. , Fernandez DI , von Hundelshausen P Corresponding author. , Randou E The endothelial cells display more columnar morphology. , Berissi S , Ullrich V , Lip GYH , Battista R , Eschenauer GA , Siasos GD , Luscinskas FW , Ustianowski A Pre-clinical and autopsy studies have fueled the hypothesis that a dysregulated vascular endothelium might play a central role in the pathogenesis of ARDS and multi-organ failure in COVID-19. , Klok FA His interests were reviewed and are managed by Brigham and Women’s Hospital and Partners HealthCare in accordance with their conflict of interest policies. , eds. , Franck G , Emmerich J , Schröder AS Tel: +1 617 525-4383, Fax: +1 617 525 4400, Email: Search for other works by this author on: Heart Division, Royal Brompton & Harefield Hospital and National Heart and Lung Institute, Evolving functions of endothelial cells in inflammation, The active roles of cells of the blood vessel wall in health and disease, Thrombo-inflammation in cardiovascular disease: an expert consensus document from the Third Maastricht Consensus Conference on Thrombosis, Tissue factor in cardiovascular diseases: molecular mechanisms and clinical implications, The endothelial cell ecto-ADPase responsible for inhibition of platelet function is CD39, Different interactions of platelets with arterial and venous coronary bypass vessels, Regulation of murine type 1 plasminogen activator inhibitor gene expression, Cultured bovine endothelial cells produce both urokinase and tissue-type plasminogen activators, Intertwining of thrombosis and inflammation in atherosclerosis, Neutrophil extracellular traps induce endothelial cell activation and tissue factor production through interleukin-1α and cathepsin G, The P-selectin, tissue factor, coagulation triad, The Weibel–Palade body: the storage granule for von Willebrand factor and P-selectin, Endothelium-dependent contractions to acetylcholine in the aorta of the spontaneously hypertensive rat, Endothelium-derived relaxing factor: discovery, early studies, and identification as nitric oxide (Nobel Lecture), Nobel lecture. To comprehensively characterize and quantify microvascular alterations in patients with COVID-19. , von Segesser L “This is actually a disease of the endothelium,” he says. A motley of studies are looking at ways to restore endothelial integrity in COVID-19 patients using various agents, including P-selectin blockers.Targeting the complement cascade—an inflammatory pathway that causes endothelial dysfunction—is another approach in clinical testing, with one exploratory Phase 2 trial recently … Sloughing of endothelial cells uncovers the thrombogenic basement membrane. 2020 Nov 21;9(11):3746. doi: 10.3390/jcm9113746. , Kanthi Y Upon activation, the endothelial cells can release this large protein that in higher molecular weight multimers provides a potent bridge for platelet aggregates and thrombus assembly, favouring formation of an organized clot.15. Endothelium-directed therapies in COVID-19. , Panagopoulos P , Mafham M The endothelium is an important target for SARS-CoV-2 infection, and vascular disorders are a major problem in COVID-19. The vascular endothelium provides the crucial interface between the blood compartment and tissues. Inflamm Res. , Balla J. Quan S , Koulouris NG Pathophysiological studies demonstrated inflammatory activation of the endothelium, destruction of intercellular contacts, and disruption of contacts with the basement membrane in COVID … , Weber A , Lindley I , Baillie JK , Libby P. Oemar BS , Hoylaerts M Therefore, it is reasonable to assume that ED contributes to COVID-19-associated vascular inflammation, particularly endotheliitis, in the lung, heart, and kidney, as well as COVID-19-associated coagulopathy, particularly pulmonary fibrinous microthrombi in the alveolar capillaries. , Ma X , Bokemeyer C , Gandhi TN JAMA Netw Open, In-hospital use of statins is associated with a reduced risk of mortality among individuals with COVID-19, Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study, Anakinra for severe forms of COVID-19: a cohort study, Effective treatment of severe COVID-19 patients with tocilizumab, Tocilizumab for treatment of mechanically ventilated patients with COVID-19, SARS-CoV-2 and COVID-19: is interleukin-6 (IL-6) the ‘culprit lesion’ of ARDS onset? , Zhang Y-Y , Loomba R , Daßler-Plenker J , Zhou N , Persson O , d Birinyi LK. Vitamin D deficiency in association with endothelial dysfunction: Implications for patients with COVID-19. , Mushumba H Clinically, it presents with mild flu-like symptoms in most cases but can cause respiratory failure in high risk population. , Milionis H , Felton T , Vercellotti GM , Tsoukalas G , Addo MM , Vavouranakis E T.L. , Xu Q 3 Whether vascular derangements in COVID-19 are due to endothelial cell involvement by the virus is currently unknown. The Contribution of Endothelial Dysfunction in Systemic Injury Subsequent to SARS-Cov-2 Infection. , Jennings LK While initial infection of type I and II pneumocytes and alveolar macrophages no doubt participates in the initiation of infection, disordered endothelial function certainly contributes to the ongoing ravages of SARS-CoV-2 in the lung as elsewhere. , van Mourik M “We found greater numbers of ACE2-positive endothelial cells and significant changes in endothelial morphology, a finding consistent with a central role of endothelial cells in the vascular phase of COVID-19,” Ackermann and colleagues write. Integrins associated with the endothelial surface also participate in these adhesive interactions and furnish cognate ligands for the adhesion molecules.25 Once tightly bound to the endothelial surface, chemoattractant cytokines of various classes can beckon the bound cells to traverse the endothelial monolayer and enter tissues where they can combat invaders or contribute to tissue repair.26. , Nydam TL , Li X , Bergmeier W The characteristic hyperinflammatory and procoagulatory state of COVID-19 implies a critical role of the endothelium, both as an effector contributing to inflammation and thrombosis, and as a target organ, whose dysfunction may contribute to poor outcome. , Kuehnel M , Safier L Published by IMR press. , Handy DE. , Cai J , Gargalianos P , Fu B Yet, rigorous, controlled, and prospective clinical trials must evaluate the balance between the potential benefits by forestalling the consequences of cytokine storm versus the potential of lowering defences against bacterial superinfections that commonly complicate individuals with impaired pulmonary protective functions and remain subject to the rigours of mechanical ventilation and endotracheal intubation. Please enable it to take advantage of the complete set of features! , Stefanini GG , Kremers B Endothelial injury and thrombosis in COVID-19. , Karel M The homeostatic mechanisms displayed by the resting endothelium include the listed properties as detailed in the text. Patients with COVID-19 can have bowel abnormalities, ... “ACE2 expression is most abundant in lung alveolar epithelial cells, enterocytes of the small intestine, and vascular endothelium suggesting that small bowel and vasculature may be susceptible to SARS-CoV-2 infection,” they wrote. , Villano A , Golob JL , Liu PP , Chadwick D , Zhao Y-C Li, a vascular biologist, likened the endothelium to newly resurfaced ice on a skating rink. Angiotensin II is one of the strongest stimulants of Na + /H + exchanger (NHE). , Martinenghi S Libby P. , Soares MP , Noll G , Welte T Epub 2020 Sep 15. high blood pressure, thrombosis, pulmonary embolism) seem to suggest that the virus is targeting the endothelium, one of the largest organs in the human body. Downstream of IL-1, antibodies that interfere with IL-6 signalling have also shown signs of benefit in some but not all preliminary studies, although this as well as other anticytokine therapies may entail an increased risk of superinfection.59,60 Other anti-IL-6 strategies also warrant consideration.61 Upon inflammatory stimulation, vascular endothelial and smooth muscle cells produce large amounts of IL-6; thus, blocking signalling of this distal mediator can limit local vascular amplification of inflammatory responses, including in the lung. , Martin-Padura I II. This observational retrospective study aims to further investigate the potential pathophysiology through assessing the pattern of microhaemorrhage and clinical characteristics of patients with COVID-19 and microhaemorrhage. However, we now recognize that SARS-CoV-2’s destructive actions range far and wide beyond the pulmonary parenchyma. , Petty LA Zhang X-J , Drosopoulos JHF , Gregg KS SARS-CoV-2 and coagulation disorders in different organs. , Tassan Din C , Prudon B , Hong Z , Deutsch M , van t Hof A , Crijns HJGM , Schoenborn M , Chen G , Sowa MA Several studies have linked COVID-19 with chilblains, or reddish-purple lesions on … , Castello L , Watson SP , Scavone G , Urban S The glycocalyx covers the entire vascular endothelium, and its thickness varies among organs. , Oldebeken SR 2020 Oct 31;12(11):3361. doi: 10.3390/nu12113361. Background Cerebral microhaemorrhages are increasingly being recognised as a complication of COVID-19. Deftereos SG , Henke P Perspective: This autopsy series outlines three distinctive findings among patients who died from COVID-19: 1) severe endothelial injury with intracellular severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and disrupted cell membranes, 2) widespread vascular thrombosis with microangiopathy and occlusion of alveolar capillaries, and 3) significantly higher new vessel … , Storey RF As noted above, the normal endothelial cells also secrete PGI2 that, in addition to its antiaggregatory effects on platelets, potently vasodilates.18 This array of vasodilatory actions can also modulate moment-to-moment local blood flow in a paracrine fashion. , Mentzer SJ , Metwally H , Edler C , Spicer JD , Vromman A , Pfefferle S , Tousoulis D , Baxter-Stoltzfus A , Mantovani A. Kang S , Vrachatis DA, Alveolar-capillary endothelial cells can be activated by severe acute respiratory syndrome coronavirus 2 infection leading to cytokine release. , Baltagiannis S In: Zipes DP Life Sci. , Posnett D , Alexopoulos D , Newton G Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School. This concept not only provides a unifying pathophysiological picture of this raging infection but also furnishes 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. 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. , Balla G Therefore, it is reasonable to assume that ED contributes to COVID-19-associated vascular inflammation, particularly endotheliitis, in the lung, heart, and kidney, as well as COVID-19-associated coagulopathy, particularly pulmonary fibrinous microthrombi in the alveolar capillaries. , Knight JS , Laplanche S Early reports suggest that there are neurologic manifestations of COVID-19, including acute cerebrovascular disease. , Hayem G. Xu X , Kniep I 2020 Jun 16;24(1):353. doi: 10.1186/s13054-020-03062-7. IL-1 not only induces leucocyte adhesion molecules but, by reducing VE-cadherin production, can contribute to impaired endothelial barrier function and thus capillary leak, a major issue that complicates COVID-19 pneumonitis.47 Agents that inhibit the inflammasome–IL-1β–IL-6 pathway may thus comprise a more endothelial-directed approach to treatment of COVID-19. , Tomaselli GF , Nierhaus A , Yang L Endothelial cells possess an endogenous mechanism for combatting platelet activation. , Pitocco D The novel coronavirus triggers a condition seen in other cardiovascular diseases called endothelial dysfunction. For full access to this pdf, sign in to an existing account, or purchase an annual subscription. , Morser J The normal endothelial surface owes its remarkable haemocompatibility to a tightly orchestrated set of functions.6 Heparan sulfate proteoglycans decorate the surface of the endothelium. 2020 Oct 31 ; 12 ( 11 ):3361. doi: 10.3390/jcm9113746, Department Medicine... 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