2021
DOI: 10.1016/j.ajpath.2021.05.007
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COVID-19 Vasculopathy: Mounting Evidence for an Indirect Mechanism of Endothelial Injury

Abstract: COVID-19 patients who are critically ill develop vascular complications characterized by thrombosis of small, medium and large vessels. Dysfunction of the vascular endothelium due to the SARS-CoV-2 infection has been implicated in the pathogenesis of the COVID-19 vasculopathy. Although initial reports suggested that endothelial injury was caused directly by the virus, recent studies indicate that endothelial cells do not express ACE2 – the receptor that SARS-CoV-2 uses to gain entry into cells – or express it … Show more

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Cited by 96 publications
(97 citation statements)
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“…7 Local erythema and edema 3 days after the second dose of the mRNA-1273 vaccine Fig. 8 Erythema and edema at the injection site, 2 days after the second dose of the mRNA-1273 vaccine Hoff et al Eur J Med Res (2021) 26:98 [6]; [7] approved vaccinations [6,7,[9][10][11][12][13][14][15][16][17][18][19][20]. While the exact mechanism of these skin reactions is still unclear, a delayed hypersensitivity reaction has been hypothesized [11].…”
Section: Discussionmentioning
confidence: 99%
“…7 Local erythema and edema 3 days after the second dose of the mRNA-1273 vaccine Fig. 8 Erythema and edema at the injection site, 2 days after the second dose of the mRNA-1273 vaccine Hoff et al Eur J Med Res (2021) 26:98 [6]; [7] approved vaccinations [6,7,[9][10][11][12][13][14][15][16][17][18][19][20]. While the exact mechanism of these skin reactions is still unclear, a delayed hypersensitivity reaction has been hypothesized [11].…”
Section: Discussionmentioning
confidence: 99%
“…Although D-dimer levels remained within the normal range in patients post COVID-19, the levels of factor VIII and PAI-1 were elevated after 4 months (51), suggesting the continuous activation of the vascular endothelium. Although SARS-CoV-2 had been considered to infect vascular endothelial cells in the early report (52), such direct infection is now considered a rare condition (53)(54)(55).…”
Section: Discussionmentioning
confidence: 99%
“…Lastly, a distinctive feature of COVID-19 lies in the coagulation/fibrinolytic abnormalities defined as elevated plasma levels of D-dimer, factor VIII, and von Willebrand factor [ 49 ]. In this regard, a self-amplifying cycle of excessive inflammation was proposed to be a primary cause of the impairment of the anti-thrombogenic properties of the vascular endothelium in COVID-19, which ultimately leads to the formation of thrombi in the vessels [ 11 ]. In particular, an upregulation of the endothelial tissue factor (TF) has been assumed to play a central role in the pathogenesis of the thrombotic complications of COVID-19 [ 50 , 51 , 52 ], although a definite demonstration still lacks.…”
Section: Discussionmentioning
confidence: 99%
“…As for the ability of the virus to infect endothelial cells directly, the question is still controversial. Indeed, while clinical evidences and post-mortem studies have provided evidences of SARS-CoV-2 entry into the cells [ 4 , 10 ], only very low levels up to the absence of the ACE2 receptor have been detected in the endothelium [ 11 ]. In this regard, however, several cell-surface receptors other than the ACE2 have been shown to mediate viral entry into the cells [ 12 , 13 ]; moreover, co-receptors such as neuropilin-1 (NRP1) and neuropilin-2 (NRP-2) are of a certain relevance in the infectivity of Sars-Cov-2 [ 14 ].…”
Section: Introductionmentioning
confidence: 99%