COVID‐19‐induced endotheliitis: emerging evidence and possible therapeutic strategies

Calabretta, Eleonora; Moraleda, José Marı́a; Iacobelli, Massimo; Jara, Rubén; Vlodavsky, Israël; O’Gorman, Peter; Pagliuca, Antonio; Mo, Clifton C.; Baron, Rebecca M.; Aghemo, Alessio; Soiffer, Robert J.; Fareed, Jawed; Carlo‐Stella, Carmelo; Richardson, Paul G.

doi:10.1111/bjh.17240

Cited by 58 publications

(67 citation statements)

References 118 publications

(211 reference statements)

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“…However, endothelial dysfunction is not only a consequence of direct virus infection with subsequent cellular death, potentially depending also on systemic inflammation [50]. Inflammatory cytokines from activated leukocytes, such as interleukin 1 (IL1) and tumor necrosis factor α (TNFα), bind specific receptors on ECs' surface, thus enhancing the expression of a number of mediators, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, P-selectin, fibrinogen and von Willebrand factor (vWF) [51,52]. This results in platelet activation as well as leukocyte adherence and extravasation [52][53][54].…”

Section: Physiopathology Of Endothelial Dysfunction In Covid-19mentioning

confidence: 99%

Clinical Assessment of Endothelial Function in Convalescent COVID-19 Patients Undergoing Multidisciplinary Pulmonary Rehabilitation

et al. 2021

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Background: Growing evidence points to a key role of endothelial dysfunction in the pathogenesis of COVID-19. In this study, we evaluated changes in endothelium-dependent flow-mediated dilation (FMD) in a cohort of convalescent COVID-19 patients undergoing pulmonary rehabilitation (PR). Methods: After swab test negativization, convalescent COVID-19 patients referring to a post-acute care facility for PR were consecutively screened for inclusion. Study procedures were performed at the time of hospitalization and discharge. Results: We enrolled 82 convalescent COVID-19 patients (85.4% males, mean age 60.4 years). After PR, a significant improvement in most pulmonary function tests and exercise capacity was documented. FMD changed from 2.48% ± 2.01 to 4.24% ± 2.81 (p < 0.001), corresponding to a 70.9% increase. Significantly higher changes in FMD were found in patients without a history of vascular events as compared to those with (+2.04% ± 2.30 vs. +0.61% ± 1.83, p = 0.013). Values of forced expiratory volume in 1 s (FEV1%), forced vital capacity (FVC%) and diffusion capacity for carbon monoxide (DLCO%) significantly and directly correlated with FMD both at baseline and after PR. Patients with normal FEV1% (≥80% predicted) during the overall study period or those normalizing FEV1% after PR showed a more significant FMD change as compared to patients with persistently impaired FEV1% (<80% predicted) (p for trend = 0.029). This finding was confirmed in a multivariate analysis. Conclusions: Clinically evaluated endothelial function improves after PR in convalescent COVID-19 patients. A direct and persistent association between the severity of pulmonary and vascular disease can be hypothesized. Endothelial function testing may be useful in the follow-up of convalescent COVID-19 patients.

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Section: Physiopathology Of Endothelial Dysfunction In Covid-19mentioning

confidence: 99%

Clinical Assessment of Endothelial Function in Convalescent COVID-19 Patients Undergoing Multidisciplinary Pulmonary Rehabilitation

et al. 2021

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“…Endothelial damage in COVID-19 is mediated by the activation of the inflammatory response, triggering an abnormal increase in pro-inflammatory cytokines (interleukin (IL) IL-1β, IL-6, IL-8, and tumour necrosis factor (TNF)-α), which alters the blood coagulation factors (D-dimer, von Willebrand factor (VWF), fibrinogen) leading to venous thrombosis, systemic vasculitis, endothelial cell apoptosis, vascular coagulopathy, and inflammation in various organs resulting in multi-organ failure [ 41 , 42 , 43 ]. The pre-existing endothelial damage in COVID-19 patients may act as an important risk factor for mucormycosis.…”

Section: Host and Iatrogenic Factors In The Pathogenesis Of Cammentioning

confidence: 99%

Connecting the Dots: Interplay of Pathogenic Mechanisms between COVID-19 Disease and Mucormycosis

Prakash

Skiada

Paul

et al. 2021

JoF

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Coronavirus disease (COVID-19)-associated mucormycosis (CAM) is an emerging threat globally, especially in India. More than 40,000 CAM cases have been reported in India. The emergence of CAM cases in India has been attributed to environmental, host, and iatrogenic factors. Mucorales spore burden has been reported globally; however, their presence is higher in tropical countries such as India, contributing to the emergence of CAM. Before the COVID-19 pandemic, patients with diabetes mellitus, haematological malignancies, solid organ transplants, corticosteroid therapy and neutropenia were more prone to mucormycosis, whereas in COVID-19 patients, virus-induced endothelial dysfunction, hyperglycaemia, and immune dysfunction following corticosteroid use increase the risk of acquiring mucormycosis. The interaction of Mucorales spores with the epithelial cells, followed by endothelial invasion, is a crucial step in the pathogenesis of mucormycosis. Endothelial damage and increased endothelial receptor expression induced by COVID-19 infection may predispose patients to CAM. COVID-19 infection may directly induce hyperglycaemia by damaging beta cells of the pancreas or by corticosteroid therapy, which may contribute to CAM pathogenesis. Iron acquisition from the host, especially in diabetic ketoacidosis (DKA) or deferoxamine therapy, is an important virulence trait of Mucorales. Similarly, the hyperferritinaemia caused by COVID-19 may act as a source of iron for Mucorales growth and invasion. In addition, corticosteroid treatment reduces or abolishes the innate immune functions of phagocytic cells contributing to the pathogenesis of CAM. This review aims to discuss primarily the host and iatrogenic factors shared between COVID-19 and mucormycosis that could explain the emergence of CAM.

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“… 32 , 33 ACE2 is expressed in various human organs including oral and nasal epithelium, nasopharynx, lung, small intestine, kidney, spleen, liver, colon, brain and also the vascular endothelium. 34 However, its expression in the lungs is relatively lower when it is compared to other organs. In fact, TMPRSS2 is expressed in the human respiratory tract and thus strongly contributes to both SARS-CoV-2 spread and pathogenesis.…”

Section: Pathophysiology Of Covid-19 and Associated Thrombosismentioning

confidence: 99%

An Update on the Pathogenesis of COVID-19 and the Reportedly Rare Thrombotic Events Following Vaccination

Kantarcıoğlu

Iqbal

Walenga

et al. 2021

Clin Appl Thromb Hemost

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Today the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become a global health problem. After more than a year with the pandemic, although our knowledge has progressed on COVID-19, there are still many unknowns in virological, pathophysiological and immunological aspects. It is obvious that the most efficient solution to end this pandemic are safe and efficient vaccines. This manuscript summarizes the pathophysiological and thrombotic features of COVID-19 and the safety and efficacy of currently approved COVID-19 vaccines with an aim to clarify the recent concerns of thromboembolic events after COVID-19 vaccination. The influx of newer information is rapid, requiring periodic updates and objective assessment of the data on the pathogenesis of COVID-19 variants and the safety and efficacy of currently available vaccines.

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COVID‐19‐induced endotheliitis: emerging evidence and possible therapeutic strategies

Cited by 58 publications

References 118 publications

Clinical Assessment of Endothelial Function in Convalescent COVID-19 Patients Undergoing Multidisciplinary Pulmonary Rehabilitation

Clinical Assessment of Endothelial Function in Convalescent COVID-19 Patients Undergoing Multidisciplinary Pulmonary Rehabilitation

Connecting the Dots: Interplay of Pathogenic Mechanisms between COVID-19 Disease and Mucormycosis

An Update on the Pathogenesis of COVID-19 and the Reportedly Rare Thrombotic Events Following Vaccination

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