Coronavirus Disease 2019 (COVID-19) Coronary Vascular Thrombosis

Johnson, Justin; McGuone, Declan; Xu, Mina L.; Jane‐wit, Dan; Mitchell, Richard N.; Libby, Peter; Pober, Jordan S.

doi:10.1016/j.ajpath.2021.09.004

Cited by 31 publications

(14 citation statements)

References 32 publications

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“…Recently, our group identified altered coagulation pathways in pulmonary vessels from patients with severe COVID-19 (16). While differential programming of endothelial cells may have contributed to our observations, investigations from McCracken et al (9) and Johnson et al (10) failed to observe significant replicative infection or activation of human endothelial cells by SARS-CoV-2. Our present investigation of the coronary endothelium suggests an interesting anatomic paradigm between local capillaries and larger coronary vessels in response to COVID-19.…”

Section: Discussionmentioning

confidence: 58%

“…While SARS-CoV-2 has been observed to infect the endothelial cells of mice expressing humanized ACE2 ( 8 ), subsequent translational efforts have failed to observe similar findings. Notably, McCracken et al reported a lack of ACE2 expression and replicative infection by SARS-CoV-2 in human endothelial cells ( 9 ), while more recent autopsy analysis of COVID-19 patients failed to observe coronary endothelial activation ( 10 ). Such discrepancies between pre-clinical animal models and translational results beg the question as to whether direct endothelial mechanisms exist linking COVID-19 to cardiovascular events.…”

Section: Introductionmentioning

confidence: 99%

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Spatial transcriptomic profiling of coronary endothelial cells in SARS-CoV-2 myocarditis

Margaroli

Benson²,

Gastanadui³

et al. 2023

Front. Med.

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ObjectivesOur objective was to examine coronary endothelial and myocardial programming in patients with severe COVID-19 utilizing digital spatial transcriptomics.BackgroundSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has well-established links to thrombotic and cardiovascular events. Endothelial cell infection was initially proposed to initiate vascular events; however, this paradigm has sparked growing controversy. The significance of myocardial infection also remains unclear.MethodsAutopsy-derived cardiac tissue from control (n = 4) and COVID-19 (n = 8) patients underwent spatial transcriptomic profiling to assess differential expression patterns in myocardial and coronary vascular tissue. Our approach enabled transcriptional profiling in situ with preserved anatomy and unaltered local SARS-CoV-2 expression. In so doing, we examined the paracrine effect of SARS-CoV-2 infection in cardiac tissue.ResultsWe observed heterogeneous myocardial infection that tended to colocalize with CD31 positive cells within coronary capillaries. Despite these differences, COVID-19 patients displayed a uniform and unique myocardial transcriptional profile independent of local viral burden. Segmentation of tissues directly infected with SARS-CoV-2 showed unique, pro-inflammatory expression profiles including upregulated mediators of viral antigen presentation and immune regulation. Infected cell types appeared to primarily be capillary endothelial cells as differentially expressed genes included endothelial cell markers. However, there was limited differential expression within the endothelium of larger coronary vessels.ConclusionOur results highlight altered myocardial programming during severe COVID-19 that may in part be associated with capillary endothelial cells. However, similar patterns were not observed in larger vessels, diminishing endotheliitis, and endothelial activation as key drivers of cardiovascular events during COVID-19.

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Section: Discussionmentioning

confidence: 58%

Section: Introductionmentioning

confidence: 99%

Spatial transcriptomic profiling of coronary endothelial cells in SARS-CoV-2 myocarditis

Margaroli

Benson²,

Gastanadui³

et al. 2023

Front. Med.

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“…However, this finding is not specific to COVID-19 since it has also been observed in other settings of diffuse alveolar injury [114]. Important insight was provided in a recently reported study by Johnson et al [115]. The investigators performed heart autopsies in patients who died of COVID-19 and compared those findings to a control group.…”

Section: Inflammation and Platelet Activation In Coronavirus Disease-19mentioning

confidence: 95%

Inflammatory Mediators of Platelet Activation: Focus on Atherosclerosis and COVID-19

Theofilis

Sagris

Antonopoulos

et al. 2021

IJMS

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Background: Atherosclerotic cardiovascular diseases are characterized by a dysregulated inflammatory and thrombotic state, leading to devastating complications with increased morbidity and mortality rates. Summary: In this review article, we present the available evidence regarding the impact of inflammation on platelet activation in atherosclerosis. Key messages: In the context of a dysfunctional vascular endothelium, structural alterations by means of endothelial glycocalyx thinning or functional modifications through impaired NO bioavailability and increased levels of von Willebrand factor result in platelet activation. Moreover, neutrophil-derived mediators, as well as neutrophil extracellular traps formation, have been implicated in the process of platelet activation and platelet-leukocyte aggregation. The role of pro-inflammatory cytokines is also critical since their receptors are also situated in platelets while TNF-α has also been found to induce inflammatory, metabolic, and bone marrow changes. Additionally, important progress has been made towards novel concepts of the interaction between inflammation and platelet activation, such as the toll-like receptors, myeloperoxidase, and platelet factor-4. The accumulating evidence is especially important in the era of the coronavirus disease-19 pandemic, characterized by an excessive inflammatory burden leading to thrombotic complications, partially mediated by platelet activation. Lastly, recent advances in anti-inflammatory therapies point towards an anti-thrombotic effect secondary to diminished platelet activation.

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“…Communication with dysfunctional endothelium and neutrophils are key points for neutrophil and platelet activation (Hottz et al, 2020). In fact, it has been recently shown that alterations in circulating neutrophils rather than in the endothelium, are major contributors to the increased thrombotic diathesis in the hearts of COVID-19 patients (Johnson et al, 2022).…”

Section: Alterations In the Number And Function Of Plateletsmentioning

confidence: 99%

Pathophysiology of COVID-19: Critical Role of Hemostasis

Andrade

Souza

Torres

et al. 2022

Front. Cell. Infect. Microbiol.

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The COVID-19 pandemic, caused by SARS-CoV-2, had its first cases identified in late 2019 and was considered a clinical pandemic in March 2020. In March 2022, more than 500 million people were infected and 6,2 million died as a result of this disease, increasingly associated with changes in human hemostasis, such as hypercoagulation. Numerous factors contribute to the hypercoagulable state, and endothelial dysfunction is the main one, since the activation of these cells can strongly activate platelets and the coagulation system. In addition, there is a dysregulation of the renin-angiotensin system due to the SARS-CoV-2 takeover of the angiotensin converting enzyme 2, resulting in a strong immune response that could further damage the endothelium. Thrombus formation in the pulmonary microvasculature structure in patients with COVID-19 is an important factor to determine the severity of the clinical picture and the outcome of this disease. This review describes the hemostatic changes that occur in SARS-CoV-2 infection, to further improve our understanding of pathogenic mechanisms and the interaction between endothelium dysfunction, kallikrein-kinins, renin angiotensin, and the Coagulation/fibrinolysis systems as underlying COVID-19 effectors. This knowledge is crucial for the development of new effective therapeutic approaches, attenuating the severity of SARS-CoV-2’s infection and to reduce the deaths.

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Coronavirus Disease 2019 (COVID-19) Coronary Vascular Thrombosis

Cited by 31 publications

References 32 publications

Spatial transcriptomic profiling of coronary endothelial cells in SARS-CoV-2 myocarditis

Spatial transcriptomic profiling of coronary endothelial cells in SARS-CoV-2 myocarditis

Inflammatory Mediators of Platelet Activation: Focus on Atherosclerosis and COVID-19

Pathophysiology of COVID-19: Critical Role of Hemostasis

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