Increased susceptibility of human endothelial cells to infections by SARS-CoV-2 variants

Wagner, Jasmin; Bojkova, Denisa; Shumliakivska, Mariana; Luxán, Guillermo; Nicin, Luka; Aslan, Galip Servet; Milting, Hendrik; Kandler, Joshua D.; Dendorfer, Andreas; Heumueller, Andreas W.; Fleming, Ingrid; Bibli, Sofia-Iris; Jakobi, Tobias; Dieterich, Christoph; Zeiher, Andreas M.; Ciesek, Sandra; Cinatl, Jindrich; Dimmeler, Stefanie

doi:10.1007/s00395-021-00882-8

Cited by 38 publications

(40 citation statements)

References 35 publications

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“…The latter cell type has been the focus of numerous studies given the mounting evidence for SARS-CoV-2-induced endotheliopathy, considered an important contributor to the pathogenesis of COVID-19 (Goshua et al 2020 ). The undetectable levels of ACE2 protein in human endothelial cells shown here is consistent with a recent report that failed to detect ACE2 mRNA in several human endothelial cell types (McCracken et al 2021 ), but inconsistent with other reports (Hamming et al 2004 ; Targosz-Korecka et al 2021 ; Wagner et al 2021 ). These disparate findings highlight the ongoing controversy over whether endothelial cells are prone to SARS-CoV-2 infection (Goldsmith et al 2020 ; McCracken et al 2021 ; Targosz-Korecka et al 2021 ; Varga et al 2020 ; Wagner et al 2021 ).…”

Section: An Ace2 -Lncrna Gene Pair and Development Of A New Mouse Model For Covid-19supporting

confidence: 84%

Of mice and human-specific long noncoding RNAs

2022

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The number of human LncRNAs has now exceeded all known protein-coding genes. Most studies of human LncRNAs have been conducted in cell culture systems where various mechanisms of action have been worked out. On the other hand, efforts to elucidate the function of human LncRNAs in an in vivo setting have been limited. In this brief review, we highlight some strengths and weaknesses of studying human LncRNAs in the mouse. Special consideration is given to bacterial artificial chromosome transgenesis and genome editing. The integration of these technical innovations offers an unprecedented opportunity to complement and extend the expansive literature of cell culture models for the study of human LncRNAs. Two different examples of how BAC transgenesis and genome editing can be leveraged to gain insight into human LncRNA regulation and function in mice are presented: the random integration of a vascular cell-enriched LncRNA and a targeted approach for a new LncRNA immediately upstream of the ACE2 gene, which encodes the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent underlying the coronavirus disease-19 (COVID-19) pandemic.

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Section: An Ace2 -Lncrna Gene Pair and Development Of A New Mouse Model For Covid-19supporting

confidence: 84%

Of mice and human-specific long noncoding RNAs

2022

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“…These HUVECs and HMVES-L cells expressed very low levels of ACE2 and TMPRSS2 and did not show any morphological changes upon virus exposure to their apical or basal surface. In agreement, Wagner and colleagues [158] could not demonstrate a productive SARS-CoV-2 infection of endothelial cell models established from the vasculature of diverse tissues, irrespective of the SARS-CoV-2 variant used for infection. Virus uptake occurred, but viral replication was not supported.…”

Section: Vasculaturementioning

confidence: 53%

Organoid Models of SARS-CoV-2 Infection: What Have We Learned about COVID-19?

et al. 2022

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which was classified as a pandemic in March 2020. As of 22 January 2022, globally more than 347 million cases of COVID-19 have been diagnosed, with 5.6 million deaths, making it the deadliest pandemic since the influenza pandemic in 1918. The clinical presentation of COVID-19-related illness spans from asymptomatic to mild respiratory symptoms akin to influenza infection to acute symptoms, including pneumonia necessitating hospitalisation and admission to intensive care units. COVID-19 starts in the upper respiratory tract and lungs but in severe cases can also involve the heart, blood vessels, brain, liver, kidneys and intestine. The increasing global health and economic burden of COVID-19 necessitates an urgent and global response. Understanding the functional characteristics and cellular tropism of SARS-CoV-2, and the pathogenesis that leads to multi-organ failure and death, has prompted an unprecedented adoption of organoid models. Successful drug discovery and vaccine development rely on pre-clinical models that faithfully recapitulate the viral life cycle and the host cell response to infection. Human stem cell-derived organoids fulfill these criteria. Here we highlight the role of organoids in the study of SARS-CoV-2 infection and modelling of COVID-19 pathogenesis.

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“…For instance, endothelial cell types such as umbilical vein endothelial cells (HUVECs), blood outgrowth and aortic endothelial cells, as well as lung-, brain-, cardiac- and glomerular microvascular endothelial cells, were subjected to viral infection, however, none of these cell were susceptible to direct infection by SARS-CoV-2 ( Nascimento Conde et al, 2020 ; Ahmetaj-Shala et al, 2020 ). Others showed marginal viral replication in coronary artery endothelial cells after 5 days of infection ( Wagner et al, 2021 ). Moreover, in an established human blood-brain barrier model where CD34 + umbilical cord blood-derived endothelial cells were grown on filter inserts in co-culture with bovine pericytes, no productive infection of endothelial cells was detected.…”

Section: Covid-19 and Vascular Cellsmentioning

confidence: 99%

COVID-19 and the Vasculature: Current Aspects and Long-Term Consequences

Martínez-Salazar

Holwerda

Stüdle

et al. 2022

Front. Cell Dev. Biol.

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Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was first identified in December 2019 as a novel respiratory pathogen and is the causative agent of Corona Virus disease 2019 (COVID-19). Early on during this pandemic, it became apparent that SARS-CoV-2 was not only restricted to infecting the respiratory tract, but the virus was also found in other tissues, including the vasculature. Individuals with underlying pre-existing co-morbidities like diabetes and hypertension have been more prone to develop severe illness and fatal outcomes during COVID-19. In addition, critical clinical observations made in COVID-19 patients include hypercoagulation, cardiomyopathy, heart arrythmia, and endothelial dysfunction, which are indicative for an involvement of the vasculature in COVID-19 pathology. Hence, this review summarizes the impact of SARS-CoV-2 infection on the vasculature and details how the virus promotes (chronic) vascular inflammation. We provide a general overview of SARS-CoV-2, its entry determinant Angiotensin-Converting Enzyme II (ACE2) and the detection of the SARS-CoV-2 in extrapulmonary tissue. Further, we describe the relation between COVID-19 and cardiovascular diseases (CVD) and their impact on the heart and vasculature. Clinical findings on endothelial changes during COVID-19 are reviewed in detail and recent evidence from in vitro studies on the susceptibility of endothelial cells to SARS-CoV-2 infection is discussed. We conclude with current notions on the contribution of cardiovascular events to long term consequences of COVID-19, also known as “Long-COVID-syndrome”. Altogether, our review provides a detailed overview of the current perspectives of COVID-19 and its influence on the vasculature.

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Increased susceptibility of human endothelial cells to infections by SARS-CoV-2 variants

Cited by 38 publications

References 35 publications

Of mice and human-specific long noncoding RNAs

Of mice and human-specific long noncoding RNAs

Organoid Models of SARS-CoV-2 Infection: What Have We Learned about COVID-19?

COVID-19 and the Vasculature: Current Aspects and Long-Term Consequences

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