Endothelial cells are not productively infected by SARS‐CoV‐2

Schimmel, Lilian; Chew, Keng Yih; Stocks, Claudia J.; Yordanov, Teodor E; Essebier, Patricia; Kulasinghe, Arutha; Monkman, James; Miggiolaro, Anna Flavia Ribeiro Santos; Cooper, Caroline; Noronha, Lúcia de; Schroder, Kate; Lagendijk, Anne Karine; Labzin, Larisa I.; Short, Kirsty R.; Gordon, Emma

doi:10.1002/cti2.1350

Cited by 109 publications

(115 citation statements)

References 76 publications

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“…Nonetheless, the extent to which the direct infection of endothelial cells by SARS-CoV-2 contributes to vascular involvement in COVID-19 remains to be determined and may indeed be organ and tissue dependent. In vitro cultures of primary human umbilical vein endothelial cells (HUVECs) and human microvascular endothelial cells from the lung (HMVEC-L) did not support SARS-CoV-2 infection [157]. 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.…”

Section: Vasculaturementioning

confidence: 96%

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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Section: Vasculaturementioning

confidence: 96%

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

et al. 2022

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“…For instance, transwell filter systems allow for initiation of the viral infection via different compartments, namely apical and basolateral. The study of Schimmel et al (2021) showed that the virus cannot actively replicate in umbilical cord and microvascular endothelial cells, but SARS-CoV-2 is able to enter the cell via either the apical or basolateral side ( Schimmel et al, 2021 ). Moreover, a pro-inflammatory response of the cells was observed, indicative of an interaction of the virus with the cells.…”

Section: Covid-19 and Vascular Cellsmentioning

confidence: 99%

“…In addition, the endothelial cells are exposed to shear stress in vivo , and therefore employing microfluidic devices is a potentially interesting technique mimicking the natural vascular environment. Endothelial cells that were seeded in a polydimethylsiloxane (PDMS) channel containing a collagen hydrogel were infected under flow, but also this method did not allow for viral replication of SARS-CoV-2 in the endothelial cells ( Schimmel et al, 2021 ). This is an interesting finding since it has been described that shear stress could upregulate ACE2 expression in brain microvascular endothelial cells, thereby allowing for attachment of the S protein, as shown in ( Kaneko et al, 2021 ) Figure 3 .…”

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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“…S3a). SARS-CoV-2 is able to infect human blood vessel organoids and ECs in vitro without undergoing viral replication and induces a clear proinflammatory response [ 17 ]. Therefore, we were able to demonstrate that in ECs, ERK1/2 activity in response to 40 ng/ml RBD increased gradually up to ~ 30% after 24 h (Fig.…”

Section: Resultsmentioning

confidence: 99%

Carbon dioxide inhibits COVID-19-type proinflammatory responses through extracellular signal-regulated kinases 1 and 2, novel carbon dioxide sensors

Gałgańska

Jarmuszkiewicz

Gałgański

2021

Cell. Mol. Life Sci.

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Mitogen-activated protein kinase (MAPK) signalling pathways are crucial for developmental processes, oncogenesis, and inflammation, including the production of proinflammatory cytokines caused by reactive oxygen species and upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. There are no drugs that can effectively prevent excessive inflammatory responses in endothelial cells in the lungs, heart, brain, and kidneys, which are considered the main causes of severe coronavirus disease 2019 (COVID-19). In this work, we demonstrate that human MAPKs, i.e. extracellular signal-regulated kinases 1 and 2 (ERK1/2), are CO2 sensors and CO2 is an efficient anti-inflammatory compound that exerts its effects through inactivating ERK1/2 in cultured endothelial cells when the CO2 concentration is elevated. CO2 is a potent inhibitor of cellular proinflammatory responses caused by H2O2 or the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2. ERK1/2 activated by the combined action of RBD and cytokines crucial for the development of severe COVID-19, i.e. interferon-gamma (IFNγ) and tumour necrosis factor-α (TNFα), are more effectively inactivated by CO2 than by dexamethasone or acetylsalicylic acid in human bronchial epithelial cells. Previously, many preclinical and clinical studies showed that the transient application of 5–8% CO2 is safe and effective in the treatment of many diseases. Therefore, our research indicates that CO2 may be used for the treatment of COVID-19 as well as the modification of hundreds of cellular pathways.

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Endothelial cells are not productively infected by SARS‐CoV‐2

Cited by 109 publications

References 76 publications

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

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

Carbon dioxide inhibits COVID-19-type proinflammatory responses through extracellular signal-regulated kinases 1 and 2, novel carbon dioxide sensors

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