SARS-CoV-2: characteristics and current advances in research

Yang, Yicheng; Xiao, Zhiqiang; Ye, Kaiyan; He, Xiaoying; Sun, Bo; Qin, Zhiran; Yu, Jianghai; Yao, Jinxiu; Wu, Qinghua; Bao, Zhenmin; Zhao, Wei

doi:10.1186/s12985-020-01369-z

Cited by 121 publications

(108 citation statements)

References 146 publications

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“…As would be expected, COVID-19 infection elicits activation of the innate and adaptive immune systems, and in a majority of cases their combined actions result in disease resolution [49][50][51][52][53]. In patients with more severe COVID-19 disease, those displaying ARDS and pneumonia, clinical findings indicate that multiple aspects of the innate and adaptive immune systems are compromised or dysregulated [50,51,53].…”

Section: Anti-inflammatory Effects Of At 2 R Activationmentioning

confidence: 73%

“…The resulting chronic pro-inflammatory milieu, termed as a 'cytokine storm' , is likely responsible for the uncontrolled inflammation within the lungs, heart, vascular endothelium and kidney, and recruitment of immune cells (macrophages, neutrophils, T cells) to these sites [7,55]. The subsequent release of pro-inflammatory cytokines from these cells and generation of reactive oxygen species results in endothelial cell and tissue damage [8,51,56].…”

Section: Anti-inflammatory Effects Of At 2 R Activationmentioning

confidence: 99%

“…In general, initial COVID-19 infection will result in activation of the innate immune system, including monocytes, macrophages, dendritic cells and the complement system [50,51,53]. Human monocytes, macrophages and dendritic cells contain AT 2 R [75][76][77] and a number of studies indicate that activation of this angiotensin receptor subtype interferes with certain aspects of the innate immune system response.…”

Section: Innate Immune Systemmentioning

confidence: 99%

“…COVID-19 infection also results in activation of the adaptive immune system, albeit over a more delayed time frame [50,51,53]. T helper (CD4 + ) and cytotoxic (CD8 + ) T cells are central to the adaptive immune response [86].…”

Section: Adaptive Immune Systemmentioning

confidence: 99%

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Correcting the imbalanced protective RAS in COVID-19 with angiotensin AT2-receptor agonists

Steckelings

Sumners

2020

Clinical Science

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that is responsible for the global corona virus disease 2019 (COVID-19) pandemic enters host cells via a mechanism that includes binding to angiotensin converting enzyme (ACE) 2 (ACE2). Membrane-bound ACE2 is depleted as a result of this entry mechanism. The consequence is that the protective renin–angiotensin system (RAS), of which ACE2 is an essential component, is compromised through lack of production of the protective peptides angiotensin-(1-7) and angiotensin-(1-9), and therefore decreased stimulation of Mas (receptor Mas) and angiotensin AT2-receptors (AT2Rs), while angiotensin AT1-receptors (AT1Rs) are overstimulated due to less degradation of angiotensin II (Ang II) by ACE2. The protective RAS has numerous beneficial actions, including anti-inflammatory, anti-coagulative, anti-fibrotic effects along with endothelial and neural protection; opposite to the deleterious effects caused by heightened stimulation of angiotensin AT1R. Given that patients with severe COVID-19 exhibit an excessive immune response, endothelial dysfunction, increased clotting, thromboses and stroke, enhancing the activity of the protective RAS is likely beneficial. In this article, we discuss the evidence for a dysfunctional protective RAS in COVID and develop a rationale that the protective RAS imbalance in COVID-19 may be corrected by using AT2R agonists. We further review preclinical studies with AT2R agonists which suggest that AT2R stimulation may be therapeutically effective to treat COVID-19-induced disorders of various organ systems such as lung, vasculature, or the brain. Finally, we provide information on the design of a clinical trial in which patients with COVID-19 were treated with the AT2R agonist Compound 21 (C21). This trial has been completed, but results have not yet been reported.

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Section: Anti-inflammatory Effects Of At 2 R Activationmentioning

confidence: 73%

Section: Anti-inflammatory Effects Of At 2 R Activationmentioning

confidence: 99%

Section: Innate Immune Systemmentioning

confidence: 99%

Section: Adaptive Immune Systemmentioning

confidence: 99%

See 2 more Smart Citations

Correcting the imbalanced protective RAS in COVID-19 with angiotensin AT2-receptor agonists

Steckelings

Sumners

2020

Clinical Science

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“…Patients most commonly present with fever, cough, fatigue, and dyspnea [6–9]. About one out of five patients develops severe disease [10,11]. The outbreak was declared a “public health emergency of international concern” on January 30, 2020, and a pandemic on March 11, 2020.…”

Section: Introductionmentioning

confidence: 99%

3D reconstruction of SARS-CoV-2 infection in ferrets emphasizes focal infection pattern in the upper respiratory tract

Zaeck

Scheibner

Sehl

et al. 2020

Preprint

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The visualization of viral pathogens in infected tissues is an invaluable tool to understand spatial virus distribution, localization, and cell tropism in vivo. Commonly, virus-infected tissues are analyzed using conventional immunohistochemistry in paraffin-embedded thin sections. Here, we demonstrate the utility of volumetric three-dimensional (3D) immunofluorescence imaging using tissue optical clearing and light sheet microscopy to investigate host-pathogen interactions of pandemic SARS-CoV-2 in ferrets at a mesoscopic scale. The superior spatial context of large, intact samples (> 150 mm3) allowed detailed quantification of interrelated parameters like focus-to-focus distance or SARS-CoV-2-infected area, facilitating an in-depth description of SARS-CoV-2 infection foci. Accordingly, we could confirm a preferential infection of the ferret upper respiratory tract by SARS-CoV-2 and emphasize a distinct focal infection pattern in nasal turbinates. Conclusively, we present a proof-of-concept study for investigating critically important respiratory pathogens in their spatial tissue morphology and demonstrate the first specific 3D visualization of SARS-CoV-2 infection.

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