Understanding COVID-19 susceptibility and presentation based on its underlying physiology

Ahmad, Shama; Matalon, Sadis; Kuebler, Wolfgang M.

doi:10.1152/physrev.00008.2022

Cited by 6 publications

(10 citation statements)

References 16 publications

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“…Our study demonstrated a novel role of DB MPs in SARS-CoV-2 infection in vascular ECs. To date, compiling evidence demonstrated viral infection-associated vascular dysfunction ( 3 , 68 , 78 , 79 ). Multiple studies have detected viral particles in vascular ECs from postmortem specimens of patients with COVID-19 ( 3 , 20 – 22 , 80 ) and a direct infection of SARS-CoV-2 in engineered human blood vessel organoids and human kidney organoids has been shown via an in vitro study ( 47 ).…”

Section: Discussionmentioning

confidence: 99%

“…To date, compiling evidence demonstrated viral infection-associated vascular dysfunction ( 3 , 68 , 78 , 79 ). Multiple studies have detected viral particles in vascular ECs from postmortem specimens of patients with COVID-19 ( 3 , 20 – 22 , 80 ) and a direct infection of SARS-CoV-2 in engineered human blood vessel organoids and human kidney organoids has been shown via an in vitro study ( 47 ). Considering the physical proximity of alveolar epithelial cells with alveolar capillary ECs that also express ACE2, it would be a rational assumption that the initial viral infection and injury at alveolar epithelial cells could easily affect the nearby ECs and propagate the viral infection to the vasculature of multiple organs.…”

Section: Discussionmentioning

confidence: 99%

“…The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has seriously affected public health worldwide, especially among patients with preexisting diseases ( 1 – 3 ). Multiple studies reported that patients with diabetes not only have a higher prevalence rate for COVID-19 but also have more severe illness and up to three times higher mortality rate when compared with patients with COVID-19 without the comorbidities ( 4 – 6 ).…”

Section: Introductionmentioning

confidence: 99%

“…Histological evidence in patients with COVID-19 has shown that SARS-CoV-2 can infect not only respiratory epithelial cells, but also vascular endothelial cells (ECs) ( 3 , 20 – 22 ). It has been suggested that microvascular dysfunction is one of the major causes of multiorgan impairment in patients with severe COVID-19 ( 68 , 78 , 79 ).…”

Section: Introductionmentioning

confidence: 99%

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Increased circulating microparticles contribute to severe infection and adverse outcomes of COVID-19 in patients with diabetes

Sun

Kumar

et al. 2022

American Journal of Physiology-Heart and Circulatory Physiology

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COVID-19 patients with diabetes have greater mortality than those without comorbidities, but the underlying mechanisms remain unknown. This study aims to identify the mechanistic interactions between diabetes and severe COVID-19. Microparticles (MPs), the cell membrane-derived vesicles released upon cell activation, are largely increased in diabetic patients. To date, many mechanisms have been postulated for increased severity of COVID-19 in patients with underlying conditions, but the contributions of excessive MPs in diabetic patients have been overlooked. This study characterizes plasma MPs from normal and type 2 diabetic human subjects in terms of amount, cell origins, surface adhesive properties, ACE2 expression, spike protein binding capacity, and their roles in SARS-CoV-2 infection. Results showed that over 90% of plasma MPs express ACE2 that binds the spike protein of SARS-CoV-2. MPs in diabetic patients increase 13-fold in quantity and 11-fold adhesiveness when compared with normal subjects. Perfusion of human plasma with pseudotyped SARS-CoV-2 virus or spike protein-bound MPs into human endothelial cells-formed microvessels-on-a chip demonstrated that MPs from diabetic patients, not normal subjects, interact with endothelium and carry SARS-CoV-2 into cells through endocytosis, providing additional virus entry pathways and enhanced infection. Results also showed a large percentage of platelet-derived tissue factor-bearing MPs in diabetic plasma, which could contribute to thrombotic complications with SARS-CoV-2 infection. This study reveals a dual role of diabetic MPs in promoting SARS-CoV-2 entry and propagating vascular inflammation. These findings provide novel mechanistic insight into the high prevalence of COVID-19 in diabetic patients and their propensity to develop severe vascular complications.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Increased circulating microparticles contribute to severe infection and adverse outcomes of COVID-19 in patients with diabetes

Sun

Kumar

et al. 2022

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…Age, diabetes, hypertension, and obesity in patients infected with SARS-CoV-2 have been identified as predictors of bad outcome ( 30 – 32 ). It may be speculated that endothelial cell dysfunction and the low-grade inflammation of obesity prime the pulmonary endothelium for injury and failure in the COVID-19 scenario.…”

Section: Conceptual Barriersmentioning

confidence: 99%

ARDS in the time of corona: context and perspective

Voelkel

Bogaard

Kuebler

2022

American Journal of Physiology-Lung Cellular and Molecular Phys

Self Cite

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For more than two years, Covid-19 has been holding the world at awe with new waves of infections, novel mutants, and still limited (albeit improved) means to combat SARS-CoV-2 induced respiratory failure, the most common and fatal presentation of severe Covid-19. In the present perspective, we draw from the successes and - mostly - failures in previous ARDS work and the experiences from Covid-19 to define conceptual barriers that have so far hindered therapeutic breakthroughs in this deadly disease, and to open up new avenues of thinking and thus, ultimately of therapy.

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Can alpha‐linolenic acid be a modulator of “cytokine storm,” oxidative stress and immune response in SARS‐CoV‐2 infection?

Cianciosi,

Diaz,

Gaddi

et al. 2023

Food Frontiers

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Alpha‐linolenic acid (ALA) is a long‐chain polyunsaturated essential fatty acid of the Ω3 series found mainly in vegetables, especially in the fatty part of oilseeds, dried fruit, berries, and legumes. It is very popular for its preventive use in several diseases: It seems to reduce the risk of the onset or decrease some phenomena related to inflammation, oxidative stress, and conditions of dysregulation of the immune response. Recent studies have confirmed these unhealthy situations also in patients with severe coronavirus disease 2019 (COVID‐19). Different findings (in vitro, in vivo, and clinical ones), summarized and analyzed in this review, have showed an important role of ALA in other various non‐COVID physiological and pathological situations against “cytokines storm,” chemokines secretion, oxidative stress, and dysregulation of immune cells that are also involved in the infection of the 2019 novel coronavirus. According to the effects of ALA against all the aforementioned situations (also present in patients with a severe clinical picture of severe acute respiratory syndrome‐(CoV‐2) infection), there may be the biologic plausibility of a prophylactic effect of this compound against COVID‐19 symptoms and fatality.

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Understanding COVID-19 susceptibility and presentation based on its underlying physiology

Cited by 6 publications

References 16 publications

Increased circulating microparticles contribute to severe infection and adverse outcomes of COVID-19 in patients with diabetes

Increased circulating microparticles contribute to severe infection and adverse outcomes of COVID-19 in patients with diabetes

ARDS in the time of corona: context and perspective

Can alpha‐linolenic acid be a modulator of “cytokine storm,” oxidative stress and immune response in SARS‐CoV‐2 infection?

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