Altered amino acid profile in patients with SARS-CoV-2 infection

Low plasma arginine bioavailability has been implicated in endothelial dysfunction and immune dysregulation. The role of arginine in COVID-19 is unknown, but could contribute to cellular damage if low. Our objective was to determine arginine bioavailability in adults and children with COVID-19 vs. healthy controls. We hypothesized that arginine bioavailability would be low in patients with COVID-19 and multisystem inflammatory syndrome in children (MIS-C). We conducted a prospective observational study of three patient cohorts; arginine bioavailability was determined in asymptomatic healthy controls, adults hospitalized with COVID-19, and hospitalized children/adolescents <21 y old with COVID-19, MIS-C, or asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection identified on admission screen. Mean patient plasma amino acids were compared to controls using the Student’s t test. Arginine-to-ornithine ratio, a biomarker of arginase activity, and global arginine bioavailability ratio (GABR, arginine/[ornithine+citrulline]) were assessed in all three groups. A total of 80 patients were included (28 controls, 32 adults with COVID-19, and 20 pediatric patients with COVID-19/MIS-C). Mean plasma arginine and arginine bioavailability ratios were lower among adult and pediatric patients with COVID-19/MIS-C compared to controls. There was no difference between arginine bioavailability in children with COVID-19 vs. MIS-C. Adults and children with COVID-19 and MIS-C in our cohort had low arginine bioavailability compared to healthy adult controls. This may contribute to immune dysregulation and endothelial dysfunction in COVID-19. Low arginine-to-ornithine ratio in patients with COVID-19 or MIS-C suggests an elevation of arginase activity. Further study is merited to explore the role of arginine dysregulation in COVID-19.

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Abstract 3636: The Effects of Arginase II Overexpression on Endothelial Function in Transgenic Mouse Model

Circulation ◽

10.1161/circ.118.suppl_18.s_455-c ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Boris L Vaisman ◽

Katherine C Wood ◽

Stephen J Demosky ◽

Catherine L Knapper ◽

Jaye Chin-Dusting ◽

...

Keyword(s):

Nitric Oxide ◽

Endothelial Dysfunction ◽

Transgenic Mice ◽

Endothelial Function ◽

Transgenic Mouse ◽

Plasma Lipid ◽

Aortic Ring ◽

Normal Function ◽

Arginase Activity

Endothelium is a major regulator of local vascular homeostasis. Its normal function is crucial for prevention of the development of atherosclerosis, hypertension and other cardiovascular disorders. Reduced nitric oxide (NO) bioavailability is one of the earliest and most important markers of endothelial dysfunction. L-arginine is the substrate for nitric oxide synthases (NOS). Arginase (Arg) can compete with eNOS for L-arginine and thus may play a role in endothelial dysfunction. To further investigate the role of ArgII in endothelial function and in atherosclerosis we generated transgenic mice with human ArgII (hArgII) gene under control of endothelial-specific Tie2 promoter. Expression of hArgII was measured by RT-PCR in eight tissues of transgenic males and compared with the level of mouse ArgII (mArgII) expression in kidneys of normal C57Bl mice, which was taken as 100%. hArgII was expressed at very high levels in all tissues, especially in aorta (2700%), heart (3500%), kidney (1600%), lung (9860%) and muscle (2000%). Arginase activity was elevated 4.6 – 62 fold in all tissues except liver. Lung endothelial cells isolated from hArgII transgenic mice had 4.4-fold greater of arginase activity than whole lung. Resident peritoneal macrophages from hArgII transgenic and normal mice had similar levels of arginase activity, confirming endothelial specificity of the Tie2 promoter. Overexpression of hArgII neither led to significant changes in plasma level of arginine, citrulline, NOHA, ADMA, SDMA and ornithine, nor to changes in plasma lipid levels. However, ArgII overexpression on apoE-knockout background was accompanied by a 10% increase in plasma total cholesterol (p<0.05). hArgII transgenic mice also had blood pressure (mean arterial and diastolic) that averaged 17% higher than controls. Aortic ring segments from hArgII transgenic mice, precontracted with phenylephrine (10 −6 M), exhibited decreased endothelium-dependent relaxation to increasing concentrations of acetylcholine (10 −9 to 10 −3.5 M), indicating endothelial dysfunction secondary to NO insufficiency. These results show that the Tie2hArgII transgenic mouse is a new model for investigating the role of ArgII in endothelial function and in atherosclerosis.

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Update on endothelial dysfunction in COVID-19: severe disease, long COVID-19 and pediatric characteristics

Journal of Laboratory Medicine ◽

10.1515/labmed-2021-0134 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Eleni Gavriilaki ◽

Ioannis Eftychidis ◽

Ioannis Papassotiriou

Keyword(s):

Endothelial Dysfunction ◽

Severe Disease ◽

Current Data ◽

Common Denominator ◽

Medline Search ◽

Previous Decade ◽

Adults And Children ◽

Improve Patient Management ◽

Improve Patient

Abstract Objectives To review current literature on the role of endothelial dysfunction in coronavirus disease-2019 (COVID-19) infection in terms of pathophysiology, laboratory features and markers, clinical phenotype in adults and children, as well as long COVID-19. Content We conducted a thorough assessment of the literature and critically analyzed current data, mostly utilizing the PubMed and Medline search engines to find original studies published in the previous decade. Summary and Outlook Accumulating evidence suggests that endothelial dysfunction may be a common denominator of severe COVID-19 in adults and children, as well as long COVID-19, implicating mutual pathophysiological pathways. This narrative review summarizes the up-to-date knowledge of endothelial dysfunction caused by COVID-19, including novel aspects of long COVID-19 and pediatric disease. This knowledge is important in order not only to understand the multisystemic attack of COVID-19, but also to improve patient management and prognosis.

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