Abstract
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/MISC). 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.
Original language | English (US) |
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Article number | e2101708118 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 118 |
Issue number | 25 |
DOIs | |
State | Published - Jun 22 2021 |
Funding
Competing interest statement: C.R.M. is the inventor or coinventor of several UCSF Beni-off Children’s Hospital Oakland patents/patent-pending applications that include nutritional supplements, and biomarkers of cardiovascular disease related to arginine bioavailability; is an inventor of several Emory University School of Medicine patents/ patent applications, including a patent filing for nutritional therapies that target coro-naviruses; and is a consultant for Pfizer, Hoffmann-La Roche Ltd., and CSL Behring. M.B.V. is a consultant for Boehringer Ingelheim, Bristol Myers Squibb, Intercept, Eli Lilly, Novo Nordisk, and Target Pharmasolutions and has research funding from Bristol Myers Squibb and Target Pharmasolutions. J.B.O. has worked for Nestle Healthcare Nutrition, Inc. This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY). 1To whom correspondence may be addressed. Email: [email protected]. Published June 4, 2021. ACKNOWLEDGMENTS. This study was funded, in part, by NIH/National Center for Complementary and Integrative Health Grant K24AT009893 (to C.R.M.); the Wilbur and Hilda Glenn Family Foundation; a donation by Michael and Natalia Beinenson; the Woodruff Health Sciences Center Synergy Award; an Emory COVID-19-CURE award made possible by philanthropic support from the O. Wayne Rollins Foundation and the William Randolph Hearst Foundation; and the Scott Hudgens Family Foundation. Sample processing was supported by the Children’s Healthcare of Atlanta and Emory University’s Children’s Clinical and Translational Discovery Core and the Biomarkers Core.
Keywords
- Arginine
- COVID-19
- multisystem inflammatory syndrome in children
- nitric oxide
- tetrahydrobiopterin
ASJC Scopus subject areas
- General