4.8 Article

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

Publisher

NATL ACAD SCIENCES
DOI: 10.1073/pnas.2101708118

Keywords

arginine; nitric oxide; multisystem inflammatory syndrome in children; tetrahydrobiopterin; COVID-19

Funding

  1. NIH/National Center for Complementary and Integrative Health [K24AT009893]
  2. Wilbur and Hilda Glenn Family Foundation
  3. Woodruff Health Sciences Center Synergy Award
  4. O. Wayne Rollins Foundation
  5. William Randolph Hearst Foundation
  6. Scott Hudgens Family Foundation

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The study found that plasma arginine bioavailability was lower in adults and children with COVID-19 compared to healthy controls, potentially contributing to immune dysregulation and endothelial dysfunction. The low arginine-to-ornithine ratio in patients with COVID-19 suggests increased arginase activity. Further research is needed to explore the role of arginine dysregulation in COVID-19.
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.

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