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

Chris A. Rees, Christina A. Rostad, Grace Mantus, Evan J. Anderson, Ann Chahroudi, Preeti Jaggi, Jens Wrammert, Juan B. Ochoa, Augusto Ochoa, Rajit K. Basu, Stacy Heilman, Frank Harris, Stacey A. Lapp, Laila Hussaini, Miriam B. Vos, Lou Ann Brown, Claudia R. Morris*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


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 languageEnglish (US)
Article numbere2101708118
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number25
StatePublished - Jun 22 2021


  • Arginine
  • COVID-19
  • multisystem inflammatory syndrome in children
  • nitric oxide
  • tetrahydrobiopterin

ASJC Scopus subject areas

  • General


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