{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:46:46Z","timestamp":1790750806530,"version":"4.1.0"},"reference-count":15,"publisher":"National Academy of Sciences","issue":"25","license":[{"start":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T00:00:00Z","timestamp":1622764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008460","name":"HHS | NIH | National Center for Complementary and Integrative Health","doi-asserted-by":"publisher","award":["K24AT009893"],"award-info":[{"award-number":["K24AT009893"]}],"id":[{"id":"10.13039\/100008460","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001136","name":"Glenn Family Foundation","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100001136","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002411","name":"Woodruff Foundation","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100002411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2021,6,22]]},"abstract":"<jats:p>\n                    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 &lt;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\u2019s\n                    <jats:italic>t<\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2101708118","type":"journal-article","created":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T16:22:32Z","timestamp":1622823752000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":100,"title":["Altered amino acid profile in patients with SARS-CoV-2 infection"],"prefix":"10.1073","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6449-0377","authenticated-orcid":false,"given":"Chris A.","family":"Rees","sequence":"first","affiliation":[{"name":"Division of Pediatric Emergency Medicine, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8439-0592","authenticated-orcid":false,"given":"Christina A.","family":"Rostad","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322;"},{"name":"Children\u2019s Healthcare of Atlanta, Atlanta, GA 30329;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Mantus","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan J.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322;"},{"name":"Children\u2019s Healthcare of Atlanta, Atlanta, GA 30329;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Chahroudi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322;"},{"name":"Children\u2019s Healthcare of Atlanta, Atlanta, GA 30329;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Preeti","family":"Jaggi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322;"},{"name":"Children\u2019s Healthcare of Atlanta, Atlanta, GA 30329;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Wrammert","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6008-3958","authenticated-orcid":false,"given":"Juan B.","family":"Ochoa","sequence":"additional","affiliation":[{"name":"Department of Pulmonary\/Critical Care, Hunterdon Medical Center, Milford, NJ 08848;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augusto","family":"Ochoa","sequence":"additional","affiliation":[{"name":"Stanley S. Scott Cancer Center, Louisiana State University Health, New Orleans, LA 70112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3184-341X","authenticated-orcid":false,"given":"Rajit K.","family":"Basu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322;"},{"name":"Children\u2019s Healthcare of Atlanta, Atlanta, GA 30329;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0214-4262","authenticated-orcid":false,"given":"Stacy","family":"Heilman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8697-7186","authenticated-orcid":false,"given":"Frank","family":"Harris","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6887-7322","authenticated-orcid":false,"given":"Stacey A.","family":"Lapp","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322;"},{"name":"Children\u2019s Healthcare of Atlanta, Atlanta, GA 30329;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laila","family":"Hussaini","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322;"},{"name":"Children\u2019s Healthcare of Atlanta, Atlanta, GA 30329;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam B.","family":"Vos","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322;"},{"name":"Children\u2019s Healthcare of Atlanta, Atlanta, GA 30329;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9745-0619","authenticated-orcid":false,"given":"Lou Ann","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6019-2858","authenticated-orcid":false,"given":"Claudia R.","family":"Morris","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322;"},{"name":"Children\u2019s Healthcare of Atlanta, Atlanta, GA 30329;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2021,6,4]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0311-8"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020003471"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines8080277"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00608.x"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1177\/0884533617691250"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-020-00920-5"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.294.1.81"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2020.10.100"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpsy.2020.10.004"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21228623"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200309-1304OC"},{"key":"e_1_3_4_12_2","unstructured":"Center for Disease Control and Prevention Information for healthcare providers about multisystem inflammatory syndrome in children (MIS-C). https:\/\/www.cdc.gov\/mis-c\/hcp\/. Accessed 15 December 2020."},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2015.00046"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-04-081703"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-244X-5-6"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.2101708118","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2101708118","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T07:31:51Z","timestamp":1649835111000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.2101708118"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,4]]},"references-count":15,"journal-issue":{"issue":"25","published-print":{"date-parts":[[2021,6,22]]}},"alternative-id":["10.1073\/pnas.2101708118"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2101708118","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,4]]},"assertion":[{"value":"2021-06-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2101708118"}}