{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:29:17Z","timestamp":1790803757781,"version":"4.1.0"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":783,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005294","name":"Massachusetts General Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005294","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014468","name":"Mallinckrodt Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014468","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the NIH","doi-asserted-by":"publisher","award":["UM1AI069412"],"award-info":[{"award-number":["UM1AI069412"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008333","name":"University of Alabama at Birmingham","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008333","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005615","name":"Beth Israel Deaconess Medical Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005615","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010932","name":"Louisiana State University Shreveport","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010932","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Danderyd Hospital"},{"DOI":"10.13039\/100027152","name":"Linde plc","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100027152","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005294","name":"Massachusetts General Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005294","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005294","name":"Mallinckrodt Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005294","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005294","name":"Foundation for the NIH","doi-asserted-by":"publisher","award":["UM1AI069412"],"award-info":[{"award-number":["UM1AI069412"]}],"id":[{"id":"10.13039\/100005294","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005294","name":"University of Alabama at Birmingham","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005294","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005294","name":"Beth Israel Deaconess Medical Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005294","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005294","name":"Louisiana State University Shreveport","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005294","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Danderyd Hospital"},{"DOI":"10.13039\/100027152","name":"Linde plc","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100027152","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>The effects of high-dose inhaled nitric oxide on hypoxemia in coronavirus disease (COVID-19) acute respiratory failure are unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>The primary outcome was the change in arterial oxygenation (PaO2\/Fi \u00a0O2) at 48 hours. The secondary outcomes included: time to reach a PaO2\/Fi \u00a0O2.300mmHg for at least 24 hours, the proportion of participants with a PaO2\/Fi \u00a0O2.300mmHg at 28 days, and survival at 28 and at 90 days.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Mechanically ventilated adults with COVID-19 pneumonia were enrolled in a phase II, multicenter, single-blind, randomized controlled parallel-arm trial. Participants in the intervention arm received inhaled nitric oxide at 80 ppm for 48 hours, compared with the control group receiving usual care (without placebo).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>A total of 193 participants were included in the modified intention-to-treat analysis. The mean change in PaO2\/Fi \u00a0O2 ratio at 48 hours was 28.3mmHg in the intervention group and 21.4mmHg in the control group (mean difference, 39.1mmHg; 95% credible interval [CrI], 18.1 to 60.3). The mean time to reach a PaO2\/Fi \u00a0O2.300mmHg in the interventional group was 8.7 days, compared with 8.4 days for the control group (mean difference, 0.44; 95% CrI, 23.63 to 4.53). At 28 days, the proportion of participants attaining a PaO2\/Fi \u00a0O2.300mmHg was 27.7% in the inhaled nitric oxide group and 17.2% in the control subjects (risk ratio, 2.03; 95% CrI, 1.11 to 3.86). Duration of ventilation and mortality at 28 and 90 days did not differ. No serious adverse events were reported.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The use of high-dose inhaled nitric oxide resulted in an improvement of PaO2\/Fi \u00a0O2 at 48 hours compared with usual care in adults with acute hypoxemic respiratory failure due to COVID-19.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202304-0637oc","type":"journal-article","created":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T14:01:32Z","timestamp":1695996092000},"page":"1293-1304","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":52,"title":["High-Dose Inhaled Nitric Oxide in Acute Hypoxemic Respiratory Failure Due to COVID-19: A Multicenter Phase II Trial"],"prefix":"10.1093","volume":"208","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5675-7139","authenticated-orcid":false,"given":"Raffaele","family":"Di Fenza","sequence":"first","affiliation":[{"name":"Department of Anesthesia, Critical Care, and Pain Medicine"},{"name":"Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naman S.","family":"Shetty","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0838-3654","authenticated-orcid":false,"given":"Stefano","family":"Gianni","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Critical Care, and Pain Medicine"},{"name":"Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vibhu","family":"Parcha","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Giammatteo","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Critical Care, and Pain Medicine"},{"name":"Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bijan","family":"Safaee Fakhr","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Critical Care, and Pain Medicine"},{"name":"Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Tornberg","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and"},{"name":"Department of Anesthesia and Intensive Care and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olof","family":"Wall","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and"},{"name":"Department of Clinical Science and Education, Sodersxjukhuset, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Harbut","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and"},{"name":"Department of Anesthesia and Intensive Care and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9501-8606","authenticated-orcid":false,"given":"Peggy S.","family":"Lai","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Medicine, Department of Medicine"},{"name":"Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan Z.","family":"Li","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachusetts"},{"name":"Division of Infectious Diseases, Brigham and Women\u2019s Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Paganoni","sequence":"additional","affiliation":[{"name":"Sean M. Healey and AMG Center for ALS"},{"name":"Neurological Clinical Research Institute"},{"name":"Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Cenci","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Critical Care, and Pain Medicine"},{"name":"Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariel L.","family":"Mueller","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Critical Care, and Pain Medicine"},{"name":"Anesthesia Research Center"},{"name":"Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy T.","family":"Houle","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Critical Care, and Pain Medicine"},{"name":"Anesthesia Research Center"},{"name":"Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oluwaseun","family":"Akeju","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Critical Care, and Pain Medicine"},{"name":"Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward A.","family":"Bittner","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Critical Care, and Pain Medicine"},{"name":"Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Somnath","family":"Bose","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachusetts"},{"name":"Department of Anesthesia, Critical Care, and Pain Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louie K.","family":"Scott","sequence":"additional","affiliation":[{"name":"Critical Care Medicine, Department of Medicine, Louisiana State University Health Shreveport, Shreveport, Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7513-7023","authenticated-orcid":false,"given":"Ryan W.","family":"Carroll","sequence":"additional","affiliation":[{"name":"Division of Pediatric Critical Care Medicine, Department of Pediatrics"},{"name":"Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumito","family":"Ichinose","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Critical Care, and Pain Medicine"},{"name":"Anesthesia Critical Care Center for Research, and"},{"name":"Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"Hedenstierna","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Danderyd Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pankaj","family":"Arora","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2702-2093","authenticated-orcid":false,"given":"Lorenzo","family":"Berra","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Critical Care, and Pain Medicine"},{"name":"Anesthesia Critical Care Center for Research, and"},{"name":"Respiratory Care Services, Massachusetts General Hospital, Boston, Massachusetts"},{"name":"Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,12,15]]},"reference":[{"key":"2026012204400881300_bib1","author":"Food and Drug Administration"},{"key":"2026012204400881300_bib2","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1161\/01.CIR.83.6.2038","article-title":"Inhaled nitric oxide: a selective pulmonary vasodilator reversing hypoxic pulmonary vasoconstriction","volume":"83","author":"Frostell","year":"1991","journal-title":"Circulation"},{"key":"2026012204400881300_bib3","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1016\/0140-6736(92)92686-A","article-title":"Inhaled nitric oxide in persistent pulmonary hypertension of the newborn","volume":"340","author":"Roberts","year":"1992","journal-title":"Lancet"},{"key":"2026012204400881300_bib4","author":"European Medicines Agency"},{"key":"2026012204400881300_bib5","author":"Japan Pharmaceuticals and Medical Devices Agency","year":"2015"},{"key":"2026012204400881300_bib6","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1056\/NEJM199302113280605","article-title":"Inhaled nitric oxide for the adult respiratory distress syndrome","volume":"328","author":"Rossaint","year":"1993","journal-title":"N Engl J Med"},{"key":"2026012204400881300_bib7","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1001\/jama.291.13.1603","article-title":"Low-dose inhaled nitric oxide in patients with acute lung injury: a randomized controlled trial","volume":"291","author":"Taylor","year":"2004","journal-title":"JAMA"},{"key":"2026012204400881300_bib8","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1164\/rccm.2108121","article-title":"Dose-response characteristics during long-term inhalation of nitric oxide in patients with severe acute respiratory distress syndrome: a prospective, randomized, controlled study","volume":"167","author":"Gerlach","year":"2003","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012204400881300_bib9","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1111\/j.1365-2362.1993.tb00797.x","article-title":"Time-course and dose-response of nitric oxide inhalation for systemic oxygenation and pulmonary hypertension in patients with adult respiratory distress syndrome","volume":"23","author":"Gerlach","year":"1993","journal-title":"Eur J Clin Invest"},{"key":"2026012204400881300_bib10","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1097\/00003246-199801000-00011","article-title":"Effects of inhaled nitric oxide in patients with acute respiratory distress syndrome: results of a randomized phase II trial","volume":"26","author":"Dellinger","year":"1998","journal-title":"Crit Care Med"},{"key":"2026012204400881300_bib11","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1164\/ajrccm.157.5.9707090","article-title":"Inhaled nitric oxide in acute respiratory distress syndrome: a pilot randomized controlled study","volume":"157","author":"Troncy","year":"1998","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012204400881300_bib12","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1007\/s001340050982","article-title":"Inhalation of nitric oxide in acute lung injury: results of a European multicentre study","volume":"25","author":"Lundin","year":"1999","journal-title":"Intensive Care Med"},{"key":"2026012204400881300_bib13","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1164\/ajrccm.157.5.96-10089","article-title":"Inhaled nitric oxide versus conventional therapy: effect on oxygenation in ARDS","volume":"157","author":"Michael","year":"1998","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012204400881300_bib14","doi-asserted-by":"crossref","first-page":"101826","DOI":"10.1016\/j.redox.2020.101826","article-title":"Antimicrobial effects of nitric oxide in murine models of Klebsiella pneumonia","volume":"39","author":"Wiegand","year":"2021","journal-title":"Redox Biol"},{"key":"2026012204400881300_bib15","doi-asserted-by":"crossref","first-page":"2818","DOI":"10.1172\/JCI119473","article-title":"Perspectives series: host\/pathogen interactions. Mechanisms of nitric oxide-related antimicrobial activity","volume":"99","author":"Fang","year":"1997","journal-title":"J Clin Invest"},{"key":"2026012204400881300_bib16","doi-asserted-by":"crossref","first-page":"101734","DOI":"10.1016\/j.redox.2020.101734","article-title":"Mitigation of the replication of SARS-CoV-2 by nitric oxide in vitro","volume":"37","author":"Akaberi","year":"2020","journal-title":"Redox Biol"},{"key":"2026012204400881300_bib17","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.ijid.2004.04.012","article-title":"Inhibition of SARS-coronavirus infection in vitro by S-nitroso-N-acetylpenicillamine, a nitric oxide donor compound","volume":"8","author":"Keyaerts","year":"2004","journal-title":"Int J Infect Dis"},{"key":"2026012204400881300_bib18","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1097\/CCM.0b013e3182a27909","article-title":"Inhaled nitric oxide does not reduce mortality in patients with acute respiratory distress syndrome regardless of severity: systematic review and meta-analysis","volume":"42","author":"Adhikari","year":"2014","journal-title":"Crit Care Med"},{"key":"2026012204400881300_bib19","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1097\/AOG.0000000000004847","article-title":"High-dose inhaled nitric oxide for the treatment of spontaneously breathing pregnant patients with severe coronavirus disease 2019 (COVID-19) pneumonia","volume":"140","author":"Valsecchi","year":"2022","journal-title":"Obstet Gynecol"},{"key":"2026012204400881300_bib20","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1513\/AnnalsATS.202103-348OC","article-title":"Inhaled nitric oxide for the treatment of acute bronchiolitis: a multicenter randomized controlled clinical trial to evaluate dose response","volume":"20","author":"Goldbart","year":"2023","journal-title":"Ann Am Thorac Soc"},{"key":"2026012204400881300_bib21","first-page":"1536714","article-title":"High-dose inhaled nitric oxide as adjunct therapy in cystic fibrosis targeting Burkholderia multivorans","volume":"2020","author":"Bartley","year":"2020","journal-title":"Case Rep Pediatr"},{"key":"2026012204400881300_bib22","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1086\/425357","article-title":"Inhalation of nitric oxide in the treatment of severe acute respiratory syndrome: a rescue trial in Beijing","volume":"39","author":"Chen","year":"2004","journal-title":"Clin Infect Dis"},{"key":"2026012204400881300_bib23","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.niox.2013.03.007","article-title":"Gaseous nitric oxide reduces influenza infectivity in vitro","volume":"31","author":"Regev-Shoshani","year":"2013","journal-title":"Nitric Oxide"},{"key":"2026012204400881300_bib24","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1007\/s15010-016-0879-x","article-title":"Gaseous nitric oxide to treat antibiotic resistant bacterial and fungal lung infections in patients with cystic fibrosis: a phase I clinical study","volume":"44","author":"Deppisch","year":"2016","journal-title":"Infection"},{"key":"2026012204400881300_bib25","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/j.jcf.2013.01.008","article-title":"Inhaled nitric oxide decreases the bacterial load in a rat model of Pseudomonas aeruginosa pneumonia","volume":"12","author":"Miller","year":"2013","journal-title":"J Cyst Fibros"},{"key":"2026012204400881300_bib26","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1097\/00003246-200202000-00029","article-title":"Beneficial effects of nitric oxide inhalation on pulmonary bacterial clearance","volume":"30","author":"Jean","year":"2002","journal-title":"Crit Care Med"},{"key":"2026012204400881300_bib27","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.niox.2008.08.002","article-title":"Gaseous nitric oxide bactericidal activity retained during intermittent high-dose short duration exposure","volume":"20","author":"Miller","year":"2009","journal-title":"Nitric Oxide"},{"key":"2026012204400881300_bib28","first-page":"1451","article-title":"The antimicrobial effect of nitric oxide on the bacteria that cause nosocomial pneumonia in mechanically ventilated patients in the intensive care unit","volume":"50","author":"McMullin","year":"2005","journal-title":"Respir Care"},{"key":"2026012204400881300_bib29","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1056\/NEJMoa0708638","article-title":"Mechanical ventilation guided by esophageal pressure in acute lung injury","volume":"359","author":"Talmor","year":"2008","journal-title":"N Engl J Med"},{"key":"2026012204400881300_bib30","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1080\/0886022X.2021.1873805","article-title":"Inhaled nitric oxide and acute kidney injury risk: a meta-analysis of randomized controlled trials","volume":"43","author":"Wang","year":"2021","journal-title":"Ren Fail"},{"key":"2026012204400881300_bib31","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1038\/s41581-021-00452-0","article-title":"Pathophysiology of COVID-19-associated acute kidney injury","volume":"17","author":"Legrand","year":"2021","journal-title":"Nat Rev Nephrol"},{"key":"2026012204400881300_bib32","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1056\/NEJM200005043421801","article-title":"Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome","volume":"342","author":"Brower","year":"2000","journal-title":"N Engl J Med"},{"key":"2026012204400881300_bib33","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1056\/NEJMoa1214103","article-title":"Prone positioning in severe acute respiratory distress syndrome","volume":"368","author":"Gu\u00e9rin","year":"2013","journal-title":"N Engl J Med"},{"key":"2026012204400881300_bib34","doi-asserted-by":"crossref","first-page":"2379","DOI":"10.1001\/jama.292.19.2379","article-title":"Effects of systematic prone positioning in hypoxemic acute respiratory failure: a randomized controlled trial","volume":"292","author":"Guerin","year":"2004","journal-title":"JAMA"},{"key":"2026012204400881300_bib35","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1056\/NEJMoa010043","article-title":"Effect of prone positioning on the survival of patients with acute respiratory failure","volume":"345","author":"Gattinoni","year":"2001","journal-title":"N Engl J Med"},{"key":"2026012204400881300_bib36","doi-asserted-by":"crossref","first-page":"2193","DOI":"10.1001\/jama.1979.03300200023016","article-title":"Extracorporeal membrane oxygenation in severe acute respiratory failure: a randomized prospective study","volume":"242","author":"Zapol","year":"1979","journal-title":"JAMA"},{"key":"2026012204400881300_bib37","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1016\/S0140-6736(09)61069-2","article-title":"Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial","volume":"374","author":"Peek","year":"2009","journal-title":"Lancet"},{"key":"2026012204400881300_bib38","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1164\/rccm.202109-2150OC","article-title":"Vasculopathy and increased vascular congestion in fatal COVID-19 and acute respiratory distress syndrome","volume":"206","author":"Villalba","year":"2022","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012204400881300_bib39","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1164\/rccm.201804-0692OC","article-title":"Physiologic analysis and clinical performance of the ventilatory ratio in acute respiratory distress syndrome","volume":"199","author":"Sinha","year":"2019","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012204400881300_bib40","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1161\/CIRCRESAHA.107.158410","article-title":"Platelet-derived nitric oxide signaling and regulation","volume":"101","author":"Gkaliagkousi","year":"2007","journal-title":"Circ Res"},{"key":"2026012204400881300_bib41","doi-asserted-by":"crossref","first-page":"5493","DOI":"10.1038\/s41467-020-19057-5","article-title":"SARS-CoV-2 viral load is associated with increased disease severity and mortality","volume":"11","author":"Fajnzylber","year":"2020","journal-title":"Nat Commun"},{"key":"2026012204400881300_bib42","doi-asserted-by":"crossref","first-page":"e148635","DOI":"10.1172\/JCI148635","article-title":"SARS-CoV-2 viremia is associated with distinct proteomic pathways and predicts COVID-19 outcomes","volume":"131","author":"Li","year":"2021","journal-title":"J Clin Invest"},{"key":"2026012204400881300_bib43","doi-asserted-by":"crossref","first-page":"100036","DOI":"10.1016\/j.lansea.2022.100036","article-title":"SARS-CoV-2 accelerated clearance using a novel nitric oxide nasal spray (NONS) treatment: a randomized trial","volume":"3","author":"Tandon","year":"2022","journal-title":"Lancet Reg Health Southeast Asia"},{"key":"2026012204400881300_bib44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.virol.2009.09.007","article-title":"Dual effect of nitric oxide on SARS-CoV replication: viral RNA production and palmitoylation of the S protein are affected","volume":"395","author":"Akerstr\u00f6m","year":"2009","journal-title":"Virology"},{"key":"2026012204400881300_bib45","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.niox.2021.08.003","article-title":"Inhaled high dose nitric oxide is a safe and effective respiratory treatment in spontaneous breathing hospitalized patients with COVID-19 pneumonia","volume":"116","author":"Safaee Fakhr","year":"2021","journal-title":"Nitric Oxide"},{"key":"2026012204400881300_bib46","doi-asserted-by":"crossref","first-page":"111573","DOI":"10.1016\/j.celrep.2022.111573","article-title":"SARS-CoV-2 infects neurons and induces neuroinflammation in a non-human primate model of COVID-19","volume":"41","author":"Beckman","year":"2022","journal-title":"Cell Rep"},{"key":"2026012204400881300_bib47","doi-asserted-by":"crossref","first-page":"2452","DOI":"10.1016\/j.cell.2022.06.008","article-title":"Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation","volume":"185","author":"Fern\u00e1ndez-Casta\u00f1eda","year":"2022","journal-title":"Cell"},{"key":"2026012204400881300_bib48","doi-asserted-by":"crossref","first-page":"2406","DOI":"10.1038\/s41591-022-02001-z","article-title":"Long-term neurologic outcomes of COVID-19","volume":"28","author":"Xu","year":"2022","journal-title":"Nat Med"},{"key":"2026012204400881300_bib49","doi-asserted-by":"crossref","first-page":"3106","DOI":"10.1161\/01.CIR.0000134595.80170.62","article-title":"Inhaled nitric oxide: a selective pulmonary vasodilator: current uses and therapeutic potential","volume":"109","author":"Ichinose","year":"2004","journal-title":"Circulation"},{"key":"2026012204400881300_bib50","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1002\/acn3.51350","article-title":"Persistent neurologic symptoms and cognitive dysfunction in non-hospitalized Covid-19 \u201clong haulers\u201d","volume":"8","author":"Graham","year":"2021","journal-title":"Ann Clin Transl Neurol"},{"key":"2026012204400881300_bib51","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1164\/rccm.201111-2025OC","article-title":"The adult respiratory distress syndrome cognitive outcomes study: long-term neuropsychological function in survivors of acute lung injury","volume":"185","author":"Mikkelsen","year":"2012","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012204400881300_bib52","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1183\/09031936.98.12051164","article-title":"Acute effects of inhaled nitric oxide in adult respiratory distress syndrome","volume":"12","author":"Iotti","year":"1998","journal-title":"Eur Respir J"}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/208\/12\/1293\/66425188\/ajrccm_208_12_1293.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/208\/12\/1293\/66425188\/ajrccm_208_12_1293.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T09:40:22Z","timestamp":1769074822000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/208\/12\/1293\/8426851"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12]]},"references-count":52,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2023,12,15]]},"published-print":{"date-parts":[[2023,12,15]]}},"URL":"https:\/\/doi.org\/10.1164\/rccm.202304-0637oc","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,12]]},"published":{"date-parts":[[2023,12]]},"assertion":[{"value":"2023-04-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}