[Skip to Content]
[Skip to Content Landing]

Assessment of Awake Prone Positioning in Hospitalized Adults With COVID-19A Nonrandomized Controlled Trial

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME
Key Points

Question  Is prone positioning associated with improved outcomes among patients with COVID-19 and hypoxemia requiring supplemental oxygen but not yet receiving mechanical ventilation?

Findings  In this nonrandomized controlled trial including 501 patients with COVID-19 and hypoxemia, the odds of having a worse outcome on study day 5 based on a modified World Health Organization ordinal scale was higher among patients receiving the awake prone positioning intervention.

Meaning  This study’s findings suggest that routine recommendation for awake prone positioning among patients with COVID-19–related hypoxemia who require supplemental oxygen but not mechanical ventilation is not beneficial.


Importance  Awake prone positioning may improve hypoxemia among patients with COVID-19, but whether it is associated with improved clinical outcomes remains unknown.

Objective  To determine whether the recommendation of awake prone positioning is associated with improved outcomes among patients with COVID-19–related hypoxemia who have not received mechanical ventilation.

Design, Setting, and Participants  This pragmatic nonrandomized controlled trial was conducted at 2 academic medical centers (Vanderbilt University Medical Center and NorthShore University HealthSystem) during the COVID-19 pandemic. A total of 501 adult patients with COVID-19–associated hypoxemia who had not received mechanical ventilation were enrolled from May 13 to December 11, 2020.

Interventions  Patients were assigned 1:1 to receive either the practitioner-recommended awake prone positioning intervention (intervention group) or usual care (usual care group).

Main Outcomes and Measures  Primary outcome analyses were performed using a bayesian proportional odds model with covariate adjustment for clinical severity ranking based on the World Health Organization ordinal outcome scale, which was modified to highlight the worst level of hypoxemia on study day 5.

Results  A total of 501 patients (mean [SD] age, 61.0 [15.3] years; 284 [56.7%] were male; and most [417 (83.2%)] were self-reported non-Hispanic or non-Latinx) were included. Baseline severity was comparable between the intervention vs usual care groups, with 170 patients (65.9%) vs 162 patients (66.7%) receiving oxygen via standard low-flow nasal cannula, 71 patients (27.5%) vs 62 patients (25.5%) receiving oxygen via high-flow nasal cannula, and 16 patients (6.2%) vs 19 patients (7.8%) receiving noninvasive positive-pressure ventilation. Nursing observations estimated that patients in the intervention group spent a median of 4.2 hours (IQR, 1.8-6.7 hours) in the prone position per day compared with 0 hours (IQR, 0-0.7 hours) per day in the usual care group. On study day 5, the bayesian posterior probability of the intervention group having worse outcomes than the usual care group on the modified World Health Organization ordinal outcome scale was 0.998 (posterior median adjusted odds ratio [aOR], 1.63; 95% credibility interval [CrI], 1.16-2.31). However, on study days 14 and 28, the posterior probabilities of harm were 0.874 (aOR, 1.29; 95% CrI, 0.84-1.99) and 0.673 (aOR, 1.12; 95% CrI, 0.67-1.86), respectively. Exploratory outcomes (progression to mechanical ventilation, length of stay, and 28-day mortality) did not differ between groups.

Conclusions and Relevance  In this nonrandomized controlled trial, prone positioning offered no observed clinical benefit among patients with COVID-19–associated hypoxemia who had not received mechanical ventilation. Moreover, there was substantial evidence of worsened clinical outcomes at study day 5 among patients recommended to receive the awake prone positioning intervention, suggesting potential harm.

Trial Registration  ClinicalTrials.gov Identifier: NCT04359797

Sign in to take quiz and track your certificates

Buy This Activity

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 Credit(s)™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

Article Information

Accepted for Publication: February 26, 2022.

Published Online: April 18, 2022. doi:10.1001/jamainternmed.2022.1070

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 Qian ET et al. JAMA Internal Medicine.

Corresponding Author: Edward Tang Qian, MD, Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, T-1218 MCN, 1161 21st Ave S, Nashville, TN 37232-2650 (edward.t.qian@vumc.org).

Author Contributions: Drs Qian and Lindsell had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Qian and Gatto contributed equally as first authors. Drs Lindsell and Rice contributed equally as senior authors.

Concept and design: Qian, Gatto, Dear, Hiser, Buie, Kripalani, Harrell, Freundlich, Burke, Billings, Pulley, Bernard, Lindsell, Rice.

Acquisition, analysis, or interpretation of data: Qian, Amusina, Dear, Hiser, Buie, Kripalani, Harrell, Freundlich, Gao, Gong, Hennessy, Grooms, Mattingly, Bellam, Zakaria, Vasilevskis, Billings, Pulley, Lindsell, Rice.

Drafting of the manuscript: Qian, Gatto, Dear, Hiser, Buie, Zakaria, Billings, Pulley, Rice.

Critical revision of the manuscript for important intellectual content: Gatto, Amusina, Dear, Hiser, Buie, Kripalani, Harrell, Freundlich, Gao, Gong, Hennessy, Grooms, Mattingly, Bellam, Burke, Vasilevskis, Billings, Pulley, Bernard, Lindsell, Rice.

Statistical analysis: Harrell, Gao, Gong, Hennessy, Lindsell.

Obtained funding: Bernard.

Administrative, technical, or material support: Qian, Gatto, Amusina, Dear, Hiser, Buie, Freundlich, Grooms, Mattingly, Zakaria, Vasilevskis, Pulley, Bernard, Rice.

Supervision: Gatto, Dear, Hiser, Kripalani, Freundlich, Vasilevskis, Pulley, Bernard, Rice.

Other–principal investigator at one of the sites: Amusina.

Conflict of Interest Disclosures: Dr Qian reported receiving grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Gatto reported receiving grants from the National Center for Advancing Translational Sciences (NCATS) during the conduct of the study. Dr Dear reported receiving grants from the NCATS during the conduct of the study. Mr Hiser reported receiving grants from the NCATS during the conduct of the study. Dr Bernard reported receiving grants from the NCATS during the conduct of the study. Dr Lindsell reported receiving grants from the NCATS during the conduct of the study; grants from the Centers for Disease Control and Prevention, the National Institutes of Health, and the US Department of Defense; fees for research services from AbbVie, bioMérieux, Endpoint Health, and Entegrion; and owning a patent for risk stratification in sepsis and septic shock (licensed to Cincinnati Children’s Hospital Medical Center) outside the submitted work. Dr Rice reported receiving grants from the NCATS during the conduct of the study and personal fees from Cumberland Pharmaceuticals, Cytovale, and Sanofi outside the submitted work. No other disclosures were reported.

Funding/Support: The work was supported by grant UL1 TR002243 from the National Center for Advancing Translational Sciences (Drs Gatto and Dear, Mr Hiser, and Drs Bernard, Lindsell, and Rice); grant T32HL087738 from the National Heart, Lung, and Blood Institute (Dr Qian); grant K23HL148640 from the National Heart, Lung, and Blood Institute (Dr Freundlich); grant R01GM112871 from the National Institute of General Medical Sciences (Dr Billings); and grants to the institution from the Dolly Parton COVID-19 Research Fund (Drs Gatto and Dear, Mr Hiser, and Dr Rice).

Role of the Funder/Sponsor: The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Group Information: A complete list of the members of the Vanderbilt Learning Healthcare System Platform Investigators appears in Supplement 3.

Disclaimer: The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the National Center for Advancing Translational Sciences or the National Institutes of Health.

Data Sharing Statement: See Supplement 4.

Additional Contributions: The authors are indebted to the patients and the frontline staff who endured the COVID-19 pandemic. Zameer Lodhi, BBA, MS, of Vanderbilt University provided assistance with data acquisition, and Elizabeth A. Rice, MD, SFHM, of Vanderbilt University provided coordination with clinical teams. We thank the COVID-19 charge nurses and the 8 nurse leaders and educators from Vanderbilt Medical Center East and the members of the Vanderbilt Coordinating Center, including Jill Janssen, RN, BSN; Jessica B. Collins, BA; Jenna Caserta, RN, BSN; Alesia Pruitt, BS; Jessica S. Marlin, CCRP; Krista K. Vermillion, MS, MPM; and David S. McKeel, BS. Osasumwen Osayimwen, MD, MPH, of the NorthShore University HealthSystem provided frontline care. We also acknowledge the contributions of the NorthShore University HealthSystem COVID-19 hospitalist team; the nursing staff of the NorthShore University HealthSystem; and the nursing administration at Glenbrook Hospital. The sensor work of Drs Qian, Gatto, Lindsell, and Rice was supported by Smith & Nephew, with guidance provided by Annemari Cooley, MBA, MA; Mike Pihulic, Meng; Angela Lin, MS; and Alvin Cheung, BS (all of whom were employed by Smith & Nephew). None of the contributors received additional compensation for their work.

World Health Organization. Coronavirus disease (COVID-19). World Health Organization; 2020. Accessed August 21, 2020. https://www.who.int/health-topics/coronavirus
Li  X , Ma  X .  Acute respiratory failure in COVID-19: is it “typical” ARDS?   Crit Care. 2020;24(1):198. doi:10.1186/s13054-020-02911-9 PubMedGoogle ScholarCrossref
Grasselli  G , Zangrillo  A , Zanella  A ,  et al; COVID-19 Lombardy ICU Network.  Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy region, Italy.   JAMA. 2020;323(16):1574-1581. doi:10.1001/jama.2020.5394 PubMedGoogle ScholarCrossref
Yang  X , Yu  Y , Xu  J ,  et al.  Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study.   Lancet Respir Med. 2020;8(5):475-481. doi:10.1016/S2213-2600(20)30079-5 PubMedGoogle ScholarCrossref
Bhatraju  PK , Ghassemieh  BJ , Nichols  M ,  et al.  Covid-19 in critically ill patients in the Seattle region—case series.   N Engl J Med. 2020;382(21):2012-2022. doi:10.1056/NEJMoa2004500 PubMedGoogle ScholarCrossref
Horby  P , Lim  WS , Emberson  JR ,  et al; RECOVERY Collaborative Group.  Dexamethasone in hospitalized patients with COVID-19.   N Engl J Med. 2021;384(8):693-704. doi:10.1056/NEJMoa2021436PubMedGoogle ScholarCrossref
Beigel  JH , Tomashek  KM , Dodd  LE .  Remdesivir for the treatment of COVID-19—preliminary report. reply.   N Engl J Med. 2020;383(10):994. Published online May 22, 2020. PubMedGoogle Scholar
Cao  B , Wang  Y , Wen  D ,  et al.  A trial of lopinavir-ritonavir in adults hospitalized with severe COVID-19.   N Engl J Med. 2020;382(19):1787-1799. doi:10.1056/NEJMoa2001282 PubMedGoogle ScholarCrossref
Cavalcanti  AB , Zampieri  FG , Rosa  RG ,  et al; Coalition COVID-19 Brazil I Investigators.  Hydroxychloroquine with or without azithromycin in mild-to-moderate COVID-19.   N Engl J Med. 2020;383(21):2041-2052. doi:10.1056/NEJMoa2019014 PubMedGoogle ScholarCrossref
Nasa  P , Azoulay  E , Khanna  AK ,  et al.  Expert consensus statements for the management of COVID-19–related acute respiratory failure using a Delphi method.   Crit Care. 2021;25(1):106. doi:10.1186/s13054-021-03491-y PubMedGoogle ScholarCrossref
Piehl  MA , Brown  RS .  Use of extreme position changes in acute respiratory failure.   Crit Care Med. 1976;4(1):13-14. doi:10.1097/00003246-197601000-00003 PubMedGoogle ScholarCrossref
Froese  AB , Bryan  AC .  Effects of anesthesia and paralysis on diaphragmatic mechanics in man.   Anesthesiology. 1974;41(3):242-255. doi:10.1097/00000542-197409000-00006 PubMedGoogle ScholarCrossref
Johnson  NJ , Luks  AM , Glenny  RW .  Gas exchange in the prone posture.   Respir Care. 2017;62(8):1097-1110. doi:10.4187/respcare.05512 PubMedGoogle ScholarCrossref
Galiatsou  E , Kostanti  E , Svarna  E ,  et al.  Prone position augments recruitment and prevents alveolar overinflation in acute lung injury.   Am J Respir Crit Care Med. 2006;174(2):187-197. doi:10.1164/rccm.200506-899OC PubMedGoogle ScholarCrossref
Pelosi  P , Brazzi  L , Gattinoni  L .  Prone position in acute respiratory distress syndrome.   Eur Respir J. 2002;20(4):1017-1028. doi:10.1183/09031936.02.00401702 PubMedGoogle ScholarCrossref
Lee  JM , Bae  W , Lee  YJ , Cho  YJ .  The efficacy and safety of prone positional ventilation in acute respiratory distress syndrome: updated study-level meta-analysis of 11 randomized controlled trials.   Crit Care Med. 2014;42(5):1252-1262. doi:10.1097/CCM.0000000000000122 PubMedGoogle ScholarCrossref
Guérin  C , Reignier  J , Richard  JC ,  et al; PROSEVA Study Group.  Prone positioning in severe acute respiratory distress syndrome.   N Engl J Med. 2013;368(23):2159-2168. doi:10.1056/NEJMoa1214103 PubMedGoogle ScholarCrossref
Scaravilli  V , Grasselli  G , Castagna  L ,  et al.  Prone positioning improves oxygenation in spontaneously breathing nonintubated patients with hypoxemic acute respiratory failure: a retrospective study.   J Crit Care. 2015;30(6):1390-1394. doi:10.1016/j.jcrc.2015.07.008 PubMedGoogle ScholarCrossref
Valter  C , Christensen  AM , Tollund  C , Schønemann  NK .  Response to the prone position in spontaneously breathing patients with hypoxemic respiratory failure.   Acta Anaesthesiol Scand. 2003;47(4):416-418. doi:10.1034/j.1399-6576.2003.00088.x PubMedGoogle ScholarCrossref
Ding  L , Wang  L , Ma  W , He  H .  Efficacy and safety of early prone positioning combined with HFNC or NIV in moderate to severe ARDS: a multi-center prospective cohort study.   Crit Care. 2020;24(1):28. doi:10.1186/s13054-020-2738-5 PubMedGoogle ScholarCrossref
Retucci  M , Aliberti  S , Ceruti  C ,  et al.  Prone and lateral positioning in spontaneously breathing patients With COVID-19 pneumonia undergoing noninvasive helmet CPAP treatment.   Chest. 2020;158(6):2431-2435. doi:10.1016/j.chest.2020.07.006 PubMedGoogle ScholarCrossref
Thompson  AE , Ranard  BL , Wei  Y , Jelic  S .  Prone positioning in awake, nonintubated patients with COVID-19 hypoxemic respiratory failure.   JAMA Intern Med. 2020;180(11):1537-1539. doi:10.1001/jamainternmed.2020.3030 PubMedGoogle ScholarCrossref
Ghelichkhani  P , Esmaeili  M .  Prone position in management of COVID-19 patients; a commentary.   Arch Acad Emerg Med. 2020;8(1):e48.PubMedGoogle Scholar
Pooni  RS .  Research in brief: prone positioning in COVID-19: what’s the evidence.   Clin Med (Lond). 2020;20(4):369. doi:10.7861/clinmed.rib.20.4.1 PubMedGoogle ScholarCrossref
Coppo  A , Bellani  G , Winterton  D ,  et al.  Feasibility and physiological effects of prone positioning in non-intubated patients with acute respiratory failure due to COVID-19 (PRON-COVID): a prospective cohort study.   Lancet Respir Med. 2020;8(8):765-774. doi:10.1016/S2213-2600(20)30268-X PubMedGoogle ScholarCrossref
Elharrar  X , Trigui  Y , Dols  AM ,  et al.  Use of prone positioning in nonintubated patients with COVID-19 and hypoxemic acute respiratory failure.   JAMA. 2020;323(22):2336-2338. doi:10.1001/jama.2020.8255 PubMedGoogle ScholarCrossref
Ferrando  C , Mellado-Artigas  R , Gea  A ,  et al; COVID-19 Spanish ICU Network.  Awake prone positioning does not reduce the risk of intubation in COVID-19 treated with high-flow nasal oxygen therapy: a multicenter, adjusted cohort study.   Crit Care. 2020;24(1):597. doi:10.1186/s13054-020-03314-6 PubMedGoogle ScholarCrossref
Ponnapa Reddy  M , Subramaniam  A , Afroz  A ,  et al.  Prone positioning of nonintubated patients with coronavirus disease 2019—a systematic review and meta-analysis.   Crit Care Med. 2021;49(10):e1001-e1014. doi:10.1097/CCM.0000000000005086 PubMedGoogle ScholarCrossref
Venus  K , Munshi  L , Fralick  M .  Prone positioning for patients with hypoxic respiratory failure related to COVID-19.   CMAJ. 2020;192(47):E1532-E1537. doi:10.1503/cmaj.201201 PubMedGoogle ScholarCrossref
Harris  PA , Taylor  R , Thielke  R , Payne  J , Gonzalez  N , Conde  JG .  Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support.   J Biomed Inform. 2009;42(2):377-381. doi:10.1016/j.jbi.2008.08.010 PubMedGoogle ScholarCrossref
WHO Working Group on the Clinical Characterisation and Management of COVID-19 Infection.  A minimal common outcome measure set for COVID-19 clinical research.   Lancet Infect Dis. 2020;20(8):e192-e197. doi:10.1016/S1473-3099(20)30483-7 PubMedGoogle ScholarCrossref
Whitehead  J .  Sample size calculations for ordered categorical data.   Stat Med. 1993;12(24):2257-2271. doi:10.1002/sim.4780122404 PubMedGoogle ScholarCrossref
Harrell  FE Jr. Hmisc: Harrell miscellaneous. Version 4.6-0. R Project. Accessed June 22, 2020. https://CRAN.R-project.org/package=Hmisc
Yao  Y , Vehtari  A , Simpson  D , Gelman  A .  Using stacking to average bayesian predictive distributions (with discussion).   Bayesian Anal. 2018;13(3):917-1007. doi:10.1214/17-BA1091Google ScholarCrossref
R Core Team. The R Project for Statistical Computing. R Foundation; 2022. Accessed June 22, 2020. https://www.R-project.org/
Harrell  FE . Rmsb: bayesian regression modeling strategies. Version 0.0.2. R Project. Accessed June 22, 2020. https://CRAN.R-project.org/package=rmsb
Ehrmann  S , Li  J , Ibarra-Estrada  M ,  et al; Awake Prone Positioning Meta-Trial Group.  Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial.   Lancet Respir Med. 2021;9(12):1387-1395. doi:10.1016/S2213-2600(21)00356-8 PubMedGoogle ScholarCrossref
Taylor  SP , Bundy  H , Smith  WM , Skavroneck  S , Taylor  B , Kowalkowski  MA .  Awake prone positioning strategy for nonintubated hypoxic patients with COVID-19: a pilot trial with embedded implementation evaluation.   Ann Am Thorac Soc. 2021;18(8):1360-1368. doi:10.1513/AnnalsATS.202009-1164OC PubMedGoogle ScholarCrossref
Johnson  SA , Horton  DJ , Fuller  MJ ,  et al.  Patient-directed prone positioning in awake patients with COVID-19 requiring hospitalization (PAPR).   Ann Am Thorac Soc. 2021;18(8):1424-1426. doi:10.1513/AnnalsATS.202011-1466RL PubMedGoogle ScholarCrossref
AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 CME points in the American Board of Surgery’s (ABS) Continuing Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

Want full access to the AMA Ed Hub?
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
Want full access to the AMA Ed Hub?
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right

Name Your Search

Save Search
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience

Lookup An Activity


My Saved Searches

You currently have no searches saved.


My Saved Courses

You currently have no courses saved.