Awake Prone Positioning for COVID-19 Acute Hypoxaemic Respiratory Failure: Retrospective Cohort Study
Conditions: Survival, Prosthesis, Oxygen Deficiency
Sponsor: Mohammed VI University Hospital

Awake prone positioning for COVID-19 acute 
hypoxaemic respiratory failure: a retrospective 
cohort study of 1069 patients  
 
Abstract: 
 
Introduction: The COVID-19 pandemic has brought the management of hypoxemic 
respiratory distress into question given the limited capacity of the intensive care units who are 
strained by the high mortality of the disease and the large numbers of patients requiring 
prolonged periods of hospitalization, as well as mechanical ventilatory support equipment 
such as ventilators and intensive care units. 
 
The objective of the study: The early and prolonged prone position (PP) reduces the 
mortality in patients with acute respiratory distress syndrome (ARDS) going under invasive 
ventilatory support, but its role in conscious patients remains a subject of debate and research. 
The main aim of this study is to evaluate the efficiency of the prone position for preventing 
intubation and mortality in spontaneously ventilated patients with COVID-19 and presenting 
an acute respiratory distress syndrome. 
 
Methods: This is a retrospective, monocentric, descriptive and analytical cohort conducted 
over a period of 22 months from March 2020 to December 2021 and involving 1069 patients 
hospitalized in the intensive care unit of our hospital for the management of acute respiratory 
failure caused by COVID-19. 
 
Results: The median survival in the total sample was 12 ± 3 days with extremes ranging from 
2 days to 39 days, the survival of the awake prone position group was superior to that of the 
non-prone position group, these results were significant with a p < 0.0001. We observed a 
statistically significant  increase in the mean ratio during the awake prone position compared 
to that at admission (143.85 ± 41.56 vs 124.30 ± 36.41; p<0.0001), the same when we 
compared the ratio after prone position to the ratio calculated at admission (131. 91 ± 41.02 
vs 124.30 ± 36.41; p<0.0001), The rate of intubation  at day 28 is about 33.20% for the 
general population, 25.58% in the awake prone position group and 46.16% in the  non-prone 
position group. 
 
Conclusion: Awake prone positioning was significantly associated with a reduction in 
28-day mortality; its use in ARDS deserves to be further studied in randomized 
controlled trials. 
 
Keywords: Acute respiratory distress syndrome, awake prone position, mortality, 
intubation, COVID-19. 

 
 
Introduction: 
 
The early and prolonged prone position (PP) reduces the mortality in patients with acute 
respiratory distress syndrome (ARDS) going under invasive ventilatory support, but its role 
in conscious patients is uncertain (1). Very few studies have examined the physiological 
effects of awake prone position in patients with ARDS and this strategy has not been 
largely adopted. (1) 
 
We have used the awake prone position in patients suffering from ARDS associated with the 
COVID-19 requiring oxygen therapy and performed a retrospective study objectifying our 
experience, reporting the physiological changes, as well as the duration and tolerance of the 
awake prone position. 
 
The upsurge in the COVID-19 pandemic is placing enormous pressure on medical facilities 
worldwide. The massive number of cases admitted to emergency departments and the rapid 
progression to respiratory failure rapidly depleted critical care resources, including 
respiratory support equipment, such as ventilators, and intensive care unit beds (2). 
 
In this circumstance, any oxygenation or therapeutic support that conserves medical 
resources should be welcomed. Prone positioning is a well-known ventilatory support 
strategy to improve oxygenation levels, usually applied in mechanically ventilated patients 
with acute respiratory distress syndrome (ARDS). The suggested mechanism of this 
strategy i s to reduce the ventilation/perfusion (V/Q) mismatch and make lung perfusion 
more uniform (2). 
 
Methods and materials: 
 
1. The study type: 
 
This is a single-center retrospective cohort conducted in the intensive care unit of our 
university hospital. 
 
2. Inclusion criteria: 
 
We enrolled all patients (1069 patients) with ARDS due to SARS-CoV2, confirmed by 
nasopharyngeal swab, who were hospitalized in COVID-19 intensive care unit from 1 
March 2020 to 31 December 2021. These 1069 patients were divided into 2 groups:  
 group A, which includes the 681 patients who were placed in the awake prone 
position.  

 group B, which includes the remaining 388 patients who did not practice the prone 
position. (figure 1) 
 
3. Exclusion criteria: 
 
Patients with negative PCR (polymerase chain reaction) (n=82), who were younger than 18 
years of age (n=14), patients who died or intubated on the day of admission (n=78) and 
those intubated on the day of admission (n=125) were excluded from the study. (figure 1). 
 
4. Prone position procedure and the judgment criteria: 
 
Each prone position session had a minimum duration of 1 hour and a maximum of 12 hours 
for a minimum of 3 session per day. FiO2 and PaO2 parameters were measured in patients 
who were put on prone position  in three phases: SP1 (supine position), PP1 (10 min after 
prone positioning), SP2 (1 hour after resuming supine position). The positive response to 
prone position was estimated by calculating the PaO2/FiO2 ratio. A response to prone 
position was defined as an improvement in the PaO2/FiO2 ratio by 10%, whereas non-
response was defined as no improvement or a deterioration of the ratio. 
The primary outcome was the death within 28 days of hospitalization. Secondary 
outcome (all censored at 28 days after enrollment) were: intubation rate, length of 
stay in  intensive care units, length of time from hospitalization to death, length of 
time from hospitalization to intubation. 
 
5. Data collection and statistical analysis: 
 
Epidemiological, clinical, paraclinical and therapeutic data were collected. These data were 
then computerized and analyzed using IBM SPSS version 21 software. Qualitative variables 
were described as numbers and/or percentages, and quantitative variables as mean ± standard 
deviation, or as median with interquartile range for variables not  having a normal distribution. 
A comparison between PaO2/FiO2 ratios at admission, during PP and 1hour after PP were 
performed in pairs using Student's t-test for paired series after graphical verification of the 
normality of the distributions. 
To determine the factors associated with a positive response to PP, an univariate analysis 
between responders and non-responders and other variables was performed in the PP 
patients, using the chi-square test or Fisher's exact test for comparison of percentages, and 
Student's T-test or Wilcoxon & Mann-Whitney test for comparison of means according to 
the distribution of variables (normal or not), after a multivariate analysis by binary logistic 
regression was performed, a p≤0.10 was chosen as a threshold to introduce the variables into 
the initial model by proceeding with the stepwise descending method; 
A survival analysis was performed to determine the factors associated with poor prognosis in 
the entire sample, our outcome was the death at day28; first a univariate analysis by Kaplan 
Meier method was performed, then a multivariate analysis by Cox regression (stepwise 
descending) was performed, PP setting was considered as our main explanatory factor, a p 
≤0.10 was chosen as a threshold to determine the variables to be included in the initial model 
still following the stepwise descending procedure. 

6. Ethical consideration: 
 
This study complies with the code of ethics of the World Medical Association (Declaration of 
Helsinki) and was approved by the Oujda Biomedical Research Ethics Committee (N° 
017/20). Written informed consent was obtained from each participant. This study is 
registered in the Research Registry under the number: **** 
 
 
Results: 
 
1. Descriptive study: 
 
During the study period, of the 1366 patients hospitalized in our department for the 
management of COVID-19 infection, 1069 patients met our inclusion criteria. 
 
1.1. Demographics and baseline characteristics: 
1069 cases were identified over 22 months, with an annual frequency of 651 cases/year. 
The mean age of our patients was 63.72 ± 15.86 years, with age extremes ranging from 21 to 
101 years, a male predominance was noted, with a sex ratio of 1.54. 
The average BMI was 28.45 ± 9.10 kg/m². The most frequent comorbidities in the sample 
were hypertension (33.70%) and diabetes (33.10%). Baseline demographic and clinical 
characteristics were well balanced between the two groups (table 1). 
 
1.2. Laboratory and radiological findings: 
On admission, all 1069 cases underwent laboratory tests, the results of which are presented in 
table 1. Regarding radiological findings, pulmonary involvement was presented according to 
the CORADS classification system (table 1). Chest CT with contrast, when performed, 
revealed pulmonary embolism in 5.63% of cases. 
 
1.3. Treatment and evolution: 
Oxygen supplementation varied from patient to patient according to individual needs, 
sometimes requiring a more efficient method of oxygenation or ventilation depending on the 
patient's response and progress. As for medications, the protocol was mainly based on 
anticoagulation, antiplatelet therapy, corticosteroids, adjuvant therapies (vitamins C and D, 
zinc), and antibiotics (table 1). 
The mean time from hospitalization to intubation in our sample was 9 ± 6 days, with 
extremes ranging from 1 day to 24 days; in the prone position group, the mean time was 
12 ± 4 days, while the non-prone position group had a mean time of 6 ± 2 days. 
The rate of intubation at day 28 was 33.20% for the total sample, those who practiced PP had 
a rate of 25.58%, and 46.16% for the non-PP group. 
 
2. 
Analytic study: 
 
2.1. PP results: 
To assess the clinical tolerance of prone position in patients, we monitored respiratory 
parameters and pulsed oxygen saturations before, during, and after PP, while retaining the 
average of their respiratory rates and peripheral saturation of oxygen (SpO2) during each of 

the three periods. We observed an improvement in both parameters during and after each PP 
session.

 The proportion of responders (SP2/SP1) to PP was 33.00% with a 95% confidence interval 
[29.50-36.70]. 
We observed a statistically significant increase in the mean PaO2/FiO2 ratio during PP 
compared to that at admission (143.85 ± 41.56 vs. 124.30 ± 36.41; p<0.0001), the same when 
we compared the ratio after PP to the ratio calculated at admission (131.91 ± 41.02 vs. 124.30 
± 36.41; p<0.0001). (figure 2) 
 
The results showed that the mean age of the patients who responded positively to the prone 
position was significantly lower than the mean age of the patients who did not respond to the 
PP (61.89 ± 14.15 vs. 64.64 ± 14.10 years; p=0.017). The mean length of stay in the intensive 
care unit was also lower in the patients who responded to the PP (19.83 ± 3.62 vs. 28.72 ± 
8.43 days; p<0.0001). 
 
Regarding pathological history, we did not find any significant difference between the two 
groups (table 2). As for toxic history, the results showed that smoking was significantly 
related to a lower response to PP (17.90 vs 33.90 %; p= 0.040). 
The proportion of responders in patients with abnormally high lactate levels was significantly 
lower than in patients with normal lactate levels (23.40 vs. 35.00%; p=0.047), and similarly, 
patients with respiratory complications, and more specifically those with Pneumothorax, had 
a lower response to PP (6.70 vs. 33.60%; p=0.027). The univariate analysis is summarized in 
table 2. 
 
Multivariate analysis showed that length of hospitalization, presence of tumor terrain, 
elevated lactate levels and presence of Pneumothorax were significantly associated with 
response to prone position, the degree of lung involvement was also associated with patients' 
response to PP (table 2), patients with critical parenchymal involvement were less likely to 
respond to PP, compared to those with involvement that did not exceed 25%, (RR=0. 34 with 
95% CI [0.15-0.76]; p=0.009). 
 
2.1. survival analysis: 
Concerning mortality, it was 26.28% (n=281) in the total sample. On average, patients with 
SARS CoV-2 in the study series were hospitalized for 20 ± 11 days, with extremes ranging 
from 3 days to 42 days. The average length of hospitalization in the PP group was 26 ± 8 
days, while in the non-PP group it was 9 ± 5 days. 
The median survival in the total sample was 12 ± 3 days with extremes ranging from 2 days 
to 39 days, survival in the PP group was higher than in the non-PP group, (p< 0.0001) 
(figure 3). 
 
The cumulative incidence of mortality at day 28 was lower in the PP group than in the 
non-PP group (Figure 3a, Table 3), (HR=0.044 with 95% CI [0.03-0.06]; p<0.0001). 
The presence of critical lung injury and high lactate levels were significantly associated with 
a high mortality rate (HR=8.43 with 95% CI [2.08-34.20]; p<0.003 / HR=1.55 with 95% CI 
[1.13-2.14]; p<0.007) (Figure 3b,3c; Table 3). 

Discussion: 
 
The PP improves the homogeneity of pulmonary ventilation through the back-lung segments, 
reducing ventilation-perfusion mismatch, and ameliorates the high pressure variations that 
exacerbate regional hyperinflation that exacerbate lung injury (15). 
 
This treatment modality could prevent disease progression by reducing the work of breathing, 
given that the high transpulmonary pressure that occurs with high work of breathing, 
exacerbates the underlying lung damage (14). 
 
Our results agree with previous studies of awake prone position in non-intubated patients 
showing an improvement in oxygenation and a tendency to improvement in symptoms (3-5). 
For example, Sartini found an improvement in oxygenation in the 15 non invasive 
ventilation (NIV) patients with mild to moderate ARDS who practiced vigilant PP for 3 hours 
per day (6). Or Coppo who found a significant improvement in the PaO2/FiO2 ratio before 
and during conscious PP (primary outcome) performed for a minimum of 3 hours in patients 
under oxygen therapy or NIV. The effect was maintained in about 50% of patients however 
this result was not significant (7). 
 
Tolerance of vigilant PP may be a means of selecting patients in whom those who will have a 
favorable evolution with an improvement of the clinical signs. For example, in their 
prospective single-center feasibility study, Elharrar et al. sought to assess the responder rate 
to awake prone position, characterized by an increase in PaO2 of more than 20% between a 
blood gas analysis performed before and during the session. The rate was 25%. Of the 
responders, half were persistent responders (defined as an increase in PaO2 of more than 
20% on blood gas before and 12 hours after DV) (8). 
 
The use of prone positioning in spontaneously breathing patients has been reported 
previously. In 2003, Valter and colleagues (9) reported on four patients in whom prone 
positioning in an awake state rapidly increased oxygenation and avoided oxygenation and 
intubation. Feltracco and colleagues (10,11) reported on five lung transplant recipients who 
successfully underwent awake prone positioning with NIV, with resolution of refractory 
hypoxemia. Scaravilli and colleagues (12) performed a retrospective study in 2015 of 15 
non-intubated patients who underwent a total of 43 prone positioning procedures. They found 
that the procedure was feasible in 95% of all procedures and reported a significant increase in 
PaO2 compared with before prone positioning. 
However, the study by Scaravilli and colleagues is limited by its retrospective nature, the 
variation in interface and ventilatory settings between procedures, and the small number of 
patients. 
 
An important study on this topic is a 2020 trial by Ding and colleagues (4), in which the 
authors evaluated the effect of adding prone positioning to the use of high-flow nasal 
cannulas and noninvasive ventilation in 20 patients with moderate to severe ARDS. They 

found that the addition of prone positioning could have helped avoid intubation in 11 of 20 
patients, and that the PaO2/FiO2 ratio was significantly higher in patients who avoided 
intubation. 
A systematic review examined the effect of awake prone position on oxygenation 
variables in a heterogeneous group of adult patients with COVID-related hypoxemic 
respiratory failure19. The patients with Pao2/Fio2 greater than 150 showed a relatively 
greater improvement in oxygenation, the clinical significance of this result is difficult to 
determine (13). 
 
To note that this study has its limitations: 
● First, although we used robust statistical techniques for adjustment, PP was not 
randomized. 
● Second, note that several studies have been found to be inconsistent regarding 
intubation. Some studies suggest a prevention of intubation with awake PP, but this 
has not confirmed in other studies (16-21), It should be  noted that the different studies 
currently published concerning awake PP in acute respiratory failure patients with 
COVID-19 use a wide variety of judgment criteria. We will take as an example, an 
observational pilot study, in which awake PP was set up from arrival in the 
emergency room until the patient was taken to the ward and analyzed the median 
SpO2 with oxygen therapy. 
● Third, this is a retrospective cohort and the collection of patients were not monitored, 
therefore we did not evaluate the tolerance during each of the PP sessions, in addition 
to the significant heterogeneity of the included patient populations and the lack of 
data on co-interventions used (steroids, antiviral therapies). 
● Fourth, the fact that the intervention was performed in some cases under conditions of 
pandemic stress that affected the availability of resources. 
 
On the whole, these considerations should not distract from the pragmatic observation that 
this positioning reduces intubation and mortality, regardless of the underlying mechanism of 
this effect. These limitations are counterbalanced by the advantage of rapidly setting up an 
international randomized study generating high-level evidence in a short period of time 
frame. 
 
PP in mechanically ventilated patients with ARDS requires the concomitant use of sedatives 
and, often, neuromuscular blocking agents. Pressure sores and compressive neuropathy are 
recognized complications. In our retrospective review, few complications were noted, even 
for longer periods of time than previously reported in conscious patients (4,6,7) and when 
performed over several consecutive days. Conscious patients were able to adjust their 
position, which probably contributes to the reduction in complications. Alternative methods 
with the use of pillows and blankets were performed in our study to reduce the adverse 
effects. 
These results highlight the need to standardize PP practices for better comparison. 
It is possible that some patients may be able to self-position, but their ability to remain in that 
position for extended periods of time is unclear. Similarly, patients who can get into the PP 

are likely to be younger, less frail and require less assistance. All these factors  introduce a 
selection bias when interpreting the potential benefits of PP. 
The selection of an appropriate patient would be the key to the success of adoption of awake 
PP. Recent studies suggest that patients with mild-moderate ARDS (Pao2/Fio2 between 100 
and 300) and a respiratory rate of less than 40 breaths/min may be considered for PP (22,23). 
A study by Mathews et al (11) strongly supports the strategy of awake prone positioning 
for COVID-19 related respiratory failure (24). 
Future studies must adjust for these confounding factors in relation to patient selection. 
 
Conclusion : 
 
Prone positioning appears to be a safe and inexpensive strategy to improve outcomes and 
save limited resources. 
Until further studies confirm or refute our findings, we recommend early and frequent use of 
the awake prone positioning in the hope that it will improve the decrease in the rate of death 
and delay or  prevent intubation. 
Prospective efforts are needed to better define the effect of awake recumbent positioning on 
oxygenation and to improve the ability of patients to tolerate this procedure. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Bibliography: 
 
1. Stuart Winearls et al... Early conscious prone positioning in patients with COVID-19 receiving 
continuous positive airway pressure: a retrospective analysis. DOI: 10.1136/bmjresp-2020-000711.  
 
2. Jaques Sztajnbok et al...Prone positioning to improve oxygenation and relieve respiratory symptoms 
in awake. spontaneously breathing non-intubated patients with COVID-19 pneumonia. 
https://doi.org/10.1016/j.rmcr.2020.101096.  
 
3. Despres C. Brunin Y. Berthier F. Pili-Floury S. Besch G. Prone positioning combined with high-flow 
nasal or conventional oxygen therapy in severe Covid-19 patients. Crit Care. 2020;24(1):256. 
doi:10.1186/s13054-020-03001-6.  
 
4. 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.  
 
5. 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. 
Published online July 2020:S0012369220318882. doi:10.1016/j.chest.2020.07.006.  
 
6. Sartini C. Tresoldi M. Scarpellini P. et al. Respiratory parameters in patients with COVID-19 after 
using noninvasive ventilation in the prone position outside the intensive care unit. JAMA 2020. 
doi:10.1001/jama.2020.7861. [Epub ahead of print: 15 May 2020].  
 
7. 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.  
 
8. Elharrar X. Trigui Y. Dols A-M. et al. Use of Prone Positioning in Nonintubated Patients With COVID-
19 and Hypoxemic Acute Respiratory Failure. JAMA. 2020;323(22):2336. doi:10.1001/jama.2020.8255.  
 
9. 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: 416–18.  
 
10. Feltracco P. Serra E. Barbieri S. et al. Noninvasive high-frequency percussive ventilation in the 
prone position after lung transplantation. Transplant Proc 2012; 44: 2016–21.  
 
11. Feltracco P. Serra E. Barbieri S. et al. Non-invasive ventilation in prone position for refractory 
hypoxemia after bilateral lung transplantation. Clin Transplant 2009; 23: 748–50.  
 
12. 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: 1390–94.  
 
13. Mallikarjuna Ponnapa Reddy et al. Prone Positioning of Nonintubated Patients With Coronavirus 
Disease 2019-A Systematic Review and Meta-Analysis. Crit care med. DOI: 
10.1097/CCM.0000000000005086.  
 
14. Munshi L. Del Sorbo L. Adhikari NKJ. et al. Prone position for acute respiratory distress syndrome. A 
systematic review and metaanalysis. Ann Am Thorac Soc 2017;14:S280–8.  
 
15. Fossali. Tommaso MD1; Pavlovsky. Bertrand MD2 et al. Effects of Prone Position on Lung 
Recruitment and Ventilation-Perfusion Matching in Patients With COVID-19 Acute Respiratory Distress 

Syndrome: A Combined CT Scan/Electrical Impedance Tomography Study. crit care med. doi: 
10.1097/CCM.0000000000005450.  
 
16. Thompson AE. Ranard BL. Wei Y. Jelic S. Prone Positioning in Awake. Nonintubated Patients With 
COVID-19 Hypoxemic Respiratory Failure. JAMA Intern Med. Published online June 17. 2020.  
 
17. Sztajnbok J. Maselli-Schoueri JH. Cunha de Resende Brasil LM. et al. Prone positioning to improve 
oxygenation and relieve respiratory symptoms in awake. spontaneously breathing non-intubated 
patients with COVID-19 pneumonia. Respir Med Case Rep. 2020;30:101096. 
doi:10.1016/j.rmcr.2020.101096.  
 
18. for the COVID-19 Spanish ICU Network. Ferrando C. Mellado-Artigas R. et al. Awake prone 
positioning does not reduce the risk of intubation in COVID-19 treated with highflow nasal oxygen 
therapy: a multicenter. adjusted cohort study. Crit Care. 2020;24(1):597. doi:10.1186/s13054-020-
03314-6.  
 
19. Jagan N. Morrow LE. Walters RW. et al. The POSITIONED Study: Prone Positioning in Nonventilated 
Coronavirus Disease 2019 Patients—A Retrospective Analysis. Crit Care Explor. 2020;2(10):e0229. 
doi:10.1097/CCE.0000000000000229.  
 
20. Padrão EMH. Valente FS. Besen BAMP. et al. Awake Prone Positioning in COVID‐19 Hypoxemic 
Respiratory Failure: Exploratory Findings in a Single‐center Retrospective Cohort Study. Hiestand B. ed. 
Acad Emerg Med. Published online November 21. 2020:acem.14160. doi:10.1111/acem.14160.  
 
21. Nauka PC. Chekuri S. Aboodi M. Hope AA. Gong MN. Chen J-T. A Case-Control Study of Prone 
Positioning in Awake and Nonintubated Hospitalized Coronavirus Disease 2019 Patients. Crit Care 
Explor. 2021;3(2):e0348. doi:10.1097/CCE.0000000000000348.  
 
22. Bower G. He H: Protocol for awake prone positioning in COVID-19 patients: To do it earlier. easier. 
and longer. Crit Care 2020; 24:371.  
 
23. Jiang LG. LeBaron J. Bodnar D. et al: Conscious proning: An introduction of a proning protocol for 
nonintubated. awake. hy poxic emergency department COVID-19 patients. Acad Emerg Med 2020; 
27:566–56.  
 
24. Kusum S Mathews 1 2. Howard Soh et al. Prone Positioning and Survival in Mechanically Ventilated 
Patients With Coronavirus Disease 2019-Related Respiratory Failure. Crit care med. doi: 
10.1097/CCM.0000000000004938.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Tables and figures : 
 
 
 
 
Figure 1: Study profile 
 
 
 
 
 
 
 
 
1366 potentially eligible patients admitted between 
March 2020 to December 2021 
PCR-négative patients 
did not participate : 
(82) 
1286 patients 
patients under 18 years 
did not 
participate :(14) 
1272 patients 
patients who died on 
the day of admission 
did not participate: 
(78) 
1194 patients 
patients intubated on 
the day of admission 
did not participate: 
(125) 
1069 patients enrolled in study 
Prone position group : 681 patients  
Non-prone position group : 388 
ti
t

Tableau 1 : Summary of the demographic and baseline characteristics, 
laboratory/radiological findings, and Treatments/outcome of the patients: 
Demographic and baseline characteristics 
Prone position 
group(n=681) 
Non-prone position 
group(n=388) 
Age, years (mean ± SD) 
63.73±14.17 
63.70±18.49 
Sex n (%): 
Female 
Male 
 
246 (36.10) 
436 (63.90) 
 
174 (45.10) 
212 (54.90) 
IMC kg/m2 (mean ± SD) 
28.4 (4.70) 
28.4 (4.70) 
Time between symptom and admission at hospital, 
days (mean ± std deviation) 
3 (1.30±2) 
3 (1.20±2) 
Symptoms, n (%) 
 
 
Fever 
582 (85.00) 
325 (84.80) 
Chills 
287 (42.30) 
166 (43.10) 
Dyspnea 
589 (86.20) 
329 (85.40) 
Cough 
513 (75.80) 
294 (76.10) 
Anosmia 
83 (12.40) 
51 (13.30) 
Asthenia 
493 (72.30) 
279 (72.50) 
Digestives signs 
238 (35.30) 
135 (35.60) 
Clinical parameter: mean (±SD) 
 
 
Respiratory rate 
32(5.40) 
31(6.10) 
PaO2 
87(10.40) 
88(11.20) 
PaO2/FiO2 
139(39.20) 
143(41.50) 
Co morbidities: n (%) 
 
 
Obesity (BMI >30) 
107 (15.70) 
64 (16.50) 
HTA 
230 (33.70) 
124 (32.00) 
Diabetes 
226 (33.10) 
131 (33.90) 
Smoker 
39 (5.70) 
36 (9.30) 
Preexisting respiratory diseases 
13 (1.90) 
12 (3.10) 
Cardiopathy 
85 (12.50) 
73 (18.90) 
Cancer 
23 (3.40) 
21 (5.40) 
Chronic renal failure (DFG<59) 
3 (0.44) 
2 (0.51) 
Immunodepression 
0 (0) 
0 (0) 
Complications 
 
 
Pulmonary embolism, n (%) 
25 (3.67) 
23 (5.92 

Pleurisy 
0 (0) 
0 (0) 
Pneumothorax 
2 (0.29) 
1 (0.25) 
Degree of pulmonary involvement in CT, n (%) 
Atteinte Modérée <25% 
Atteinte importante (25-50%) 
Atteinte sévère (50-75%) 
Atteinte critique >75% 
 
39 (5.72) 
121 (17.74) 
290 (42.52) 
231 (34.02) 
 
45 (11.60) 
80 (20.70) 
166 (42.90) 
97(24.80) 
Oxygène delivery interface at admission, n (%) 
 
 
Nasal oxygen therapy 
47 (7.00) 
34 (9.00) 
High concentration oxygen therapy 
129 (19.10) 
87 (22.00) 
High flow nasal oxygen therapy 
202 (29.50) 
120 (31.00) 
Continuous positive airway pressure (CPAP) therapy 
108 (16.00) 
54 (14.00) 
Noninvasive ventilation (NIV) 
195 (28.40) 
93 (24.00) 
Laboratory and radiological findings 
 
 
High WBC, n (%) 
299 (44.05) 
166 (43.01) 
Leucopenia, n (%) 
34 (4.92) 
19 (4.83) 
Lymphocytopenia n (%) 
585 (86.70) 
329 (85.80) 
Thrombocytosis, n (%) 
204 (29.17) 
112 (28.24) 
CRP, mean (range) (mg/L) 
398 (10 – 837) 
379 (10-826) 
Ferritin, mean (range) (μg/L) 
1742,2 (10 – 4000) 
1724,5 (10 – 4000) 
Procalcitonin, mean (range) (ng/L) 
207,17 (0,12 – 692) 
202,17 (0,12 – 692) 
Interleukin 6, mean (range) (pg/mL) 
194,82 (0,35 – 6000) 
192,82 (0,35 – 6000) 
D-dimers mean (range) (mg/L) 
7,23 (0,31 – 45,20) 
7,16 (0,31 – 45,20) 
Fibrinogen, mean (+/-SD) (g/L) 
5.25 ±2,79 (0,41 – 9,10) 
5.24 ±2,79 (0,41 – 9,10) 
Corticosteroids therapy, n (%)  
 
 
Methylprednisolone 
374 (55,64) 
217 (56,34) 
Dexamethasone 
82 (12,65) 
47 (12,53) 
Hydrocortisone 
231 (3,47) 
12 (3,51) 
Anticoagulation, n (%) 
 
 
Enoxaparine 
652 (95,60) 
376 (96,30) 
Tinzaparine 
29 (4,40) 
12 (3,70) 
Platelet anti-aggregation inhibitors, n (%) 
 
 
Acetylsalicylic acid 
531 (78,84) 
306 (79,67) 
Anti-interleukin-6 therapy  
 
 
Tocilizumab 
129 (18,45) 
69 (18,65) 

Antibiotics, n (%) 
 
 
Amoxicillin + clavulanic acid 
217 (32,20) 
128 (33,70) 
Ceftriaxone 
306 (44,70) 
170 (43,90) 
Ceftriaxone + ciprofloxacin 
102 (14,40) 
58 (14,70) 
Piperacillin-Tazobactam + voriconazole + amikacin 
61 (8,70) 
32 (8,90) 
 
 
 
SP1
PP1
SP2
0
100
200
300
400
Timepoint
PaO2/FiO2 ratio (mm Hg)
 Figure 2 : PaO2/FiO2 ratio per patient, at the three time points of the study, SP1, PP1 and SP2 
Each datapoint is showing the PaO2/FiO2 ratio at the three timepoints. Responders were defined as 
patients with an increased PaO2/FiO2 ratio between SP1 to SP2 for the main analysis. All other patients 
who were successfully put in the prone position were non-responders. PaO2=partial pressure of oxygen. 
FiO2=fractional concentration of oxygen in inspired air. SP1=baseline supine position. PP1=10 min 
after prone positioning. SP2=1 h after resuming supine position 
 
 
 
 
 
 
 
 

Tableau 2 : Factors associated with a positive response in patients with Covid-19, having benefited 
from the prone position during their hospitalization in the intensive care unit 
 
Variable 
Univariate analysis 
Multivariate analysis 
Responders 
n (%) 
Non- Responders 
n (%) 
P 
Value 
OR [95% CI] 
 
P 
Value 
Age (mean ± SD) 
 
61.89 ± 14.15 
 
64.64 ± 14.10 
0.017 
 
BMI, kg/m2 (mean ± 
SD) 
 
26.64 ±3.86 
 
26.72 ± 3.76 
0.783 
Respiratory rate at 
admission, breaths/min 
(mean ± SD) 
 
34.04 ± 4.61 
 
33.81 ± 4.54 
0,540 
Length of 
hospitalization  
(median (Q1-Q3) 
 
19.00 
(17.00-21.00) 
 
31.00  
(26.00-35.00) 
<0.0001 0.828 [0,798-
0,858] 
<0,0001 
Sex 
 
 
 
0,755 
 
Male 
Female 
142 (32,6) 
83 (33,7) 
294 (67,4) 
163 (66,3) 
Diabetes 
79 (35) 
147 (65) 
0,442 
 
hypertension 
 
 
 
Active smoker 
7 (17,9) 
32 (82,1) 
0,040 
Asthma  
3 (23,1) 
10 (76,9) 
0,561 
Obstructive sleep apnea 
syndrome 
2 (66,7) 
1 (33,3) 
0,254 
Cardiopathy 
21 (24,7) 
64 (75,3) 
0,082 
Gout 
4 (20) 
16 (80) 
0,210 
Hypothyroidism  
6 (26,1) 
17 (73,9) 
0,471 
Chronic obstructive 
pulmonary disease 
4 (50) 
4 (50) 
0,450 
Cancer 
4 (17,4) 
19 (82,6) 
0,106 
0.156 [0,027-
0,910] 
0,039 
Chronic renal failure 
8 (36,4) 
14 (63,6) 
0,732 
 
Immunosuppression 
3 (23,1) 
10 (76,9) 
0,561 
Tuberculosis 
2 (40) 
3 (60) 
0,667 
Hemopathy 
1 (11,1) 
8 (88,9) 
0,284 
Stroke 
 
 
 
Pulmonary embolism 
12 (33,3) 
24 (66,7) 
0,964 

Pneumothorax 
1 (6,7) 
14 (93,3) 
0,027 
0.052 [0,005-
0,574] 
0,016 
Pleurisy 
14 (26,9) 
38 (73,1) 
0,329 
 
Pneumomediastinum 
3 (21,4) 
11 (78,6) 
0,566 
pH 
 
 
0.252 
 
High 
90 (35.4) 
164 (64.6) 
 
 
Normal 
86 (32.5) 
179 (67.5) 
 
 
Low 
31 (26.7) 
85 (73.3) 
 
 
Lactate (>2mmol/l) 
18 (23,4) 
59 (76,6) 
0,047 
0.379 [0,188-
0,765] 
0,007 
HCO3 
 
 
 
0.013 
 
 
High 
68 (34.3) 
130 (65.7) 
 
 
 
Normal 
98 (37.3) 
165 (62.7) 
 
 
 
Low 
42 (24) 
133 (76) 
 
 
 
PaO2 
 
 
0.093 
 
 
Normal 
117 (36.2) 
206 (63.8) 
 
 
 
Low 
108 (30.2) 
250 (69.8) 
 
 
 
PaCO2 
 
 
0.220 
 
 
High 
18 (24) 
57 (76) 
 
 
 
Normal 
88 (34.5) 
167 (65.5) 
 
 
 
Low 
102 (33.4) 
203 (66.6) 
 
 
 
 
 
 
Tableau 3 : Survival analysis in patients with Covid-19 during their hospitalization in the 
intensive care unit 
 
 
Variables 
Staff 
Number 
of deaths 
Median 
survival * 
(IQR) 
Log 
Rank 
test (p) 
Hazard ratio [IC 95%] 
(Cox regression)  
p value  
Sex 
Men  
Women  
1067 
647 
420 
 
160 
122 
 
**(13 - **) 
** (24 - **) 
0.025 
 
 
Prone position  
Yes  
No  
1068 
682 
386 
 
104 
178 
 
** (** -**) 
13 (9 – 18) 
<0.0001 
0.044 [0.03- 0.06] 
<0.0001 
Obesity  
Yes  
No  
1068 
171 
897 
 
52 
230 
 
** (17 - **) 
** (23 - **) 
0.301 
 
 
Age 
1068 
 
 
0.001 
 
 
<65years 
519 
112 
** (26 - **) 
 
 
 
>65years 
549 
170 
** (18 - **) 
 
 
 

Hypertension 
1068 
 
 
0.195 
 
 
Yes 
354 
104 
** (20 - **) 
 
 
 
No 
714 
178 
** (22 - **) 
 
 
 
Diabetes 
1068 
 
 
0 .252 
 
 
Yes 
357 
102 
** (20 - **) 
 
 
 
No 
711 
180 
** (22 - **) 
 
 
 
Active smoker 
1068 
 
 
0.467 
 
 
Yes 
75 
21 
** (16 - **) 
 
 
 
No 
993 
261 
** (22 - **) 
 
 
 
Asthma 
1068 
 
 
0.323 
 
 
Yes 
25 
7 
** (12 - **) 
 
 
 
No 
1043 
275 
** (22 - **) 
 
 
 
Obstructive sleep 
apnea syndrome 
1068 
 
 
0.320 
 
 
Yes 
3 
0 
** (** - **) 
 
 
 
No 
1065 
282 
** (21 - **) 
 
 
 
Chronic obstructive 
pulmonary disease 
1068 
 
 
0.820 
 
 
Yes 
14 
4 
** (13 - **) 
 
 
 
No 
1054 
278 
** (22 - **) 
 
 
 
Cardiopathy 
1068 
 
 
0.241 
 
 
Yes 
158 
46 
** (17 - **) 
 
 
 
No 
910 
236 
** (23 - **) 
 
 
 
Cancer 
1068 
 
 
0.359 
 
 
Yes 
44 
13 
** (13 - **) 
 
 
 
No 
1024 
269 
** (22 - **) 
 
 
 
Chronic renal failure 
1068 
 
 
0.359 
 
 
Yes 
50 
15 
34 (18 - **) 
 
 
 
No 
1018 
267 
** (22 - **) 
 
 
 
Immunosuppression 
1068 
 
 
0.053 
 
 
Yes 
26 
10 
27 (12 - **) 
 
 
 
No 
1042 
272 
** (22 - **) 
 
 
 
Pulmonary embolism 
1068 
 
 
0.436 
 
 
Yes 
54 
17 
** (20 - **) 
 
 
 
No 
1014 
265 
** (22 - **) 
 
 
 
Stroke 
1065 
 
 
<0.0001 
 
 
Yes 
28 
16 
14 (06 - **) 
 
 
 
No 
1037 
266 
** (23 - **) 
 
 
 
Pneumothorax 
1068 
 
 
0.339 
 
 
Yes 
20 
8 
** (13 - **) 
 
 
 
No 
1048 
274 
** (22 - **) 
 
 
 
Pleurisy 
1067 
 
 
0.072 
 
 
Yes 
96 
33 
** (13 - **) 
 
 
 
No 
971 
249 
** (23 - **) 
 
 
 
Pneumomediastinum 
1068 
 
 
0.351 
 
 
Yes 
14 
3 
** (** - **) 
 
 
 
No 
1054 
279 
** (21 - **) 
 
 
 
Pulmonary damage 
(CT scan) 
<25% 
25 - 50% 
50 – 75%  
>75%  
1068 
 
84 
201 
455 
328 
 
 
2 
7 
118 
155 
 
 
** (**-**) 
** (**-**) 
** (20-**) 
27 (09-**) 
 
 
 
1 
0.78 [0.15-4.03] 
3.75 [0.92-15.26] 
8.43 [2.08-34.20] 
<0.0001 
 
 
0.768 
0.065 
0.003 
Time between 
symptom and 
hospitalization 
1024 
 
 
0.009 
 
 
<5days 
919 
242 
** (21 - **) 
 
 
 
>5days 
105 
18 
** (** - **) 
 
 
 

 
 
 
 
 
 
 
Lactate 
 
 
 
<0.0001 
1.557 [1.130-2.143] 
0.007 
Normal 
(<2mmol/l) 
615 
142 
** (25 - **) 
 
 
 
High 
(>2mmol/l) 
126 
52 
** (12 - **) 
 
 
 
pH 
 
 
 
0.229 
 
 
High (>7.35) 
387 
106 
** (21 - **) 
 
 
 
Normal 
420 
107 
** (21 - **) 
 
 
 
Low (<7.35) 
171 
59 
** (18 - **) 
 
 
 
HCO3 
979 
 
 
0.041 
 
 
High (>22) 
297 
68 
** (25 - **) 
 
 
 
Normal 
406 
112 
** (20 - **) 
 
 
 
Low (<22) 
276 
92 
** (14 - **) 
 
 
 
PaO2 
1024 
 
 
0.015 
 
 
Normal 
524 
113 
** (24 - **) 
 
 
 
Low 
500 
161 
** (19 - **) 
 
 
 
PaCO2 
 
 
 
0.155 
 
 
High 
120 
41 
** (17 - **) 
 
 
 
Normal 
372 
95 
** (22 - **) 
 
 
 
Low 
486 
136 
** (20 - **) 
 
 
 
Median survival*: the value of ti for which S(ti) = 0.5: Probability of living being = 50%; IQR: the value 
of ti for which S(ti) = 0.75 and S(ti) = 0.25 respectively. 
(**): Median survival or IQR is not available: ti could not be calculated because we did not observe a 
percentage of 50% or 75% of deaths. 
 
 
 
 
 
 
 
 
 
 
 
 
Figure 3a : Estimation of the probabilities of survival by the Kaplan Meier method in the 
study population at day28 according to the practice or not of awake prone positioning 
 
 

 
 
 
 
 
Figure 3b : Estimation of survival probabilities by the Kaplan Meier method in the study 
population at day28 according to the degree of pulmonary damage 
 
 
 
 
Figure 3c : Estimation of survival probabilities by the Kaplan Meier method in the study 
population at day28 according to the lactate level at admission