Effect of Prone Positioning on Clinical Outcomes of Non-Intubated Subjects with COVID-19: A Comparative Systematic Review and Meta-Analysis.

Introduction: Awake Prone positioning (APP) has been recently proposed as an adjunctive treatment for non-intubated coronavirus disease 2019 (COVID-19) patients requiring oxygen therapy to improve oxygenation and reduce the risk of intubation. However, the magnitude of the effect of APP on clinical outcomes in these patients remains uncertain. We performed a comparative systematic review and meta-analysis to evaluate the effectiveness of APP to improve the clinical outcomes in non-intubated subjects with COVID-19.Methods: The primary outcomes were the need for endotracheal intubation and mortality. The secondary outcome was the length of hospital stay. Pooled risk ratio (RR) and mean difference (MD) with the corresponding 95% confidence intervals (CIs) were obtained by the Mantel-Haenszel method within a random-effect model.Results: A total of fourteen studies (five randomized controlled trials [RCT] and nine observational studies) involving 3324 subjects (1495 received APP and 1829 did not) were included. There was a significant reduction in the mortality rate in APP group compared to control (RR 0.68, 95% CI 0.51-0.90, P = 0.008, I2 = 52%) with no significant effect on intubation (RR 0.85, 95% CI 0.66-1.08, P = 0.17, I2 = 63%) or length of hospital stay (MD -3.09 days, 95% CI -10.14, 3.96, P = 0.39, I2 = 97%). Subgroup analysis of RCTs showed significant reduction in intubation rate (RR 0.83, 95% CI 0.72-0.97, P = 0.02, I2 = 0%).Conclusions: APP has the potential to reduce the in-hospital mortality rate in COVID-19 subjects with hypoxia without a significant effect on the need for intubation or length of hospital stay. However, there was a significant decrease in the need for intubation on subgroup analysis of RCTs. More large-scale trials with a standardized protocol for prone positioning are needed to better evaluate its effectiveness in this select population.