To the best of our knowledge, this is the first multicenter study that prospectively evaluated the benefits and the role of HFNO combined with awake prone positioning in the prevention of intubation in an adjusted large cohort of COVID-19 patients.

We found that this combined approach did not reduce the risk of intubation, but could increase the risk of delaying intubation. In the current study, awake-PP did not affect 28-day mortality.

The interpretation of these results may be limited by the observational design, and therefore future studies are needed to identify potential subpopulations that may benefit from awake prone positioning in COVID-19 patients with acute hypoxemic respiratory failure.

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