Table 2.

Key articles for the interventions in patients with COVID-19 covered in this review.

	Study	Design	Method	Main result	Key point
HFNC	Teng [32]	RCT	Population, severe COVID-19 patients (n = 22); intervention, HFNC (n = 12) vs. COT (n = 10)	P/F ratio at 72 h 321 ± 5 vs. 286 ± 7 (p = 0.001)	This is the only available RCT that compared the efficacy of HFNC and COT.
	Hernandez-Romieu [40]	Retrospective observational study	Population, COVID-19 patients admitted to ICUs; exposure, HFNC prior to intubation (n = 78) vs. intubated without preceding HFNC (n = 97)	Mortality 30.8% vs. 40.2% (p = 0.2)	This is the largest study which explored the safety of HFNC use before the intubation
NPPV	Grieco [78]	RCT	Population, COVID-19 ARF patients (n = 109); intervention, Helmet NPPV (n = 54) vs. HFNC (n = 55)	Intubation rate 30 vs. 51% (95% CI, −38 to −3%, p = 0.03)	This is the only RCT, which investigated the efficacy of helmet NPPV vs. HFNC
	Potalivo [73]	Retrospective observational study	Population, COVID-19 ARF patients who needed respiratory support; exposure IMV after NIV (n = 25) vs. IMV only (n = 41)	Overall 60-day mortality 32.0 vs. 36.6% (p = 0.165)	This is the largest study, which explored the safety of preceding NPPV use before the intubation
Awake proning	Coppo [90]	Prospective observational study	Population, non-intubated patients with COVID-19 ARF; exposure awake proning (n = 47)	P/F ratio before vs. after 180.5 vs. 285.5 (p < 0.001)	This study reported that the awake proning improved P/F ratio in patients with COVID-19
	Padrão [91]	Retrospective observational study	Population, patients with COVID-19 ARF (n = 166); exposure, awake proning (n = 57) vs. usual care (n = 109)	Intubation rate 58 vs. 49% (95% CI, 0.78–1.88, p = 0.39)	This larger study investigated the effect of awake proning in patients with COVID-19, reporting no benefits to avoid the intubation