COVID-PRONE is a multicenter, pragmatic, single-blind, 2-arm, parallel, randomized controlled trial. The intervention is not a medication or a medical device. Instead, the intervention is instructing patients to lie on their stomach while they are in bed.

Patients will be randomized to receive either standard-of-care or pre-emptive prone positioning while in bed (target > 12 hours per day) plus standard of care. Randomization will be stratified by site. Patients randomized to prone positioning will be instructed to i) lie on their stomach supported by their arms and a pillow at the level of their shoulders and another pillow at the level of the pelvis, ii) immediately thereafter their oxygen saturation will be checked, iii) after a two hour period they can reposition to supine (but should be educated on the use of prone position and encouraged to adopt prone position as often as tolerated while in bed); the 2-hour period will be encouraged four times each day in addition to during sleep overnight.

Since there are limited data on the potential risks and benefits of prone positioning, a feasibility analysis will be performed after 30 patients are randomized to identify the rate of serious adverse events in the prone group (e.g., rate of pneumonia, death, intubation) and to understand the change in oxygenation as a result of prone positioning.