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Prone positioning is a well-established treatment in mechanically ventilated patients with acute respiratory distress syndrome. Although recommended by guidelines, limited evidence exists on the benefits of prone positioning in awake Corona Virus Disease 2019 (COVID-19) patients. Aim of our systematic review was to provide an overview of all published evidence on this intervention in the setting of COVID-19. Moreover, we aimed to investigate feasibility, efficacy and safety of awake prone positioning in COVID-19 patients with acute respiratory failure. Inclusion criteria were: adult hospitalized, awake, COVID-19 patients, lying in the prone position for respiratory failure. All kind of studies were included without language restriction. Eighty manuscripts involving 3226 patients were included. Need for mechanical ventilation was reported in 26.8% of patients. No periprocedural death or severe adverse events were reported. During prone positioning, a significant improvement in peripheral capillary oxygen saturation (SpO2) and ratio of arterial oxygen partial pressure (PaO2) to fractional inspired oxygen (FiO2) was obtained, together with a reduction in respiratory rate. These improvements persisted after resupination. Awake prone positioning in non-intubated COVID-19 patients is safe and improves oxygenation both during and after the end of proning cycles. Large, high-quality, randomized clinical trials are warranted to determine the impact of prone positioning on survival. [ABSTRACT FROM AUTHOR]