Objective:Coronavirus disease 2019 (COVID-19) can cause acute respiratory distress syndrome (ARDS). Invasive mechanical ventilation (IMV) support and prone positioning are essential treatments for severe COVID-19 ARDS. We aimed to determine the combined effect of prone position and airway pressure release ventilation (APRV) modes on oxygen improvement in mechanically-ventilated patients with COVID-19.Methods:This prospective observational study included 40 eligible patients (13 female, 27 male). Of 40 patients, 23 (57.5%) were ventilated with APRV and 17 (42.5%) were ventilated with controlled modes. A prone position was applied when the PaO2/FiO2ratio <150 mmHg despite IMV in COVID-19 ARDS. The numbers of patients who completed the first, second, and third prone were 40, 25, and 15, respectively. Incident barotrauma events were diagnosed by both clinical findings and radiological images.Results:After the second prone, the PaO2/FiO2ratio of the APRV group was higher compared to the PaO2/FiO2ratio of the control group [189 (150-237)] vs. 127 (100-146) mmHg, respectively, (P=0.025). Similarly, after the third prone, the PaO2/FiO2ratio of the APRV group was higher compared to the PaO2/FiO2ratio of the control group [194 (132-263)] vs. 83 (71-136) mmHg, respectively, (P=0.021). Barotrauma events were detected in 13.0% of the patients in the APRV group and 11.8% of the patients in the control group (P=1000). The 28-day mortality was not different in the APRV group than in the control group (73.9% vs. 70.6%, respectively,P=1000).Conclusion:Using the APRV mode during prone positioning improves oxygenation, especially in the second and third prone positions, without increasing the risk of barotrauma. However, no benefit on mortality was detected.