| Summary: | Patients receiving mechanical ventilation for coronavirus disease 2019 (COVID-19) related, moderate-to-severe acute respiratory distress syndrome (CARDS) have mortality rates between 76–98%. The objective of this retrospective cohort study was to identify differences in prone ventilation effects on oxygenation, pulmonary infiltrates (as observed on chest X-ray (CXR)), and systemic inflammation in CARDS patients by survivorship and to identify baseline characteristics associated with survival after prone ventilation. The study cohort included 23 patients with moderate-to-severe CARDS who received prone ventilation for ≥16 h/day and was segmented by living status: living (<i>n</i> = 6) and deceased (<i>n</i> = 17). Immediately after prone ventilation, PaO<sub>2</sub>/FiO<sub>2</sub> improved by 108% (<i>p</i> < 0.03) for the living and 150% (<i>p</i> < 3 × 10<sup>−4</sup>) for the deceased. However, the 48 h change in lung infiltrate severity in gravity-dependent lung zones was significantly better for the living than for the deceased (<i>p</i> < 0.02). In CXRs of the lower lungs before prone ventilation, we observed 5 patients with confluent infiltrates bilaterally, 12 patients with ground-glass opacities (GGOs) bilaterally, and 6 patients with mixed infiltrate patterns; 80% of patients with confluent infiltrates were alive vs. 8% of patients with GGOs. In conclusion, our small study indicates that CXRs may offer clinical utility in selecting patients with moderate-to-severe CARDS who will benefit from prone ventilation. Additionally, our study suggests that lung infiltrate severity may be a better indicator of patient disposition after prone ventilation than PaO<sub>2</sub>/FiO<sub>2</sub>.
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