Rationale: Patients with severe coronavirus disease (COVID-19) meet clinical criteria for the acute respiratory distress syndrome (ARDS), yet early reports suggested they differ physiologically and clinically from patients with non-COVID-19 ARDS, prompting treatment recommendations that deviate from standard evidence-based practices for ARDS. Objectives: To compare respiratory physiology, clinical outcomes, and extrapulmonary clinical features of severe COVID-19 with non-COVID-19 ARDS. Methods: We performed a retrospective cohort study, comparing 130 consecutive mechanically ventilated patients with severe COVID-19 with 382 consecutive mechanically ventilated patients with non-COVID-19 ARDS. Initial respiratory physiology and 28-day outcomes were compared. Extrapulmonary manifestations (inflammation, extrapulmonary organ injury, and coagulation) were compared in an exploratory analysis. Results: Comparison of patients with COVID-19 and non-COVID-19 ARDS suggested small differences in respiratory compliance, ventilatory efficiency, and oxygenation. The 28-day mortality was 30% in patients with COVID-19 and 38% in patients with non-COVID-19 ARDS. In adjusted analysis, point estimates of differences in time to breathing unassisted at 28 days (adjusted subdistributional hazards ratio, 0.98 [95% confidence interval (CI), 0.77-1.26]) and 28-day mortality (risk ratio, 1.01 [95% CI, 0.72-1.42]) were small for COVID-19 versus non-COVID-19 ARDS, although the confidence intervals for these estimates include moderate differences. Patients with COVID-19 had lower neutrophil counts but did not differ in lymphocyte count or other measures of systemic inflammation. Conclusions: In this single-center cohort, we found no evidence for large differences between COVID-19 and non-COVID-19 ARDS. Many key clinical features of severe COVID-19 were similar to those of non-COVID-19 ARDS, including respiratory physiology and clinical outcomes, although our sample size precludes definitive conclusions. Further studies are needed to define COVID-19-specific pathophysiology before a deviation from evidence-based treatment practices can be recommended.

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