Rapidly improving acute respiratory distress syndrome in COVID-19: a multi-centre observational study

Abstract

Background: Before the pandemic of coronavirus disease (COVID-19), rapidly improving acute respiratory distress syndrome (ARDS), mostly defined by early extubation, had been recognized as an increasingly prevalent subphenotype (making up 15-24% of all ARDS cases), associated with good prognosis (10% mortality in ARDSNet trials). We attempted to determine the prevalence and prognosis of rapidly improving ARDS and of persistent severe ARDS related to COVID-19.

Methods: We included consecutive patients with COVID-19 receiving invasive mechanical ventilation in three intensive care units (ICU) during the second pandemic wave in Greece. We defined rapidly improving ARDS as extubation or a partial pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO₂:FiO₂) greater than 300 on the first day following intubation. We defined persistent severe ARDS as PaO₂:FiO₂ of equal to or less than 100 on the second day following intubation.

Results: A total of 280 intubated patients met criteria of ARDS with a median PaO₂:FiO₂ of 125.0 (interquartile range 93.0-161.0) on day of intubation, and overall ICU-mortality of 52.5% (ranging from 24.3 to 66.9% across the three participating sites). Prevalence of rapidly improving ARDS was 3.9% (11 of 280 patients); no extubation occurred on the first day following intubation. ICU-mortality of patients with rapidly improving ARDS was 54.5%. This low prevalence and high mortality rate of rapidly improving ARDS were consistent across participating sites. Prevalence of persistent severe ARDS was 12.1% and corresponding mortality was 82.4%.

Conclusions: Rapidly improving ARDS was not prevalent and was not associated with good prognosis among patients with COVID-19. This is starkly different from what has been previously reported for patients with ARDS not related to COVID-19. Our results on both rapidly improving ARDS and persistent severe ARDS may contribute to our understanding of trajectory of ARDS and its association with prognosis in patients with COVID-19.

Keywords: Acute respiratory distress syndrome; Acute respiratory failure; Coronavirus; Pneumonia; Trajectory.

Fig. 1

Distribution of included patients with acute respiratory distress (ARDS) across the three participating study sites. Out of the intubated patients with new coronavirus disease (COVID-19) who were hospitalized in the participating intensive care units during the study period, six patients (three from Athens and three from Larissa) did not meet the oxygenation criterion [i.e., they had partial pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO₂:FiO₂) more than 300] of the Berlin definition of ARDS on the day of intubation and therefore were excluded from our study

Fig. 2

Kaplan–Meier curves of mortality for the three study groups. Differences in mortality between rapidly improving acute respiratory distress (ARDS) group, intermediate group and persistent severe ARDS group were assessed using the log-rank test. There was no statistically significant difference between rapidly improving ARDS group and intermediate group, while there were statistically significant differences between persistent severe ARDS group and rapidly improving ARDS group (p = 0.018) or intermediate group (p < 0.001). Patients discharged from the intensive care unit with unassisted breathing before 28 days considered to be alive at 28 days following intubation