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Comparing Clinical Features and Outcomes in Mechanically Ventilated Patients with COVID-19 and the Acute Respiratory Distress Syndrome

Our take —

Patients with severe COVID-19 requiring mechanical ventilation meet the criteria for acute respiratory distress syndrome (ARDS), but it is not clear whether symptom severity and clinical outcomes differ between ARDS patients with and without COVID-19. This study, from a single center at the University of Michigan, compared 130 COVID-19 patients who required mechanical ventilation to 382 non-COVID-19 ARDS patients, and found similar degrees of lung impairment, extrapulmonary organ damage, and clinical outcomes between the two groups. Among patients with available laboratory measurements, COVID-19 patients had higher fibrinogen levels and platelet counts, suggesting differences in coagulopathy. The data do not suggest large differences in clinical features of severe COVID-19 relative to non-COVID-19 ARDS, but the study was fairly small and limited in its ability to control sources of bias. Moreover, study design choices may have artificially reduced disease severity in the cohort of COVID-19 patients.

Study design

Retrospective Cohort

Study population and setting

This study compared 130 COVID-19 patients who required mechanical ventilation to 382 patients with non-COVID-19 acute respiratory distress syndrome (ARDS) on mechanical ventilation. COVID-19 patients were consecutively admitted between March 1 and June 30, 2020 to a single center in the United States (University of Michigan); non-COVID-19 ARDS patients were consecutively admitted to the same center between January 1, 2016 and December 31, 2017. Patients were excluded from analysis if they received extracorporeal membrane oxygenation (ECMO) or were intubated for multiple days prior to transfer. Measures of hypoxemia, ventilation, lung function, and the highest sequential organ failure assessment score (SOFA) were extracted from electronic health records from the first 24 hours of mechanical ventilation. Laboratory values were taken from the nearest time within 48 hours of intubation. Lung compliance, ventilatory ratio, and oxygenation index were compared between cases and controls, both unmatched and matched by age, sex, BMI, and the first positive end expiratory pressure (PEEP) level. Time to unassisted breathing after intubation (up to 28 days) was assessed via competing risks survival analysis; patients who died before 28 days were assigned a time-to-event of more than 28 days. Patient status at 28 days and laboratory values (among patients with nonmissing values) were also compared between patients with COVID-19 and patients without COVID-19.

Summary of Main Findings

Respiratory compliance at time of ventilation was low among both COVID-19 (median 34.6 mL/cm H2O) and non-COVID-19 ARDS patients (median 30.0 mL/cm H2O). In a matched subgroup analysis (n=82 in each cohort), there were no statistically significant differences in median respiratory compliance or median oxygenation index between cohorts, while median ventilatory ratio was lower in COVID-19 patients than in non-COVID-19 patients (difference -0.21, 95% CI: -0.35, -0.07). At 28 days after ventilation, 30% of COVID-19 ARDS patients had died, while 38% of non-COVID-19 ARDS patients had died; neither the unadjusted risk ratio nor an adjusted risk ratio was statistically significant. When examining time to unassisted breathing, treating death as a competing risk in multivariable regression, the subdistribution hazard ratio comparing COVID-19 patients to non-COVID-19 patients was null (0.97, 95% CI: 0.73, 1.29). In exploratory analyses among the subset of patients with laboratory values available, measures of extrapulmonary organ injury at initiation of mechanical ventilation were similar between the two cohorts. Total white blood cell counts and neutrophil counts were lower among COVID-19 patients than among non-COVID-19 patients. Some measures of coagulopathy (platelet counts and fibrinogen) were higher among COVID-19 patients than among non-COVID-19 patients.

Study Strengths

The authors examined a range of functional and clinical outcomes, and performed competing risks survival analysis to appropriately examine potential differences in incidence of unassisted breathing after mechanical ventilation.

Limitations

Exclusion of patients who received ECMO or were intubated for several days prior to transfer may have biased results, particularly since the proportion of such patients was much higher in the COVID-19 cohort than in the non-COVID-19 ARDS cohort (70/214 vs. 10/414). Matching on PEEP may have been inappropriate if it was associated with ARDS severity. There were only 130 COVID-19 patients in the analysis, which limited generalizability and the ability to adjust for covariates. Because this was a retrospective cohort study, many patients were missing laboratory parameters that had not been measured at time of mechanical ventilation. The non-COVID-19 ARDS patients were treated during 2016-17, so clinical practices such as prone positioning may have varied between cohorts. COVID-19 patients were far more likely to be Black than non-COVID-19 ARDS patients (42% vs. 10%), and several analyses were not adjusted for self-reported race. With the exception of death and time to unassisted breathing, all indices were compared at time of initiation of mechanical ventilation; longitudinal differences in lung function and laboratory parameters following mechanical ventilation may also be of interest.

Value added

This is the largest direct comparison to date between mechanically ventilated COVID-19 patients and patients with non-COVID-19 ARDS.

This review was posted on: 26 March 2021