COVID-19 versus Non-COVID-19 Acute Respiratory Distress Syndrome: Comparison of Demographics, Physiologic Parameters, Inflammatory Biomarkers, and Clinical Outcomes

Abstract

Rationale: There is an urgent need for improved understanding of the mechanisms and clinical characteristics of acute respiratory distress syndrome (ARDS) due to coronavirus disease (COVID-19).Objectives: To compare key demographic and physiologic parameters, biomarkers, and clinical outcomes of COVID-19 ARDS and ARDS secondary to direct lung injury from other etiologies of pneumonia.Methods: We enrolled 27 patients with COVID-19 ARDS in a prospective, observational cohort study and compared them with a historical, pre-COVID-19 cohort of patients with viral ARDS (n = 14), bacterial ARDS (n = 21), and ARDS due to culture-negative pneumonia (n = 30). We recorded clinical demographics; measured respiratory mechanical parameters; collected serial peripheral blood specimens for measurement of plasma interleukin (IL)-6, IL-8, and IL-10; and followed patients prospectively for patient-centered outcomes. We conducted between-group comparisons with nonparametric tests and analyzed time-to-event outcomes with Kaplan-Meier and Cox proportional hazards models.Results: Patients with COVID-19 ARDS had higher body mass index and were more likely to be Black, or residents of skilled nursing facilities, compared with those with non-COVID-19 ARDS (P < 0.05). Patients with COVID-19 had lower delivered minute ventilation compared with bacterial and culture-negative ARDS (post hoc P < 0.01) but not compared with viral ARDS. We found no differences in static compliance, hypoxemic indices, or carbon dioxide clearance between groups. Patients with COVID-19 had lower IL-6 levels compared with bacterial and culture-negative ARDS at early time points after intubation but no differences in IL-6 levels compared with viral ARDS. Patients with COVID-19 had longer duration of mechanical ventilation but similar 60-day mortality in both unadjusted and adjusted analyses.Conclusions: COVID-19 ARDS bears several similarities to viral ARDS but demonstrates lower minute ventilation and lower systemic levels of IL-6 compared with bacterial and culture-negative ARDS. COVID-19 ARDS was associated with longer dependence on mechanical ventilation compared with non-COVID-19 ARDS. Such detectable differences of COVID-19 do not merit deviation from evidence-based management of ARDS but suggest priorities for clinical research to better characterize and treat this new clinical entity.

Keywords: COVID-19; SARS-CoV-2; acute respiratory distress syndrome; pneumonia.

Figure 1.

Comparison of select mechanical ventilation parameters between COVID-19 ARDS and non–COVID-19 ARDS cohorts obtained on the day of intubation. (A) Baseline Pa_O2:Fi _O2 ratio. (B) Minute ventilation (L/min) and (C) static compliance of the respiratory system (ml/cm H₂O) obtained during the first 24 hours of intubation. Statistical analysis was by Kruskal-Wallis test with Benjamini-Hochberg post hoc test for multiple comparisons of historical groups in relation to the COVID-19 group; asterisks represent post hoc statistical relationships. **P < 0.01. ARDS = acute respiratory distress syndrome; COVID-19 = coronavirus disease; Fi _O2= fraction of inspired oxygen; Pa_O2= arterial oxygen tension/pressure.

Figure 2.

Comparison of select plasma cytokine levels between COVID-19 ARDS and non–COVID-19 ARDS cohorts. Log-transformed plasma levels of (A) IL-6 (pg/ml), (B) IL-8 (pg/ml), and (C) IL-10 (pg/ml) at early (0–4 d), middle (5–10 d), and late (>10 d) time intervals after intubation in patients with COVID-19 ARDS (n = 27 patients) quantified by multiplex assay compared with historical cohorts including ARDS due to viral pneumonia (n = 14 patients), bacterial pneumonia (n = 21 patients), and culture-negative etiology (n = 30 patients) quantified by prior multiplex assay. Statistical analysis was by Kruskal-Wallis test with Benjamini-Hochberg post hoc test for multiple comparisons of historical groups in relation to the COVID-19 group; asterisks represent post hoc statistical relationships. *P < 0.05, **P < 0.01, and ****P < 0.0001. ARDS = acute respiratory distress syndrome; COVID-19 = coronavirus disease; IL = interleukin.

Figure 3.

Comparison of time to ventilator liberation and survival at 60 days between COVID-19 and non–COVID-19 ARDS cohorts. Kaplan-Meier curves of (A) probability of liberation from mechanical ventilation up to 60 days after intubation during COVID-19 ARDS compared with non–COVID-19 ARDS. A Cox proportional hazards model revealed a hazard ratio of 0.48 (95% confidence interval, 0.24–0.98; P < 0.05) after adjustment for age, sex, and nursing home residence, and (B) probability of 60-day survival from date of intensive care unit admission during COVID-19 ARDS compared with non–COVID-19 ARDS. A Cox proportional hazards model revealed a hazard ratio of 0.71 (95% confidence interval, 0.33–1.56; P = 0.39) after adjustment for age, sex, and nursing home residence. ARDS = acute respiratory distress syndrome; COVID-19 = coronavirus disease.