Interleukin-6 and Pulmonary Compliance in COVID-19-Related Acute Respiratory Distress Syndrome

Abstract

Rationale: Higher levels of circulating interleukin-6 (IL-6) and lower respiratory system compliance have each been associated with increased mortality in severe coronavirus 2019 (COVID-19). IL-6 levels are associated with disease severity and mortality in non-COVID-19-related acute respiratory distress syndrome (ARDS). The purpose of this study was to examine the relationship between IL-6 and respiratory mechanics in COVID-19-related ARDS. Methods: This retrospective cohort study took place at two Columbia University Irving Medical Center hospitals. We identified patients age >18 years with laboratory confirmed COVID-19, who were intubated from March 1st through April 30th, 2020, and met the Berlin definition of ARDS. Electronic medical records were reviewed for clinical data. Outcomes were censored at 90 days after intubation. For patients without IL-6 levels recorded on the initial day of intubation, serum samples were obtained from the Columbia University Biobank and tested using the Quantikine Human IL-6 Immunoassay. IL-6 values were log-transformed. The primary outcome was respiratory system compliance. Secondary outcomes were calculated ventilatory ratio, PaO2:FiO2 ratio, and mortality. Linear regression and logistic regression were used for statistical analyses. Results: During the study period, 483 patients had COVID-19-associated ARDS. Median time of follow up was 37 days (IQR 11-90). At 90 days, 260 (53.8%) patients were deceased, 206 (42.7%) had been discharged, and 17 (3.5%) were still admitted. Two hundred sixteen (44.7%) patients had available data on respiratory system compliance and serum IL-6 levels from the initial day of mechanical ventilation. The median IL-6 value was 204.1 pg/ml (IQR 110-469.7). Median compliance was 25.5 ml/cmH2O (IQR 21.4-33.3), median ventilatory ratio was 1.96 (IQR 1.51-2.57), and median PaO2:FiO2 ratio was 134 (IQR 87-196). In unadjusted linear regression, higher IL-6 was associated with lower respiratory system compliance (log [IL-6] coefficient-1.80, p = 0.001) (Figure 1). This relationship remained significant when adjusting for age, sex, body mass index, race, ethnicity, and Sequential Organ Failure Assessment (SOFA) score (coefficient-2.43, p<0.001). There was no significant association between IL-6 and ventilatory ratio (0.76 p=0.08) or PaO2:FiO2 ratio (-6.15 p=0.06). Higher IL-6 was associated with higher odds of death at 90 days (OR 1.35 per unit increase in log [IL-6], p-value 0.022) when adjusting for age, sex, body mass index, race, ethnicity, and SOFA score. Conclusion: In COVID-19-associated ARDS, higher levels of IL-6 were associated with lower respiratory system compliance even adjusting for measured confounders. Higher IL-6 was also associated with higher mortality.