The Correlation of Respiratory System Compliance and Mortality in COVID-19 Acute Respiratory Distress Syndrome: Do Phenotypes Really Exist?

Background: Recent literature suggests respiratory system compliance (Crs) based phenotypes exist among COVID-19 ARDS patients. We sought to determine whether these phenotypes exist and whether Crs predicts mortality. Methods: A retrospective observational cohort study of 111 COVID-19 ARDS patients admitted March 11-July 8, 2020. Crs was averaged for the first 72-hours of mechanical ventilation. Crs < 30ml/cmH2O was defined as poor Crs(phenotype-H) whereas Crs ≥ 30ml/cmH2O as preserved Crs(phenotype-L). Results: 111 COVID-19 ARDS patients were included, 40 phenotype-H and 71 phenotype-L. Both the mean PaO2/FiO2 ratio for the first 72-hours of mechanical ventilation and the PaO2/FiO2 ratio hospital nadir were lower in phenotype-H than L(115[IQR87] vs 165[87], p = 0.016), (63[32] vs 75[59], p = 0.026). There were no difference in characteristics, diagnostic studies, or complications between groups. Twenty-seven (67.5%) phenotype-H patients died vs 37(52.1%) phenotype-L(p = 0.115). Multivariable regression did not reveal a mortality difference between phenotypes; however, a 2-fold mortality increase was noted in Crs < 20 vs > 50ml/cmH2O when analyzing ordinal Crs groups. Moving up one group level (ex. Crs30-39.9ml/cmH2O to 40-49.9ml/cmH2O), was marginally associated with 14% lower risk of death(RR = 0.86, 95%CI 0.72, 1.01, p = 0.065). This attenuated(RR = 0.94, 95%CI 0.80, 1.11) when adjusting for pH nadir and PaO2/FiO2 ratio nadir. Conclusion: We identified a spectrum of Crs in COVID-19 ARDS similar to Crs distribution in non-COVID-19 ARDS. While we identified increasing mortality as Crs decreased, there was no specific threshold marking significantly different mortality based on phenotype. We therefore would not define COVID-19 ARDS patients by phenotypes-H or L and would not stray from traditional ARDS ventilator management strategies.