Identifying clinical and biochemical phenotypes in acute respiratory distress syndrome secondary to coronavirus disease-2019

Ranjeva, Sylvia; Pinciroli, Riccardo; Hodell, Evan; Mueller, Ariel; Hardin, C.Corey; Thompson, B.Taylor; Berra, Lorenzo

BACKGROUND: Acute respiratory distress syndrome (ARDS) secondary to coronavirus disease-2019 (COVID-19) is characterized by substantial heterogeneity in clinical, biochemical, and physiological characteristics. However, the pathophysiology of severe COVID-19 infection is poorly understood. Previous studies established clinical and biological phenotypes among classical ARDS cohorts, with important therapeutic implications. The phenotypic profile of COVID-19 associated ARDS remains unknown. METHODS: We used latent class modeling via a multivariate mixture model to identify phenotypes from clinical and biochemical data collected from 263 patients admitted to Massachusetts General Hospital intensive care unit with COVID-19-associated ARDS between March 13 and August 2, 2020. FINDINGS: We identified two distinct phenotypes of COVID-19-associated ARDS, with substantial differences in biochemical profiles despite minimal differences in respiratory dynamics. The minority phenotype (class 2, n = 70, 26·6%) demonstrated increased markers of coagulopathy, with mild relative hyper-inflammation and dramatically increased markers of end-organ dysfunction (e.g., creatinine, troponin). The odds of 28-day mortality among the class 2 phenotype was more than double that of the class 1 phenotype (40·0% vs.· 23·3%, OR = 2·2, 95% CI [1·2, 3·9]). INTERPRETATION: We identified distinct phenotypic profiles in COVID-19 associated ARDS, with little variation according to respiratory physiology but with important variation according to systemic and extra-pulmonary markers. Phenotypic identity was highly associated with short-term mortality. The class 2 phenotype exhibited prominent signatures of coagulopathy, suggesting that vascular dysfunction may play an important role in the clinical progression of severe COVID-19-related disease.