Study identifies two distinct phenotypes of COVID-19-associated ARDS
Researchers identified distinct phenotypes of COVID-19-associated acute respiratory distress syndrome were that have substantial differences in their response to disease and risk for mortality.
“The motivation for our work is that if we can identify subsets of patients with different biochemical characteristics, and then those patients respond differently to treatment or have different clinical outcomes, we would be one step closer to a more mechanism-based understanding of ARDS,” Sylvia Ranjeva, MD, PhD, investigator in the department of anesthesia, critical care and pain medicine at Massachusetts General Hospital, said in a press release.
Researchers collected clinical and biochemical data from 263 patients (mean age, 58.8 years; 66.5% men) admitted to the ICU at Massachusetts General Hospital with COVID-19-associated ARDS from March to August 2020. To identify distinct phenotypes, researchers used latent class modeling via a multivariate mixture model in the cohort.
The results were published in EClinicalMedicine.
There were substantial differences in the biochemical profiles of the two distinct phenotypes of COVID-19-associated ARDS that were identified. Seventy patients (26.6%) had the minority class 2 phenotype, with increased biomarker levels in the bloodstream that indicated blood-clotting disorders (D-dimer: 2,335 ng/L vs. 1,326 ng/L; P < .001), higher inflammation (prothrombin time: 17.2 seconds vs. 14.2 seconds; P < .001) and organ dysfunction (pH: 7.34 vs. 7.36; P = .046) compared with 193 patients (72.2%) who had the class 1 phenotype.
Among the class 2 phenotype, odds for 28-day mortality were more than double that of the class 1 phenotype (40% vs. 23.3%; OR = 2.2; 95% CI, 1.2-3.9).
According to Ranjeva, treatment decisions for patients with ARDS are typically based on how their bodies and immune systems respond to disease. Although previous studies have suggested some patients have a “hyperinflammatory” phenotype due to their bodies responding by unleashing cytokines and other substances to fight disease, several studies found that these subsets of patients have a 20% greater risk for mortality compared with other patients.
“Overall, our results suggest that phenotypic profiles in COVID-19-associated ARDS reflect a distinct disease process, with important variation according to systemic and extrapulmonary markers,” the researchers wrote. “Vascular dysfunction may play an important role in severe COVID-19-related disease.”