Identifying organ dysfunction trajectory-based subphenotypes in critically ill patients with COVID-19

Area of Science:

• Critical Care Medicine
• Infectious Diseases
• Pathophysiology

Background:

• COVID-19 respiratory failure presents a uniform insult, allowing study of differential host responses.
• Understanding COVID-19 subphenotypes is crucial for elucidating severe disease pathophysiology.

Purpose of the Study:

• To identify and characterize distinct subphenotypes of critical COVID-19 illness.
• To analyze subphenotypes based on the post-intubation trajectory of Sequential Organ Failure Assessment (SOFA) scores.

Main Methods:

• Utilized intubated COVID-19 patient data from two New York City hospitals for development and validation cohorts.
• Employed hierarchical agglomerative clustering with Dynamic Time Warping to analyze SOFA score trajectories within mild, intermediate, and severe baseline strata.
• Grouped patients based on baseline post-intubation SOFA scores.

Main Results:

• Identified distinct worsening and recovering subphenotypes within each baseline severity stratum.
• Worsening subphenotypes demonstrated significantly higher mortality rates compared to recovering subphenotypes across all strata.
• Distinct pathophysiologic biomarkers, including inflammation and hemophagocytic lymphohistiocytosis, were associated with progression at different baseline severity levels.

Conclusions:

• Clear worsening and recovering subphenotypes of COVID-19 respiratory failure exist post-intubation.
• These subphenotypes are more predictive of patient outcomes than baseline illness severity.
• Heterogeneous pathobiology in COVID-19 progression is suggested by distinct biomarkers at differential baseline severity.