Faculty Collaboration Database

Identification of Distinct Clinical Subphenotypes in Critically Ill Patients With COVID-19. Chest 2021 Sep;160(3):929-943

Date

05/09/2021

Pubmed ID

33964301

Pubmed Central ID

PMC8099539

DOI

10.1016/j.chest.2021.04.062

Scopus ID

2-s2.0-85111778652 (requires institutional sign-in at Scopus site)   21 Citations

Abstract

BACKGROUND: Subphenotypes have been identified in patients with sepsis and ARDS and are associated with different outcomes and responses to therapies.

RESEARCH QUESTION: Can unique subphenotypes be identified among critically ill patients with COVID-19?

STUDY DESIGN AND METHODS: Using data from a multicenter cohort study that enrolled critically ill patients with COVID-19 from 67 hospitals across the United States, we randomly divided centers into discovery and replication cohorts. We used latent class analysis independently in each cohort to identify subphenotypes based on clinical and laboratory variables. We then analyzed the associations of subphenotypes with 28-day mortality.

RESULTS: Latent class analysis identified four subphenotypes (SP) with consistent characteristics across the discovery (45 centers; n = 2,188) and replication (22 centers; n = 1,112) cohorts. SP1 was characterized by shock, acidemia, and multiorgan dysfunction, including acute kidney injury treated with renal replacement therapy. SP2 was characterized by high C-reactive protein, early need for mechanical ventilation, and the highest rate of ARDS. SP3 showed the highest burden of chronic diseases, whereas SP4 demonstrated limited chronic disease burden and mild physiologic abnormalities. Twenty-eight-day mortality in the discovery cohort ranged from 20.6% (SP4) to 52.9% (SP1). Mortality across subphenotypes remained different after adjustment for demographics, comorbidities, organ dysfunction and illness severity, regional and hospital factors. Compared with SP4, the relative risks were as follows: SP1, 1.67 (95% CI, 1.36-2.03); SP2, 1.39 (95% CI, 1.17-1.65); and SP3, 1.39 (95% CI, 1.15-1.67). Findings were similar in the replication cohort.

INTERPRETATION: We identified four subphenotypes of COVID-19 critical illness with distinct patterns of clinical and laboratory characteristics, comorbidity burden, and mortality.

Author List

Vasquez CR, Gupta S, Miano TA, Roche M, Hsu J, Yang W, Holena DN, Reilly JP, Schrauben SJ, Leaf DE, Shashaty MGS, STOP-COVID Investigators

Authors

Daniel N. Holena MD Professor in the Surgery department at Medical College of Wisconsin
Christina Mariyam Joy MD Assistant Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acute Kidney Injury
Aged
Comorbidity
Critical Illness
Female
Humans
Male
Middle Aged
Pandemics
Renal Replacement Therapy
United States