TY - JOUR
T1 - Latent class analysis reveals COVID-19-related acute respiratory distress syndrome subgroups with differential responses to corticosteroids
AU - Sinha, Pratik
AU - Furfaro, David
AU - Cummings, Matthew J.
AU - Abrams, Darryl
AU - Delucchi, Kevin
AU - Maddali, Manoj V.
AU - He, June
AU - Thompson, Alison
AU - Murn, Michael
AU - Fountain, John
AU - Rosen, Amanda
AU - Robbins-Juarez, Shelief Y.
AU - Adan, Matthew A.
AU - Satish, Tejus
AU - Madhavan, Mahesh
AU - Gupta, Aakriti
AU - Lyashchenko, Alexander K.
AU - Agerstrand, Cara
AU - Yip, Natalie H.
AU - Burkart, Kristin M.
AU - Beitler, Jeremy R.
AU - Baldwin, Matthew R.
AU - Calfee, Carolyn S.
AU - Brodie, Daniel
AU - O'Donnell, Max R.
N1 - Publisher Copyright:
Copyright © 2021 by the American Thoracic Society
PY - 2021/12/1
Y1 - 2021/12/1
N2 - Rationale: Two distinct subphenotypes have been identified in acute respiratory distress syndrome (ARDS), but the presence of subgroups in ARDS associated with coronavirus disease (COVID-19) is unknown. Objectives: To identify clinically relevant, novel subgroups in COVID-19-related ARDS and compare them with previously described ARDS subphenotypes. Methods: Eligible participants were adults with COVID-19 and ARDS at Columbia University Irving Medical Center. Latent class analysis was used to identify subgroups with baseline clinical, respiratory, and laboratory data serving as partitioning variables. A previously developed machine learning model was used to classify patients as the hypoinflammatory and hyperinflammatory subphenotypes. Baseline characteristics and clinical outcomes were compared between subgroups. Heterogeneity of treatment effect for corticosteroid use in subgroups was tested. Measurements and Main Results: From March 2, 2020, to April 30, 2020, 483 patients with COVID-19-related ARDS met study criteria. A two-class latent class analysis model best fit the population (P = 0.0075). Class 2 (23%) had higher proinflammatory markers, troponin, creatinine, and lactate, lower bicarbonate, and lower blood pressure than class 1 (77%). Ninety-day mortality was higher in class 2 versus class 1 (75% vs. 48%; P, 0.0001). Considerable overlap was observed between these subgroups and ARDS subphenotypes. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR cycle threshold was associated with mortality in the hypoinflammatory but not the hyperinflammatory phenotype. Heterogeneity of treatment effect to corticosteroids was observed (P = 0.0295), with improved mortality in the hyperinflammatory phenotype and worse mortality in the hypoinflammatory phenotype, with the caveat that corticosteroid treatment was not randomized. Conclusions: We identified two COVID-19-related ARDS subgroups with differential outcomes, similar to previously described ARDS subphenotypes. SARS-CoV-2 PCR cycle threshold had differential value for predicting mortality in the subphenotypes. The subphenotypes had differential treatment responses to corticosteroids.
AB - Rationale: Two distinct subphenotypes have been identified in acute respiratory distress syndrome (ARDS), but the presence of subgroups in ARDS associated with coronavirus disease (COVID-19) is unknown. Objectives: To identify clinically relevant, novel subgroups in COVID-19-related ARDS and compare them with previously described ARDS subphenotypes. Methods: Eligible participants were adults with COVID-19 and ARDS at Columbia University Irving Medical Center. Latent class analysis was used to identify subgroups with baseline clinical, respiratory, and laboratory data serving as partitioning variables. A previously developed machine learning model was used to classify patients as the hypoinflammatory and hyperinflammatory subphenotypes. Baseline characteristics and clinical outcomes were compared between subgroups. Heterogeneity of treatment effect for corticosteroid use in subgroups was tested. Measurements and Main Results: From March 2, 2020, to April 30, 2020, 483 patients with COVID-19-related ARDS met study criteria. A two-class latent class analysis model best fit the population (P = 0.0075). Class 2 (23%) had higher proinflammatory markers, troponin, creatinine, and lactate, lower bicarbonate, and lower blood pressure than class 1 (77%). Ninety-day mortality was higher in class 2 versus class 1 (75% vs. 48%; P, 0.0001). Considerable overlap was observed between these subgroups and ARDS subphenotypes. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR cycle threshold was associated with mortality in the hypoinflammatory but not the hyperinflammatory phenotype. Heterogeneity of treatment effect to corticosteroids was observed (P = 0.0295), with improved mortality in the hyperinflammatory phenotype and worse mortality in the hypoinflammatory phenotype, with the caveat that corticosteroid treatment was not randomized. Conclusions: We identified two COVID-19-related ARDS subgroups with differential outcomes, similar to previously described ARDS subphenotypes. SARS-CoV-2 PCR cycle threshold had differential value for predicting mortality in the subphenotypes. The subphenotypes had differential treatment responses to corticosteroids.
KW - ARDS
KW - COVID-19
KW - Latent class analysis
KW - Phenotyping
UR - http://www.scopus.com/inward/record.url?scp=85119103475&partnerID=8YFLogxK
U2 - 10.1164/rccm.202105-1302OC
DO - 10.1164/rccm.202105-1302OC
M3 - Article
C2 - 34543591
AN - SCOPUS:85119103475
SN - 1073-449X
VL - 204
SP - 1274
EP - 1285
JO - American journal of respiratory and critical care medicine
JF - American journal of respiratory and critical care medicine
IS - 11
ER -