Latent Class Analysis Reveals COVID-19-related ARDS Subgroups with Differential Responses to Corticosteroids.

Sinha, Pratik; Furfaro, David; Cummings, Matthew J; Abrams, Darryl; Delucchi, Kevin; Maddali, Manoj V; He, June; Thompson, Alison; Murn, Michael; Fountain, John; Rosen, Amanda; Robbins-Juarez, Shelief Y; Adan, Matthew A; Satish, Tejus; Madhavan, Mahesh; Gupta, Aakriti; Lyashchenko, Alexander K; Agerstrand, Cara; Yip, Natalie H; Burkart, Kristin M; Beitler, Jeremy R; Baldwin, Matthew R; Calfee, Carolyn S; Brodie, Daniel; O'Donnell, Max R

Rationale Two distinct subphenotypes have been identified in acute respiratory distress syndrome (ARDS), but the presence of subgroups in ARDS associated with COVID-19 is unknown. The objective of this study was to identify clinically relevant, novel subgroups in COVID-19-related ARDS, and compare them to previously described ARDS subphenotypes. Methods Eligible participants were adults with COVID-19 and ARDS at Columbia University Irving Medical Center. Latent class analysis (LCA) 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 (HTE) for corticosteroid-use in subgroups was tested. Measurements and Main Results From 3/2-4/30/2020, 483 patients with COVID-19-related ARDS met study criteria. A two-class LCA model best fit the population (p=0.0075). Class 2 (23%) had higher pro-inflammatory markers, troponin, creatinine and lactate, lower bicarbonate and lower blood pressure than Class 1 (77%). 90-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. SARS-CoV-2 RT-PCR cycle threshold was associated with mortality in the hypoinflammatory but not the hyperinflammatory phenotype. HTE 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. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).