• Hui Chen, Jianfeng Xie, Nan Su, Jun Wang, Qin Sun, Shusheng Li, Jun Jin, Jing Zhou, Min Mo, Yao Wei, Yali Chao, Weiwei Hu, Bin Du, and Haibo Qiu.
• Department of Critical Care Medicine, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou.
• Chest. 2021 May 1; 159 (5): 1793-1802.

BackgroundCorticosteroid therapy is used commonly in patients with COVID-19, although its impact on outcomes and which patients could benefit from corticosteroid therapy are uncertain.Research QuestionAre clinical phenotypes of COVID-19 associated with differential response to corticosteroid therapy?Study Design And MethodsCritically ill patients with COVID-19 from Tongji Hospital treated between January and February 2020 were included, and the main exposure of interest was the administration of IV corticosteroids. The primary outcome was 28-day mortality. Marginal structural modeling was used to account for baseline and time-dependent confounders. An unsupervised machine learning approach was carried out to identify phenotypes of COVID-19.ResultsA total of 428 patients were included; 280 of 428 patients (65.4%) received corticosteroid therapy. The 28-day mortality was significantly higher in patients who received corticosteroid therapy than in those who did not (53.9% vs 19.6%; P < .0001). After marginal structural modeling, corticosteroid therapy was not associated significantly with 28-day mortality (hazard ratio [HR], 0.80; 95% CI, 0.54-1.18; P = .26). Our analysis identified two phenotypes of COVID-19, and compared with the hypoinflammatory phenotype, the hyperinflammatory phenotype was characterized by elevated levels of proinflammatory cytokines, higher Sequential Organ Failure Assessment scores, and higher rates of complications. Corticosteroid therapy was associated with a reduced 28-day mortality (HR, 0.45; 95% CI, 0.25-0.80; P = .0062) in patients with the hyperinflammatory phenotype.InterpretationFor critically ill patients with COVID-19, corticosteroid therapy was not associated with 28-day mortality, but the use of corticosteroids showed significant survival benefits in patients with the hyperinflammatory phenotype.Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

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