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

Abstract COVID-19-associated respiratory failure offers the unprecedented opportunity to evaluate the differential host response to a uniform pathogenic insult. Understanding whether there are distinct subphenotypes of severe COVID-19 may offer insight into its pathophysiology. Sequential Organ Fail...

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Autores principales:	Chang Su, Zhenxing Xu, Katherine Hoffman, Parag Goyal, Monika M. Safford, Jerry Lee, Sergio Alvarez-Mulett, Luis Gomez-Escobar, David R. Price, John S. Harrington, Lisa K. Torres, Fernando J. Martinez, Thomas R. Campion, Fei Wang, Edward J. Schenck
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/60c0ec0f788e43808f9f647ba6275bcc
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spelling	oai:doaj.org-article:60c0ec0f788e43808f9f647ba6275bcc2021-12-02T16:35:37ZIdentifying organ dysfunction trajectory-based subphenotypes in critically ill patients with COVID-1910.1038/s41598-021-95431-72045-2322https://doaj.org/article/60c0ec0f788e43808f9f647ba6275bcc2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95431-7https://doaj.org/toc/2045-2322Abstract COVID-19-associated respiratory failure offers the unprecedented opportunity to evaluate the differential host response to a uniform pathogenic insult. Understanding whether there are distinct subphenotypes of severe COVID-19 may offer insight into its pathophysiology. Sequential Organ Failure Assessment (SOFA) score is an objective and comprehensive measurement that measures dysfunction severity of six organ systems, i.e., cardiovascular, central nervous system, coagulation, liver, renal, and respiration. Our aim was to identify and characterize distinct subphenotypes of COVID-19 critical illness defined by the post-intubation trajectory of SOFA score. Intubated COVID-19 patients at two hospitals in New York city were leveraged as development and validation cohorts. Patients were grouped into mild, intermediate, and severe strata by their baseline post-intubation SOFA. Hierarchical agglomerative clustering was performed within each stratum to detect subphenotypes based on similarities amongst SOFA score trajectories evaluated by Dynamic Time Warping. Distinct worsening and recovering subphenotypes were identified within each stratum, which had distinct 7-day post-intubation SOFA progression trends. Patients in the worsening suphenotypes had a higher mortality than those in the recovering subphenotypes within each stratum (mild stratum, 29.7% vs. 10.3%, p = 0.033; intermediate stratum, 29.3% vs. 8.0%, p = 0.002; severe stratum, 53.7% vs. 22.2%, p < 0.001). Pathophysiologic biomarkers associated with progression were distinct at each stratum, including findings suggestive of inflammation in low baseline severity of illness versus hemophagocytic lymphohistiocytosis in higher baseline severity of illness. The findings suggest that there are clear worsening and recovering subphenotypes of COVID-19 respiratory failure after intubation, which are more predictive of outcomes than baseline severity of illness. Distinct progression biomarkers at differential baseline severity of illness suggests a heterogeneous pathobiology in the progression of COVID-19 respiratory failure.Chang SuZhenxing XuKatherine HoffmanParag GoyalMonika M. SaffordJerry LeeSergio Alvarez-MulettLuis Gomez-EscobarDavid R. PriceJohn S. HarringtonLisa K. TorresFernando J. MartinezThomas R. CampionFei WangEdward J. SchenckNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chang Su Zhenxing Xu Katherine Hoffman Parag Goyal Monika M. Safford Jerry Lee Sergio Alvarez-Mulett Luis Gomez-Escobar David R. Price John S. Harrington Lisa K. Torres Fernando J. Martinez Thomas R. Campion Fei Wang Edward J. Schenck Identifying organ dysfunction trajectory-based subphenotypes in critically ill patients with COVID-19
description	Abstract COVID-19-associated respiratory failure offers the unprecedented opportunity to evaluate the differential host response to a uniform pathogenic insult. Understanding whether there are distinct subphenotypes of severe COVID-19 may offer insight into its pathophysiology. Sequential Organ Failure Assessment (SOFA) score is an objective and comprehensive measurement that measures dysfunction severity of six organ systems, i.e., cardiovascular, central nervous system, coagulation, liver, renal, and respiration. Our aim was to identify and characterize distinct subphenotypes of COVID-19 critical illness defined by the post-intubation trajectory of SOFA score. Intubated COVID-19 patients at two hospitals in New York city were leveraged as development and validation cohorts. Patients were grouped into mild, intermediate, and severe strata by their baseline post-intubation SOFA. Hierarchical agglomerative clustering was performed within each stratum to detect subphenotypes based on similarities amongst SOFA score trajectories evaluated by Dynamic Time Warping. Distinct worsening and recovering subphenotypes were identified within each stratum, which had distinct 7-day post-intubation SOFA progression trends. Patients in the worsening suphenotypes had a higher mortality than those in the recovering subphenotypes within each stratum (mild stratum, 29.7% vs. 10.3%, p = 0.033; intermediate stratum, 29.3% vs. 8.0%, p = 0.002; severe stratum, 53.7% vs. 22.2%, p < 0.001). Pathophysiologic biomarkers associated with progression were distinct at each stratum, including findings suggestive of inflammation in low baseline severity of illness versus hemophagocytic lymphohistiocytosis in higher baseline severity of illness. The findings suggest that there are clear worsening and recovering subphenotypes of COVID-19 respiratory failure after intubation, which are more predictive of outcomes than baseline severity of illness. Distinct progression biomarkers at differential baseline severity of illness suggests a heterogeneous pathobiology in the progression of COVID-19 respiratory failure.
format	article
author	Chang Su Zhenxing Xu Katherine Hoffman Parag Goyal Monika M. Safford Jerry Lee Sergio Alvarez-Mulett Luis Gomez-Escobar David R. Price John S. Harrington Lisa K. Torres Fernando J. Martinez Thomas R. Campion Fei Wang Edward J. Schenck
author_facet	Chang Su Zhenxing Xu Katherine Hoffman Parag Goyal Monika M. Safford Jerry Lee Sergio Alvarez-Mulett Luis Gomez-Escobar David R. Price John S. Harrington Lisa K. Torres Fernando J. Martinez Thomas R. Campion Fei Wang Edward J. Schenck
author_sort	Chang Su
title	Identifying organ dysfunction trajectory-based subphenotypes in critically ill patients with COVID-19
title_short	Identifying organ dysfunction trajectory-based subphenotypes in critically ill patients with COVID-19
title_full	Identifying organ dysfunction trajectory-based subphenotypes in critically ill patients with COVID-19
title_fullStr	Identifying organ dysfunction trajectory-based subphenotypes in critically ill patients with COVID-19
title_full_unstemmed	Identifying organ dysfunction trajectory-based subphenotypes in critically ill patients with COVID-19
title_sort	identifying organ dysfunction trajectory-based subphenotypes in critically ill patients with covid-19
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/60c0ec0f788e43808f9f647ba6275bcc
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Identifying organ dysfunction trajectory-based subphenotypes in critically ill patients with COVID-19

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