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Intensive Care Med
. 2024 Aug 26.
doi: 10.1007/s00134-024-07593-3. Online ahead of print. Clinical phenotyping uncovers heterogeneous associations between corticosteroid treatment and survival in critically ill COVID-19 patients
Niklas Bruse 1 , Anna Motos # 2 3 , Rombout van Amstel # 4 , Eckart de Bie 1 , Emma J Kooistra 1 , Aron Jansen 1 , Dirk van Lier 1 , Jason Kennedy 5 , Daniel Schwarzkopf 6 , Daniel Thomas-Rüddel 6 , Jesus F Bermejo-Martin 2 , Ferran Barbe 2 , Nicolette F de Keizer 7 8 9 , Michael Bauer 6 , Johannes G van der Hoeven 1 , Antoni Torres 10 11 , Christopher Seymour 5 , Lonneke van Vught 4 , Peter Pickkers # 1 , Matthijs Kox # 12
Affiliations
Purpose: Disease heterogeneity in coronavirus disease 2019 (COVID-19) may render the current one-size-fits-all treatment approach suboptimal. We aimed to identify and immunologically characterize clinical phenotypes among critically ill COVID-19 patients, and to assess heterogeneity of corticosteroid treatment effect.
Methods: We applied consensus k-means clustering on 21 clinical parameters obtained within 24 h after admission to the intensive care unit (ICU) from 13,279 COVID-19 patients admitted to 82 Dutch ICUs from February 2020 to February 2022. Derived phenotypes were reproduced in 6225 COVID-19 ICU patients from Spain (February 2020 to December 2021). Longitudinal immunological characterization was performed in three COVID-19 ICU cohorts from the Netherlands and Germany, and associations between corticosteroid treatment and survival were assessed across phenotypes.
Results: We derived three phenotypes: COVIDICU1 (43% of patients) consisted of younger patients with the lowest Acute Physiology And Chronic Health Evaluation (APACHE) scores, highest body mass index (BMI), lowest PaO2/FiO2 ratio, and a 90-day in-hospital mortality rate of 18%. COVIDICU2 patients (37%) had the lowest BMI, were older and had higher APACHE scores and mortality rate (24%) than COVIDICU1. Patients with COVIDICU3 (20%) were the eldest with the most comorbidities, the highest APACHE scores, acute kidney injury and metabolic dysregulations, and the highest mortality rate (47%). These patients also displayed the most pronounced inflammatory response. Corticosteroid therapy started at day 5 [2-9] after ICU admission and administered for 5 [3-7] days was associated with an increased risk for 90-day mortality in patients with the COVIDICU1 and COVIDICU2 phenotypes (hazard ratio [HR] 1.59 [1.09-2.31], p = 0.015 and HR 1.79 [1.42-2.26], p < 0.001, respectively), but not in patients with the COVIDICU3 phenotype (HR 1.08 [0.76-1.54], p = 0.654).
Conclusion: Our multinational study identified three distinct clinical COVID-19 phenotypes, each exhibiting marked differences in demographic, clinical, and immunological features, and in the response to late and short-term corticosteroid treatment.
Keywords: COVID-19; Corticosteroids; Heterogeneity; Inflammation; Machine learning; Phenotypes.
. 2024 Aug 26.
doi: 10.1007/s00134-024-07593-3. Online ahead of print. Clinical phenotyping uncovers heterogeneous associations between corticosteroid treatment and survival in critically ill COVID-19 patients
Niklas Bruse 1 , Anna Motos # 2 3 , Rombout van Amstel # 4 , Eckart de Bie 1 , Emma J Kooistra 1 , Aron Jansen 1 , Dirk van Lier 1 , Jason Kennedy 5 , Daniel Schwarzkopf 6 , Daniel Thomas-Rüddel 6 , Jesus F Bermejo-Martin 2 , Ferran Barbe 2 , Nicolette F de Keizer 7 8 9 , Michael Bauer 6 , Johannes G van der Hoeven 1 , Antoni Torres 10 11 , Christopher Seymour 5 , Lonneke van Vught 4 , Peter Pickkers # 1 , Matthijs Kox # 12
Affiliations
- PMID: 39186112
- DOI: 10.1007/s00134-024-07593-3
Purpose: Disease heterogeneity in coronavirus disease 2019 (COVID-19) may render the current one-size-fits-all treatment approach suboptimal. We aimed to identify and immunologically characterize clinical phenotypes among critically ill COVID-19 patients, and to assess heterogeneity of corticosteroid treatment effect.
Methods: We applied consensus k-means clustering on 21 clinical parameters obtained within 24 h after admission to the intensive care unit (ICU) from 13,279 COVID-19 patients admitted to 82 Dutch ICUs from February 2020 to February 2022. Derived phenotypes were reproduced in 6225 COVID-19 ICU patients from Spain (February 2020 to December 2021). Longitudinal immunological characterization was performed in three COVID-19 ICU cohorts from the Netherlands and Germany, and associations between corticosteroid treatment and survival were assessed across phenotypes.
Results: We derived three phenotypes: COVIDICU1 (43% of patients) consisted of younger patients with the lowest Acute Physiology And Chronic Health Evaluation (APACHE) scores, highest body mass index (BMI), lowest PaO2/FiO2 ratio, and a 90-day in-hospital mortality rate of 18%. COVIDICU2 patients (37%) had the lowest BMI, were older and had higher APACHE scores and mortality rate (24%) than COVIDICU1. Patients with COVIDICU3 (20%) were the eldest with the most comorbidities, the highest APACHE scores, acute kidney injury and metabolic dysregulations, and the highest mortality rate (47%). These patients also displayed the most pronounced inflammatory response. Corticosteroid therapy started at day 5 [2-9] after ICU admission and administered for 5 [3-7] days was associated with an increased risk for 90-day mortality in patients with the COVIDICU1 and COVIDICU2 phenotypes (hazard ratio [HR] 1.59 [1.09-2.31], p = 0.015 and HR 1.79 [1.42-2.26], p < 0.001, respectively), but not in patients with the COVIDICU3 phenotype (HR 1.08 [0.76-1.54], p = 0.654).
Conclusion: Our multinational study identified three distinct clinical COVID-19 phenotypes, each exhibiting marked differences in demographic, clinical, and immunological features, and in the response to late and short-term corticosteroid treatment.
Keywords: COVID-19; Corticosteroids; Heterogeneity; Inflammation; Machine learning; Phenotypes.