tetano
Editor, Senior Moderator
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[SUP] 1 [/SUP], Anna Motos[SUP] #[/SUP][SUP] 2 3 [/SUP], Rombout van Amstel[SUP] #[/SUP][SUP] 4 [/SUP], Eckart de Bie[SUP] 1 [/SUP], Emma J Kooistra[SUP] 1 [/SUP], Aron Jansen[SUP] 1 [/SUP], Dirk van Lier[SUP] 1 [/SUP], Jason Kennedy[SUP] 5 [/SUP], Daniel Schwarzkopf[SUP] 6 [/SUP], Daniel Thomas-Rüddel[SUP] 6 [/SUP], Jesus F Bermejo-Martin[SUP] 2 [/SUP], Ferran Barbe[SUP] 2 [/SUP], Nicolette F de Keizer[SUP] 7 8 9 [/SUP], Michael Bauer[SUP] 6 [/SUP], Johannes G van der Hoeven[SUP] 1 [/SUP], Antoni Torres[SUP] 10 11 [/SUP], Christopher Seymour[SUP] 5 [/SUP], Lonneke van Vught[SUP] 4 [/SUP], Peter Pickkers[SUP] #[/SUP][SUP] 1 [/SUP], Matthijs Kox[SUP] #[/SUP][SUP] 12 [/SUP]
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 PaO[SUB]2[/SUB]/FiO[SUB]2[/SUB] 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
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[SUP] 1 [/SUP], Anna Motos[SUP] #[/SUP][SUP] 2 3 [/SUP], Rombout van Amstel[SUP] #[/SUP][SUP] 4 [/SUP], Eckart de Bie[SUP] 1 [/SUP], Emma J Kooistra[SUP] 1 [/SUP], Aron Jansen[SUP] 1 [/SUP], Dirk van Lier[SUP] 1 [/SUP], Jason Kennedy[SUP] 5 [/SUP], Daniel Schwarzkopf[SUP] 6 [/SUP], Daniel Thomas-Rüddel[SUP] 6 [/SUP], Jesus F Bermejo-Martin[SUP] 2 [/SUP], Ferran Barbe[SUP] 2 [/SUP], Nicolette F de Keizer[SUP] 7 8 9 [/SUP], Michael Bauer[SUP] 6 [/SUP], Johannes G van der Hoeven[SUP] 1 [/SUP], Antoni Torres[SUP] 10 11 [/SUP], Christopher Seymour[SUP] 5 [/SUP], Lonneke van Vught[SUP] 4 [/SUP], Peter Pickkers[SUP] #[/SUP][SUP] 1 [/SUP], Matthijs Kox[SUP] #[/SUP][SUP] 12 [/SUP]
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 PaO[SUB]2[/SUB]/FiO[SUB]2[/SUB] 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
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.