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. 2023 Jan;47(1):23-33.
doi: 10.1016/j.medin.2021.10.002. Epub 2021 Oct 26.

A differential therapeutic consideration for use of corticosteroids according to established COVID-19 clinical phenotypes in critically ill patients

G Moreno  1 , M Ruiz-Botella  2 , I Martín-Loeches  3 , J Gómez Álvarez  2 , M Jiménez Herrera  4 , M Bodí  1   5 , F Armestar  6 , A Marques Parra  7 , Á Estella  8 , S Trefler  1 , R Jorge García  9 , J Murcia Paya  10 , P Vidal Cortes  11 , E Díaz  12 , R Ferrer  13 , A Albaya-Moreno  14 , L Socias-Crespi  15 , J M Bonell Goytisolo  16 , S Sancho Chinesta  17 , A Loza  18 , L Forcelledo Espina  19 , J C Pozo Laderas  20 , M deAlba-Aparicio  20 , L Sánchez Montori  21 , I Vallverdú Perapoch  22 , V Hidalgo  23 , V Fraile Gutiérrez  24 , A M Casamitjana Ortega  25 , F Martín Serrano  26 , M Nieto  27 , M Blasco Cortes  28 , J Marín-Corral  29   30 , J Solé-Violán  31 , A Rodríguez  1   5 ; on behalf COVID-19 SEMICYUC Working Group
Affiliations

A differential therapeutic consideration for use of corticosteroids according to established COVID-19 clinical phenotypes in critically ill patients

G Moreno et al. Med Intensiva. 2023 Jan.

Abstract
in English, Spanish

Objective: To determine if the use of corticosteroids was associated with Intensive Care Unit (ICU) mortality among whole population and pre-specified clinical phenotypes.

Design: A secondary analysis derived from multicenter, observational study.

Setting: Critical Care Units.

Patients: Adult critically ill patients with confirmed COVID-19 disease admitted to 63 ICUs in Spain.

Interventions: Corticosteroids vs. no corticosteroids.

Main variables of interest: Three phenotypes were derived by non-supervised clustering analysis from whole population and classified as (A: severe, B: critical and C: life-threatening). We performed a multivariate analysis after propensity optimal full matching (PS) for whole population and weighted Cox regression (HR) and Fine-Gray analysis (sHR) to assess the impact of corticosteroids on ICU mortality according to the whole population and distinctive patient clinical phenotypes.

Results: A total of 2017 patients were analyzed, 1171 (58%) with corticosteroids. After PS, corticosteroids were shown not to be associated with ICU mortality (OR: 1.0; 95% CI: 0.98-1.15). Corticosteroids were administered in 298/537 (55.5%) patients of "A" phenotype and their use was not associated with ICU mortality (HR = 0.85 [0.55-1.33]). A total of 338/623 (54.2%) patients in "B" phenotype received corticosteroids. No effect of corticosteroids on ICU mortality was observed when HR was performed (0.72 [0.49-1.05]). Finally, 535/857 (62.4%) patients in "C" phenotype received corticosteroids. In this phenotype HR (0.75 [0.58-0.98]) and sHR (0.79 [0.63-0.98]) suggest a protective effect of corticosteroids on ICU mortality.

Conclusion: Our finding warns against the widespread use of corticosteroids in all critically ill patients with COVID-19 at moderate dose. Only patients with the highest inflammatory levels could benefit from steroid treatment.

Objetivo: Evaluar si el uso de corticoesteroides (CC) se asocia con la mortalidad en la unidad de cuidados intensivos (UCI) en la población global y dentro de los fenotipos clínicos predeterminados.

Diseño: Análisis secundario de estudio multicéntrico observacional.

Ámbito: UCI.

Pacientes: Pacientes adultos con COVID-19 confirmado ingresados en 63 UCI de España.

Intervención: Corticoides vs. no corticoides.

Variables de interés principales: A partir del análisis no supervisado de grupos, 3 fenotipos clínicos fueron derivados y clasificados como: A grave, B crítico y C potencialmente mortal. Se efectuó un análisis multivariado después de un propensity optimal full matching (PS) y una regresión ponderada de Cox (HR) y análisis de Fine-Gray (sHR) para evaluar el impacto del tratamiento con CC sobre la mortalidad en la población general y en cada fenotipo clínico.

Resultados: Un total de 2.017 pacientes fueron analizados, 1.171 (58%) con CC. Después del PS, el uso de CC no se relacionó significativamente con la mortalidad en UCI (OR: 1,0; IC 95%: 0,98-1,15). Los CC fueron administrados en 298/537 (55,5%) pacientes del fenotipo A y no se observó asociación significativa con la mortalidad (HR = 0,85; 0,55-1,33). Un total de 338/623 (54,2%) pacientes del fenotipo B recibieron CC sin efecto significativo sobre la mortalidad (HR = 0,72; 0,49-1,05). Por último, 535/857 (62,4%) pacientes del fenotipo C recibieron CC. En este fenotipo, se evidenció un efecto protector de los CC sobre la mortalidad HR (0,75; 0,58-0,98).

Conclusión: Nuestros hallazgos alertan sobre el uso indiscriminado de CC a dosis moderadas en todos los pacientes críticos con COVID-19. Solamente pacientes con elevado estado de inflamación podrían beneficiarse con el tratamiento con CC.

Keywords: COVID-19; Corticosteroids; ICU mortality; Phenotypes; SARS-CoV2-pneumonia; Unsupervised clustering.

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Figures

Figure 1
Figure 1
Weighted Cox hazard regression plot for ICU mortality among A phenotype patient's.
Figure 2
Figure 2
Weighted Cox hazard regression plot for ICU mortality among B phenotype patient's.
Figure 3
Figure 3
Weighted Cox hazard regression plot for ICU mortality among C phenotype patient's.
See this image and copyright information in PMC

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