ORIGINAL ARTICLE   

Minerva Anestesiologica 2024 March;90(3):172-80

DOI: 10.23736/S0375-9393.23.17765-0

Copyright © 2023 EDIZIONI MINERVA MEDICA

language: English

Corticosteroids induce an early but limited decrease in IL-6 dependent pro-inflammatory responses in critically ill COVID-19 patients

Tomas URBINA ¹ ✉, Paul GABARRE ^{1, 2}, Vincent BONNY ^{1, 2}, Jean-Rémi LAVILLEGRAND ^{1, 2}, Marc GARNIER ^{2, 3}, Jérémie JOFFRE ^{1, 2}, Nathalie MARIO ⁴, Guillaume DUMAS ⁵, Geoffroy HARIRI ^{1, 2}, Matthieu TURPIN ^{2, 6}, Emmanuel PARDO ³, Muriel FARTOUKH ^{2, 6}, Bertrand GUIDET ^{1, 2}, Eric MAURY ^{1, 2}, Yannick CHANTRAN ⁷, Pierre-Yves BOELLE ⁸, Guillaume VOIRIOT ^{2, 6}, Hafid AIT-OUFELLA ^{1, 2, 9}

¹ Intensive Care Unit, Saint-Antoine Hospital, Public Assistance-Hospitals of Paris, Paris, France; ² Sorbonne University, Faculty of Medicine, Paris, France; ³ Anesthesiology and Critical Care Medicine Department, Saint-Antoine Hospital, Public Assistance-Hospitals of Paris, Paris, France; ⁴ Department of Biochemistry, Hormonology and Therapeutic Follow-Up, Saint-Antoine Hospital, Public Assistance-Hospitals of Paris, Paris, France; ⁵ Intensive Care Unit, Saint-Louis Hospital, Public Assistance-Hospitals of Paris, Paris, France; ⁶ Intensive Care Unit, Tenon Hospital, Public Assistance-Hospitals of Paris, Paris, France; ⁷ Department of Biological Immunology, Saint-Antoine Hospital, Public Assistance-Hospitals of Paris, Paris, France; ⁸ INSERM, Sorbonne University, Pierre Louis Institute of Epidemiology and Public Health, Paris, France; ⁹ Inserm U970, Cardiovascular Research Center, University of Paris, Paris, France

BACKGROUND: Corticosteroids have become standard of care for COVID-19 but their effect on the systemic immune-inflammatory response has been little investigated.
METHODS: Multicenter prospective cohort, including critically ill COVID-19 patients between March and November 2020. C-reactive protein (CRP), lymphocyte count and fibrinogen levels were collected upon hospital admission before initiation of steroid treatment and at ICU admission, three days and seven days later, along with interleukin (IL)-6, IL-10 and tumor necrosis factor-alpha (TNF-α) plasma levels.
RESULTS: A hundred and fifty patients were included, 47 received corticosteroids, 103 did not. Median age was 62 [53-70], and 96 (65%) patients were mechanically ventilated. Propensity score matching rendered 45 well-balanced pairs of treated and non-treated patients, particularly on pre-treatment CRP levels. Using a mixed model, CRP (P=0.019), fibrinogen (P=0.003) and lymphocyte counts (P=0.006) remained lower in treated patients over ICU stay. Conversely, there was no significant difference over the ICU stay for Il-6 (P=0.146) and IL-10 (0.301), while TNF- α levels were higher in the treated group (P=0.013). Among corticosteroid-treated patients, CRP (P=0.012), fibrinogen (P=0.041) and lymphocyte count (P=0.004) over time were associated with outcome, whereas plasma cytokine levels were not.
CONCLUSIONS: Steroid treatment was associated with an early and sustained decrease in the downstream IL-6-dependent inflammatory signature but an increase in TNF-α levels. In corticosteroid-treated patients, CRP and lymphocyte count were associated with outcome, conversely to plasma cytokine levels. Further research on using these biomarker’s kinetics to individualize immunomodulatory treatments is warranted.

KEY WORDS: COVID-19; Cytokines, Adrenal cortex hormones; C-reactive protein; Interleukin-6