Raphael Borie1, Laurent Savale2, Antoine Dossier3, Jade Ghosn4, Camille Taillé1, Benoit Visseaux5, Kamel Jebreen6, Abourahmane Diallo6, Chloe Tesmoingt7, Lise Morer1, Tiphaine Goletto1, Nathalie Faucher8, Linda Hajouji1, Catherine Neukirch1, Mathilde Phillips1, Sandrine Stelianides1, Lila Bouadma9, Solenn Brosseau1, Sébastien Ottaviani10, Johan Pluvy1, Diane Le Pluart4, Marie-Pierre Debray11, Agathe Raynaud-Simon7, Diane Descamps5, Antoine Khalil11, Jean Francois Timsit9, Francois-Xavier Lescure4, Vincent Descamps12, Thomas Papo3, Marc Humbert2, Bruno Crestani1, Philippe Dieude10, Eric Vicaut6, Gérard Zalcman1. 1. Pulmonology and Thoracic Oncology Department, University Hospital Bichat-Claude Bernard, AP-HP, Université de Paris, Paris, France. 2. Pulmonology Department, Kremlin-Bicêtre University Hospital, AP-HP, Paris-Saclay University, Kremlin-Bicêtre, France. 3. Internal Medicine Department, University Hospital Bichat-Claude Bernard, AP-HP, Université de Paris, Paris, France. 4. Infectious Disease Department, University Hospital Bichat-Claude Bernard, AP-HP, Université de Paris, Paris, France. 5. Virology Department, University Hospital Bichat-Claude Bernard, AP-HP, Université de Paris, Paris, France. 6. Biostatistics and Clinical Research Department, University Hospital Lariboisière, AP-HP, Université de Paris, Paris, France. 7. Pharmacy Department, University Hospital Bichat-Claude Bernard, AP-HP, Université de Paris, Paris, France. 8. Geriatrics Department, University Hospital Bichat-Claude Bernard, AP-HP, Université de Paris, Paris, France. 9. Medical and infectious Diseases ICU, Intensive Care Department, University Hospital Bichat-Claude Bernard, AP-HP, Université de Paris, Paris, France. 10. Rheumatology Department, University Hospital Bichat-Claude Bernard, AP-HP, Université de Paris, Paris, France. 11. Radiology Department, University Hospital Bichat-Claude Bernard, AP-HP, Université de Paris, Paris, France. 12. Dermatology Department, University Hospital Bichat-Claude Bernard, AP-HP, Université de Paris, Paris, France.
Abstract
BACKGROUND: The optimal treatment for patients with severe coronavirus-19 disease (COVID-19) and hyper-inflammation remains debated. MATERIAL AND METHODS: A cohort study was designed to evaluate whether a therapeutic algorithm using steroids with or without interleukin-1 antagonist (anakinra) could prevent death/invasive ventilation. Patients with a ≥5-day evolution since symptoms onset, with hyper-inflammation (CRP≥50mg/L), requiring 3-5 L/min oxygen, received methylprednisolone alone. Patients needing ≥6 L/min received methylprednisolone + subcutaneous anakinra daily either frontline or in case clinical deterioration upon corticosteroids alone. Death rate and death or intensive care unit (ICU) invasive ventilation rate at Day 15, with Odds Ratio (OR) and 95% CIs, were determined according to logistic regression and propensity scores. A Bayesian analysis estimated the treatment effects. RESULTS: Of 108 consecutive patients, 70 patients received glucocorticoids alone. The control group comprised 63 patients receiving standard of care. In the corticosteroid±stanakinra group (n = 108), death rate was 20.4%, versus 30.2% in the controls, indicating a 30% relative decrease in death risk and a number of 10 patients to treat to avoid a death (p = 0.15). Using propensity scores a per-protocol analysis showed an OR for COVID-19-related death of 0.9 (95%CI [0.80-1.01], p = 0.067). On Bayesian analysis, the posterior probability of any mortality benefit with corticosteroids+/-anakinra was 87.5%, with a 7.8% probability of treatment-related harm. Pre-existing diabetes exacerbation occurred in 29 of 108 patients (26.9%). CONCLUSION: In COVID-19 non-ICU inpatients at the cytokine release phase, corticosteroids with or without anakinra were associated with a 30% decrease of death risk on Day 15.
BACKGROUND: The optimal treatment for patients with severe coronavirus-19 disease (COVID-19) and hyper-inflammation remains debated. MATERIAL AND METHODS: A cohort study was designed to evaluate whether a therapeutic algorithm using steroids with or without interleukin-1 antagonist (anakinra) could prevent death/invasive ventilation. Patients with a ≥5-day evolution since symptoms onset, with hyper-inflammation (CRP≥50mg/L), requiring 3-5 L/min oxygen, received methylprednisolone alone. Patients needing ≥6 L/min received methylprednisolone + subcutaneous anakinra daily either frontline or in case clinical deterioration upon corticosteroids alone. Death rate and death or intensive care unit (ICU) invasive ventilation rate at Day 15, with Odds Ratio (OR) and 95% CIs, were determined according to logistic regression and propensity scores. A Bayesian analysis estimated the treatment effects. RESULTS: Of 108 consecutive patients, 70 patients received glucocorticoids alone. The control group comprised 63 patients receiving standard of care. In the corticosteroid±stanakinra group (n = 108), death rate was 20.4%, versus 30.2% in the controls, indicating a 30% relative decrease in death risk and a number of 10 patients to treat to avoid a death (p = 0.15). Using propensity scores a per-protocol analysis showed an OR for COVID-19-related death of 0.9 (95%CI [0.80-1.01], p = 0.067). On Bayesian analysis, the posterior probability of any mortality benefit with corticosteroids+/-anakinra was 87.5%, with a 7.8% probability of treatment-related harm. Pre-existing diabetes exacerbation occurred in 29 of 108 patients (26.9%). CONCLUSION: In COVID-19 non-ICU inpatients at the cytokine release phase, corticosteroids with or without anakinra were associated with a 30% decrease of death risk on Day 15.
Authors: Fanny Pojero; Giuseppina Candore; Calogero Caruso; Danilo Di Bona; David A Groneberg; Mattia E Ligotti; Giulia Accardi; Anna Aiello Journal: Int J Mol Sci Date: 2021-03-05 Impact factor: 5.923