Dataset Information

Glucocorticoids with low-dose anti-IL1 anakinra rescue in severe non-ICU COVID-19 infection: A cohort study.

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.

SUBMITTER: Borie R

PROVIDER: S-EPMC7743937 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Glucocorticoids with low-dose anti-IL1 anakinra rescue in severe non-ICU COVID-19 infection: A cohort study.

Borie Raphael R Savale Laurent L Dossier Antoine A Ghosn Jade J Taillé Camille C Visseaux Benoit B Jebreen Kamel K Diallo Abourahmane A Tesmoingt Chloe C Morer Lise L Goletto Tiphaine T Faucher Nathalie N Hajouji Linda L Neukirch Catherine C Phillips Mathilde M Stelianides Sandrine S Bouadma Lila L Brosseau Solenn S Ottaviani Sébastien S Pluvy Johan J Le Pluart Diane D Debray Marie-Pierre MP Raynaud-Simon Agathe A Descamps Diane D Khalil Antoine A Timsit Jean Francois JF Lescure Francois-Xavier FX Descamps Vincent V Papo Thomas T Humbert Marc M Crestani Bruno B Dieude Philippe P Vicaut Eric E Zalcman Gérard G

PloS one 20201216 12

<h4>Background</h4>The optimal treatment for patients with severe coronavirus-19 disease (COVID-19) and hyper-inflammation remains debated.<h4>Material and methods</h4>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 al ...[more]

PMID: 33326457

Similar Datasets

Project description:BackgroundCoronaviruses can induce the production of interleukin (IL)-1β, IL-6, tumour necrosis factor, and other cytokines implicated in autoinflammatory disorders. It has been postulated that anakinra, a recombinant IL-1 receptor antagonist, might help to neutralise the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related hyperinflammatory state, which is considered to be one cause of acute respiratory distress among patients with COVID-19. We aimed to assess the off-label use of anakinra in patients who were admitted to hospital for severe forms of COVID-19 with symptoms indicative of worsening respiratory function.MethodsThe Ana-COVID study included a prospective cohort from Groupe Hospitalier Paris Saint-Joseph (Paris, France) and a historical control cohort retrospectively selected from the Groupe Hospitalier Paris Saint-Joseph COVID cohort, which began on March 18, 2020. Patients were included in the prospective cohort if they were aged 18 years or older and admitted to Groupe Hospitalier Paris Saint-Joseph with severe COVID-19-related bilateral pneumonia on chest x-ray or lung CT scan. The other inclusion criteria were either laboratory-confirmed SARS-CoV-2 or typical lung infiltrates on a lung CT scan, and either an oxygen saturation of 93% or less under oxygen 6 L/min or more, or aggravation (saturation ≤93% under oxygen 3 L/min) with a loss of 3% of oxygen saturation in ambient air over the previous 24 h. The historical control group of patients had the same inclusion criteria. Patients in the anakinra group were treated with subcutaneous anakinra (100 mg twice a day for 72 h, then 100 mg daily for 7 days) as well as the standard treatments at the institution at the time. Patients in the historical group received standard treatments and supportive care. The main outcome was a composite of either admission to the intensive care unit (ICU) for invasive mechanical ventilation or death. The main analysis was done on an intention-to-treat basis (including all patients in the anakinra group who received at least one injection of anakinra).FindingsFrom March 24 to April 6, 2020, 52 consecutive patients were included in the anakinra group and 44 historical patients were identified in the Groupe Hospitalier Paris Saint-Joseph COVID cohort study. Admission to the ICU for invasive mechanical ventilation or death occurred in 13 (25%) patients in the anakinra group and 32 (73%) patients in the historical group (hazard ratio [HR] 0·22 [95% CI 0·11-0·41; p<0·0001). The treatment effect of anakinra remained significant in the multivariate analysis (HR 0·22 [95% CI 0·10-0·49]; p=0·0002). An increase in liver aminotransferases occurred in seven (13%) patients in the anakinra group and four (9%) patients in the historical group.InterpretationAnakinra reduced both need for invasive mechanical ventilation in the ICU and mortality among patients with severe forms of COVID-19, without serious side-effects. Confirmation of efficacy will require controlled trials.FundingGroupe Hospitalier Paris Saint-Joseph.

Project description:Background and aimsAbdominal sepsis refers to a severe and potentially life-threatening condition characterized by the presence of infection, inflammation, and tissue damage within the abdominal cavity. Glucocorticoids (GCs) play an important role in regulation of the host immune and inflammation responses involved in sepsis and surgery. This study aimed to investigate the potential impact of intraoperative GCs administration on the clinical outcome of surgical patients with abdominal sepsis.MethodsThis retrospective cohort study included a 1:1 propensity score-matched cohort of surgical patients afflicted with abdominal sepsis at two medical centers from January 2008 to December 2022. Patients were classified into low-GCs, high-GCs, and non-GCs groups according to the dosage of steroids used intraoperatively, and in-hospital mortality was designated as the primary outcome.ResultsThis study included a total of 476 patients, with 217 in the non-GCs group, 213 in the low-GCs group, and 46 in the high-GCs group. The overall in-hospital mortality rate was 7.56%. After propensity score matching (PSM), there were 168 cases in both the low-GCs group and the non-GCs group, with no significant differences observed between the groups regarding mortality rate, length of hospital-stay, and duration of intensive care unit (ICU) stay. In patients with septic shock, the use of low-dose GCs increased the urine output and decreased the requirements for vasopressors on the first postoperative day, however, it had no impact on the in-hospital mortality or ICU stay. Moreover, prophylactic use of GCs during anesthesia induction did not decrease the incidence of intraoperative hypotension or necessity of vasopressors use.ConclusionIntraoperative administration of low-dose GCs demonstrates a transient improvement in hemodynamics of patients with septic shock, however, it did not lead to improved clinical outcomes. Further research remains necessary to elucidate the optimal perioperative dosing strategy.

Project description:BackgroundLow-dose glucocorticoids are frequently used for the management of rheumatoid arthritis (RA) and other chronic conditions, but the safety of long-term use remains uncertain.ObjectiveTo quantify the risk for hospitalized infection with long-term use of low-dose glucocorticoids in patients with RA receiving stable disease-modifying antirheumatic drug (DMARD) therapy.DesignRetrospective cohort study.SettingMedicare claims data and Optum's deidentified Clinformatics Data Mart database from 2006 to 2015.PatientsAdults with RA receiving a stable DMARD regimen for more than 6 months.MeasurementsAssociations between glucocorticoid dose (none, ≤5 mg/d, >5 to 10 mg/d, and >10 mg/d) and hospitalized infection were evaluated using inverse probability-weighted analyses, with 1-year cumulative incidence predicted from weighted models.Results247 297 observations were identified among 172 041 patients in Medicare and 58 279 observations among 44 118 patients in Optum. After 6 months of stable DMARD use, 47.1% of Medicare patients and 39.5% of Optum patients were receiving glucocorticoids. The 1-year cumulative incidence of hospitalized infection in Medicare patients not receiving glucocorticoids was 8.6% versus 11.0% (95% CI, 10.6% to 11.5%) for glucocorticoid dose of 5 mg or less per day, 14.4% (CI, 13.8% to 15.1%) for greater than 5 to 10 mg/d, and 17.7% (CI, 16.5% to 19.1%) for greater than 10 mg/d (all P < 0.001 vs. no glucocorticoids). The 1-year cumulative incidence of hospitalized infection in Optum patients not receiving glucocorticoids was 4.0% versus 5.2% (CI, 4.7% to 5.8%) for glucocorticoid dose of 5 mg or less per day, 8.1% (CI, 7.0% to 9.3%) for greater than 5 to 10 mg/d, and 10.6% (CI, 8.5% to 13.2%) for greater than 10 mg/d (all P < 0.001 vs. no glucocorticoids).LimitationPotential for residual confounding and misclassification of glucocorticoid dose.ConclusionIn patients with RA receiving stable DMARD therapy, glucocorticoids were associated with a dose-dependent increase in the risk for serious infection, with small but significant risks even at doses of 5 mg or less per day. Clinicians should balance the benefits of low-dose glucocorticoids with this potential risk.Primary funding sourceNational Institute of Arthritis and Musculoskeletal and Skin Diseases.

Dataset Information

Glucocorticoids with low-dose anti-IL1 anakinra rescue in severe non-ICU COVID-19 infection: A cohort study.

Background

Material and methods

Results

Conclusion

Publications

Glucocorticoids with low-dose anti-IL1 anakinra rescue in severe non-ICU COVID-19 infection: A cohort study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets