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Delayed inflammation decrease is associated with mortality in Tocilizumab-treated critically ill SARS-CoV-2 patients: A retrospective matched-cohort analysis.

ABSTRACT: Little is known about the immuno-inflammatory response to Tocilizumab and its association with outcome in critically-ill SARS-CoV2 pneumonia. In this multicenter retrospective cohort of SARS-CoV-2 patients admitted to three intensive care units between March and April 2020, we matched on gender and SAPS II 21 Tocilizumab-treated patients to 42 non-treated patients. Need for mechanical ventilation was 76% versus 79%. IL-6, C-reactive protein, and fibrinogen had been collected within the first days of admission (T1), 3 d (T2) and 7 d (T3) later. Tocilizumab-treated patients had persistently higher IL-6 plasma levels and persistently lower C-Reactive protein and fibrinogen levels. Among Tocilizumab-treated patients, baseline levels of inflammatory biomarkers were not different according to outcome. Conversely, C-reactive protein and fibrinogen decrease was delayed in non-survivors. C-Reactive protein decreased at T1 in survivors (45 [30-98] vs 170 [69-204] mg/l, P < 0.001) but only at T2 in non-survivors (37 [13-74] vs 277 [235-288], P = 0.03). Fibrinogen decreased at T2 in survivors (4.11 [3.58-4.69] vs 614 [5.61-7.85] g/l, P = 0.005) but not in non-survivors (4.79 [4.12-7.58] vs 7.24 [6.22-9.24] g/l, P = 0.125). Tocilizumab treatment was thus associated with a persistent both increase in plasma IL-6, and decrease in C-reactive protein and fibrinogen. Among Tocilizumab-treated patients, the decrease in inflammatory biomarkers was delayed in non-survivors.

SUBMITTER: Urbina T

PROVIDER: S-EPMC8841634 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Delayed inflammation decrease is associated with mortality in Tocilizumab-treated critically ill SARS-CoV-2 patients: A retrospective matched-cohort analysis.

Urbina Tomas T Lavillegrand Jean-Rémi JR Garnier Marc M Mekinian Arsene A Pacanowski Jerome J Mario Nathalie N Dumas Guillaume G Hariri Geoffroy G Pilon Antoine A Darrivère Lucie L Fartoukh Muriel M Guidet Bertrand B Maury Eric E Leblanc Judith J Chantran Yannick Y Fain Olivier O Lacombe Karine K Voiriot Guillaume G Ait-Oufella Hafid H

Innate immunity 20220128 1

Little is known about the immuno-inflammatory response to Tocilizumab and its association with outcome in critically-ill SARS-CoV2 pneumonia. In this multicenter retrospective cohort of SARS-CoV-2 patients admitted to three intensive care units between March and April 2020, we matched on gender and SAPS II 21 Tocilizumab-treated patients to 42 non-treated patients. Need for mechanical ventilation was 76% versus 79%. IL-6, C-reactive protein, and fibrinogen had been collected within the first day ...[more]

PMID: 35089113

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Project description:ImportanceTherapies that improve survival in critically ill patients with coronavirus disease 2019 (COVID-19) are needed. Tocilizumab, a monoclonal antibody against the interleukin 6 receptor, may counteract the inflammatory cytokine release syndrome in patients with severe COVID-19 illness.ObjectiveTo test whether tocilizumab decreases mortality in this population.Design, setting, and participantsThe data for this study were derived from a multicenter cohort study of 4485 adults with COVID-19 admitted to participating intensive care units (ICUs) at 68 hospitals across the US from March 4 to May 10, 2020. Critically ill adults with COVID-19 were categorized according to whether they received or did not receive tocilizumab in the first 2 days of admission to the ICU. Data were collected retrospectively until June 12, 2020. A Cox regression model with inverse probability weighting was used to adjust for confounding.ExposuresTreatment with tocilizumab in the first 2 days of ICU admission.Main outcomes and measuresTime to death, compared via hazard ratios (HRs), and 30-day mortality, compared via risk differences.ResultsAmong the 3924 patients included in the analysis (2464 male [62.8%]; median age, 62 [interquartile range {IQR}, 52-71] years), 433 (11.0%) received tocilizumab in the first 2 days of ICU admission. Patients treated with tocilizumab were younger (median age, 58 [IQR, 48-65] vs 63 [IQR, 52-72] years) and had a higher prevalence of hypoxemia on ICU admission (205 of 433 [47.3%] vs 1322 of 3491 [37.9%] with mechanical ventilation and a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen of <200 mm Hg) than patients not treated with tocilizumab. After applying inverse probability weighting, baseline and severity-of-illness characteristics were well balanced between groups. A total of 1544 patients (39.3%) died, including 125 (28.9%) treated with tocilizumab and 1419 (40.6%) not treated with tocilizumab. In the primary analysis, during a median follow-up of 27 (IQR, 14-37) days, patients treated with tocilizumab had a lower risk of death compared with those not treated with tocilizumab (HR, 0.71; 95% CI, 0.56-0.92). The estimated 30-day mortality was 27.5% (95% CI, 21.2%-33.8%) in the tocilizumab-treated patients and 37.1% (95% CI, 35.5%-38.7%) in the non-tocilizumab-treated patients (risk difference, 9.6%; 95% CI, 3.1%-16.0%).Conclusions and relevanceAmong critically ill patients with COVID-19 in this cohort study, the risk of in-hospital mortality in this study was lower in patients treated with tocilizumab in the first 2 days of ICU admission compared with patients whose treatment did not include early use of tocilizumab. However, the findings may be susceptible to unmeasured confounding, and further research from randomized clinical trials is needed.

Project description:Background: Tocilizumab (TCZ) has been proposed as potential rescue therapy for severe COVID-19. No previous study has primarily assessed the role of TCZ in preventing severe COVID-19-related multiorgan dysfunction. Hence, this multicenter cohort study aimed to evaluate the effectiveness of TCZ early use versus standard of care in preventing severe COVID-19-related multiorgan dysfunction in COVID-19 critically ill patients during intensive care unit (ICU) stay. Methods: A multicenter, retrospective cohort study includes critically ill adult patients with COVID-19 admitted to the ICUs. Patients were categorized into two groups, the treatment group includes patients who received early TCZ therapy within 24 hours of ICU admission and the control group includes patients who received standard of care. The primary outcome was the multiorgan dysfunction on day three of the ICU admission. The secondary outcomes were 30-day, and in-hospital mortality, ventilator-free days, hospital length of stay (LOS), ICU LOS, and ICU-related complications. Results: After propensity score matching, 300 patients were included in the analysis based on predefined criteria with a ratio of 1:2. Patients who received TCZ had lower multiorgan dysfunction score on day three of ICU admission compared to the control group (beta coefficient: -0.13, 95% CI: -0.26, -0.01, P-value = 0.04). Moreover, respiratory failure requiring MV was statistically significantly lower in patients who received early TCZ compared to the control group (OR 0.52; 95% CI 0.31, 0.91, P-value = 0.02). The 30-day and in-hospital mortality were significantly lower in patients who received TCZ than those who did not (HR 0.56; 95% CI 0.37, 0.85, P-value = 0 .006 and HR 0.54; 95% CI 0.36, 0.82, P-value = 0.003, respectively). Conclusion: In addition to the mortality benefits associated with early TCZ use within 24 hours of ICU admission, the use of TCZ was associated with a significantly lower multiorgan dysfunction score on day three of ICU admission in critically ill patients with COVID-19.

Project description:Heart failure with preserved ejection fraction (HFpEF) emerges as a singular subclass of heart failure, bereft of specific therapeutic options. Magnesium, an indispensable trace element, is essential to the preservation of cardiac integrity. However, the association between magnesium supplementation and mortality in HFpEF patients remains unclear. This study extracted HFpEF patient data from the MIMIC-IV database between 2008 and 2019. Propensity score matching was conducted to ensure that patients receiving magnesium supplementation (including magnesium sulfate and magnesium oxide) were balanced with those not receiving it in terms of baseline characteristics. The primary analysis focused on the 28-day all-cause mortality rate, with secondary endpoints encompassing ICU and one-year mortality rates, along with the duration of hospitalization. After matching, the study's final cohort balanced at 1970 patients, with 985 patients per group. The results showed that magnesium intake significantly contributed to a decrease in the 28-day all-cause mortality rate (hazard ratio [HR], 0.682; 95% confidence interval [CI], 0.539-0.863), particularly in subgroups such as older patients (HR, 0.65; 95% CI 0.52-0.81), females (HR, 0.55; 95% CI 0.41-0.73), and those with hypertension (HR, 0.62; 95% CI 0.48-0.79) or without diabetes (HR, 0.54; 95% CI 0.41-0.71). Although magnesium treatment improved both ICU and one-year mortality rates, it concurrently resulted in extended ICU and hospital stays. Mediation analysis indicated that blood urea nitrogen partially mediated the association between magnesium intake and mortality, accounting for approximately 22.73% of the observed effect. Magnesium supplementation has illustrated a significant potential for mitigating the mortality rate in the HFpEF patient, particularly among the elderly, female, and individuals with hypertension. Therefore, magnesium supplementation stands as a potentially valuable supplementary treatment modality for patients with HFpEF. Further comprehensive research is warranted to explore its effects more deeply.

Project description:Background: Hypertension is a rather common comorbidity among critically ill patients and hospital mortality might be higher among critically ill patients with hypertension (SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg). This study aimed to explore the association between ACEI/ARB medication during ICU stay and all-cause in-hospital mortality in these patients. Methods: A retrospective cohort study was conducted based on data from Medical Information Mart for Intensive Care IV (MIMIC-IV) database, which consisted of more than 40,000 patients in ICU between 2008 and 2019 at Beth Israel Deaconess Medical Center. Adults diagnosed with hypertension on admission and those had high blood pressure (SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg) during ICU stay were included. The primary outcome was all-cause in-hospital mortality. Patients were divided into ACEI/ARB treated and non-treated group during ICU stay. Propensity score matching (PSM) was used to adjust potential confounders. Nine machine learning models were developed and validated based on 37 clinical and laboratory features of all patients. The model with the best performance was selected based on area under the receiver operating characteristic curve (AUC) followed by 5-fold cross-validation. After hyperparameter optimization using Grid and random hyperparameter search, a final LightGBM model was developed, and Shapley Additive exPlanations (SHAP) values were calculated to evaluate feature importance of each feature. The features closely associated with hospital mortality were presented as significant features. Results: A total of 15,352 patients were enrolled in this study, among whom 5,193 (33.8%) patients were treated with ACEI/ARB. A significantly lower all-cause in-hospital mortality was observed among patients treated with ACEI/ARB (3.9 vs. 12.7%) as well as a lower 28-day mortality (3.6 vs. 12.2%). The outcome remained consistent after propensity score matching. Among nine machine learning models, the LightGBM model had the highest AUC = 0.9935. The SHAP plot was employed to make the model interpretable based on LightGBM model after hyperparameter optimization, showing that ACEI/ARB use was among the top five significant features, which were associated with hospital mortality. Conclusions: The use of ACEI/ARB in critically ill patients with hypertension during ICU stay is related to lower all-cause in-hospital mortality, which was independently associated with increased survival in a large and heterogeneous cohort of critically ill hypertensive patients with or without kidney dysfunction.

Project description:Corticosteroids use in coronavirus disease 2019 (COVID-19) is controversial, especially in mild to severe patients who do not require invasive/noninvasive ventilation. Moreover, many factors remain unclear regarding the appropriate use of corticosteroids for COVID-19. In this context, this multicenter, retrospective, propensity score-matched study was launched to evaluate the efficacy of systemic corticosteroid administration for hospitalized patients with COVID-19 ranging in the degree of severity from mild to critically-ill disease. This multicenter, retrospective study enrolled consecutive hospitalized COVID-19 patients diagnosed January-April 2020 across 30 institutions in Japan. Clinical outcomes were compared for COVID-19 patients who received or did not receive corticosteroids, after adjusting for propensity scores. The primary endpoint was the odds ratio (OR) for improvement on a 7-point ordinal score on Day 15. Of 1092 COVID-19 patients analyzed, 118 patients were assigned to either the corticosteroid and non-corticosteroid group, after propensity score matching. At baseline, most patients did not require invasive/noninvasive ventilation (85.6% corticosteroid group vs. 89.8% non-corticosteroid group). The odds of improvement in a 7-point ordinal score on Day 15 was significantly lower for the corticosteroid versus non-corticosteroid group (OR, 0.611; 95% confidence interval [CI], 0.388-0.962; p = 0.034). The time to improvement in radiological findings was significantly shorter in the corticosteroid versus non-corticosteroid group (hazard ratio [HR], 1.758; 95% CI, 1.323-2.337; p < 0.001), regardless of baseline clinical status. The duration of invasive mechanical ventilation was shorter in corticosteroid versus non-corticosteroid group (HR, 1.466; 95% CI, 0.841-2.554; p = 0.177). Of the 106 patients who received methylprednisolone, the duration of invasive mechanical ventilation was significantly shorter in the pulse/semi-pulse versus standard dose group (HR, 2.831; 95% CI, 1.347-5.950; p = 0.006). In conclusion, corticosteroids for hospitalized patients with COVID-19 did not improve clinical status on Day 15, but reduced the time to improvement in radiological findings for all patients regardless of disease severity and also reduced the duration of invasive mechanical ventilation in patients who required intubation.Trial registration: This study was registered in the University hospital Medical Information Network Clinical Trials Registry on April 21, 2020 (ID: UMIN000040211).

Dataset Information

Delayed inflammation decrease is associated with mortality in Tocilizumab-treated critically ill SARS-CoV-2 patients: A retrospective matched-cohort analysis.

Publications

Delayed inflammation decrease is associated with mortality in Tocilizumab-treated critically ill SARS-CoV-2 patients: A retrospective matched-cohort analysis.

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