Relationship between ventilator-associated pneumonia and mortality in COVID-19 patients: a planned ancillary analysis of the coVAPid cohort

Background Patients with SARS-CoV-2 infection are at higher risk for ventilator-associated pneumonia (VAP). No study has evaluated the relationship between VAP and mortality in this population, or compared this relationship between SARS-CoV-2 patients and other populations. The main objective of our study was to determine the relationship between VAP and mortality in SARS-CoV-2 patients. Methods Planned ancillary analysis of a multicenter retrospective European cohort. VAP was diagnosed using clinical, radiological and quantitative microbiological criteria. Univariable and multivariable marginal Cox's regression models, with cause-specific hazard for duration of mechanical ventilation and ICU stay, were used to compare outcomes between study groups. Extubation, and ICU discharge alive were considered as events of interest, and mortality as competing event. Findings Of 1576 included patients, 568 were SARS-CoV-2 pneumonia, 482 influenza pneumonia, and 526 no evidence of viral infection at ICU admission. VAP was associated with significantly higher risk for 28-day mortality in SARS-CoV-2 group (adjusted HR 1.65 (95% CI 1.11-2.46), p = 0.013), but not in influenza (1.74 (0.99-3.06), p = 0.052), or no viral infection groups (1.13 (0.68-1.86), p = 0.63). VAP was associated with significantly longer duration of mechanical ventilation in the SARS-CoV-2 group, but not in the influenza or no viral infection groups. VAP was associated with significantly longer duration of ICU stay in the 3 study groups. No significant difference was found in heterogeneity of outcomes related to VAP between the 3 groups, suggesting that the impact of VAP on mortality was not different between study groups. Interpretation VAP was associated with significantly increased 28-day mortality rate in SARS-CoV-2 patients. However, SARS-CoV-2 pneumonia, as compared to influenza pneumonia or no viral infection, did not significantly modify the relationship between VAP and 28-day mortality

a retrospective multicenter study

Funding This study was supported in part by a grant from the French government through the « Programme Investissement d’Avenir» (I-SITE ULNE) managed by the Agence Nationale de la Recherche (coVAPid project). Prof. Ignacio Martin-Loeches has been supported by SFI (Science Foundation Ireland), Grant number 20/COV/0038. The funders of the study had no role in the study design, data collection, analysis or interpretation, writing of the report or deci sion to submit for publication.BACKGROUND: Ventilator-associated pneumonia (VAP) is common in patients with severe SARS-CoV-2 pneumonia. The aim of this ancillary analysis of the coVAPid multicenter observational retrospective study is to assess the relationship between adjuvant corticosteroid use and the incidence of VAP. METHODS: Planned ancillary analysis of a multicenter retrospective European cohort in 36 ICUs. Adult patients receiving invasive mechanical ventilation for more than 48 h for SARS-CoV-2 pneumonia were consecutively included between February and May 2020. VAP diagnosis required strict definition with clinical, radiological and quantitative microbiological confirmation. We assessed the association of VAP with corticosteroid treatment using univariate and multivariate cause-specific Cox's proportional hazard models with adjustment on pre-specified confounders. RESULTS: Among the 545 included patients, 191 (35%) received corticosteroids. The proportional hazard assumption for the effect of corticosteroids on the incidence of VAP could not be accepted, indicating that this effect varied during ICU stay. We found a non-significant lower risk of VAP for corticosteroid-treated patients during the first days in the ICU and an increased risk for longer ICU stay. By modeling the effect of corticosteroids with time-dependent coefficients, the association between corticosteroids and the incidence of VAP was not significant (overall effect p = 0.082), with time-dependent hazard ratios (95% confidence interval) of 0.47 (0.17-1.31) at day 2, 0.95 (0.63-1.42) at day 7, 1.48 (1.01-2.16) at day 14 and 1.94 (1.09-3.46) at day 21. CONCLUSIONS: No significant association was found between adjuvant corticosteroid treatment and the incidence of VAP, although a time-varying effect of corticosteroids was identified along the 28-day follow-up.publishersversionpublishe

a planned ancillary analysis of the coVAPid cohort

Funding: This study was supported in part by a grant from the French government through the «Programme Investissement d’Avenir» (I-SITE ULNE) managed by the Agence Nationale de la Recherche (coVAPid project). The funders of the study had no role in the study design, data collection, analysis, or interpreta tion, writing of the report, or decision to submit for publication.BACKGROUND: Patients with SARS-CoV-2 infection are at higher risk for ventilator-associated pneumonia (VAP). No study has evaluated the relationship between VAP and mortality in this population, or compared this relationship between SARS-CoV-2 patients and other populations. The main objective of our study was to determine the relationship between VAP and mortality in SARS-CoV-2 patients. METHODS: Planned ancillary analysis of a multicenter retrospective European cohort. VAP was diagnosed using clinical, radiological and quantitative microbiological criteria. Univariable and multivariable marginal Cox's regression models, with cause-specific hazard for duration of mechanical ventilation and ICU stay, were used to compare outcomes between study groups. Extubation, and ICU discharge alive were considered as events of interest, and mortality as competing event. FINDINGS: Of 1576 included patients, 568 were SARS-CoV-2 pneumonia, 482 influenza pneumonia, and 526 no evidence of viral infection at ICU admission. VAP was associated with significantly higher risk for 28-day mortality in SARS-CoV-2 (adjusted HR 1.70 (95% CI 1.16-2.47), p = 0.006), and influenza groups (1.75 (1.03-3.02), p = 0.045), but not in the no viral infection group (1.07 (0.64-1.78), p = 0.79). VAP was associated with significantly longer duration of mechanical ventilation in the SARS-CoV-2 group, but not in the influenza or no viral infection groups. VAP was associated with significantly longer duration of ICU stay in the 3 study groups. No significant difference was found in heterogeneity of outcomes related to VAP between the 3 groups, suggesting that the impact of VAP on mortality was not different between study groups. INTERPRETATION: VAP was associated with significantly increased 28-day mortality rate in SARS-CoV-2 patients. However, SARS-CoV-2 pneumonia, as compared to influenza pneumonia or no viral infection, did not significantly modify the relationship between VAP and 28-day mortality. CLINICAL TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov, number NCT04359693.publishersversionpublishe

Pulmonary infections prime the development of subsequent ICU-acquired pneumonia in septic shock

Abstract Purpose To investigate the determinants and the prognosis of intensive care unit (ICU)-acquired pneumonia in patients with septic shock. Methods This single-center retrospective study was conducted in a medical ICU in a tertiary care center from January 2008 to December 2016. All consecutive patients diagnosed for septic shock within the first 48 h of ICU admission were included. Patients were classified in three groups: no ICU-acquired infections (no ICU-AI), ICU-acquired pneumonia and non-pulmonary ICU-AI. The determinants of ICU-acquired pneumonia and death were investigated by multivariate competitive risk analysis. Results A total of 1021 patients were admitted for septic shock, and 797 patients were alive in the ICU after 48 h of management. The incidence of a first episode of ICU-AI was 31%, distributed into pulmonary (17%) and non-pulmonary ICU-AI (14%). Patients with septic shock caused by pneumonia were at increased risk of further pulmonary ICU-AI with a cumulated incidence of 34.4%. A pulmonary source of the initial septic shock was an independent risk factor for subsequent ICU-acquired pneumonia (cause-specific hazard 2.33, 95% confidence interval [1.55–3.52], p < 0.001). ICU-AI were not associated with a higher risk of ICU mortality after adjustment in a multivariate-adjusted cause-specific proportional hazard model. Conclusion Septic shock of pulmonary origin may represent a risk factor for subsequent ICU-acquired pneumonia without affecting mortality

Impaired biological response to aspirin in therapeutic hypothermia comatose patients resuscitated from out-of-hospital cardiac arrest

International audienc

The balance of thrombosis and hemorrhage in STEMI patients with or without associated cardiac arrest: An observational study

International audienceBackground: Data is scarce on hemorrhagic and thrombotic complications in patients with ST-elevation myocardial infarction (STEMI) associated with out-of-hospital cardiac arrest (OHCA).Methods: This is a monocentric, retrospective study conducted from January 2012 to December 2017 in a tertiary university hospital, which serves as a cardiac arrest center for a large urban area. Over the study period, all consecutive patients who were treated with stent implantation for STEMI with or without OHCA were included. Baseline characteristics, treatments, hemorrhagic and thrombotic events were compared between STEMI patients with and without OHCA. Univariate and multivariate analysis were performed in order to identify predictors of 30-day mortality, occurrence of major bleeding (MB), and early stent thrombosis (ST).Results: A total of 549 patients treated for STEMI without OHCA and 146 patients for STEMI with OHCA were included. The incidence of definite ST and MB after coronary angioplasty was significantly higher in patients with OHCA (2.6% vs. 7.5%, p = 0.004 and 3.3% vs. 19.2%, p < 0.001, respectively). Independent predictors of MB in OHCA patients were anticoagulation therapy (HR = 3.11, 95%CI [1.22-7.98], p = 0.02) and the use of glycoprotein IIb/IIIa inhibitors (HR = 4.16, 95%CI [1.61-10.79], p = 0.003). Independent predictors of mortality in OHCA patients were age (HR = 1.05, 95%CI [1.02-1.09], p = 0.004) and ST (HR = 5.62, 95%CI [1.61-19.65], p = 0.007, with a protective effect of new anti-P2Y12 treatments (HR = 0.20, 95%CI [0.08-0.46], p < 0.001).Conclusion: Patients treated for STEMI associated with OHCA are at higher-risk of ST and MB than those who did not experience cardiac arrest. In this subset of patients, prospective studies are needed to better evaluate the balance of thrombosis and hemorrhage

Identification of a sub-group of critically ill patients with high risk of intensive care unit-acquired infections and poor clinical course using a transcriptomic score

International audienceBackground The development of stratification tools based on the assessment of circulating mRNA of genes involved in the immune response is constrained by the heterogeneity of septic patients. The aim of this study is to develop a transcriptomic score based on a pragmatic combination of immune-related genes detected with a prototype multiplex PCR tool. Methods As training cohort, we used the gene expression dataset obtained from 176 critically ill patients enrolled in the REALISM study (NCT02638779) with various etiologies and still hospitalized in intensive care unit (ICU) at day 5–7. Based on the performances of each gene taken independently to identify patients developing ICU-acquired infections (ICU-AI) after day 5–7, we built an unweighted score assuming the independence of each gene. We then determined the performances of this score to identify a subgroup of patients at high risk to develop ICU-AI, and both longer ICU length of stay and mortality of this high-risk group were assessed. Finally, we validated the effectiveness of this score in a retrospective cohort of 257 septic patients. Results This transcriptomic score (TScore) enabled the identification of a high-risk group of patients (49%) with an increased rate of ICU-AI when compared to the low-risk group (49% vs. 4%, respectively), with longer ICU length of stay (13 days [95% CI 8–30] vs. 7 days [95% CI 6–9], p < 0.001) and higher ICU mortality (15% vs. 2%). High-risk patients exhibited biological features of immune suppression with low monocytic HLA-DR levels, higher immature neutrophils rates and higher IL10 concentrations. Using the TScore, we identified 160 high-risk patients (62%) in the validation cohort, with 30% of ICU-AI (vs. 18% in the low-risk group, p = 0.06), and significantly higher mortality and longer ICU length of stay. Conclusions The transcriptomic score provides a useful and reliable companion diagnostic tool to further develop immune modulating drugs in sepsis in the context of personalized medicine

Immune Profiling Panel Gene Set Identifies Critically Ill Patients With Low Monocyte Human Leukocyte Antigen-DR Expression: Preliminary Results From the REAnimation Low Immune Status Marker (REALISM) Study

OBJECTIVES: There is a crucial unmet need for biomarker-guided diagnostic andprognostic enrichment in clinical trials evaluating immune modulating therapies incritically ill patients. Low monocyte expression of human leukocyte antigen-DR(mHLA-DR), considered as a reference surrogate to identify immunosuppressedpatients, has been proposed for patient stratification in immunostimulationapproaches. However, its widespread use in clinic has been somewhat hamperedby technical constraints inherent to flow cytometry technology. The objective ofthe present study was to evaluate the ability of a prototype multiplex polymerasechain reaction tool (immune profiling panel [IPP]) to identify immunosuppressedICU patients characterized by a low mHLA-DR expression.DESIGN: Retrospective observational cohort study.SETTING: Adult ICU in a University Hospital, Lyon, France.PATIENTS: Critically ill patients with various etiologies enrolled in the REAnimationLow Immune Status Marker study (NCT02638779).INTERVENTIONS: None.MEASUREMENTS AND MAIN RESULTS: mHLA-DR and IPP data were obtained from 1,731 blood samples collected from critically ill patients with various etiologies and healthy volunteers. A partial least square regression model combining the expression levels of IPP markers was trained and used for the identification of samples from patients presenting with evidence of immunosuppression, defined here as mHLADR less than 8,000 antibodies bound per cell (AB/C). The IPP gene set had an area under the receiver operating characteristic curve (AUC) of 0.86 (95% CI 0.83–0.89) for the identification of immunosuppressed patients. In addition, when applied to the 123 patients still in the ICU at days 5–7 after admission, IPP similarly enriched the number of patients with ICU-acquired infections in the immunosuppressed group (26%), in comparison with low mHLA-DR (22%).CONCLUSIONS: This study reports on the potential of the IPP gene set to identify ICU patients presenting with mHLA-DR less than 8,000 AB/C. Upon further optimizationand validation, this molecular tool may help in the stratification of patients that could benefit from immunostimulation in the context of personalized medicine

Remdesivir for Patients Hospitalized with COVID-19 Severe Pneumonia: A National Cohort Study (Remdeco-19)

International audienceBackground. Given the rapidly evolving pandemic of COVID-19 in 2020, authorities focused on the repurposing of available drugs to develop timely and cost-effective therapeutic strategies. Evidence suggested the potential utility of remdesivir in the framework of an early access program. REMDECO-19 is a multicenter national cohort study assessing the ability of remdesivir to improve the outcome of patients hospitalized with COVID-19. Methods. We conducted a retrospective real-life study that included all patients from the early access program of remdesivir in France. The primary endpoint was the clinical course evolution of critically ill and hospitalized COVID-19 patients treated with remdesivir. Secondary endpoints were the SOFA score evolution within 29 days following the admission and mortality at 29 and 90 days. Results. Eighty-five patients were enrolled in 22 sites from January to April 2020. The median WHO and SOFA scores were respectively reduced by two and six points between days 1 and 29. Improvement in the WHO-CPS and the SOFA score were observed in 83.5% and 79.3% of patients, respectively, from day 10. However, there was no effect of remdesivir on the 90-day survival based on the control cohort for hospitalized COVID-19 patients with invasive ventilation. Conclusions. SOFA score appeared to be an attractive approach to assess remdesivir efficacy and stratify its utilization or not in critically ill patients with COVID-19. This study brings a new clinical benchmark for therapeutic decision making and supports the use of remdesivir for some hospitalized COVID-19 patients