Publications by authors named "Charles-Edouard Luyt"

198 Publications

Nucleocapsid-specific and PD-L1+CXCR3+ CD8 polyfunctional T-cell abundances are associated with survival of critical SARS-CoV2-infected patients.

JCI Insight 2021 Jul 20. Epub 2021 Jul 20.

Centre d'Immunologie et des Maladies Infectieuses, INSERM UMR 1135, Paris, France.

Rationale: The importance of the adaptative T cell response in the control and resolution of viral infection has been well-established. However, the nature of T cell-mediated viral control mechanisms in life-threatening stages of COVID-19 has yet to be determined.

Objective: The aim of the present study was to determine the function and phenotype of T cell populations associated with survival or death of COVID-19 patients under intensive care as a result of phenotypic and functional profiling by mass cytometry.

Findings: Increased frequencies of circulating, polyfunctional, CD4+CXCR5+HLA-DR+ stem cell memory T cells (TSCM) and decreased proportions of Granzyme-B and Perforin-expressing effector memory T cells (TEM) were detected in recovered and deceased patients, respectively. The higher abundance of polyfunctional CD8+PD-L1+CXCR3+ T effector cells, CXCR5+HLA-DR+ TSCM, as well as anti-nucleocapsid (NC) cytokine-producing T cells permitted to differentiate between recovered and deceased patients. The results from a principal component analysis showed an imbalance in the T cell compartment allowed for the separation of recovered and deceased patients. The paucity of circulating CD8+PD-L1+CXCR3+ Teff-cells and NC-specific CD8+ T-cells accurately forecasts fatal disease outcome.

Conclusion: This study provides insight into the nature of the T cell populations involved in the control of COVID-19 and therefor might impact T cell-based vaccine designs for this infectious disease.
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http://dx.doi.org/10.1172/jci.insight.151571DOI Listing
July 2021

Prone-Positioning for Severe Acute Respiratory Distress Syndrome Requiring Extracorporeal Membrane Oxygenation.

Crit Care Med 2021 Jul 14. Epub 2021 Jul 14.

Service de Médecine Intensive-Réanimation, Institut de Cardiologie, APHP, Sorbonne Université Hôpital Pitié-Salpêtrière, Paris, France. SAMOVAR, Telecom SudParis, Institut Polytechnique de Paris, Evry, France. Service de Radiologie, APHP, Université de Paris, Hôpital Bichat-Claude-Bernard, Paris, France. Université de Picardie Jules Verne, Amiens, France. Sorbonne Université, INSERM, UMRS_1166-ICAN, Institute of Cardiometabolism and Nutrition, Paris, France. Service de Chirurgie Cardiaque, Institut de Cardiologie, APHP, Sorbonne Université Hôpital Pitié-Salpêtrière, Paris, France.

Objectives: To determine the characteristics and outcomes of patients prone-positioned during extracorporeal membrane oxygenation for severe acute respiratory distress syndrome and lung CT pattern associated with improved respiratory system static compliance after that intervention.

Design: Retrospective, single-center study over 8 years.

Settings: Twenty-six bed ICU in a tertiary center.

Measurements And Main Results: A propensity score-matched analysis compared patients with prone-positioning during extracorporeal membrane oxygenation and those without. An increase of the static compliance greater than or equal to 3 mL/cm H2O after 16 hours of prone-positioning defined prone-positioning responders. The primary outcome was the time to successful extracorporeal membrane oxygenation weaning within 90 days of postextracorporeal membrane oxygenation start, with death as a competing risk. Among 298 venovenous extracorporeal membrane oxygenation-treated adults with severe acute respiratory distress syndrome, 64 were prone-positioning extracorporeal membrane oxygenation. Although both propensity score-matched groups had similar extracorporeal membrane oxygenation durations, prone-positioning extracorporeal membrane oxygenation patients' 90-day probability of being weaned-off extracorporeal membrane oxygenation and alive was higher (0.75 vs 0.54, p = 0.03; subdistribution hazard ratio [95% CI], 1.54 [1.05-2.58]) and 90-day mortality was lower (20% vs 42%, p < 0.01) than that for no prone-positioning extracorporeal membrane oxygenation patients. Extracorporeal membrane oxygenation-related complications were comparable for the two groups. Patients without improved static compliance had higher percentages of nonaerated or poorly aerated ventral and medial-ventral lung regions (p = 0.047).

Conclusions: Prone-positioning during venovenous extracorporeal membrane oxygenation was safe and effective and was associated with a higher probability of surviving and being weaned-off extracorporeal membrane oxygenation at 90 days. Patients with greater normally aerated lung tissue in the ventral and medial-ventral regions on quantitative lung CT-scan performed before prone-positioning are more likely to improve their static compliance after that procedure during extracorporeal membrane oxygenation.
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http://dx.doi.org/10.1097/CCM.0000000000005145DOI Listing
July 2021

Simple and accurate quantitative analysis of cefiderocol and ceftobiprole in human plasma using liquid chromatography-isotope dilution tandem mass spectrometry: interest for their therapeutic drug monitoring and pharmacokinetic studies.

Clin Chem Lab Med 2021 Jul 9. Epub 2021 Jul 9.

AP-HP. Sorbonne Université, Pitié-Salpêtrière Hospital, Department of Pharmacology, CIC-1901, Pharmacokinetics and Therapeutic Drug Monitoring Unit, UMR-S 1166, Paris, France.

Objectives: Cefiderocol and ceftobiprole are new generation cephalosporin antibiotics that exhibit high inter-individual plasma concentration variability that potentially impact their efficacy or toxicity. The aim of this study was to develop and validate a selective, simple, and fast UPLC-MS/MS method for simultaneous quantification of cefiderocol and ceftobiprole in human plasma to enable their therapeutic drug monitoring (TDM) and support PK and PK/PD studies, in particular in critically ill patients.

Methods: After a simple and fast single-step protein precipitation, cefiderocol and ceftobiprole were separated on a Waters Acquity UPLC BEH C18 column by linear gradient elution; with subsequent detection by Shimadzu MS 8060 triple quadrupole tandem mass spectrometer in a positive ionization mode.

Results: Analysis time was 5 min per run. The analytical performance of the method in terms of specificity, sensitivity, linearity, precision, accuracy, matrix effect (ME), extraction recovery (ER), limit of quantification, dilution integrity, and stability of analytes under different conditions met all criteria for a bioanalytical method for the quantification of drugs. The calibration curves were linear over the range of 1-200 mg/L for cefiderocol and 0.5-100 mg/L for ceftobiprole with a linear regression coefficient above 0.995 for both.

Conclusions: A simple, fast, and selective liquid chroma-tography-tandem mass spectrometry method was developed and validated for the simultaneous quantification of cefiderocol and ceftobiprole. This new method was successfully applied to the measurement of plasma concentration of cefiderocol and ceftobiprole in critically ill patients and showed good performance for their therapeutic monitoring and optimizing antibiotic therapy.
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http://dx.doi.org/10.1515/cclm-2021-0423DOI Listing
July 2021

Extracorporeal Membrane Oxygenation Induces Early Alterations in Coagulation and Fibrinolysis Profiles in COVID-19 Patients with Acute Respiratory Distress Syndrome.

Thromb Haemost 2021 Jun 15. Epub 2021 Jun 15.

Sorbonne Université, INSERM UMRS_1166, Institute of Cardiometabolism And Nutrition, Paris, France.

Hemostatic changes induced by extracorporeal membrane oxygenation (ECMO) support have been yet poorly documented in coronavirus-19 (COVID-19) patients who have a baseline complex hypercoagulable state. In this prospective monocentric study of patients with severe acute respiratory distress syndrome (ARDS) rescued by ECMO, we performed longitudinal measurements of coagulation and fibrinolysis markers throughout the course of ECMO support in 20 COVID-19 and 10 non-COVID-19 patients. Blood was sampled before and then 24 hours, 7, and 14 days after ECMO implantation. Clinical outcomes were prospectively assessed until discharge from the intensive care unit or death. The median age of participants was 47 (35-56) years, with a median body mass index of 30 (27-35) kg/m, and a Sepsis-related Organ Failure Assessment score of 12 (8-16). Baseline levels of von Willebrand factor, fibrinogen, factor VIII, prothrombin F1 + 2, thrombin-antithrombin, D-dimer, and plasminogen activator inhibitor-1 (PAI-1) were elevated in both COVID-19 and non-COVID-19 ARDS patients, indicating that endothelial activation, endogenous thrombin generation, and fibrinolysis shutdown occur in all ARDS patients before ECMO implantation. From baseline to day 7, thrombin generation (prothrombin F1 + 2,  < 0.01) and fibrin formation markers (fibrin monomers,  < 0.001) significantly increased, further resulting in significant decreases in platelet count ( < 0.0001) and fibrinogen level ( < 0.001). PAI-1 levels significantly decreased from baseline to day 7 ( < 0.0001) in all ARDS patients. These changes were more marked in COVID-19 patients, resulting in 14 nonfatal and 3 fatal bleeding. Additional studies are warranted to determine whether monitoring of thrombin generation and fibrinolysis markers might help to early predict bleeding complications in COVID-19 patients supported by ECMO.
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http://dx.doi.org/10.1055/a-1529-2257DOI Listing
June 2021

Duration of antibiotic treatment using procalcitonin-guided treatment algorithms in older patients: a patient-level meta-analysis from randomized controlled trials.

Age Ageing 2021 May 17. Epub 2021 May 17.

Critical Care and Peri-operative Medicine, Monash Health, Melbourne, Australia.

Background: Older patients have a less pronounced immune response to infection, which may also influence infection biomarkers. There is currently insufficient data regarding clinical effects of procalcitonin (PCT) to guide antibiotic treatment in older patients.

Objective And Design: We performed an individual patient data meta-analysis to investigate the association of age on effects of PCT-guided antibiotic stewardship regarding antibiotic use and outcome.

Subjects And Methods: We had access to 9,421 individual infection patients from 28 randomized controlled trials comparing PCT-guided antibiotic therapy (intervention group) or standard care. We stratified patients according to age in four groups (<75 years [n = 7,079], 75-80 years [n = 1,034], 81-85 years [n = 803] and >85 years [n = 505]). The primary endpoint was the duration of antibiotic treatment and the secondary endpoints were 30-day mortality and length of stay.

Results: Compared to control patients, mean duration of antibiotic therapy in PCT-guided patients was significantly reduced by 24, 22, 26 and 24% in the four age groups corresponding to adjusted differences in antibiotic days of -1.99 (95% confidence interval [CI] -2.36 to -1.62), -1.98 (95% CI -2.94 to -1.02), -2.20 (95% CI -3.15 to -1.25) and - 2.10 (95% CI -3.29 to -0.91) with no differences among age groups. There was no increase in the risk for mortality in any of the age groups. Effects were similar in subgroups by infection type, blood culture result and clinical setting (P interaction >0.05).

Conclusions: This large individual patient data meta-analysis confirms that, similar to younger patients, PCT-guided antibiotic treatment in older patients is associated with significantly reduced antibiotic exposures and no increase in mortality.
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http://dx.doi.org/10.1093/ageing/afab078DOI Listing
May 2021

Distinct cytokine profiles associated with COVID-19 severity and mortality.

J Allergy Clin Immunol 2021 06 22;147(6):2098-2107. Epub 2021 Apr 22.

Sorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris, Paris, France; AP-HP, Hôpital Pitié-Salpêtrière, Département d'Immunologie, Paris, France. Electronic address:

Background: Markedly elevated levels of proinflammatory cytokines and defective type-I interferon responses were reported in patients with coronavirus disease 2019 (COVID-19).

Objective: We sought to determine whether particular cytokine profiles are associated with COVID-19 severity and mortality.

Methods: Cytokine concentrations and severe acute respiratory syndrome coronavirus 2 antigen were measured at hospital admission in serum of symptomatic patients with COVID-19 (N = 115), classified at hospitalization into 3 respiratory severity groups: no need for mechanical ventilatory support (No-MVS), intermediate severity requiring mechanical ventilatory support (MVS), and critical severity requiring extracorporeal membrane oxygenation (ECMO). Principal-component analysis was used to characterize cytokine profiles associated with severity and mortality. The results were thereafter confirmed in an independent validation cohort (N = 86).

Results: At time of hospitalization, ECMO patients presented a dominant proinflammatory response with elevated levels of TNF-α, IL-6, IL-8, and IL-10. In contrast, an elevated type-I interferon response involving IFN-α and IFN-β was characteristic of No-MVS patients, whereas MVS patients exhibited both profiles. Mortality at 1 month was associated with higher levels of proinflammatory cytokines in ECMO patients, higher levels of type-I interferons in No-MVS patients, and their combination in MVS patients, resulting in a combined mortality prediction accuracy of 88.5% (risk ratio, 24.3; P < .0001). Severe acute respiratory syndrome coronavirus 2 antigen levels correlated with type-I interferon levels and were associated with mortality, but not with proinflammatory response or severity.

Conclusions: Distinct cytokine profiles are observed in association with COVID-19 severity and are differentially predictive of mortality according to oxygen support modalities. These results warrant personalized treatment of COVID-19 patients based on cytokine profiling.
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http://dx.doi.org/10.1016/j.jaci.2021.03.047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061091PMC
June 2021

Awake venoarterial extracorporeal membrane oxygenation for refractory cardiogenic shock.

Eur Heart J Acute Cardiovasc Care 2021 Apr 5. Epub 2021 Apr 5.

Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Medical Intensive Care Unit, Paris Cedex 13 75651, France.

Background : Venoarterial-extracorporeal membrane oxygenation (VA-ECMO) is currently one of the first-line therapies for refractory cardiogenic shock (CS), but its applicability is undermined by the high morbidity associated with its complications, especially those related to mechanical ventilation (MV). We aimed to assess the prognostic impact of keeping patients in refractory CS awake at cannulation and during the VA-ECMO run.

Methods : A 7-year database of patients given peripheral VA-ECMO support was used to conduct a propensity-score (PS)-matched analysis to balance their clinical profiles. Patients were classified as 'awake ECMO' or 'non-awake ECMO', respectively, if invasive MV was used during ≤50% or >50% of the VA-ECMO run. Primary outcomes included ventilator-associated pneumonia and ECMO-related complication rates, and secondary outcomes were 60-day and 1-year mortality. A multivariate logistic-regression analysis was used to identify whether MV at cannulation was independently associated with 60-day mortality.

Results : Among 231 patients included, 91 (39%) were 'awake' and 140 (61%) 'non-awake'. After PS-matching adjustment, the 'awake ECMO' group had significantly lower rates of pneumonia (35% vs. 59%, P = 0.017), tracheostomy, renal replacement therapy, and less antibiotic and sedative consumption. This strategy was also associated with reduced 60-day (20% vs. 41%, P = 0.018) and 1-year mortality rates (31% vs. 54%, P = 0.021) compared to the 'non-awake' group, respectively. Lastly, MV at ECMO cannulation was independently associated with 60-day mortality.

Conclusion : An 'awake ECMO' management in VA-ECMO-supported CS patients is feasible, safe, and associated with improved short- and long-term outcomes.
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http://dx.doi.org/10.1093/ehjacc/zuab018DOI Listing
April 2021

Arrhythmia-induced cardiomyopathy: A potentially reversible cause of refractory cardiogenic shock requiring venoarterial extracorporeal membrane oxygenation.

Heart Rhythm 2021 Jul 12;18(7):1106-1112. Epub 2021 Mar 12.

Service de Médecine Intensive Réanimation, Institute of Cardiology, Pierre et Marie Curie Sorbonne Université, APHP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France; UPMC Université Paris 06, INSERM, UMRS_1166-ICAN, Institute of Cardiometabolism and Nutrition, Paris, France.

Background: The most severe form of arrhythmia-induced cardiomyopathy in adults- refractory cardiogenic shock requiring mechanical circulatory support-has rarely been reported.

Objective: The purpose of this study was to describe the management of critically ill patients admitted for acute, nonischemic, or worsening of previously known cardiac dysfunction and recent-onset supraventricular arrhythmia who developed refractory cardiogenic shock requiring venoarterial extracorporeal membrane oxygenation (VA-ECMO).

Methods: This study is a retrospective analysis of prospectively collected data.

Results: Between 2004 and 2018, 35 patients received VA-ECMO for acute, nonischemic cardiogenic shock and recent supraventricular arrhythmia (77% atrial fibrillation [AF]). Cardiogenic shock was the first disease manifestation in 21 patients (60%). Characteristics at ECMO implantation [median (interquartile range)] were Sequential Organ Failure Assessment score 10 (7-13); inotrope score 29 (11-80); left ventricular ejection (LVEF) fraction 10% (10%-15%); and lactate level 8 (4-11) mmol/L. For 12 patients, amiodarone and/or electric cardioversion successfully reduced arrhythmia, improved LVEF, and enabled weaning off VA-ECMO; 11 had long-term survival without transplantation or long-term assist device. Eight patients experiencing arrhythmia-reduction failure underwent ablation procedures (7 atrioventricular node [AVN] with pacing, 1 atrial tachycardia) and were weaned off VA-ECMO; 7 survived. Of the remaining 15 patients without arrhythmia reduction or ablation, only the 6 bridged to heart transplantation or left ventricular (LV) assist device survived.

Conclusion: Arrhythmia-induced cardiomyopathy, mainly AF-related, is an underrecognized cause of refractory cardiogenic shock and should be considered in patients with nonischemic cardiogenic shock and recent-onset supraventricular arrhythmia. VA-ECMO support allowed safe arrhythmia reduction or rate control by AVN ablation while awaiting recovery, even among those with severe LV dilation.
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http://dx.doi.org/10.1016/j.hrthm.2021.03.014DOI Listing
July 2021

Association of Clinical, Biological, and Brain Magnetic Resonance Imaging Findings With Electroencephalographic Findings for Patients With COVID-19.

JAMA Netw Open 2021 03 1;4(3):e211489. Epub 2021 Mar 1.

Sorbonne Université, Paris Brain Institute, Institut du Cerveau, Institut National de la Santé et de la Recherche Médicale U 1127, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7225, Paris, France.

Importance: There is evidence of central nervous system impairments associated with coronavirus disease 2019 (COVID-19) infection, including encephalopathy. Multimodal monitoring of patients with COVID-19 may delineate the specific features of COVID-19-related encephalopathy and guide clinical management.

Objectives: To investigate clinical, biological, and brain magnetic resonance imaging (MRI) findings in association with electroencephalographic (EEG) features for patients with COVID-19, and to better refine the features of COVID-19-related encephalopathy.

Design, Setting, And Participants: This retrospective cohort study conducted in Pitié-Salpêtrière Hospital, Paris, France, enrolled 78 hospitalized adults who received a diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-Cov2) and underwent EEG between March 30 and June 11, 2020.

Exposures: Detection of SARS-CoV-2 from a nasopharyngeal specimen using a reverse transcription-polymerase chain reaction assay or, in the case of associated pneumonia, on a computed tomography scan of the chest.

Main Outcomes And Measures: Data on the clinical and paraclinical features of the 78 patients with COVID-19 were retrieved from electronic patient records.

Results: Of 644 patients who were hospitalized for COVID-19, 78 (57 men [73%]; mean [SD] age, 61 [12] years) underwent EEG. The main indications for EEG were delirium, seizure-like events, and delayed awakening in the intensive care unit after stopping treatment with sedatives. Sixty-nine patients showed pathologic EEG findings, including metabolic-toxic encephalopathy features, frontal abnormalities, periodic discharges, and epileptic activities. Of 57 patients who underwent brain MRI, 41 showed abnormalities, including perfusion abnormalities, acute ischemic lesions, multiple microhemorrhages, and white matter-enhancing lesions. Fifty-five patients showed biological abnormalities, including dysnatremia, kidney failure, and liver dysfunction, the same day as the EEG. The results of cerebrospinal fluid analysis were negative for SARS-Cov-2 for all tested patients. Nine patients who had no identifiable cause of brain injury outside COVID-19 were further isolated; their brain injury was defined as COVID-19-related encephalopathy. They represented 1% (9 of 644) of patients with COVID-19 requiring hospitalization. Six of these 9 patients had movement disorders, 7 had frontal syndrome, 4 had brainstem impairment, 4 had periodic EEG discharges, and 3 had MRI white matter-enhancing lesions.

Conclusions And Relevance: The results from this cohort of patients hospitalized with COVID-19 suggest there are clinical, EEG, and MRI patterns that could delineate specific COVID-19-related encephalopathy and guide treatment strategy.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.1489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961310PMC
March 2021

Response.

Chest 2021 Mar;159(3):1303-1304

Sorbonne Université, INSERM, UMRS_1166-ICAN Institute of Cardiometabolism and Nutrition, and Service de Médecine Intensive Réanimation, Institut de Cardiologie, Groupe Hospitalier Pitié-Salpêtrière, APHP, Paris, France. Electronic address:

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http://dx.doi.org/10.1016/j.chest.2020.10.004DOI Listing
March 2021

Plasma Exchange to Rescue Patients with Autoantibodies Against Type I Interferons and Life-Threatening COVID-19 Pneumonia.

J Clin Immunol 2021 04 22;41(3):536-544. Epub 2021 Feb 22.

Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Médecine Intensive Réanimation, AP-HP and INSERM UMRS_1166-iCAN, Institute of Cardiometabolism and Nutrition, Paris, France.

Purpose: To report four cases of life-threatening COVID-19 pneumonia in patients with high blood concentrations of neutralizing autoantibodies against type I interferons (IFNs), who were treated with plasma exchange (PE) as a rescue therapy.

Methods: Prospective case series, which included patients, diagnosed with RT-PCR-confirmed SARS-CoV-2 infection and positive autoantibodies against type I IFNs in two French intensive care units (ICUs) between October 8 and November 14, 2020. Six critically ill COVID-19 patients with no anti-IFN antibodies were used as controls. Anti-IFN autoantibodies and IFN concentrations, together with the levels of anti-SARS-CoV-2 antibodies, were measured sequentially in serum. Viral load was determined in the upper and lower respiratory tract. Patients were followed during hospital stay.

Results: Three men and one woman were included. Three of the patients had four PE sessions each, while another had three PE sessions. PE decreased the concentrations of autoantibodies against type I IFN in all four patients, whereas anti-SARS-CoV-2 antibody levels remained stable. Autoantibodies against type I IFN levels were high in tracheal aspirates of one patient and decreased after three PE sessions. By contrast, anti-IFN autoantibodies were not detected in tracheal aspirates from five control patients without detectable anti-IFN autoantibodies in serum. During PE, serum IFN-α levels slightly increased in three out of four patients, and upper respiratory tract viral load decreased in all patients. All patients were alive at day 28 of ICU admission. Two patients eventually died in the ICU, while the two survivors were discharged from the ICU at days 50 and 66.

Conclusions: PE efficiently removes autoantibodies against type I IFNs, including those detected in tracheal aspirates, without affecting anti-SARS-CoV-2 antibody levels, in patients with life-threatening COVID-19 pneumonia. The clinical benefit of PE in patients with autoantibodies against type I IFNs should be tested in a larger study.
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http://dx.doi.org/10.1007/s10875-021-00994-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899072PMC
April 2021

Human ACE2 peptide-mimics block SARS-CoV-2 pulmonary cells infection.

Commun Biol 2021 02 12;4(1):197. Epub 2021 Feb 12.

Sorbonne Université, École Normale Supérieure, PSL University, CNRS, Laboratoire des Biomolécules, LBM, 75005, Paris, France.

In light of the recent accumulated knowledge on SARS-CoV-2 and its mode of human cells invasion, the binding of viral spike glycoprotein to human Angiotensin Converting Enzyme 2 (hACE2) receptor plays a central role in cell entry. We designed a series of peptides mimicking the N-terminal helix of hACE2 protein which contains most of the contacting residues at the binding site, exhibiting a high helical folding propensity in aqueous solution. Our best peptide-mimics are able to block SARS-CoV-2 human pulmonary cell infection with an inhibitory concentration (IC) in the nanomolar range upon binding to the virus spike protein with high affinity. These first-in-class blocking peptide mimics represent powerful tools that might be used in prophylactic and therapeutic approaches to fight the coronavirus disease 2019 (COVID-19).
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http://dx.doi.org/10.1038/s42003-021-01736-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881012PMC
February 2021

Preemptive ganciclovir for mechanically ventilated patients with cytomegalovirus reactivation.

Ann Intensive Care 2021 Feb 11;11(1):33. Epub 2021 Feb 11.

Sorbonne Université, INSERM, Médecine Intensive Réanimation, Institut de Cardiologie, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, Assistance Publique-Hôpitaux de Paris, Paris, France.

Background: The effect of cytomegalovirus (CMV) reactivation on the length of mechanical ventilation and mortality in immunocompetent ICU patients requiring invasive mechanical ventilation remains controversial. The main objective of this study was to determine whether preemptive intravenous ganciclovir increases the number of ventilator-free days in patients with CMV blood reactivation.

Methods: This double-blind, placebo-controlled, randomized clinical trial involved 19 ICUs in France. Seventy-six adults ≥ 18 years old who had been mechanically ventilated for at least 96 h, expected to remain on mechanical ventilation for ≥ 48 h, and exhibited reactivation of CMV in blood were enrolled between February 5th, 2014, and January 23rd, 2019. Participants were randomized to receive ganciclovir 5 mg/kg bid for 14 days (n = 39) or a matching placebo (n = 37).

Results: The primary endpoint was ventilator-free days from randomization to day 60. Prespecified secondary outcomes included day 60 mortality. The trial was stopped for futility based on the results of an interim analysis by the DSMB. The subdistribution hazard ratio for being alive and weaned from mechanical ventilation at day 60 for patients receiving ganciclovir (N = 39) compared with control patients (N = 37) was 1.14 (95% CI from 0.63 to 2.06; P = 0.66). The median [IQR] numbers of ventilator-free days for ganciclovir-treated patients and controls were 10 [0-51] and 0 [0-43] days, respectively (P = 0.46). Mortality at day 60 was 41% in patients in the ganciclovir group and 43% in the placebo group (P = .845). Creatinine levels and blood cells counts did not differ significantly between the two groups.

Conclusions: In patients mechanically ventilated for ≥ 96 h with CMV reactivation in blood, preemptive ganciclovir did not improve the outcome.
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http://dx.doi.org/10.1186/s13613-020-00793-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876264PMC
February 2021

Outcomes of severe systemic rheumatic disease patients requiring extracorporeal membrane oxygenation.

Ann Intensive Care 2021 Feb 9;11(1):29. Epub 2021 Feb 9.

Service de Médecine Intensive-Réanimation, Hôpital La Pitié-Salpêtrière, Sorbonne Université, Assistance Publique-Hôpitaux de Paris (APHP), Paris, France.

Background: Systemic rheumatic diseases (SRDs) are a group of inflammatory disorders that can require intensive care unit (ICU) admission because of multiorgan involvement with end-organ failure(s). Critically ill SRD patients requiring extracorporeal membrane oxygenation (ECMO) were studied to gain insight into their characteristics and outcomes.

Methods: This French monocenter, retrospective study included all SRD patients requiring venovenous (VV)- or venoarterial (VA)-ECMO admitted to a 26-bed ECMO-dedicated ICU from January 2006 to February 2020. The primary endpoint was in-hospital mortality.

Results: Ninety patients (male/female ratio: 0.5; mean age at admission: 41.6 ± 15.2 years) admitted to the ICU received VA/VV-ECMO, respectively, for an SRD-related flare (n = 69, n = 38/31) or infection (n = 21, n = 10/11). SRD was diagnosed in-ICU for 31 (34.4%) patients. In-ICU and in-hospital mortality rates were 48.9 and 51.1%, respectively. Nine patients were bridged to cardiac (n = 5) or lung transplantation (n = 4), or left ventricular assist device (n = 2). The Cox multivariable model retained the following independent predictors of in-hospital mortality: in-ICU SRD diagnosis, day-0 Simplified Acute Physiology Score (SAPS) II score ≥ 70 and arterial lactate ≥ 7.5 mmol/L for VA-ECMO-treated patients; diagnosis other than vasculitis, day-0 SAPS II score ≥ 70, ventilator-associated pneumonia and arterial lactate ≥ 7.5 mmol/L for VV-ECMO-treated patients.

Conclusions: ECMO support is a relevant rescue technique for critically ill SRD patients, with 49% survival at hospital discharge. Vasculitis was independently associated with favorable outcomes of VV-ECMO-treated patients. Further studies are needed to specify the role of ECMO for SRD patients.
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http://dx.doi.org/10.1186/s13613-021-00819-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871308PMC
February 2021

Considering Personalized Interferon Beta Therapy for COVID-19.

Antimicrob Agents Chemother 2021 03 18;65(4). Epub 2021 Mar 18.

Sorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France.

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http://dx.doi.org/10.1128/AAC.00065-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097459PMC
March 2021

Occurrence of Invasive Pulmonary Fungal Infections in Patients with Severe COVID-19 Admitted to the ICU.

Am J Respir Crit Care Med 2021 02;203(3):307-317

Parasitologie Mycologie.

Whether severe coronavirus disease (COVID-19) is a significant risk factor for the development of invasive fungal superinfections is of great medical interest and remains, for now, an open question. We aim to assess the occurrence of invasive fungal respiratory superinfections in patients with severe COVID-19. We conducted the study on patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related pneumonia admitted to five ICUs in France who had respiratory and serum sampling performed for specific screening of fungal complications. The study population included a total of 145 patients; the median age was 55 years old. Most of them were male ( = 104; 72%), were overweight ( = 99; 68%), and had hypertension ( = 83; 57%) and diabetes ( = 46; 32%). Few patients presented preexisting host risk factors for invasive fungal infection ( = 20; 14%). Their global severity was high; all patients were on invasive mechanical ventilation, and half ( = 73, 54%) were on extracorporeal membrane oxygenation support. Mycological analysis included 2,815 mycological tests (culture, galactomannan, β-glucan, and PCR) performed on 475 respiratory samples and 532 sera. A probable/putative invasive pulmonary mold infection was diagnosed in 7 (4.8%) patients and linked to high mortality. Multivariate analysis indicates a significantly higher risk for solid organ transplant recipients (odds ratio,  = 4.66; interquartile range, 1.98-7.34;  = 0.004). False-positive fungal test and clinically irrelevant colonization, which did not require the initiation of antifungal treatment, was observed in 25 patients (17.2%). In patients with no underlying immunosuppression, severe SARS-CoV-2-related pneumonia seems at low risk of invasive fungal secondary infection, especially aspergillosis.
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http://dx.doi.org/10.1164/rccm.202009-3400OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874326PMC
February 2021

Clinical features and outcome of patients with primary central nervous system lymphoma admitted to the intensive care unit: a French national expert center experience.

J Neurol 2021 Jun 16;268(6):2141-2150. Epub 2021 Jan 16.

Service de Pneumologie, Médecine Intensive et Réanimation (Département R3S), AP-HP, Groupe Hospitalier Universitaire APHP-Sorbonne Université, Site Pitié-Salpêtrière, 47-83 Boulevard de l'Hôpital, 75013, Paris, France.

Introduction: To describe the reasons for intensive care unit (ICU) admission and to evaluate the outcomes and prognostic factors of patients with primary central nervous system lymphoma (PCNSL) admitted to the ICU.

Patients And Methods: Retrospective observational cohort study of 101 PCNSL patients admitted to 3 ICUs over a two-decade period.

Results: Acute respiratory failure, mainly secondary to aspiration pneumonia and Pneumocystis jirovecii pneumonia, was the leading reason for ICU admission (33%). Aspiration pneumonia was more common in patients with brainstem tumor (67% vs. 0%, p < 0.001), whereas patients with intracranial hypertension were more frequently admitted for coma without seizures (61% vs. 9%, p = 0.004). Hospital and 6-month mortality were 47% and 53%, respectively. In multivariate analysis, admission for coma without seizures (OR 7.28), cancer progression (OR 3.47), mechanical ventilation (OR 6.58) and vasopressors (OR 4.07) were associated with higher 6-month mortality. Karnofsky performance status prior to ICU admission was independently associated with lower 6-month mortality (OR 0.96).

Discussion: Six-month survival of PCNSL patients admitted to the ICU appears to be relatively favorable (around 50%) and the presence of PCNSL alone is not a relevant criterion for ICU refusal. Predictive factors of mortality may help clinicians to make optimal triage decisions.
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http://dx.doi.org/10.1007/s00415-021-10396-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810601PMC
June 2021

Venous or arterial thromboses after venoarterial extracorporeal membrane oxygenation support: Frequency and risk factors.

J Heart Lung Transplant 2021 Apr 30;40(4):307-315. Epub 2020 Dec 30.

Service de Médecine Intensive Réanimation; INSERM, UMRS_1166-ICAN, Institute of Cardiometabolism and Nutrition, Sorbonne Université, Paris, France. Electronic address:

Background: Although venous thrombosis after venovenous-extracorporeal membrane oxygenation (ECMO) is well described, vascular complications occurring after venoarterial ECMO (VA-ECMO) removal have not yet been thoroughly described. Our aim was to evaluate the frequency of vascular (arterial and venous) complications after VA-ECMO removal and try to identify the risk factors associated with them.

Methods: Retrospective analysis of data prospectively collected in 2 intensive care units was performed. Consecutive patients successfully weaned off VA-ECMO during year 1 were screened for cannula-associated deep vein thrombosis (CaDVT) or arterial complications (arterial thrombosis/stenosis) using Doppler ultrasonography.

Results: From November 2018 to November 2019, a total of 107 patients with a median (interquartile range [IQR]) age of 54 (42-63) years and a median (IQR) ECMO support duration of 8 (2-5) days were successfully weaned off VA-ECMO and included. CaDVT occurred in 44 patients (41%), and arterial complications occurred in 15 (14%) (9 acute leg ischemia, 1 arteriovenous femoral fistula, and 5 late femoral stenosis). Multivariable analysis retained longer duration of ECMO support (odds ratio [OR]: 1.12 per day; 95% CI: 1.02-1.22) and infection occurring on ECMO (OR: 3.03; 95% CI: 1.14-8.03) as independent risk factors for CaDVT, whereas older age (OR: 0.97 per year; 95% CI: 0.94-0.99) and previous anti-coagulation use (OR: 0.21; 95% CI: 0.06-0.68) were protective factors for CaDVT. No risk factors for arterial complications were identified.

Conclusions: In patients requiring VA-ECMO support, vascular complications occurred frequently after its removal, especially CaDVT. Arterial complications, either early leg ischemia or late arterial stenosis, were observed less often. Strategies aimed at preventing CaDVT after VA-ECMO remain to be determined.
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http://dx.doi.org/10.1016/j.healun.2020.12.007DOI Listing
April 2021

Clarkson's Disease Episode or Secondary Systemic Capillary Leak-Syndrome: That Is the Question!

Chest 2021 01;159(1):441

Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Service de Médecine Interne 2, Centre de Référence National Lupus et SAPL et Autres Maladies Auto-immunes et Systémiques Rares, Paris, France.

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http://dx.doi.org/10.1016/j.chest.2020.07.084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831696PMC
January 2021

Relationship between SARS-CoV-2 infection and the incidence of ventilator-associated lower respiratory tract infections: a European multicenter cohort study.

Intensive Care Med 2021 02 3;47(2):188-198. Epub 2021 Jan 3.

Assistance Publique-Hôpitaux de Paris, CHU Henri Mondor, Service de réanimation médicale, Créteil, France.

Purpose: Although patients with SARS-CoV-2 infection have several risk factors for ventilator-associated lower respiratory tract infections (VA-LRTI), the reported incidence of hospital-acquired infections is low. We aimed to determine the relationship between SARS-CoV-2 pneumonia, as compared to influenza pneumonia or no viral infection, and the incidence of VA-LRTI.

Methods: Multicenter retrospective European cohort performed in 36 ICUs. All adult patients receiving invasive mechanical ventilation > 48 h were eligible if they had: SARS-CoV-2 pneumonia, influenza pneumonia, or no viral infection at ICU admission. VA-LRTI, including ventilator-associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP), were diagnosed using clinical, radiological and quantitative microbiological criteria. All VA-LRTI were prospectively identified, and chest-X rays were analyzed by at least two physicians. Cumulative incidence of first episodes of VA-LRTI was estimated using the Kalbfleisch and Prentice method, and compared using Fine-and Gray models.

Results: 1576 patients were included (568 in SARS-CoV-2, 482 in influenza, and 526 in no viral infection groups). VA-LRTI incidence was significantly higher in SARS-CoV-2 patients (287, 50.5%), as compared to influenza patients (146, 30.3%, adjusted sub hazard ratio (sHR) 1.60 (95% confidence interval (CI) 1.26 to 2.04)) or patients with no viral infection (133, 25.3%, adjusted sHR 1.7 (95% CI 1.2 to 2.39)). Gram-negative bacilli were responsible for a large proportion (82% to 89.7%) of VA-LRTI, mainly Pseudomonas aeruginosa, Enterobacter spp., and Klebsiella spp.

Conclusions: The incidence of VA-LRTI is significantly higher in patients with SARS-CoV-2 infection, as compared to patients with influenza pneumonia, or no viral infection after statistical adjustment, but residual confounding may still play a role in the effect estimates.
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http://dx.doi.org/10.1007/s00134-020-06323-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778569PMC
February 2021

IgA dominates the early neutralizing antibody response to SARS-CoV-2.

Sci Transl Med 2021 01 7;13(577). Epub 2020 Dec 7.

Sorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 91 boulevard de l'Hôpital, 75013 Paris, France.

Humoral immune responses are typically characterized by primary IgM antibody responses followed by secondary antibody responses associated with immune memory and composed of IgG, IgA, and IgE. Here, we measured acute humoral responses to SARS-CoV-2, including the frequency of antibody-secreting cells and the presence of SARS-CoV-2-specific neutralizing antibodies in the serum, saliva, and bronchoalveolar fluid of 159 patients with COVID-19. Early SARS-CoV-2-specific humoral responses were dominated by IgA antibodies. Peripheral expansion of IgA plasmablasts with mucosal homing potential was detected shortly after the onset of symptoms and peaked during the third week of the disease. The virus-specific antibody responses included IgG, IgM, and IgA, but IgA contributed to virus neutralization to a greater extent compared with IgG. Specific IgA serum concentrations decreased notably 1 month after the onset of symptoms, but neutralizing IgA remained detectable in saliva for a longer time (days 49 to 73 post-symptoms). These results represent a critical observation given the emerging information as to the types of antibodies associated with optimal protection against reinfection and whether vaccine regimens should consider targeting a potent but potentially short-lived IgA response.
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http://dx.doi.org/10.1126/scitranslmed.abd2223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857408PMC
January 2021

Ventilator-associated pneumonia in patients with SARS-CoV-2-associated acute respiratory distress syndrome requiring ECMO: a retrospective cohort study.

Ann Intensive Care 2020 Nov 23;10(1):158. Epub 2020 Nov 23.

Service de Médecine Intensive Réanimation, Institut de Cardiologie, ICAN, Assistance Publique-Hôpitaux de Paris (APHP), Sorbonne-Université, Groupe Hospitalier Pitié-Salpêtrière, 47-83, Boulevard de L'Hôpital, 75651, Paris Cedex 13, France.

Background: The data on incidence, clinical presentation, and outcomes of ventilator-associated pneumonia (VAP) in patients with severe coronavirus disease 2019 (COVID-19) pneumonia requiring mechanical ventilation (MV) are limited. We performed this retrospective cohort study to assess frequency, clinical characteristics, responsible pathogens, and outcomes of VAP in patients COVID-19 pneumonia requiring MV between March 12th and April 24th, 2020 (all had RT-PCR-confirmed SARS-CoV-2 infection). Patients with COVID-19-associated acute respiratory distress syndrome (ARDS) requiring ECMO were compared with an historical cohort of 45 patients with severe influenza-associated ARDS requiring ECMO admitted to the same ICU during the preceding three winter seasons.

Results: Among 50 consecutive patients with Covid-19-associated ARDS requiring ECMO included [median (IQR) age 48 (42-56) years; 72% male], 43 (86%) developed VAP [median (IQR) MV duration before the first episode, 10 (8-16) days]. VAP-causative pathogens were predominantly Enterobacteriaceae (70%), particularly inducible AmpC-cephalosporinase producers (40%), followed by Pseudomonas aeruginosa (37%). VAP recurred in 34 (79%) patients and 17 (34%) died. Most recurrences were relapses (i.e., infection with the same pathogen), with a high percentage occurring on adequate antimicrobial treatment. Estimated cumulative incidence of VAP, taking into account death and extubation as competing events, was significantly higher in Covid-19 patients than in influenza patients (p = 0.002). Despite a high P. aeruginosa-VAP rate in patients with influenza-associated ARDS (54%), the pulmonary infection recurrence rate was significantly lower than in Covid-19 patients. Overall mortality was similar for the two groups.

Conclusions: Patients with severe Covid-19-associated ARDS requiring ECMO had a very high late-onset VAP rate. Inducible AmpC-cephalosporinase-producing Enterobacteriaceae and Pseudomonas aeruginosa frequently caused VAP, with multiple recurrences and difficulties eradicating the pathogen from the lung.
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http://dx.doi.org/10.1186/s13613-020-00775-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682692PMC
November 2020

Pulmonary infections complicating ARDS.

Intensive Care Med 2020 12 11;46(12):2168-2183. Epub 2020 Nov 11.

IAME 1137, INSERM, Université de Paris, Paris, France.

Pulmonary infection is one of the main complications occurring in patients suffering from acute respiratory distress syndrome (ARDS). Besides traditional risk factors, dysregulation of lung immune defenses and microbiota may play an important role in ARDS patients. Prone positioning does not seem to be associated with a higher risk of pulmonary infection. Although bacteria associated with ventilator-associated pneumonia (VAP) in ARDS patients are similar to those in patients without ARDS, atypical pathogens (Aspergillus, herpes simplex virus and cytomegalovirus) may also be responsible for infection in ARDS patients. Diagnosing pulmonary infection in ARDS patients is challenging, and requires a combination of clinical, biological and microbiological criteria. The role of modern tools (e.g., molecular methods, metagenomic sequencing, etc.) remains to be evaluated in this setting. One of the challenges of antimicrobial treatment is antibiotics diffusion into the lungs. Although targeted delivery of antibiotics using nebulization may be interesting, their place in ARDS patients remains to be explored. The use of extracorporeal membrane oxygenation in the most severe patients is associated with a high rate of infection and raises several challenges, diagnostic issues and pharmacokinetics/pharmacodynamics changes being at the top. Prevention of pulmonary infection is a key issue in ARDS patients, but there is no specific measure for these high-risk patients. Reinforcing preventive measures using bundles seems to be the best option.
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http://dx.doi.org/10.1007/s00134-020-06292-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656898PMC
December 2020

Co-infection of SARS-CoV-2 with other respiratory viruses and performance of lower respiratory tract samples for the diagnosis of COVID-19.

Int J Infect Dis 2021 Jan 25;102:10-13. Epub 2020 Oct 25.

AP-HP, Sorbonne Université, Hôpital Pitié-Salpêtrière, Service de Virologie, Paris, France; Sorbonne Université, INSERM U1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP), Paris, France. Electronic address:

Objectives: This study was performed during the early outbreak period of coronavirus disease 2019 (COVID-19) and the seasonal epidemics of other respiratory viral infections, in order to describe the extent of co-infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with other respiratory viruses. It also compared the diagnostic performances of upper respiratory tract (URT) and lower respiratory tract (LRT) samples for SARS-CoV-2 infection.

Methods: From 25 January to 29 March 2020, all URT and LRT samples collected from patients with suspected COVID-19 received in the virology laboratory of Pitié-Salpêtrière University Hospital (Paris, France) were simultaneously tested for SARS-CoV-2 and other respiratory viruses.

Results: A total of 1423 consecutive patients were tested: 677 (47.6%) males, 746 (52.4%) females, median age 50 (range, 1-103) years. Twenty-one (1.5%) patients were positive for both SARS-CoV-2 and other respiratory viruses. The detection rate of SARS-CoV-2 was significantly higher in LRT than in URT (53.6% vs. 13.4%; p<0.0001). The analysis of paired samples from 117 (8.2%) patients showed that SARS-CoV-2 load was lower in URT than in LRT samples in 65% of cases.

Conclusion: The detection of other respiratory viruses in patients during this epidemic period could not rule out SARS-CoV-2 co-infection. Furthermore, LRT samples increased the accuracy of diagnosis of COVID-19.
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http://dx.doi.org/10.1016/j.ijid.2020.10.040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585729PMC
January 2021

[Herpes simplex virus pneumonia].

Virologie (Montrouge) 2020 Oct;24(5):307-313

Service de Médecine intensive réanimation, Institut de Cardiologie, Groupe hospitalier Pitié-Salpêtrière, Assistance publique-Hôpitaux de Paris, Sorbonne Université.

Herpes simplex virus 1 (HSV-1) reactivation is frequent in intensive care unit patients (20% to 50%, depending on case-mix): it begins in the throat after 3 to 5 days of hospital stay, then progress towards the respiratory tract to reach the lung after 7 to 10 days. In few cases, a HSV-1 bronchopneumonitis (defined by clinical symptom, HSV-1 in the lower respiratory tract and either specific cytopathic effect on cells collected during bronchoalveolar lavage or a HSV-1 load above 10 copies/million cells), can occur. HSV-1 reactivation is associated with mortality, but whether it is only a bystander or it has its own morbidity/mortality is unknown. Two randomized trials have shown lack of efficacy of acyclovir prophylactic or preemptive treatment, but observational studies suggest that acyclovir may be beneficial as a curative treatment. To date, we can only recommend acyclovir in patients with HSV-1 bronchopneumonitis or with HSV-1 load above 10 copies/million cells in the bronchoalveolar lavage.
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http://dx.doi.org/10.1684/vir.2020.0860DOI Listing
October 2020

Effect of antiviral therapy on the outcomes of mechanically ventilated patients with herpes simplex virus detected in the respiratory tract: a systematic review and meta-analysis.

Crit Care 2020 09 29;24(1):584. Epub 2020 Sep 29.

Institute for Infectious Diseases and Infection Control, Jena University Hospital - Friedrich Schiller University Jena, Jena, Germany.

Background: Herpes simplex virus (HSV) is frequently detected in the respiratory tract of mechanically ventilated patients. The aim of this study was to assess current evidence to determine whether antiviral therapy is associated with better outcomes in these patients.

Methods: MEDLINE, ISI Web of Science, Cochrane Database and ClinicalTrials.gov were searched from inception to 25 May 2020. All clinical studies investigating the effects of antiviral therapy on the outcome of mechanically ventilated ICU patients in whom HSV was detected in the respiratory tract were eligible for inclusion, regardless of study design, publication status or language. Titles and abstracts were reviewed independently by two authors. If the articles seemed eligible, full-text articles were reviewed and data extracted. We performed a random-effects meta-analysis to estimate relative risks (RRs) with corresponding 95% confidence intervals (CIs). The primary endpoint was hospital all-cause mortality.

Results: Nine studies were included in the meta-analysis (one randomized controlled trial, eight cohort studies). Antiviral treatment was associated with lower hospital mortality (with antiviral treatment, 40.6% (189 out of 465 patients); without, 52.7% (193 out of 366 patients); RR 0.74 [0.64, 0.85]; eight studies, low quality of evidence). Furthermore, antiviral treatment was associated with lower 30-day mortality (RR 0.75 [0.59, 0.94]; three studies, very low quality of evidence). We did not observe evidence for differences in ICU mortality (RR 0.73 [0.51, 1.05]; three studies, very low quality of evidence).

Conclusions: This meta-analysis of the available data shows that antiviral therapy might result in lower hospital and 30-day all-cause mortality in mechanically ventilated ICU patients who are positive for HSV in the respiratory tract. However, this result must be interpreted with great caution due to the high risk of bias and limited number of patients. Large, well-designed randomized controlled clinical trials are urgently needed.

Trial Registration: The study was registered in advance on International Prospective Register of Systematic Reviews (CRD42020180053) .
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http://dx.doi.org/10.1186/s13054-020-03296-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522924PMC
September 2020

Association of kidney function with effectiveness of procalcitonin-guided antibiotic treatment: a patient-level meta-analysis from randomized controlled trials.

Clin Chem Lab Med 2020 Sep 28;59(2):441-453. Epub 2020 Sep 28.

Medical University Department, Kantonsspital Aarau, Aarau, Switzerland.

Objectives: Patients with impaired kidney function have a significantly slower decrease of procalcitonin (PCT) levels during infection. Our aim was to study PCT-guided antibiotic stewardship and clinical outcomes in patients with impairments of kidney function as assessed by creatinine levels measured upon hospital admission.

Methods: We pooled and analyzed individual data from 15 randomized controlled trials who were randomly assigned to receive antibiotic therapy based on a PCT-algorithms or based on standard of care. We stratified patients on the initial glomerular filtration rate (GFR, ml/min/1.73 m2) in three groups (GFR >90 [chronic kidney disease; CKD 1], GFR 15-89 [CKD 2-4] and GFR<15 [CKD 5]). The main efficacy and safety endpoints were duration of antibiotic treatment and 30-day mortality.

Results: Mean duration of antibiotic treatment was significantly shorter in PCT-guided (n=2,492) compared to control patients (n=2,510) (9.5-7.6 days; adjusted difference in days -2.01 [95% CI, -2.45 to -1.58]). CKD 5 patients had overall longer treatment durations, but a 2.5-day reduction in treatment duration was still found in patients receiving in PCT-guided care (11.3 vs. 8.6 days [95% CI -3.59 to -1.40]). There were 397 deaths in 2,492 PCT-group patients (15.9%) compared to 460 deaths in 2,510 control patients (18.3%) (adjusted odds ratio, 0.88 [95% CI 0.78 to 0.98)]. Effects of PCT-guidance on antibiotic treatment duration and mortality were similar in subgroups stratified by infection type and clinical setting (p interaction >0.05).

Conclusions: This individual patient data meta-analysis confirms that the use of PCT in patients with impaired kidney function, as assessed by admission creatinine levels, is associated with shorter antibiotic courses and lower mortality rates.
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http://dx.doi.org/10.1515/cclm-2020-0931DOI Listing
September 2020

Patients with acute heart failure treated with the CARRESS-HF diuretic protocol in association with canrenoate potassium: Tolerance of high doses of canrenoate potassium.

Arch Cardiovasc Dis 2020 Nov 15;113(11):679-689. Epub 2020 Sep 15.

Unité de soins intensifs cardiologiques, Hôpital cardio-vasculaire Louis Pradel, groupement hospitalier Est, Hospices civils de Lyon, 28, avenue du Doyen-Lépine, 69677 Bron, France.

Background: Oral mineralocorticoid receptor antagonists have failed to prove their efficacy for decongestion and potassium homeostasis in acute heart failure. Intravenous mineralocorticoid receptor antagonists have yet to be studied.

Aim: The aim of this study was to confirm the safety of high-dose potassium canrenoate in association with classic diuretics in acute heart failure.

Methods: This retrospective single-centre study included consecutive patients who were hospitalized with acute heart failure between 2013 and 2018. One hundred patients with overload treated with the standardized diuretic protocol from the CARRESS-HF trial were included. There were no exclusion criteria relating to creatinine or kalaemia at the time of admission. Two groups were constituted on the basis of potassium canrenoate posology: a low-dose group (<300mg/day) and a high-dose group (≥300mg/day); the groups were similar in terms of baseline characteristics.

Results: Mean daily potassium canrenoate doses were 198mg/day (range 100-280mg/day) in the low-dose group and 360mg/day (range 300-600mg/day) in the high-dose group. There was no significant difference between the high-dose and low-dose groups in terms of mortality, dialysis, renal function, hyperkalaemia, haemorrhage, sepsis or confusion.

Conclusions: Potassium canrenoate at high doses can be used safely in association with standard diuretics in acute heart failure, even in patients with altered renal function. A prospective study is required to evaluate the efficacy of high-dose potassium canrenoate in preventing hypokalaemia and improving decongestion.
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http://dx.doi.org/10.1016/j.acvd.2020.05.017DOI Listing
November 2020
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