J Clin Immunol

We report a longitudinal analysis of the immune response associated with a fatal case of COVID-19 in Europe. This patient exhibited a rapid evolution towards multiorgan failure. SARS-CoV-2 was detected in multiple nasopharyngeal, blood, and pleural samples, despite antiviral and immunomodulator treatment. Clinical evolution in the blood was marked by an increase (2–3-fold) in differentiated effector T cells expressing exhaustion (PD-1) and senescence (CD57) markers, an expansion of antibody-secreting cells, a 15-fold increase in γδ T cell and proliferating NK-cell populations, and the total disappearance of monocytes, suggesting lung trafficking. In the serum, waves of a pro-inflammatory cytokine storm, Th1 and Th2 activation, and markers of T cell exhaustion, apoptosis, cell cytotoxicity, and endothelial activation were observed until the fatal outcome. This case underscores the need for well-designed studies to investigate complementary approaches to control viral replication, the source of the hyperinflammatory status, and immunomodulation to target the pathophysiological response. The investigation was conducted as part of an overall French clinical cohort assessing patients with COVID-19 and registered in clinicaltrials.gov under the following number: NCT04262921

Incremental research approach to describing the pharmacokinetics of ciprofloxacin during extracorporeal membrane oxygenation

Significant interactions between drugs, extracorporeal membrane oxygenation (ECMO) circuits and critical illness may affect the pharmacokinetic properties of antibiotics in critically ill patients receiving ECMO.To describe the pharmacokinetic properties of ciprofloxacin during ECMO by integrating pre-clinical findings (ie, ex vivo and in vivo ovine models) to a critically ill patient.An ex vivo model of an ECMO circuit was used to describe ciprofloxacin concentration changes over 24 hours. An in vivo ovine model of ECMO was used to describe the population pharmacokinetic properties of ciprofloxacin in three different groups of sheep, and to investigate sources of pharmacokinetic variability. In the final phase, data from a 39-year-old critically ill man was used to validate the findings from the ovine pharmacokinetic model.In the ex vivo model of ECMO circuits, the median concentrations of ciprofloxacin at baseline and at 24 hours after ciprofloxacin infusion were similar. The time course of ciprofloxacin in the in vivo ovine on ECMO model was adequately described by a two-compartment model. The final population primary parameter mean estimates were: clearance (CL), 0.21 L/kg/h (SD, 0.09 L/kg/h) and volume of distribution (Vd), 0.84 L/kg (SD, 0.12 L/kg). In the critically ill ECMO patient, the primary pharmacokinetic parameter estimates were: CL, 0.15 L/kg/h and Vd, 0.99 L/kg.We provide preliminary evidence that ciprofloxacin dosing in ECMO patients should remain in line with the recommended dosing strategies for critically ill patients not receiving ECMO

Correction to: Changes in the clinical presentation and outcomes of patients treated for severe malaria in a referral French university intensive care unit from 2004 to 2017

International audienceAfter publication of the original article [1], we were notified that family names have been exchanged with the first names for all authors. Below the name are tagged correctly

High-Dose Dexamethasone and Oxygen Support Strategies in Intensive Care Unit Patients With Severe COVID-19 Acute Hypoxemic Respiratory Failure

International audienc