; for the CORIMUNO-19 Collaborative Group IMPORTANCE Severe pneumonia with hyperinflammation and elevated interleukin-6 is a common presentation of coronavirus disease 2019 (COVID-19). OBJECTIVE To determine whether tocilizumab (TCZ) improves outcomes of patients hospitalized with moderate-to-severe COVID-19 pneumonia. DESIGN, SETTING, AND PARTICPANTS This cohort-embedded, investigator-initiated, multicenter, open-label, bayesian randomized clinical trial investigating patients with COVID-19 and moderate or severe pneumonia requiring at least 3 L/min of oxygen but without ventilation or admission to the intensive care unit was conducted between March 31, 2020, to April 18, 2020, with follow-up through 28 days. Patients were recruited from 9 university hospitals in France. Analyses were performed on an intention-to-treat basis with no correction for multiplicity for secondary outcomes. INTERVENTIONS Patients were randomly assigned to receive TCZ, 8 mg/kg, intravenously plus usual care on day 1 and on day 3 if clinically indicated (TCZ group) or to receive usual care alone (UC group). Usual care included antibiotic agents, antiviral agents, corticosteroids, vasopressor support, and anticoagulants. MAIN OUTCOMES AND MEASURES Primary outcomes were scores higher than 5 on the World Health Organization 10-point Clinical Progression Scale (WHO-CPS) on day 4 and survival without need of ventilation (including noninvasive ventilation) at day 14. Secondary outcomes were clinical status assessed with the WHO-CPS scores at day 7 and day 14, overall survival, time to discharge, time to oxygen supply independency, biological factors such as C-reactive protein level, and adverse events. RESULTS Of 131 patients, 64 patients were randomly assigned to the TCZ group and 67 to UC group; 1 patient in the TCZ group withdrew consent and was not included in the analysis. Of the 130 patients, 42 were women (32%), and median (interquartile range) age was 64 (57.1-74.3) years. In the TCZ group, 12 patients had a WHO-CPS score greater than 5 at day 4 vs 19 in the UC group (median posterior absolute risk difference [ARD] −9.0%; 90% credible interval [CrI], −21.0 to 3.1), with a posterior probability of negative ARD of 89.0% not achieving the 95% predefined efficacy threshold. At day 14, 12% (95% CI −28% to 4%) fewer patients needed noninvasive ventilation (NIV) or mechanical ventilation (MV) or died in the TCZ group than in the UC group (24% vs 36%, median posterior hazard ratio [HR] 0.58; 90% CrI, 0.33-1.00), with a posterior probability of HR less than 1 of 95.0%, achieving the predefined efficacy threshold. The HR for MV or death was 0.58 (90% CrI, 0.30 to 1.09). At day 28, 7 patients had died in the TCZ group and 8 in the UC group (adjusted HR, 0.92; 95% CI 0.33-2.53). Serious adverse events occurred in 20 (32%) patients in the TCZ group and 29 (43%) in the UC group (P = .21). CONCLUSIONS AND RELEVANCE In this randomized clinical trial of patients with COVID-19 and pneumonia requiring oxygen support but not admitted to the intensive care...

To identify the potential impact of novel therapeutic approaches, we studied the early predictive factors of survival at the onset of acute respiratory distress syndrome (ARDS) in a 24-bed medical ICU of an academic tertiary care hospital. Over a 48-mo period, a total of 3,511 adult patients were admitted and 259 mechanically ventilated patients met ARDS criteria, as defined by American-European consensus conference, i.e., bilateral pulmonary infiltrates and PaO2/FIO2 lower than 200 without left atrial hypertension. These patients were randomly included in a developmental sample (177 patients) and a validation sample (82 patients). Demographic variables, hemodynamic and respiratory parameters, underlying diseases, as well as several severity scores (SAPS, SAPS-II, OSF) and Lung Injury Score (LIS) were collected. These variables were compared between survivors and nonsurvivors and entered into a stepwise logistic regression model to evaluate their independent prognostic roles. The overall mortality rate was 65%. SAPS-II, the severity of the underlying medical conditions, the oxygenation index (mean airway pressure x FIO2 x 100/PaO2), the length of mechanical ventilation prior to ARDS, the mechanism of lung injury, cirrhosis, and occurrence of right ventricular dysfunction were independently associated with an elevated risk of death. Model calibration was very good in the developmental and validation samples (p = 0.84 and p = 0.72, respectively), as was model discrimination (area under the ROC curves of 0.95 and 0.92, respectively). Thus, the prognosis of ARDS seems to be related to the triggering risk factor, the severity of the respiratory illness, and the occurrence of a right ventricle dysfunction, after adjustment for a general severity score.

Background Patients with COVID-19 pneumonia have an excess of inflammation and increased concentrations of cytokines including interleukin-1 (IL-1). We aimed to determine whether anakinra, a recombinant human IL-1 receptor antagonist, could improve outcomes in patients in hospital with mild-to-moderate COVID-19 pneumonia.Methods In this multicentre, open-label, Bayesian randomised clinical trial (CORIMUNO-ANA-1), nested within the CORIMUNO-19 cohort, we recruited patients from 16 University hospitals in France with mild-to-moderate COVID-19 pneumonia, severe acute respiratory syndrome coronavirus 2 infection confirmed by real-time RT-PCR, requiring at least 3 L/min of oxygen by mask or nasal cannula but without ventilation assistance, a score of 5 on the WHO Clinical Progression Scale (WHO-CPS), and a C-reactive protein serum concentration of more than 25 mg/L not requiring admission to the intensive care unit at admission to hospital. Eligible patients were randomly assigned (1:1) using a web-based secure centralised system, stratified by centre and blocked with varying block sizes (randomly of size two or four), to either usual care plus anakinra (200 mg twice a day on days 1-3, 100 mg twice on day 4, 100 mg once on day 5) or usual care alone. Usual care was provided at the discretion of the site clinicians. The two coprimary outcomes were the proportion of patients who had died or needed non-invasive or mechanical ventilation by day 4 (ie, a score of >5 on the WHO-CPS) and survival without need for mechanical or non-invasive ventilation (including high-flow oxygen) at day 14. All analyses were done on an intention-to-treat basis. The trial is registered with ClinicalTrials.gov, NCT04341584, and is now closed to accrual. FindingsBetween April 8 and April 26, 2020, we screened 153 patients. The study was stopped early following the recommendation of the data and safety monitoring board, after the recruitment of 116 patients: 59 were assigned to the anakinra group, and 57 were assigned to the usual care group. Two patients in the usual care group withdrew consent and were not analysed. In the analysable population, the median age was 66 years (IQR 59 to 76) and 80 (70%) participants were men. In the anakinra group, 21 (36%) of 59 patients had a WHO-CPS score of more than 5 at day 4 versus 21 (38%) of 55 in the usual care group (median posterior absolute risk difference [ARD] -2•5%, 90% credible interval [CrI] -17•1 to 12•0), with a posterior probability of ARD of less than 0 (ie, anakinra better than usual care) of 61•2%. At day 14, 28 (47%; 95% CI 33 to 59) patients in the anakinra group and 28 (51%; 95% CI 36 to 62) in the usual care group needed ventilation or died, with a posterior probability of any efficacy of anakinra (hazard ratio [HR] being less than 1) of 54•5% (median posterior HR 0•97; 90% CrI 0•62 to 1•52). At day 90, 16 (27%) patients in the anakinra group and 15 (27%) in the usual care group had died. Serious adverse events occurred in 27 (46%) patients in the anakinra group and 21 (38%) in the usu...

We compared the properties of common carotid and femoral arteries of 16 normotensive and 14 hypertensive men. Arterial pressure and diameter were recorded noninvasively in each vessel by tonometric and echotracking devices. The x-y composition of pressure and diameter waves provided the diameter-pressure hysteresis loop. The elastic diameter-pressure curve and wall viscosity index were deduced after hysteresis elimination. The compliance-pressure and distensibility-pressure curves were derived from the diameter-pressure curve, allowing the calculation of effective compliance and distensibility at the prevailing pressure of each subject and isobaric compliance and distensibility at the same standard pressure in all subjects. Systolic, diastolic, mean, and pulse pressures and diameters in each vessel were higher in the hypertensive than the normotensive group, except carotid pulse diameter, which did not differ. The carotid diameter-pressure, compliance-pressure, and distensibility-pressure curves did not differ between groups. In the carotid artery hypertensive patients had isobaric compliance and distensibility values similar to those of normotensive subjects, despite lower effective compliance (P < .05) and distensibility (P < .01). The femoral diameter-pressure curve was higher (P < .05) and the femoral compliance-pressure and distensibility-pressure curves were lower (P < .01) in the hypertensive than the normotensive group. Hypertensive patients had effective and isobaric femoral compliance and distensibility values lower than to those of normotensive subjects (P < .001). In both arteries, viscosity index was higher in the hypertensive than the normotensive group (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)