Background Limited data are available regarding antiviral therapy efficacy in most severe patients under mechanical ventilation for Covid-19-related acute respiratory distress syndrome (ARDS). Methods Comparison of antiviral strategies (none, hydroxychloroquine (OHQ), lopinavir/ritonavir (L/R), others (combination or remdesivir) in an observational multicentre cohort of patients with moderate-to-severe Covid-19 ARDS. The primary endpoint was the number of day 28 ventilator-free days (VFD). Patients who died before d28 were considered as having 0 VFD. The variable was dichotomized into “patients still ventilated or dead at day 28” versus “patients weaned and alive at day 28”. Results We analyzed 415 patients (85 treated with standard of care (SOC), 57 with L/R, 220 with OHQ, and 53 others). The median number of d28-VFD was 0 (IQR 0–13) and differed between groups (P = 0.03), SOC patients having the highest d28-VFD. After adjustment for age, sex, Charlson Comorbidity Index, PaO2/FiO2 ratio and plateau pressure and accounting for center effect with a generalized linear mixed model, none of the antiviral strategies increased the chance of being alive and weaned from MV at day 28 compared to the SOC strategy (OR 0.48 CI95% (0.18–1.25); OR 0.96 (0.47–2.02) and OR 1.43 (0.53–4.04) for L/R, OHQ and other treatments, respectively). Acute kidney injury during ICU stay was frequent (55%); its incidence was higher in patients receiving lopinavir (66 vs 53%, P = 0.03). After adjustment for age, sex, BMI, chronic hypertension and chronic renal disease, the use of L/R was associated with an increased risk of renal replacement therapy (RRT). (OR 2.52 CI95% 1.16–5.59). Conclusion In this multicentre observational study of moderate-to-severe Covid-19 ARDS patients, we did not observe any benefit among patients treated with OHQ or L/R compared with SOC. The use of L/R treatment was associated with an increased need for RRT. Take home message Neither hydroxychloroquine nor lopinavir/ritonavir as COVID-19 antiviral treatment is associated with higher ventilator-free days at day 28 when compared with standard of care (no antiviral treatment) in ICU patients under invasive mechanical ventilation. Lopinavir/ritonavir is associated with an increased risk of renal replacement therapy requirement. Tweet COVID-19: Insights from ARDS cohort: no signal of efficacy of any antiviral drugs. Lopinavir/ritonavir may be associated with need for RRT

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Background: Staphylococcus aureus remains a common cause of ventilatorassociated pneumonia, with little change in infection rates over the past 15 years. This phase 2 study evaluated suvratoxumab, an anti-alpha-toxin monoclonal antibody, in reducing incidence of S. aureus pneumonia in intensive care unit (ICU) subjects on mechanical ventilation (MV). Methods:We did a multicenter, single-dose, randomized, placebo-controlled, doubleblind, phase 2 pilot trial in 9 countries. Eligible subjects were patients in an ICU ≥18 years of age, currently intubated and on MV, positive for S. aureus lower respiratory tract (LRT) colonization as assessed by polymerase chain reaction (PCR) of endotracheal aspirate, and with no diagnosis of new-onset pneumonia. Subjects were excluded if they had confirmed or suspected acute ongoing staphylococcal disease; had received anti-S. aureus antibiotics for >48 hours; had a CPIS ≥6, APACHE-II score ≥25, a SOFA score ≥9; or had active pulmonary disease that would impair the ability to diagnose pneumonia. Subjects were screened for S. aureus lower respiratory tract (LRT) colonization using real-time polymerase chain reaction (PCR).Colonized subjects were randomly assigned 1:1:1 to a single intravenous infusion of suvratoxumab 2000 mg, 5000 mg or placebo. Randomization was stratified by country and by whether subjects received anti-S. aureus systemic antibiotic therapy. Based on pre-defined PK criteria, the 2000 mg arm was discontinued upon the recommendation of the data monitoring committee at an interim analysis. Primary efficacy endpoint was incidence of S. aureus pneumonia, adjudicated by a blinded independent panel, through 30 days post dose in the modified intent-to-treat study population. Primary safety endpoints were Francois et al. Suvratoxumab Ph2 (NCT02296320) D3 5 treatment-emergent AEs assessed through 30 and 90 days, treatment-emergent SAEs, adverse events of special interest, and new onset chronic disease, all assessed through 190 days. Findings: PCR screening of 737 ICU subjects identified 213 with S. aureus colonization; of these, 96 were randomized to receive suvratoxumab 5000 mg and 100 to placebo. At 30 days, 17/96 (17•7%) suvratoxumab and 26/100 (26•0%) placebo subjects had developed S. aureus pneumonia (relative risk reduction, 31.9%; 90% confidence interval [CI], −7•5 to 56•8; P = 0•166). At 30 days, incidences of treatmentemergent adverse events (AEs) and serious AEs were similar in suvratoxumab and placebo groups (90•6% [87/96] vs. 90•0% [90/100] and 37•5% [36/96] vs 32•0% [32/100], respectively). At 90 and 190 days, incidence of treatment-emergent AEs was still similar in suvratoxumab and placebo groups (92.

Objectives: In the context of COVID-19 pandemic, the aim of this manuscript is to provide a standard of care of patients with ARDS for non-emergency medicine trained physicians who are not customary with mechanical ventilation. Methods: We conducted a systematic review of the literature to investigate the best practice recommendations regarding the mechanical ventilation of patients with ARDS. Conclusion: We summarized the principal strategies for lung-protective ventilation of patients with ARDS. This focus is particularly addressed to physicians who are not experienced in the invasive respiratory management of ARDS patients. Nevertheless, it remains fundamental to acknowledge that new insights concerning this quickly spreading illness become available on a regular base.

Invasive aspergillosis(IA) is a potentially lethal complication of Aspergillus infection affecting mainly immunocompromised hosts; however, during the last two decades its incidence was increasingly observed in critically ill immunocompetent patients. The objective of this study is to describe the clinical characteristics of histologically proven endomyocardial and pericardial invasion, in the context of IA, in critically ill patients. Eight critically ill patients with histopathological confirmation of endomyocardial/pericardial aspergillosis were evaluated. Risk factors, clinical and laboratory characteristics, treatment, histopathological characteristics and mortality were recorded. Signs and symptoms of cardiac dysfunction were not observed in any of the patients. Therapy was administered to six of them shortly after the first positive culture. The observed histopathological lesions included haemorrhagic lesions, small vessels with central thrombosis and surrounding consolidated tissue with necrosis. Voriconazole, caspofungin, lipid amphotericin B and itraconazole were the used antifungals. The mortality rate was high (87.5%). Endomyocardial and pericardial aspergillosis are devastating complications of invasive aspergillosis. Clinical suspicion is low making the diagnosis difficult, therefore histopathological examination of tissues are required. The mortality is high.