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.

Sarcoidosis is a granulomatous disorder of unknown etiology, associated with an accumulation of CD4+ T cells and a TH1 immune response. Since previous studies of HLA associations with sarcoidosis were limited by serologic or low-resolution molecular identification, we performed high-resolution typing for the HLA-DPB1, HLA-DQB1, HLA-DRB1, and HLA-DRB3 loci and the presence of the DRB4 or DRB5 locus, to define HLA class II associations with sarcoidosis. A Case Control Etiologic Study of Sarcoidosis (ACCESS) enrolled biopsy-confirmed cases (736 total) from 10 centers in the United States. Seven hundred six (706) controls were case matched for age, race, sex, and geographic area. We studied the first 474 ACCESS patients and case-matched controls. The HLA-DRB1 alleles were differentially distributed between cases and controls (P<.0001). The HLA-DRB1*1101 allele was associated (P<.01) with sarcoidosis in blacks and whites and had a population attributable risk of 16% in blacks and 9% in whites. HLA-DRB1-F(47) was the amino acid residue most associated with sarcoidosis and independently associated with sarcoidosis in whites. The HLA-DPB1 locus also contributed to susceptibility for sarcoidosis and, in contrast to chronic beryllium disease, a non-E(69)-containing allele, HLA-DPB1*0101, conveyed most of the risk. Although significant differences were observed in the distribution of HLA class II alleles between blacks and whites, only HLA-DRB1*1501 was differentially associated with sarcoidosis (P<.003). In addition to being susceptibility markers, HLA class II alleles may be markers for different phenotypes of sarcoidosis (DRB1*0401 for eye in blacks and whites, DRB3 for bone marrow in blacks, and DPB1*0101 for hypercalcemia in whites). These studies confirm a genetic predisposition for sarcoidosis and present evidence for the allelic variation at the HLA-DRB1 locus as a major contributor.

Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research. Patient consent for publication Not required.Provenance and peer review Not commissioned; externally peer reviewed. This article is made freely available for use in accordance with BMJ's website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.

ObjectiveTo investigate the pathophysiologic mechanism of encephalopathy and prolonged comatose or stuporous state in severally ill patients with coronavirus disease 2019 (COVID-19).MethodsEight COVID-19 patients with signs of encephalopathy were tested for antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the serum and CSF using a Food and Drug Administration-approved and independently validated ELISA. Blood-brain barrier (BBB) integrity and immunoglobulin G (IgG) intrathecal synthesis were further tested using albumin and IgG indices. The CSF was also tested for autoimmune encephalitis antibodies and 14-3-3, a marker of ongoing neurodegeneration.ResultsAll patients had anti–SARS-CoV-2 antibodies in their CSF, and 4 of 8 patients had high titers, comparable to high serum values. One patient had anti–SARS-CoV-2 IgG intrathecal synthesis, and 3 others had disruption of the blood-brain barrier. The CSF in 4 patients was positive for 14-3-3-protein suggesting ongoing neurodegeneration. In all patients, the CSF was negative for autoimmune encephalitis antibodies and SARS-CoV-2 by PCR. None of the patients, apart from persistent encephalopathic signs, had any focal neurologic signs or history or specific neurologic disease.ConclusionsHigh-titer anti-SARS-CoV-2 antibodies were detected in the CSF of comatose or encephalopathic patients demonstrating intrathecal IgG synthesis or BBB disruption. A disrupted BBB may facilitate the entry of cytokines and inflammatory mediators into the CNS enhancing neuroinflammation and neurodegeneration. The observations highlight the need for prospective CSF studies to determine the pathogenic role of anti–SARS-CoV-2 antibodies and identify early therapeutic interventions.

Antoine, Maladies métaboliques, biliaires et fibroinflammatoire du foie, Institute of Cardiometabolism and Nutrition (ICAN).

In acute respiratory distress syndrome (ARDS), recruitment sessions of highfrequency oscillation (HFO) and tracheal gas insufflation (TGI) with short-lasting recruitment manoeuvres (RMs) may improve oxygenation and enable reduction of subsequent conventional mechanical ventilation (CMV) pressures. We determined the effect of adding HFO-TGI sessions to lung-protective CMV on early/severe ARDS outcome.We conducted a prospective clinical trial, subdivided into a first single-centre period and a second two-centre period. We enrolled 125 (first period, n554) patients with arterial oxygen tension (Pa,O 2 )/inspiratory oxygen fraction (FI,O 2 ) of ,150 mmHg for .12 consecutive hours at an end-expiratory pressure of o8 cmH 2 O. Patients were randomly assigned to an HFO-TGI group (receiving HFO-TGI sessions with RMs, interspersed with lung-protective CMV; n561) or CMV group (receiving lung-protective CMV and RMs; n564). The primary outcome was survival to hospital discharge.Pre-enrolment ventilation duration was variable. During days 1-10 post-randomisation, Pa,O 2 / FI,O 2 , oxygenation index, plateau pressure and respiratory compliance were improved in the HFO-TGI group versus the CMV group (p,0.001 for group6time). Within days 1-60, the HFO-TGI group had more ventilator-free days versus the CMV group (median (interquartile range) 31.0 (0.0-42.0) versus 0.0 (0.0-23.0) days; p,0.001), and more days without respiratory, circulatory, renal, coagulation and liver failure (pf0.003). Survival to hospital discharge was higher in the HFO-TGI group versus the CMV group (38 (62.3%) out of 61 versus 23 (35.9%) out of 64 subjects; p50.004).Intermittent recruitment with HFO-TGI and RMs may improve survival in early/severe ARDS.

Highlights Critically ill Covid-19 patients with type-2 diabetes show decreased survival rate. Obese critically ill Covid-19 pneumonia patients are more often of younger age. Non-obese Covid-19 pneumonia survivors are older than obese survivors. Age and cardiovascular disease in Covid-19 patients are not related to early death.

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.