Explore the vast range of titles available.

COVID-19 can lead to life-threatening respiratory failure, with increased inflammatory mediators and viral load. Here, we perform single-cell RNA-sequencing to establish a high-resolution map of blood antigen-presenting cells (APCs) in 15 patients with moderate or severe COVID-19 pneumonia, at day 1 and day 4 post admission to intensive care unit or pulmonology department, as well as in 4 healthy donors. We generated a unique dataset of 81,643 APCs, including monocytes and rare dendritic cell (DC) subsets. We uncovered multi-process defects in antiviral immune defence in specific APCs from patients with severe disease: (1) increased pro-apoptotic pathways in plasmacytoid DCs (pDCs, key effectors of antiviral immunity), (2) a decrease of the innate sensors TLR9 and DHX36 in pDCs and CLEC9a + DCs, respectively, (3) downregulation of antiviral interferon-stimulated genes in monocyte subsets and (4) a decrease of major histocompatibility complex (MHC) class II-related genes and MHC class II transactivator activity in cDC1c + DCs, suggesting viral inhibition of antigen presentation. These novel mechanisms may explain patient aggravation and suggest strategies to restore the defective immune defence. Saichi et al. performed single-cell RNA-seq analysis of antigen-presenting cells (APCs) isolated from the peripheral blood of patients with moderate and severe COVID-19 and uncovered defects in antiviral immune response in specific APC subsets.

Acute respiratory distress syndrome (ARDS) related to Coronavirus disease (COVID-19) is associated with high mortality. It has been suggested that venovenous extracorporeal membrane oxygenation (ECMO) was suitable in this indication, albeit the effects of ECMO on the mechanical respiratory parameters have been scarcely described. In this case-series, we prospectively described the use of venovenous ECMO and its effects on mechanical respiratory parameters in eleven COVID-19 patients with severe ARDS. Implantation of ECMO occurred 6 [3–11] days after the onset of mechanical ventilation. At the time of ECMO implantation, all patients received neuromuscular blocking agents, three (27%) received inhaled nitric oxide and prone positioning was performed in all patients with 4 [3−5] sessions of PP per patient. Under ECMO, the tidal volume was significantly decreased from 6.1 [4.0–6.3] to 3.4 [2.5–3.6] mL/kg of predicted body weight and the positive end-expiratory pressure level was increased by 25 ± 27% whereas the driving pressure and the mechanical power decreased by 33 ± 25% and 71 ± 27%, respectively. The PaO 2 /FiO 2 ratio significantly increased from 68 [58–89] to 168 [137–218] and the oxygenation index significantly decreased from 28 [26–35] to 13 [10–15]. The duration of ECMO was 12 [8–25] days. Nine (82%) patients experienced ECMO-related complications and the main complication was major bleeding requiring blood transfusions. Intensive care unit mortality rate was 55% but no patient died from ECMO-related complications. In COVID-19 patients with severe ARDS, venovenous ECMO allowed ultra-protective ventilation, improved oxygenation and should be considered in highly selected patients with the most severe ARDS.

The cholinergic system has been proposed as a potential regulator of COVID-19-induced hypercytokinemia. We investigated whole-blood expression of cholinergic system members and correlated it with COVID-19 severity. Patients with confirmed SARS-CoV-2 infection and healthy aged-matched controls were included in this non-interventional study. A whole blood sample was drawn between 9–11 days after symptoms onset, and peripheral leukocyte phenotyping, cytokines measurement, RNA expression and plasma viral load were determined. Additionally, whole-blood expression of native alpha-7 nicotinic subunit and its negative dominant duplicate (CHRFAM7A), choline acetyltransferase and acetylcholine esterase (AchE) were determined. Thirty-seven patients with COVID-19 (10 moderate, 11 severe and 16 with critical disease) and 14 controls were included. Expression of CHRFAM7A was significantly lower in critical COVID-19 patients compared to controls. COVID-19 patients not expressing CHRFAM7A had higher levels of CRP, more extended pulmonary lesions and displayed more pronounced lymphopenia. COVID-19 patients without CHRFAM7A expression also showed increased TNF pathway expression in whole blood. AchE was also expressed in 30 COVID-19 patients and in all controls. COVID-19-induced hypercytokinemia is associated with decreased expression of the pro-inflammatory dominant negative duplicate CHRFAM7A. Expression of this duplicate might be considered before targeting the cholinergic system in COVID-19 with nicotine.

Purpose Prognosis of solid organ transplant (SOT) recipients has improved, mainly because of better prevention of rejection by immunosuppressive therapies. However, SOT recipients are highly susceptible to conventional and opportunistic infections, which represent a major cause of morbidity, graft dysfunction and mortality. Methods Narrative review. Results We cover the current epidemiology and main aspects of infections in SOT recipients including risk factors such as postoperative risks and specific risks for different transplant recipients, key points on anti-infective prophylaxis as well as diagnostic and therapeutic approaches. We provide an up-to-date guide for management of the main syndromes that can be encountered in SOT recipients including acute respiratory failure, sepsis or septic shock, and central nervous system infections as well as bacterial infections with multidrug-resistant strains, invasive fungal diseases, viral infections and less common pathogens that may impact this patient population. Conclusion We provide state-of the art review of available knowledge of critically ill SOT patients with infections.

Background Previous studies reporting the causes of death in patients with severe COVID-19 have provided conflicting results. The objective of this study was to describe the causes and timing of death in patients with severe COVID-19 admitted to the intensive care unit (ICU). Methods We performed a retrospective study in eight ICUs across seven French hospitals. All consecutive adult patients (aged ≥ 18 years) admitted to the ICU with PCR-confirmed SARS-CoV-2 infection and acute respiratory failure were included in the analysis. The causes and timing of ICU deaths were reported based on medical records. Results From March 1, 2020, to April 28, 287 patients were admitted to the ICU for SARS-CoV-2 related acute respiratory failure. Among them, 93 patients died in the ICU (32%). COVID-19-related multiple organ dysfunction syndrome (MODS) was the leading cause of death (37%). Secondary infection-related MODS accounted for 26% of ICU deaths, with a majority of ventilator-associated pneumonia. Refractory hypoxemia/pulmonary fibrosis was responsible for death in 19% of the cases. Fatal ischemic events (venous or arterial) occurred in 13% of the cases. The median time from ICU admission to death was 15 days (25th–75th IQR, 7–27 days). COVID-19-related MODS had a median time from ICU admission to death of 14 days (25th–75th IQR: 7–19 days), while only one death had occurred during the first 3 days since ICU admission. Conclusions In our multicenter observational study, COVID-19-related MODS and secondary infections were the two leading causes of death, among severe COVID-19 patients admitted to the ICU.

The objective is to identify the risk markers of multi-drug resistant bacteria (MDRB) related ventilator-associated pneumonia (VAP) in septic shock patients with previous MDRB carriage. This retrospective study was conducted in a medical ICU from 2010 to 2020. Consecutive patients with septic shock and still in the ICU after 48 h, were eligible. The following microorganisms were defined as MDRB: extended-spectrum beta-lactamase producing enterobacteriaceae, methicillin-resistant Staphylococcus aureus, multi-drug resistant Pseudomonas aeruginosa, imipenem-resistant Acinetobacter baumanii and Stenotrophomonas maltophilia. Screening for MDRB colonization was performed at ICU admission and during ICU stay. The determinants of MDRB-related VAP were assessed using a time-dependent cause-specific Cox model. 643 patients were analyzed and 122 (18.9%) had at least one episode of VAP. The overall ICU mortality was 32.5%. The incidence of MDRB carriage was 31%, distributed into MDRB carriage at admission (14.3%) and MDRB acquired during ICU stay (16.7%). In multivariate analysis, MDRB colonization in ICU was independently associated with an increased risk of VAP (CSH: 1.85; 95% CI: 1.05–3.23; p = 0.03) whereas carriage prior to admission was not. Imported and acquired MDRB carriage harbor different risks of subsequent MDRB-related VAP in patients with septic shock. •16.5% of septic shock patients acquire multidrug resistant bacteria colonization.•Multidrug resistant bacteria carriage precede ventilator associated pneumonia.•Timing of colonization impact risk of ventilator associated pneumonia.

Purpose Little attention has been given to ARDS in cancer patients, despite their high risk for pulmonary complications. We sought to describe outcomes in cancer patients with ARDS meeting the Berlin definition. Methods Data from a cohort of patients admitted to 14 ICUs between 1990 and 2011 were used for a multivariable analysis of risk factors for hospital mortality. Results Of 1,004 included patients (86 % with hematological malignancies and 14 % with solid tumors), 444 (44.2 %) had neutropenia. Admission SOFA score was 12 (10–13). Etiological categories were primary infection-related ARDS ( n  = 662, 65.9 %; 385 bacterial infections, 213 invasive aspergillosis, 64 Pneumocystis pneumonia); extrapulmonary septic shock-related ARDS ( n  = 225, 22.4 %; 33 % candidemia); noninfectious ARDS ( n  = 76, 7.6 %); and undetermined cause ( n  = 41, 4.1 %). Of 387 (38.6 %) patients given noninvasive ventilation (NIV), 276 (71 %) subsequently required endotracheal ventilation. Hospital mortality was 64 % overall. According to the Berlin definition, 252 (25.1 %) patients had mild, 426 (42.4 %) moderate and 326 (32.5 %) severe ARDS; mortality was 59, 63 and 68.5 %, respectively ( p  = 0.06). Mortality dropped from 89 % in 1990–1995 to 52 % in 2006–2011 ( p  < 0.0001). Solid tumors, primary ARDS, and later admission period were associated with lower mortality. Risk factors for higher mortality were allogeneic bone-marrow transplantation, modified SOFA, NIV failure, severe ARDS, and invasive fungal infection. Conclusions In cancer patients, 90 % of ARDS cases are infection-related, including one-third due to invasive fungal infections. Mortality has decreased over time. NIV failure is associated with increased mortality. The high mortality associated with invasive fungal infections warrants specific studies of early treatment strategies.

Managing patients with acute respiratory distress syndrome (ARDS) requires frequent changes in mechanical ventilator respiratory settings to optimize arterial oxygenation assessed by arterial oxygen partial pressure (PaO 2 ) and saturation (SaO 2 ). Pulse oxymetry (SpO 2 ) has been suggested as a non-invasive surrogate for arterial oxygenation however its accuracy in COVID-19 patients is unknown. In this study, we aimed to investigate the influence of COVID-19 status on the association between SpO 2 and arterial oxygenation. We prospectively included patients with ARDS and compared COVID-19 to non-COVID-19 patients, regarding SpO 2 and concomitant arterial oxygenation (SaO 2 and PaO 2 ) measurements, and their association. Bias was defined as mean difference between SpO 2 and SaO 2 measurements. Occult hypoxemia was defined as a SpO 2  ≥ 92% while concomitant SaO 2  < 88%. Multiple linear regression models were built to account for confounders. We also assessed concordance between positive end-expiratory pressure (PEEP) trial-induced changes in SpO 2 and in arterial oxygenation. We included 55 patients, among them 26 (47%) with COVID-19. Overall, SpO 2 and SaO 2 measurements were correlated (r = 0.70; p  < 0.0001), however less so in COVID-19 than in non-COVID-19 patients (r = 0.55, p  < 0.0001 vs. r = 0.84, p  < 0.0001, p  = 0.002 for intergroup comparison). Bias was + 1.1%, greater in COVID-19 than in non-COVID-19 patients (2.0 vs. 0.3%; p  = 0.02). In multivariate analysis, bias was associated with COVID-19 status (unstandardized β = 1.77, 95%CI = 0.38–3.15, p  = 0.01), ethnic group and ARDS severity. Occult hypoxemia occurred in 5.5% of measurements (7.7% in COVID-19 patients vs. 3.4% in non-COVID-19 patients, p  = 0.42). Concordance rate between PEEP trial-induced changes in SpO 2 and SaO 2 was 84%, however less so in COVID-19 than in non-COVID-19 patients (69% vs. 97%, respectively). Similar results were observed for PaO 2 regarding correlations, bias, and concordance with SpO 2 changes. In patients with ARDS, SpO 2 was associated with arterial oxygenation, but COVID-19 status significantly altered this association.

Immune system dysfunction is paramount in coronavirus disease 2019 (COVID-19) severity and fatality rate. Mucosal-associated invariant T (MAIT) cells are innate-like T cells involved in mucosal immunity and protection against viral infections. Here, we studied the immune cell landscape, with emphasis on MAIT cells, in cohorts totaling 208 patients with various stages of disease. MAIT cell frequency is strongly reduced in blood. They display a strong activated and cytotoxic phenotype that is more pronounced in lungs. Blood MAIT cell alterations positively correlate with the activation of other innate cells, proinflammatory cytokines, notably interleukin (IL)-18, and with the severity and mortality of severe acute respiratory syndrome coronavirus 2 infection. We also identified a monocyte/macrophage interferon (IFN)-α–IL-18 cytokine shift and the ability of infected macrophages to induce the cytotoxicity of MAIT cells in an MR1-dependent manner. Together, our results suggest that altered MAIT cell functions due to IFN-α–IL-18 imbalance contribute to disease severity, and their therapeutic manipulation may prevent deleterious inflammation in COVID-19 aggravation. Severe COVID-19 is characterized by hyperinflammation, and there is a need for accurate predictive biomarkers of progression. Lehuen et al. demonstrate that patients with severe COVID-19 show a dramatic loss of MAIT cells, and those that do remain are in a highly activated state.