Alveolar cytokines and interferon autoantibodies in COVID-19 ARDS.

Background: Type I interferon (IFN-I) and IFN autoantibodies play a crucial role in controlling SARS-CoV-2 infection. The levels of these mediators have only rarely been studied in the alveolar compartment in patients with COVID-19 acute respiratory distress syndrome (CARDS) but have not been compared across different ARDS etiologies, and the potential effect of dexamethasone (DXM) on these mediators is not known.

Methods: We assessed the integrity of the alveolo-capillary membrane, interleukins, type I, II, and III IFNs, and IFN autoantibodies by studying the epithelial lining fluid (ELF) volumes, alveolar concentration of protein, and ELF-corrected concentrations of cytokines in two patient subgroups and controls.

Long-term outcomes in COVID-19 patients admitted to intensive care in Denmark: A nationwide observational study.

Background: Among ICU patients with COVID-19, it is largely unknown how the overall outcome and resource use have changed with time, different genetic variants, and vaccination status.

Methods: For all Danish ICU patients with COVID-19 from March 10, 2020 to March 31, 2022, we manually retrieved data on demographics, comorbidities, vaccination status, use of life support, length of stay, and vital status from medical records. We compared patients based on the period of admittance and vaccination status and described changes in epidemiology related to the Omicron variant.

PaCO trajectories in mechanically ventilated patients with COVID-19: A population-based cohort study.

Objective: To identify PaCO trajectories and assess their associations with mortality in critically ill patients with coronavirus disease 2019 (COVID-19) during the first and second waves of the pandemic in Denmark.

Design: A population-based cohort study with retrospective data collection.

Patients: All COVID-19 patients were treated in eight intensive care units (ICUs) in the Capital Region of Copenhagen, Denmark, between March 1, 2020 and March 31, 2021.

Thromboembolic and bleeding events in ICU patients with COVID-19: A nationwide, observational study.

Background: Intensive care unit (ICU) patients with Coronavirus disease 2019 (COVID-19) have an increased risk of thromboembolic complications. We describe the occurrence of thromboembolic and bleeding events in all ICU patients with COVID-19 in Denmark during the first and second waves of the pandemic.

Methods: This was a sub-study of the Danish Intensive Care Covid database, in which all patients with SARS-CoV-2 admitted to Danish ICUs from 10th March 2020 to 30th June 2021 were included.

Diagnostic and prognostic performance of Mxa and transfer function analysis-based dynamic cerebral autoregulation metrics.

Dynamic cerebral autoregulation is often assessed by continuously recorded arterial blood pressure (ABP) and transcranial Doppler-derived mean cerebral blood flow velocity followed by analysis in the time and frequency domain, respectively. Sequential correlation (in the time domain, yielding e.g.

Changes over time in characteristics, resource use and outcomes among ICU patients with COVID-19-A nationwide, observational study in Denmark.

Background: Characteristics and care of intensive care unit (ICU) patients with COVID-19 may have changed during the pandemic, but longitudinal data assessing this are limited. We compared patients with COVID-19 admitted to Danish ICUs in the first wave with those admitted later.

Methods: Among all Danish ICU patients with COVID-19, we compared demographics, chronic comorbidities, use of organ support, length of stay and vital status of those admitted 10 March to 19 May 2020 (first wave) versus 20 May 2020 to 30 June 2021.

[Local immunopathology in COVID-19 associated lung injury].

Mechanisms of COVID-19-induced lung injury involve complex immunopathological events which are currently being elucidated. Studying immune mechanisms at the primary site of injury, i.e.

A Distinct Dexamethasone-Dependent Gene Expression Profile in the Lungs of COVID-19 Patients.

The effects of dexamethasone (DXM) treatment on pulmonary immunity in COVID-19-associated acute respiratory distress syndrome (CARDS) remain insufficiently understood. We performed transcriptomic RNA-seq analysis of bronchoalveolar lavage fluid from 20 mechanically ventilated patients: 12 with CARDS (with or without DXM) and 8 non-COVID-19 critically ill controls. CARDS with DXM was characterized by upregulation of genes related to B-cell and complement pathway activation, antigen presentation, phagocytosis, and FC-γ receptor signaling.

Reduced levels of pulmonary surfactant in COVID-19 ARDS.

To provide novel data on surfactant levels in adult COVID-19 patients, we collected bronchoalveolar lavage fluid less than 72 h after intubation and used Fourier Transform Infrared Spectroscopy to measure levels of dipalmitoylphosphatidylcholine (DPPC). A total of eleven COVID-19 patients with moderate-to-severe ARDS (CARDS) and 15 healthy controls were included. CARDS patients had lower DPPC levels than healthy controls.

Host Genetics and Antiviral Immune Responses in Adult Patients With Multisystem Inflammatory Syndrome.

COVID-19 associated multisystem inflammatory syndrome (MIS) is a rare condition mostly affecting children but also adults (MIS-A). Although severe systemic inflammation and multiorgan dysfunction are hallmarks of the syndrome, the underlying pathogenesis is unclear. We aimed to provide novel immunological and genetic descriptions of MIS-A patients.

[Hyperlactataemia].

It is a common but flawed presumption that blood lactate reflects the lactic acid production in the body's tissues. Lactate is formed directly from pyruvate and functions to dampen reductions in intracellular pH through lactate-H+ cotransport to the extracellular space. Though this may give rise to elevated blood lactate, increased lactate production is not the cause of metabolic acidosis in such instances.

Therapeutic benefits of proning to improve pulmonary gas exchange in severe respiratory failure: focus on fundamentals of physiology.

New Findings: What is the topic of this review? The use of proning for improving pulmonary gas exchange in critically ill patients. What advances does it highlight? Proning places the lung in its 'natural' posture, and thus optimises the ventilation-perfusion distribution, which enables lung protective ventilation and the alleviation of potentially life-threatening hypoxaemia in COVID-19 and other types of critical illness with respiratory failure.

Abstract: The survival benefit of proning patients with acute respiratory distress syndrome (ARDS) is well established and has recently been found to improve pulmonary gas exchange in patients with COVID-19-associated ARDS (CARDS).

Reliability of the mean flow index (Mx) for assessing cerebral autoregulation in healthy volunteers.

Background: Mean flow index (Mxa) for evaluating dynamic cerebral autoregulation is derived using varying approaches for calculation, which may explain that the reliability ranges from poor to excellent. The comparability, repeatability, stability, and internal consistency of approaches have not previously been assessed.

Methods: We included 60 recordings from resting healthy volunteers and calculated Mxa using four different approaches: three without overlapping calculations, using intervals for averaging wave-form data (blocks) of 3, 6, and 10 s, and correlation periods (epochs) of 60, 240, and 300 s (3-60-F, 6-240-F, and 10-300-F); and one using 10-second blocks, 300 s epochs, and overlaps of 60 s (10-300-60).

The role of lactate in sepsis and COVID-19: Perspective from contracting skeletal muscle metabolism.

New Findings: What is the topic of this review? Lactate is considered an important substrate for mitochondria in the muscles, heart and brain during exercise and is the main gluconeogenetic precursor in the liver and kidneys. In this light, we review the (patho)physiology of lactate metabolism in sepsis and coronavirus disease 2019 (COVID-19). What advances does it highlight? Elevated blood lactate is strongly associated with mortality in septic patients.

Compartmental immunophenotyping in COVID-19 ARDS: A case series.

Background: Severe immunopathology may drive the deleterious manifestations that are observed in the advanced stages of coronavirus disease 2019 (COVID-19) but are poorly understood.

Objective: Our aim was to phenotype leukocyte subpopulations and the cytokine milieu in the lungs and blood of critically ill patients with COVID-19 acute respiratory distress syndrome (ARDS).

Methods: We consecutively included patients less than 72 hours after intubation following informed consent from their next of kin.

Characteristics, interventions, and longer term outcomes of COVID-19 ICU patients in Denmark-A nationwide, observational study.

Background: Most data on intensive care unit (ICU) patients with COVID-19 originate in selected populations from stressed healthcare systems with shorter term follow-up. We present characteristics, interventions and longer term outcomes of the entire, unselected cohort of all ICU patients with COVID-19 in Denmark where the ICU capacity was not exceeded.

Methods: We identified all patients with SARS-CoV-2 admitted to any Danish ICU from 10 March to 19 May 2020 and registered demographics, chronic comorbidities, use of organ support, length of stay, and vital status from patient files.

Lung Protection Strategies during Cardiopulmonary Bypass Affect the Composition of Bronchoalveolar Fluid and Lung Tissue in Cardiac Surgery Patients.

Pulmonary dysfunction is among the most frequent complications to cardiac surgeries. Exposure of blood to the cardiopulmonary bypass (CPB) circuit with subsequent lung ischemia-reperfusion leads to the production of inflammatory mediators and increases in microvascular permeability. The study aimed to elucidate histological, cellular, and metabolite changes following two lung protective regimens during CPB with Histidine-Tryptophan-Ketoglutarate (HTK) enriched or warm oxygenated blood pulmonary perfusion compared to standard regimen with no pulmonary perfusion.

Soluble ectodomain CD163 and extracellular vesicle-associated CD163 are two differently regulated forms of 'soluble CD163' in plasma.

CD163 is the macrophage receptor for uptake of hemoglobin-haptoglobin complexes. The human receptor can be shed from the macrophage surface owing to a cleavage site for the inflammation-inducible TACE/ADAM17 enzyme. Accordingly, plasma 'soluble CD163' (sCD163) has become a biomarker for macrophage activity and inflammation.

Changes in ventilatory capacity and pulmonary gas exchange during systemic and pulmonary inflammation in humans.

The exact mechanism linking the systemic inflammatory response associated with sepsis to changes in lung function remains to be determined. In a human experimental model of inflammation, we investigated how acute systemic and local pulmonary inflammation affects ventilatory capacity and pulmonary gas exchange. Fifteen volunteers received Escherichia coli lipopolysaccharide (LPS) intravenously or endobronchially on two different study days.

Dynamic cerebral autoregulation to induced blood pressure changes in human experimental and clinical sepsis.

Previous studies have demonstrated that dynamic cerebral autoregulation to spontaneous fluctuations in blood pressure is enhanced following lipopolysaccharide (LPS) infusion, a human experimental model of early sepsis, whereas by contrast it is impaired in patients with severe sepsis or septic shock. In this study, we hypothesized that this pattern of response would be identical during induced changes in blood pressure. Dynamic cerebral autoregulation was assessed in nine healthy volunteers and six septic patients.