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1.
Exp Physiol ; 2021 Jul 09.
Article in English | MEDLINE | ID: covidwho-1909549

ABSTRACT

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). This review outlines the physiological implications of transitioning from supine to prone on alveolar ventilation-perfusion ( V ̇ A -- Q ̇ ) relationships during spontaneous breathing and during general anaesthesia in the healthy state, as well as during invasive mechanical ventilation in patients with ARDS and CARDS. Spontaneously breathing, awake healthy individuals maintain a small vertical (ventral-to-dorsal) V ̇ A / Q ̇ ratio gradient in the supine position, which is largely neutralised in the prone position, mainly through redistribution of perfusion. In anaesthetised and mechanically ventilated healthy individuals, a vertical V ̇ A / Q ̇ ratio gradient is present in both postures, but with better V ̇ A -- Q ̇ matching in the prone position. In ARDS and CARDS, the vertical V ̇ A / Q ̇ ratio gradient in the supine position becomes larger, with intrapulmonary shunting in gravitationally dependent lung regions due to compression atelectasis of the dorsal lung. This is counteracted by proning, mainly through a more homogeneous distribution of ventilation combined with a largely unaffected high perfusion dorsally, and a consequent substantial improvement in arterial oxygenation. The data regarding proning as a therapy in patients with CARDS is still limited and whether the associated improvement in arterial oxygenation translates to a survival benefit remains unknown. Proning is nonetheless an attractive and lung protective manoeuvre with the potential benefit of improving life-threatening hypoxaemia in patients with ARDS and CARDS.

2.
Sci Rep ; 12(1): 4040, 2022 03 08.
Article in English | MEDLINE | ID: covidwho-1908245

ABSTRACT

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. Moreover, a principal component analysis was able to separate patient groups into distinguishable subgroups. Our findings indicate markedly impaired pulmonary surfactant levels in COVID-19 patients, justifying further studies and clinical trials of exogenous surfactant.


Subject(s)
Bronchoalveolar Lavage Fluid/chemistry , COVID-19/pathology , Pulmonary Surfactants/analysis , 1,2-Dipalmitoylphosphatidylcholine/analysis , Adult , Aged , COVID-19/virology , Case-Control Studies , Female , Humans , Male , Middle Aged , Principal Component Analysis , Pulmonary Surfactants/metabolism , SARS-CoV-2/isolation & purification , Severity of Illness Index , Spectrophotometry, Infrared/methods
3.
J Infect Dis ; 2022 May 27.
Article in English | MEDLINE | ID: covidwho-1873928

ABSTRACT

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 (DXM+ or DXM-) and 8 non-COVID-19 critically ill controls. CARDS (+DXM) was characterized by upregulation of genes related to B-cell and complement pathway activation, antigen presentation, phagocytosis and FC-gamma receptor signalling. Most ISGs were upregulated in CARDS, particularly in CARDS (-DXM). In conclusion, DXM treatment was not associated with regulation of pro-inflammatory pathways in CARDS but with regulation of other local immune responses.

4.
J Infect Dis ; 225(8): 1308-1316, 2022 04 19.
Article in English | MEDLINE | ID: covidwho-1705456

ABSTRACT

BACKGROUND: To quantify the potential decline in dynamic lung volumes following coronavirus disease 2019 (COVID-19) in the general population. METHODS: A prospective matched cohort study of adult Copenhagen General Population Study (CGPS) participants with a prepandemic spirometry available. CGPS individuals with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) test performed repeat spirometry, a questionnaire regarding respiratory symptoms, and diffusing capacity test for carbon monoxide. A matched uninfected CGPS control sample was used, and simple regression and linear mixed effect models were computed to study lung function decline. RESULTS: A total of 606 individuals were included; 92/107 (85.9%) with positive SARS-CoV-2 PCR test experienced coronavirus disease 2019 (COVID-19) symptoms and 12 (11.2%) were hospitalized. Spirometry was performed at median 5.6 months (interquartile range, 3.9-12.8) after positive SARS-CoV-2 PCR test. COVID-19 was associated with adjusted 7.3 mL (95% confidence interval [CI], .3-14.3) and 22.6 mL (95% CI, 13.1-32.0) steeper decline in annual forced expiratory volume in first second (FEV1) and FVC or total 113.8 and 301.3 mL lower FEV1 and FVC from baseline to follow-up. Results were robust in analyses restricted to individuals not requiring hospitalization. CONCLUSIONS: COVID-19-related declines of dynamic lung volume in the general population not requiring hospitalization were small but measurable.


Subject(s)
COVID-19 , Adult , Cohort Studies , Humans , Lung , Prospective Studies , SARS-CoV-2 , Vital Capacity
6.
Front Immunol ; 12: 718744, 2021.
Article in English | MEDLINE | ID: covidwho-1417083

ABSTRACT

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. Cytokine responses (IL-6, IL-1ß, TNFα, CXCL10, type I, II and III interferons) following SARS-CoV-2 infection of peripheral blood mononuclear cells in vitro were analyzed as well as antibodies against IFNα and IFNω (by ELISA) in patients and healthy controls. We also performed whole exome sequencing (WES) of patient DNA. A total of five patients (ages 19, 23, 33, 38, 50 years) were included. The patients shared characteristic features, although organ involvement and the time course of disease varied slightly. SARS-CoV-2 in vitro infection of patient PBMCs revealed impaired type I and III interferon responses and reduced CXCL10 expression, whereas production of proinflammatory cytokines were less affected, compared to healthy controls. Presence of interferon autoantibodies was not detected. Whole exome sequencing analysis of patient DNA revealed 12 rare potentially disease-causing variants in genes related to autophagy, classical Kawasaki disease, restriction factors and immune responses. In conclusion, we observed an impaired production of type I and III interferons in response to SARS-CoV-2 infection and detected several rare potentially disease-causing gene variants potentially contributing to MIS-A.


Subject(s)
COVID-19/pathology , Cytokines/blood , Interferon-alpha/biosynthesis , Interferons/biosynthesis , Systemic Inflammatory Response Syndrome/pathology , Adult , Autoantibodies/blood , Chemokine CXCL10/biosynthesis , Comorbidity , Exome/genetics , Female , Humans , Interferon-alpha/immunology , Interferons/immunology , Leukocytes, Mononuclear/immunology , Male , Middle Aged , SARS-CoV-2/immunology , Whole Exome Sequencing , Young Adult
8.
J Allergy Clin Immunol ; 147(1): 81-91, 2021 01.
Article in English | MEDLINE | ID: covidwho-802735

ABSTRACT

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. Bronchoalveolar lavage fluid was evaluated by microscopy; bronchoalveolar lavage fluid and blood were assessed by 10-color flow cytometry and a multiplex cytokine panel. RESULTS: Four mechanically ventilated patients (aged 40-75 years) with moderate-to-severe COVID-19 ARDS were included. Immature neutrophils dominated in both blood and lungs, whereas CD4 and CD8 T-cell lymphopenia was observed in the 2 compartments. However, regulatory T cells and TH17 cells were found in higher fractions in the lung. Lung CD4 and CD8 T cells and macrophages expressed an even higher upregulation of activation markers than in blood. A wide range of cytokines were expressed at high levels both in the blood and in the lungs, most notably, IL-1RA, IL-6, IL-8, IP-10, and monocyte chemoattactant protein-1, consistent with hyperinflammation. CONCLUSION: COVID-19 ARDS exhibits a distinct immunologic profile in the lungs, with a depleted and exhausted CD4 and CD8 T-cell population that resides within a heavily hyperinflammatory milieu.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Lung/immunology , Lymphopenia/immunology , Respiratory Distress Syndrome/immunology , SARS-CoV-2/immunology , Th17 Cells/immunology , Adult , Aged , CD8-Positive T-Lymphocytes/pathology , COVID-19/pathology , Cross-Sectional Studies , Cytokines/immunology , Female , Humans , Immunophenotyping , Lung/pathology , Lymphopenia/pathology , Male , Middle Aged , Respiratory Distress Syndrome/pathology , Th17 Cells/pathology
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