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1.
Exp Physiol ; 107(7): 759-770, 2022 Jul.
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 ̇ ${\dot V_{\rm{A}}}\hbox{--}\dot Q$ ) 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 ̇ ${\dot V_{\rm{A}}}/\dot Q$ 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 ̇ ${\dot V_{\rm{A}}}/\dot Q$ ratio gradient is present in both postures, but with better V ̇ A -- Q ̇ ${\dot V_{\rm{A}}}\hbox{--}\dot Q$ matching in the prone position. In ARDS and CARDS, the vertical V ̇ A / Q ̇ ${\dot V_{\rm{A}}}/\dot Q$ 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.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Respiratory Insufficiency , Humans , Hypoxia/therapy , Prone Position/physiology , Pulmonary Gas Exchange/physiology , Respiration, Artificial , Respiratory Distress Syndrome/therapy , Respiratory Insufficiency/therapy
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.
Exp Physiol ; 107(7): 665-673, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1807292

ABSTRACT

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. Lactate seems unrelated to tissue hypoxia but is likely to reflect mitochondrial dysfunction and high adrenergic stimulation. Patients with severe COVID-19 exhibit near-normal blood lactate, indicating preserved mitochondrial function, despite a systemic hyperinflammatory state similar to sepsis. ABSTRACT: In critically ill patients, elevated plasma lactate is often interpreted as a sign of organ hypoperfusion and/or tissue hypoxia. This view on lactate is likely to have been influenced by the pioneering exercise physiologists around 1920. August Krogh identified an oxygen deficit at the onset of exercise that was later related to an oxygen 'debt' and lactate accumulation by A. V. Hill. Lactate is considered to be the main gluconeogenetic precursor in the liver and kidneys during submaximal exercise, but hepatic elimination is attenuated by splanchnic vasoconstriction during high-intensity exercise, causing an exponential increase in blood lactate. With the development of stable isotope tracers, lactate has become established as an important energy source for muscle, brain and heart tissue, where it is used for mitochondrial respiration. Plasma lactate > 4 mM is strongly associated with mortality in septic shock, with no direct link between lactate release and tissue hypoxia. Herein, we provide evidence for mitochondrial dysfunction and adrenergic stimulation as explanations for the sepsis-induced hyperlactataemia. Despite profound hypoxaemia and intense work of breathing, patients with severe coronavirus disease 2019 (COVID-19) rarely exhibit hyperlactataemia (> 2.5 mM), while presenting a systemic hyperinflammatory state much like sepsis. However, lactate dehydrogenase, which controls the formation of lactate, is markedly elevated in plasma and strongly associated with mortality in severe COVID-19. We briefly review the potential mechanisms of the lactate dehydrogenase elevation in COVID-19 and its relationship to lactate metabolism based on mechanisms established in contracting skeletal muscle and the acute respiratory distress syndrome.


Subject(s)
COVID-19 , Sepsis , Adrenergic Agents/metabolism , Humans , Hypoxia , Lactate Dehydrogenases/metabolism , Lactic Acid/metabolism , Muscle, Skeletal/metabolism , Oxygen/metabolism , Sepsis/complications , Sepsis/diagnosis
5.
Eur Respir J ; 2022 Mar 02.
Article in English | MEDLINE | ID: covidwho-1724400

ABSTRACT

BACKGROUND: Many people recovering from COVID-19 experience prolonged symptoms, particularly breathlessness. We urgently need to identify safe and effective COVID-19 rehabilitative strategies. The aim of the current study was to investigate the potential rehabilitative role of inspiratory muscle training (IMT). METHODS: 281 adults (46.6±12.2 years; 88% female) recovering from self-reported COVID-19 (9.0±4.2 months post-acute infection) were randomised 4:1 to an 8-week IMT or a "usual care" wait list control arm. Health-related quality of life and breathlessness questionnaires (King's Brief Interstitial Lung Disease (KBILD) and Transition Dyspnoea Index (TDI)), respiratory muscle strength and fitness (Chester Step Test) were assessed pre- and post-intervention. The primary endpoint was KBILD total score, with the KBILD subdomains and TDI being key secondary outcomes. RESULTS: According to intention to treat (ITT), there was no difference between groups in KBILD total score post-intervention (Control: 59.5±12.4; IMT: 58.2±12.3; p<0.05) but IMT elicited clinically meaningful improvements in the KBILD subdomains of breathlessness (Control: 59.8±12.6; IMT: 62.2±16.2; p<0.05) and chest symptoms (Control: 59.2±18.7; IMT: 64.5±18.2; p<0.05), along with clinically meaningful improvements in breathlessness according to TDI (Control: 0.9±1.7 versus 2.0±2.0; p<0.05). IMT also improved respiratory muscle strength and estimated aerobic fitness. CONCLUSIONS: IMT may represent an important home-based rehabilitation strategy for wider implementation as part of COVID-19 rehabilitative strategies. Given the diverse nature of long-COVID, further research is warranted on the individual responses to rehabilitation - the withdrawal rate herein highlights that no one strategy is likely to be appropriate for all.

6.
BMJ Open ; 11(11): e048281, 2021 11 18.
Article in English | MEDLINE | ID: covidwho-1526501

ABSTRACT

INTRODUCTION: COVID-19 is associated with a marked systemic inflammatory response with concomitant cardiac injury and remodelling, but it is currently unknown whether the latter is reversible. Given that high-intensity interval training (HIIT) is a powerful stimulus to improve cardiorespiratory fitness while also eliciting marked anti-inflammatory effects, it may be an important countermeasure of reducing cardiopulmonary morbidity following COVID-19. METHODS AND ANALYSIS: 40 COVID-19 survivors who have been discharged from hospital will be included in this investigator-blinded randomised study with a 12-week HIIT intervention. Patients will be 1:1 block-randomised by sex to either a supervised HIIT exercise group or standard care (control group). The main hypothesis is that a 12-week HIIT scheme is a safe way to improve loss of cardiac mass and associated cardiorespiratory fitness, despite hypothesised limited HIIT-induced changes in conventional lung function indices per se. Ultimately, we hypothesise that the HIIT scheme will reduce post-COVID-19 symptoms and improve quality of life. ETHICS AND DISSEMINATION: This study is approved by the Scientific Ethical Committee at the Capital Region of Denmark (H-20033733, including amendments 75068 and 75799) and registered at ClinicalTrials.gov (NCT04647734, pre-results). The findings will be published in a peer-reviewed journal, including cases of positive, negative and inconclusive results.Trial registration number NCT04549337.


Subject(s)
COVID-19 , Cardiorespiratory Fitness , High-Intensity Interval Training , Humans , Quality of Life , Randomized Controlled Trials as Topic , SARS-CoV-2 , Treatment Outcome
7.
Int J Environ Res Public Health ; 18(21)2021 Oct 29.
Article in English | MEDLINE | ID: covidwho-1488586

ABSTRACT

Understanding of strategies to support individuals recovering from coronavirus disease 2019 (COVID-19) is limited. 'Long COVID' is a multisystem disease characterised by a range of respiratory, gastrointestinal, cardiovascular, neurological, and musculoskeletal symptoms extending beyond 12 weeks. The aim of this study was to explore individuals' experiences of recovering from COVID-19 to provide a better understanding of the acute and long-term impact of the disease on physical activity (PA). Individualised semi-structured interviews were conducted with 48 adults recovering from COVID-19 at 6-11 months post-infection. An inductive thematic analysis approach was used, reaching saturation at 14 interviews (10 female; 47 ± 7 years). Four overarching themes were identified: (i) Living with COVID-19, including managing activities of daily living; (ii) Dealing with the Unknown and self-management strategies; (iii) Re-introducing physical activity; and (iv) Challenges of returning to work. The return to PA, whether through activities of daily living, work or exercise, is often associated with the exacerbation of symptoms, presenting a range of challenges for individuals recovering from COVID-19. Individually tailored support is therefore required to address the unique challenges posed by COVID-19.


Subject(s)
Activities of Daily Living , COVID-19 , Adult , COVID-19/complications , Exercise , Female , Humans , SARS-CoV-2
9.
Front Cardiovasc Med ; 8: 643626, 2021.
Article in English | MEDLINE | ID: covidwho-1191676
11.
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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