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1.
EBioMedicine ; 85: 104296, 2022 Nov.
Статья в английский | MEDLINE | ID: covidwho-2158739

Реферат

BACKGROUND: COVID-19 is characterized by a heterogeneous clinical presentation, ranging from mild symptoms to severe courses of disease. 9-20% of hospitalized patients with severe lung disease die from COVID-19 and a substantial number of survivors develop long-COVID. Our objective was to provide comprehensive insights into the pathophysiology of severe COVID-19 and to identify liquid biomarkers for disease severity and therapy response. METHODS: We studied a total of 85 lungs (n = 31 COVID autopsy samples; n = 7 influenza A autopsy samples; n = 18 interstitial lung disease explants; n = 24 healthy controls) using the highest resolution Synchrotron radiation-based hierarchical phase-contrast tomography, scanning electron microscopy of microvascular corrosion casts, immunohistochemistry, matrix-assisted laser desorption ionization mass spectrometry imaging, and analysis of mRNA expression and biological pathways. Plasma samples from all disease groups were used for liquid biomarker determination using ELISA. The anatomic/molecular data were analyzed as a function of patients' hospitalization time. FINDINGS: The observed patchy/mosaic appearance of COVID-19 in conventional lung imaging resulted from microvascular occlusion and secondary lobular ischemia. The length of hospitalization was associated with increased intussusceptive angiogenesis. This was associated with enhanced angiogenic, and fibrotic gene expression demonstrated by molecular profiling and metabolomic analysis. Increased plasma fibrosis markers correlated with their pulmonary tissue transcript levels and predicted disease severity. Plasma analysis confirmed distinct fibrosis biomarkers (TSP2, GDF15, IGFBP7, Pro-C3) that predicted the fatal trajectory in COVID-19. INTERPRETATION: Pulmonary severe COVID-19 is a consequence of secondary lobular microischemia and fibrotic remodelling, resulting in a distinctive form of fibrotic interstitial lung disease that contributes to long-COVID. FUNDING: This project was made possible by a number of funders. The full list can be found within the Declaration of interests / Acknowledgements section at the end of the manuscript.


Тема - темы
COVID-19 , Lung Diseases, Interstitial , Humans , Lung/diagnostic imaging , Lung/pathology , Lung Diseases, Interstitial/pathology , Fibrosis , Biomarkers/analysis , Ischemia/pathology
2.
Chest ; 162(1): 256-264, 2022 07.
Статья в английский | MEDLINE | ID: covidwho-2158581

Реферат

BACKGROUND: In 2019, the United States experienced a nationwide outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI). More than one-half of these patients required admission to an ICU. RESEARCH QUESTION: What are the recent literature and expert opinions which inform the diagnosis and management of patients with critical illness with EVALI? STUDY DESIGN AND METHODS: To synthesize information critical to pulmonary/critical care specialists in the care of patients with EVALI, this study examined data available from patients hospitalized with EVALI between August 2019 and January 2020; reviewed the clinical course and critical care experience with those patients admitted to the ICU; and compiled opinion of national experts. RESULTS: Of the 2,708 patients with confirmed or probable EVALI requiring hospitalization as of January 21, 2020, a total of 1,604 (59.2%) had data available on ICU admission; of these, 705 (44.0%) were admitted to the ICU and are included in this analysis. The majority of ICU patients required respiratory support (88.5%) and in severe cases required intubation (36.1%) or extracorporeal membrane oxygenation (6.7%). The majority (93.0%) of these ICU patients survived to discharge. Review of the clinical course and expert opinion provided insight into: imaging; considerations for bronchoscopy; medical treatment, including use of empiric antibiotics, antiviral agents, and corticosteroids; respiratory support, including considerations for intubation, positioning maneuvers, and extracorporeal membrane oxygenation; and patient outcomes. INTERPRETATION: Review of the clinical course of patients with EVALI requiring ICU admission and compilation of expert opinion provided critical insight into pulmonary/critical care-specific considerations for this patient population. Because a large proportion of patients hospitalized with EVALI required ICU admission, it is important to remain prepared to care for patients with EVALI.


Тема - темы
Electronic Nicotine Delivery Systems , Lung Injury , Vaping , Critical Care , Humans , Lung , Lung Injury/chemically induced , Lung Injury/epidemiology , United States/epidemiology , Vaping/adverse effects
3.
Monaldi Arch Chest Dis ; 92(4)2022 Mar 03.
Статья в английский | MEDLINE | ID: covidwho-2155498

Реферат

Dear Editor, we read the original study by De Michele et al. titled "Post severe COVID-19 infection lung damages study. The experience of early three months multidisciplinary follow-up" with great interest...


Тема - темы
COVID-19 , Follow-Up Studies , Humans , Lung/diagnostic imaging
4.
Front Immunol ; 13: 954339, 2022.
Статья в английский | MEDLINE | ID: covidwho-2154721

Реферат

The vast diversity of microbial communities reside in various locations of the human body, and they are collectively named as the 'Human Microbiota.' The majority of those microbes are found in the gastrointestinal and respiratory tracts. The microorganisms present in the gastrointestinal and the respiratory tracts are called the gut microbiota and the airway microbiota, respectively. These microbial communities are known to affect both the metabolic functions and the immune responses of the host. Among multiple factors determining the composition of gut microbiota, diet has played a pivotal role. The gut microbes possess enzymatic machinery for assimilating dietary fibers and releasing different metabolites, primarily short-chain fatty acids (SCFAs). The SCFAs modulate the immune responses of not only the gut but other distal mucosal sites as well, such as the lungs. Dysbiosis in normal gut flora is one of the factors involved in the development of asthma and other respiratory disorders. Of note, several human and murine studies have indicated significant cross-talk between gut microbiota and lung immunity, known as the gut-lung axis. Here, in this review, we summarize the recent state of the field concerning the effect of dietary metabolites, particularly SCFAs, on the "gut-lung axis" as well as discuss its impact on lung health. Moreover, we have highlighted the role of the "gut-lung axis" in SARS-CoV-2 mediated inflammation. Also, to analyze the global research progress on the gut-lung axis and to identify the knowledge gap in this field, we have also utilized the bibliographic tools Dimension database and VOS viewer analysis software. Through network mapping and visualization analysis, we can predict the present research trend and the possibility to explore new directions.


Тема - темы
COVID-19 , Gastrointestinal Microbiome , Humans , Animals , Mice , SARS-CoV-2 , Fatty Acids, Volatile/metabolism , Lung/metabolism , Homeostasis , Dietary Fiber , Immunity
5.
Front Cell Infect Microbiol ; 12: 928704, 2022.
Статья в английский | MEDLINE | ID: covidwho-2154680

Реферат

In the lungs of infected individuals, the downstream molecular signaling pathways induced by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are incompletely understood. Here, we describe and examine predictions of a model in which NOTCH may represent a central signaling axis in lung infection in Coronavirus Disease 2019 (COVID-19). A pathway involving NOTCH signaling, furin, ADAM17, and ACE2 may be capable of increasing SARS-CoV-2 viral entry and infection. NOTCH signaling can also upregulate IL-6 and pro-inflammatory mediators induced to hyperactivation in COVID-19. Furthermore, if NOTCH signaling fails to turn down properly and stays elevated, airway regeneration during lung healing can be inhibited-a process that may be at play in COVID-19. With specific NOTCH inhibitor drugs in development and clinical trials for other diseases being conducted, the roles of NOTCH in all of these processes central to both infection and healing merit contemplation if such drugs might be applied to COVID-19 patients.


Тема - темы
COVID-19 , SARS-CoV-2 , Angiotensin-Converting Enzyme 2 , Humans , Lung , Peptidyl-Dipeptidase A/metabolism
6.
Technol Health Care ; 30(6): 1299-1314, 2022.
Статья в английский | MEDLINE | ID: covidwho-2154631

Реферат

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a deadly viral infection spreading rapidly around the world since its outbreak in 2019. In the worst case a patient's organ may fail leading to death. Therefore, early diagnosis is crucial to provide patients with adequate and effective treatment. OBJECTIVE: This paper aims to build machine learning prediction models to automatically diagnose COVID-19 severity with clinical and computed tomography (CT) radiomics features. METHOD: P-V-Net was used to segment the lung parenchyma and then radiomics was used to extract CT radiomics features from the segmented lung parenchyma regions. Over-sampling, under-sampling, and a combination of over- and under-sampling methods were used to solve the data imbalance problem. RandomForest was used to screen out the optimal number of features. Eight different machine learning classification algorithms were used to analyze the data. RESULTS: The experimental results showed that the COVID-19 mild-severe prediction model trained with clinical and CT radiomics features had the best prediction results. The accuracy of the GBDT classifier was 0.931, the ROUAUC 0.942, and the AUCPRC 0.694, which indicated it was better than other classifiers. CONCLUSION: This study can help clinicians identify patients at risk of severe COVID-19 deterioration early on and provide some treatment for these patients as soon as possible. It can also assist physicians in prognostic efficacy assessment and decision making.


Тема - темы
COVID-19 , Humans , COVID-19/diagnostic imaging , Tomography, X-Ray Computed/methods , Machine Learning , Lung/diagnostic imaging , Algorithms , Retrospective Studies
7.
PLoS Pathog ; 18(10): e1010734, 2022 10.
Статья в английский | MEDLINE | ID: covidwho-2154305

Реферат

The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS2) affected the geriatric population. Among research models, Golden Syrian hamsters (GSH) are one of the most representative to study SARS2 pathogenesis and host responses. However, animal studies that recapitulate the effects of SARS2 in the human geriatric population are lacking. To address this gap, we inoculated 14 months old GSH with a prototypic ancestral strain of SARS2 and studied the effects on virus pathogenesis, virus shedding, and respiratory and gastrointestinal microbiome changes. SARS2 infection led to high vRNA loads in the nasal turbinates (NT), lungs, and trachea as well as higher pulmonary lesions scores later in infection. Dysbiosis throughout SARS2 disease progression was observed in the pulmonary microbial dynamics with the enrichment of opportunistic pathogens (Haemophilus, Fusobacterium, Streptococcus, Campylobacter, and Johnsonella) and microbes associated with inflammation (Prevotella). Changes in the gut microbial community also reflected an increase in multiple genera previously associated with intestinal inflammation and disease (Helicobacter, Mucispirillum, Streptococcus, unclassified Erysipelotrichaceae, and Spirochaetaceae). Influenza A virus (FLUAV) pre-exposure resulted in slightly more pronounced pathology in the NT and lungs early on (3 dpc), and more notable changes in lungs compared to the gut microbiome dynamics. Similarities among aged GSH and the microbiome in critically ill COVID-19 patients, particularly in the lower respiratory tract, suggest that GSHs are a representative model to investigate microbial changes during SARS2 infection. The relationship between the residential microbiome and other confounding factors, such as SARS2 infection, in a widely used animal model, contributes to a better understanding of the complexities associated with the host responses during viral infections.


Тема - темы
COVID-19 , Gastrointestinal Microbiome , Cricetinae , Animals , Humans , Aged , Infant , SARS-CoV-2 , Mesocricetus , Dysbiosis/pathology , Lung/pathology , Inflammation/pathology
8.
Curr Opin Crit Care ; 28(6): 660-666, 2022 Dec 01.
Статья в английский | MEDLINE | ID: covidwho-2152245

Реферат

PURPOSE OF REVIEW: To review the clinical problem and noninvasive treatments of hypoxemia in critically-ill patients with coronavirus disease 2019 pneumonia and describe recent advances in evidence supporting bedside decision making. RECENT FINDINGS: High-flow nasal oxygen and noninvasive ventilation, along with awake prone positioning are potentially helpful therapies for acute hypoxemic respiratory failure. High-flow nasal oxygen therapy has been widely implemented as a form of oxygen support supported by prepandemic randomized controlled trials showing possible benefit over noninvasive ventilation. Given the sheer volume of patients, noninvasive ventilation was often required, and based on a well conducted randomized controlled trial there was a developing role for helmet-interface noninvasive. Coupled with noninvasive supports, the use of awake prone positioning demonstrated physiological benefits, but randomized controlled trial data did not demonstrate clear outcome superiority. SUMMARY: The use of noninvasive oxygen strategies and our understanding of the proposed mechanisms are evolving. Variability in patient severity and physiology may dictate a personalized approach to care. High-flow nasal oxygen may be paired with awake and spontaneously breathing prone-positioning to optimize oxygen and lung mechanics but requires further insight before widely applying to clinical practice.


Тема - темы
COVID-19 , Noninvasive Ventilation , Respiratory Insufficiency , Humans , COVID-19/therapy , Respiratory Insufficiency/therapy , Oxygen Inhalation Therapy , Hypoxia/therapy , Oxygen , Critical Care , Lung , Randomized Controlled Trials as Topic
9.
J Microbiol Biotechnol ; 30(3): 427-438, 2020 Mar 28.
Статья | MEDLINE | ID: covidwho-2163802

Реферат

Middle East respiratory syndrome coronavirus (MERS-CoV) infects the lower respiratory airway of humans, leading to severe acute respiratory failure. Unlike human dipeptidyl peptidase 4 (hDPP4), a receptor for MERS-CoV, mouse DPP4 (mDPP4) failed to support MERS-CoV infection. Consequently, diverse transgenic mouse models expressing hDPP4 have been developed using diverse methods, although some models show no mortality and/or only transient and mild-to-moderate clinical signs following MERS-CoV infection. Additionally, overexpressed hDPP4 is associated with neurological complications and breeding difficulties in some transgenic mice, resulting in impeding further studies. Here, we generated stable hDPP4-transgenic mice that were sufficiently susceptible to MERS-CoV infection. The transgenic mice showed weight loss, decreased pulmonary function, and increased mortality with minimal perturbation of overexpressed hDPP4 after MERS-CoV infection. In addition, we observed histopathological signs indicative of progressive pulmonary fibrosis, including thickened alveolar septa, infiltration of inflammatory monocytes, and macrophage polarization as well as elevated expression of profibrotic molecules and acute inflammatory response in the lung of MERS-CoV-infected hDPP4-transgenic mice. Collectively, we suggest that this hDPP4-transgenic mouse is useful in understanding the pathogenesis of MERS-CoV infection and for antiviral research and vaccine development against the virus.


Тема - темы
Coronavirus Infections/immunology , Dipeptidyl Peptidase 4/immunology , Lung/pathology , Middle East Respiratory Syndrome Coronavirus/immunology , Pulmonary Fibrosis/pathology , Animals , Coronavirus Infections/complications , Dipeptidyl Peptidase 4/genetics , Disease Models, Animal , Female , Humans , Mice , Mice, Transgenic , Pulmonary Fibrosis/etiology
10.
Circ Heart Fail ; 13(5): e007175, 2020 05.
Статья в английский | MEDLINE | ID: covidwho-2153214

Реферат

The severe acute respiratory syndrome-CoV-2 is an emerging viral pathogen responsible for the global coronavirus disease 2019 pandemic resulting in significant human morbidity and mortality. Based on preliminary clinical reports, hypoxic respiratory failure complicated by acute respiratory distress syndrome is the leading cause of death. Further, septic shock, late-onset cardiac dysfunction, and multiorgan system failure are also described as contributors to overall mortality. Although extracorporeal membrane oxygenation and other modalities of mechanical cardiopulmonary support are increasingly being utilized in the treatment of respiratory and circulatory failure refractory to conventional management, their role and efficacy as support modalities in the present pandemic are unclear. We review the rapidly changing epidemiology, pathophysiology, emerging therapy, and clinical outcomes of coronavirus disease 2019; and based on these data and previous experience with artificial cardiopulmonary support strategies, particularly in the setting of infectious diseases, provide consensus recommendations from American Society for Artificial Internal Organs. Of note, this is a living document, which will be updated periodically, as additional information and understanding emerges.


Тема - темы
Betacoronavirus , Coronavirus Infections/therapy , Heart , Lung , Pneumonia, Viral/therapy , COVID-19 , Humans , Pandemics , SARS-CoV-2 , Societies, Medical
11.
Crit Care ; 26(1): 211, 2022 07 11.
Статья в английский | MEDLINE | ID: covidwho-1925796

Реферат

PURPOSE: In the acute respiratory distress syndrome (ARDS), decreasing Ventilation-Perfusion [Formula: see text] mismatch might enhance lung protection. We investigated the regional effects of higher Positive End Expiratory Pressure (PEEP) on [Formula: see text] mismatch and their correlation with recruitability. We aimed to verify whether PEEP improves regional [Formula: see text] mismatch, and to study the underlying mechanisms. METHODS: In fifteen patients with moderate and severe ARDS, two PEEP levels (5 and 15 cmH2O) were applied in random order. [Formula: see text] mismatch was assessed by Electrical Impedance Tomography at each PEEP. Percentage of ventilation and perfusion reaching different ranges of [Formula: see text] ratios were analyzed in 3 gravitational lung regions, leading to precise assessment of their distribution throughout different [Formula: see text] mismatch compartments. Recruitability between the two PEEP levels was measured by the recruitment-to-inflation ratio method. RESULTS: In the non-dependent region, at higher PEEP, ventilation reaching the normal [Formula: see text] compartment (p = 0.018) increased, while it decreased in the high [Formula: see text] one (p = 0.023). In the middle region, at PEEP 15 cmH2O, ventilation and perfusion to the low [Formula: see text] compartment decreased (p = 0.006 and p = 0.011) and perfusion to normal [Formula: see text] increased (p = 0.003). In the dependent lung, the percentage of blood flowing through the non-ventilated compartment decreased (p = 0.041). Regional [Formula: see text] mismatch improvement was correlated to lung recruitability and changes in regional tidal volume. CONCLUSIONS: In patients with ARDS, higher PEEP optimizes the distribution of both ventilation (in the non-dependent areas) and perfusion (in the middle and dependent lung). Bedside measure of recruitability is associated with improved [Formula: see text] mismatch.


Тема - темы
Respiratory Distress Syndrome , Humans , Lung , Perfusion , Positive-Pressure Respiration/methods , Respiratory Distress Syndrome/therapy , Respiratory Physiological Phenomena
12.
Crit Care ; 26(1): 154, 2022 05 27.
Статья в английский | MEDLINE | ID: covidwho-1866391

Реферат

BACKGROUND: The physiological effects of prone ventilation in ARDS patients have been discussed for a long time but have not been fully elucidated. Electrical impedance tomography (EIT) has emerged as a tool for bedside monitoring of pulmonary ventilation and perfusion, allowing the opportunity to obtain data. This study aimed to investigate the effect of prone positioning (PP) on ventilation-perfusion matching by contrast-enhanced EIT in patients with ARDS. DESIGN: Monocenter prospective physiologic study. SETTING: University medical ICU. PATIENTS: Ten mechanically ventilated ARDS patients who underwent PP. INTERVENTIONS: We performed EIT evaluation at the initiation of PP, 3 h after PP initiation and the end of PP during the first PP session. MEASUREMENTS AND MAIN RESULTS: The regional distribution of ventilation and perfusion was analyzed based on EIT images and compared to the clinical variables regarding respiratory and hemodynamic status. Prolonged prone ventilation improved oxygenation in the ARDS patients. Based on EIT measurements, the distribution of ventilation was homogenized and dorsal lung ventilation was significantly improved by PP administration, while the effect of PP on lung perfusion was relatively mild, with increased dorsal lung perfusion observed. The ventilation-perfusion matched region was found to increase and correlate with the increased PaO2/FiO2 by PP, which was attributed mainly to reduced shunt in the lung. CONCLUSIONS: Prolonged prone ventilation increased dorsal ventilation and perfusion, which resulted in improved ventilation-perfusion matching and oxygenation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04725227. Registered on 25 January 2021.


Тема - темы
Lung , Respiratory Distress Syndrome , Electric Impedance , Humans , Perfusion , Prone Position , Prospective Studies , Respiratory Distress Syndrome/therapy , Tomography, X-Ray Computed
13.
Eur Respir J ; 60(5)2022 11.
Статья в английский | MEDLINE | ID: covidwho-2139117

Реферат

BACKGROUND: Coronavirus disease 2019 (COVID-19) social distancing measures led to a dramatic decline in non-COVID-19 respiratory virus infections, providing a unique opportunity to study their impact on annual forced expiratory volume in 1 s (FEV1) decline, episodes of temporary drop in lung function (TDLF) suggestive of infection and chronic lung allograft dysfunction (CLAD) in lung transplant recipients (LTRs). METHODS: All FEV1 values of LTRs transplanted between 2009 and April 2020 at the University Medical Center Groningen (Groningen, The Netherlands) were included. Annual FEV1 change was estimated with separate estimates for pre-social distancing (2009-2020) and the year with social distancing measures (2020-2021). Patients were grouped by individual TDLF frequency (frequent/infrequent). Respiratory virus circulation was derived from weekly hospital-wide respiratory virus infection rates. Effect modification by TDLF frequency and respiratory virus circulation was assessed. CLAD and TDLF rates were analysed over time. RESULTS: 479 LTRs (12 775 FEV1 values) were included. Pre-social distancing annual change in FEV1 was -114 (95% CI -133- -94) mL, while during social distancing FEV1 did not decline: 5 (95% CI -38-48) mL (difference pre-social distancing versus during social distancing: p<0.001). The frequent TDLF subgroup showed faster annual FEV1 decline compared with the infrequent TDLF subgroup (-150 (95% CI -181- -120) versus -90 (95% CI -115- -65) mL; p=0.003). During social distancing, we found significantly lower odds for any TDLF (OR 0.53, 95% CI 0.33-0.85; p=0.008) and severe TDLF (OR 0.34, 0.16-0.71; p=0.005) as well as lower CLAD incidence (OR 0.53, 95% CI 0.27-1.02; p=0.060). Effect modification by respiratory virus circulation indicated a significant association between TDLF/CLAD and respiratory viruses. CONCLUSIONS: During COVID-19 social distancing the strong reduction in respiratory virus circulation coincided with markedly less FEV1 decline, fewer episodes of TDLF and possibly less CLAD. Effect modification by respiratory virus circulation suggests an important role for respiratory viruses in lung function decline in LTRs.


Тема - темы
COVID-19 , Lung Transplantation , Viruses , Humans , Transplant Recipients , Physical Distancing , Follow-Up Studies , Lung
14.
J Investig Med High Impact Case Rep ; 10: 23247096221140250, 2022.
Статья в английский | MEDLINE | ID: covidwho-2139082

Реферат

Unvaccinated patients with comorbidities that impair the immune function, such as type 2 diabetes mellitus, are more likely to develop severe COVID-19. The COVID-19-associated acute respiratory distress syndrome has raised new concerns in intensive care units globally owing to the presence of secondary fungal infections. We report the case of a 71-year-old man from Ecuador with a history of type 2 diabetes mellitus, severe COVID-19 pneumonia, and lung cavitation associated with triple infections with Trichosporon asahii, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The patient with a history of high blood pressure and type 2 diabetes was admitted to our hospital from a private care center with a diagnosis of COVID-19-associated acute respiratory distress syndrome. On arrival, the patient presented with signs of hypoxemic respiratory failure. During his stay at another hospital, he had received tocilizumab and corticosteroid therapy. Therefore, intubation was performed and mechanical ventilation was initiated. The patient developed a septic shock and renal failure with a glomerular filtration rate of 27.5 mL/min/1.73 m2; therefore, two hemodiafiltration sessions were started. The bronchoalveolar lavage revealed erythematous lesions in the bronchial tree and abundant purulent secretions and erosions in the bronchial mucosa, with a cavitary lesion in the right bronchial tree. The bronchoalveolar lavage samples were used to isolate Trichosporon asahii, Klebsiella pneumoniae, and Pseudomonas aeruginosa carbapenemase class A. Matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) Biotyper mass spectrometry and polymerase chain reaction (PCR) molecular identification were performed. This case report suggested that patients with severe COVID-19 pneumonia, with or without comorbidities, are more susceptible to opportunistic infections.


Тема - темы
COVID-19 , Coinfection , Diabetes Mellitus, Type 2 , Respiratory Distress Syndrome , Male , Humans , Aged , Klebsiella pneumoniae , Pseudomonas aeruginosa , COVID-19/complications , Diabetes Mellitus, Type 2/complications , Ecuador , Lung
15.
Am J Respir Cell Mol Biol ; 67(5): 520-527, 2022 Nov.
Статья в английский | MEDLINE | ID: covidwho-2138375

Реферат

Coronavirus disease (COVID-19) begins with upper airway symptoms but proceeds in a significant proportion of patients to life-threatening infection of the lower respiratory tract, where an exuberant inflammatory response, edema, and adverse parenchymal remodeling impair gas exchange. Respiratory failure is caused initially by flooding of the airspaces with plasma exudate, sloughed epithelium, and inflammatory cells. For many patients with COVID-19, this acute phase has been observed to give way to a prolonged course of acute respiratory distress syndrome, and a significant proportion of patients go on to develop fibroproliferative remodeling of the lung parenchyma, which lengthens the duration of respiratory impairment and mechanical ventilation. Monocyte-derived macrophages have previously been implicated in the fibrotic phase of lung injury in multiple models. From several recent studies that used single-cell genomic techniques, a profile of the transcriptomic state of COVID-19 lung macrophages has emerged. Linkages have been made between these macrophages, which are monocyte-derived and CD163+, and profibrotic macrophages found in other contexts, including animal models of fibrosis and idiopathic pulmonary fibrosis. Here, emerging concepts of macrophage profibrotic function in COVID-19 are highlighted with a focus on gaps in knowledge to be addressed by future research.


Тема - темы
COVID-19 , Respiratory Insufficiency , Animals , Transcriptome , Macrophages, Alveolar , Lung
16.
Acute Med ; 21(3): 131-138, 2022.
Статья в английский | MEDLINE | ID: covidwho-2146878

Реферат

BACKGROUND: Coronavirus disease 2019 has had a dramatic impact on the delivery of acute care globally. Accurate risk stratification is fundamental to the efficient organisation of care. Point-of-care lung ultrasound offers practical advantages over conventional imaging with potential to improve the operational performance of acute care pathways during periods of high demand. The Society for Acute Medicine and the Intensive Care Society undertook a collaborative evaluation of point-of-care imaging in the UK to describe the scope of current practice and explore performance during real-world application. METHODS: A retrospective service evaluation was undertaken of the use of point-of-care lung ultrasound during the initial wave of coronavirus infection in the UK. We report an evaluation of all imaging studies performed outside the intensive care unit. An ordinal scale was used to measure the severity of loss of lung aeration. The relationship between lung ultrasound, polymerase chain reaction for SARS-CoV-2 and 30-day outcomes were described using logistic regression models. RESULTS: Data were collected from 7 hospitals between February and September 2020. In total, 297 ultrasound examinations from 295 patients were recorded. Nasopharyngeal swab samples were positive in 145 patients (49.2% 95%CI 43.5-54.8). A multivariate model combining three ultrasound variables showed reasonable discrimination in relation to the polymerase chain reaction reference (AUC 0.77 95%CI 0.71-0.82). The composite outcome of death or intensive care admission at 30 days occurred in 83 (28.1%, 95%CI 23.3-33.5). Lung ultrasound was able to discriminate the composite outcome with a reasonable level of accuracy (AUC 0.76 95%CI 0.69-0.83) in univariate analysis. The relationship remained statistically significant in a multivariate model controlled for age, sex and the time interval from admission to scan Conclusion: Point-of-care lung ultrasound is able to discriminate patients at increased risk of deterioration allowing more informed clinical decision making.


Тема - темы
COVID-19 , Humans , COVID-19/diagnostic imaging , Point-of-Care Systems , Retrospective Studies , SARS-CoV-2 , Lung/diagnostic imaging , United Kingdom/epidemiology
17.
S Afr Med J ; 112(11): 850-854, 2022 Nov 01.
Статья в английский | MEDLINE | ID: covidwho-2144965

Реферат

BACKGROUND: Available clinical data have revealed that COVID-19 is associated with a risk of pulmonary microthrombosis and small airway disease, especially in patients with severe disease. These patients present with persistent pulmonary symptoms after recovery, with ventilation and perfusion abnormalities present on several imaging modalities. Few data are available on the occurrence of this complication in patients who earlier presented with a milder form of COVID-19, and their long-term follow-up. OBJECTIVE: To assess the incidence of persistent lung perfusion abnormalities as a result of suspected air trapping or microthrombosis in non-hospitalised patients diagnosed with COVID-19. The long-term follow-up of these patients will also be investigated. METHODS: This was a retrospective study conducted at the nuclear medicine department of Universitas Academic Hospital, Bloemfontein. We reviewed the studies of 78 non-hospitalised patients with SARS-CoV-2 infection referred to our department from July 2020 to June 2021 for a perfusion-only single-photon emission computed tomography/computed tomography (SPECT/CT) study or a ventilation perfusion (VQ) SPECT/CT study. All 78 patients were suspected of having pulmonary embolism, and had raised D-dimer levels, with persistent, worsening or new onset of cardiopulmonary symptoms after the diagnosis of COVID-19. RESULTS: Seventy-eight patients were studied. The median (interquartile range) age was 45 (41 - 58) years and the majority (88.5%) were females. Twenty-two (28.2%) of these patients had matching VQ defects with mosaic attenuation on CT. All 9 of the patients who had follow-up studies had abnormalities that persisted, even after 1 year. CONCLUSION: We confirm that persistent ventilation and perfusion abnormalities suspicious of small airway disease and pulmonary microthrombosis can occur in non-hospitalised patients diagnosed with a milder form of COVID-19. Our study also shows that these complications remain present even 1 year after the initial diagnosis of COVID-19.


Тема - темы
COVID-19 , Lung Diseases , Female , Humans , Middle Aged , Male , COVID-19/epidemiology , Pandemics , Incidence , Retrospective Studies , Follow-Up Studies , Tomography, Emission-Computed, Single-Photon/methods , Tomography, X-Ray Computed/methods , SARS-CoV-2 , South Africa , Lung/diagnostic imaging , Perfusion
18.
World J Gastroenterol ; 28(42): 6017-6033, 2022 Nov 14.
Статья в английский | MEDLINE | ID: covidwho-2143843

Реферат

Liver injury is an increasingly recognized extra-pulmonary manifestation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Coronavirus disease 2019 (COVID-19) associated liver injury (COVALI) is a clinical syndrome encompassing all patients with biochemical liver injury identified in the setting of SARS-CoV-2 infection. Despite profound clinical implications, its pathophysiology is poorly understood. Unfortunately, most information on COVALI is derived from the general population and may not be applicable to individuals under-represented in research, including pregnant individuals. This manuscript reviews: Clinical features of COVALI, leading theories of COVALI, and existing literature on COVALI during pregnancy, a topic not widely explored in the literature. Ultimately, we synthesized data from the general and perinatal populations that demonstrates COVALI to be a hepatocellular transaminitis that is likely induced by systemic inflammation and that is strongly associated with disease severity and poorer clinical outcome, and offered perspective on approaching transaminitis in the potentially COVID-19 positive patient in the obstetric setting.


Тема - темы
COVID-19 , Humans , Pregnancy , Female , COVID-19/complications , SARS-CoV-2 , Lung , Liver
19.
Cells ; 11(22)2022 Nov 16.
Статья в английский | MEDLINE | ID: covidwho-2142561

Реферат

Alveolar macrophage (AM) proliferation and self-renewal play an important role in the lung tissue microenvironment. However, the impact of immune cells, especially the neutrophils, on AM homeostasis or function is not well characterized. In this study, we induced in vivo migration of neutrophils into bronchoalveolar lavage (BAL) fluid and lung using CXCL1, and then co-cultured these with AMs in vitro. Neutrophils in the BAL (BAL-neutrophils), rather than neutrophils of bone marrow (BM-neutrophils), were found to inhibit AM proliferation. Analysis of publicly available data showed high heterogeneity of lung neutrophils with distinct molecular signatures of BM- and blood-neutrophils. Unexpectedly, BAL-neutrophils from influenza virus PR8-infected mice (PR8-neutrophils) did not inhibit the proliferation of AMs. Bulk RNA sequencing further revealed that co-culture of AMs with PR8-neutrophils induced IFN-α and -γ responses and inflammatory response, and AMs co-cultured with BAL-neutrophils showed higher expression of metabolism- and ROS-associated genes; in addition, BAL-neutrophils from PR8-infected mice modulated AM polarization and phagocytosis. BAL-neutrophil-mediated suppression of AM proliferation was abrogated by a combination of inhibitors of different neutrophil death pathways. Collectively, our findings suggest that multiple cell death pathways of neutrophils regulate the proliferation of AMs. Targeting neutrophil death may represent a potential therapeutic strategy for improving AM homeostasis during respiratory diseases.


Тема - темы
Macrophages, Alveolar , Neutrophils , Mice , Animals , Macrophages, Alveolar/metabolism , Neutrophils/metabolism , Bronchoalveolar Lavage Fluid , Lung , Cell Proliferation
20.
Front Immunol ; 13: 1028613, 2022.
Статья в английский | MEDLINE | ID: covidwho-2142034

Реферат

SARS-CoV-2 infection causes a variety of physiological responses in the lung, and understanding how the expression of SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), and its proteolytic activator, transmembrane serine protease 2 (TMPRSS2), are affected in patients with underlying disease such as interstitial pneumonia will be important in considering COVID-19 progression. We examined the expression of ACE2 and TMPRSS2 in an induced usual interstitial pneumonia (iUIP) mouse model and patients with IPF as well as the changes in whole-lung ACE2 and TMPRSS2 expression under physiological conditions caused by viral infection. Histopathological and biochemical characteristics were analyzed using human specimens from patients with IPF and precision-cut lung slices (PCLS) from iUIP mouse model showing UIP with honeycombing and severe fibrosis after non-specific interstitial pneumonia. ACE2 expression decreased with acute lung inflammation and increased in the abnormal lung epithelium of the iUIP mouse model. ACE2 is also expressed in metaplastic epithelial cells. Poly(I:C), interferons, and cytokines associated with fibrosis decreased ACE2 expression in PCLS in the iUIP model. Hypoxia also decreases ACE2 via HIF1α in PCLS. Antifibrotic agent, nintedanib attenuates ACE2 expression in invasive epithelial cells. Patients with IPF are at a higher risk of SARS-CoV-2 infection due to the high expression of ACE2. However, ACE2 and TMPRSS2 expression is decreased by immune intermediaries, including interferons and cytokines that are associated with viral infection and upon administration of antifibrotic agents, suggesting that most of the viral infection-induced pathophysiological responses aid the development of resistance against SARS-CoV-2 infection.


Тема - темы
COVID-19 , Idiopathic Pulmonary Fibrosis , Lung Diseases , Humans , Mice , Animals , Angiotensin-Converting Enzyme 2/genetics , Peptidyl-Dipeptidase A/metabolism , SARS-CoV-2 , Lung/pathology , Lung Diseases/pathology , Idiopathic Pulmonary Fibrosis/pathology , Cytokines , Interferons , Fibrosis
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