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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.
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
3.
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
4.
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
5.
Front Public Health ; 10: 931480, 2022.
Статья в английский | MEDLINE | ID: covidwho-2123468

Реферат

Background: Omicron has become the dominant variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) globally. We aimed to compare the clinical and pulmonary computed tomography (CT) characteristics of the patients infected with SARS-CoV-2 Omicron with those of patients infected with the Alpha viral strain. Methods: Clinical profiles and pulmonary CT images of 420 patients diagnosed with coronavirus disease-2019 (COVID-19) at Ningbo First Hospital between January 2020 and April 2022 were collected. Demographic characteristics, symptoms, and imaging manifestations of patients infected with the SARS-CoV-2 Omicron variant were compared with those of patients infected with the Alpha strain. Results: A total of 38 patients were diagnosed to be infected with the Alpha strain of SARS-CoV-2, whereas 382 patients were thought to be infected with the Omicron variant. Compared with patients infected with the Alpha strain, those infected with the Omicron variant were younger, and a higher proportion of men were infected (P < 0.001). Notably, 93 (24.3%) of the patients infected with Omicron were asymptomatic, whereas only two (5.3%) of the patients infected with the Alpha strain were asymptomatic. Fever (65.8%), cough (63.2%), shortness of breath (21.1%), and diarrhea (21.1%) were more common in patients infected with the SARS-CoV-2 Alpha strain, while runny nose (24.1%), sore throat (31.9%), body aches (13.6%), and headache (12.3%) were more common in patients with the Omicron variant. Compared with 33 (86.84%) of 38 patients infected with the Alpha strain, who had viral pneumonia on pulmonary CT images, only 5 (1.3%) of 382 patients infected with the Omicron variant had mild foci. In addition, the distribution of opacities in the five patients was unilateral and centrilobular, whereas most patients infected with the Alpha strain had bilateral involvement and multiple lesions in the peripheral zones of the lung. Conclusion: The SARS-CoV-2 Alpha strain mainly affects the lungs, while Omicron is confined to the upper respiratory tract in patients with COVID-19.


Тема - темы
COVID-19 , SARS-CoV-2 , COVID-19/diagnostic imaging , Humans , Lung/diagnostic imaging , Lung/pathology , Male , Tomography, X-Ray Computed
6.
Front Immunol ; 13: 950666, 2022.
Статья в английский | MEDLINE | ID: covidwho-2113954

Реферат

The on-going COVID-19 pandemic has given rise to SARS-CoV-2 clades and variants with differing levels of symptoms and severity. To this end, we aim to systematically elucidate the changes in the pathogenesis as SARS-CoV-2 evolved from ancestral to the recent Omicron VOC, on their mechanisms (e.g. cytokine storm) resulting in tissue damage, using the established K18-hACE2 murine model. We reported that among the SARS-CoV-2 viruses tested, infection profiles were initially similar between viruses from early clades but started to differ greatly starting from VOC Delta, where the trend continues in Omicron. VOCs Delta and Omicron both accumulated a significant number of mutations, and when compared to VOCs Alpha, Beta, and earlier predecessors, showed reduced neurotropism and less apparent gene expression in cytokine storm associated pathways. They were shown to leverage on other pathways to cause tissue damage (or lack of in the case of Omicron). Our study highlighted the importance of elucidating the response profiles of individual SARS-CoV-2 iterations, as their propensity of severe infection via pathways like cytokine storm changes as more variant evolves. This will then affect the overall threat assessment of each variant as well as the use of immunomodulatory treatments as management of severe infections of each variant.


Тема - темы
COVID-19 , SARS-CoV-2 , Animals , Mice , COVID-19/genetics , Cytokine Release Syndrome , Lung/pathology , Pandemics
7.
Medicine (Baltimore) ; 101(39): e30744, 2022 Sep 30.
Статья в английский | MEDLINE | ID: covidwho-2113766

Реферат

OBJECTIVE: The aim of this study was to compare the radiographic features of patients with progressive and nonprogressive coronavirus disease 2019 (COVID-19) pneumonia. METHODS: PubMed, Embase, and Cochrane Library databases were searched from January 1, 2020, to February 28, 2022, by using the keywords: "COVID-19", "novel Coronavirus", "2019-novel coronavirus", "CT", "radiology" and "imaging". We summarized the computed tomography manifestations of progressive and nonprogressive COVID-19 pneumonia. The meta-analysis was performed using the Stata statistical software version 16.0. RESULTS: A total of 10 studies with 1092 patients were included in this analysis. The findings of this meta-analysis indicated that the dominating computed tomography characteristics of progressive patients were a crazy-paving pattern (odds ratio [OR] = 2.10) and patchy shadowing (OR = 1.64). The dominating lesions distribution of progressive patients were bilateral (OR = 11.62), central mixed subpleural (OR = 1.37), and central (OR = 1.36). The other dominating lesions of progressive patients were pleura thickening (OR = 2.13), lymphadenopathy (OR = 1.74), vascular enlargement (OR = 1.39), air bronchogram (OR = 1.29), and pleural effusion (OR = 1.29). Two patterns of lesions showed significant links with the progression of disease: nodule (P = .001) and crazy-paving pattern (P = .023). Four lesions distribution showed significant links with the progression of disease: bilateral (P = .004), right upper lobe (P = .003), right middle lobe (P = .001), and left upper lobe (P = .018). CONCLUSION: Nodules, crazy-paving pattern, and/or new lesions in bilateral, upper and middle lobe of right lung, and lower lobe of left lung may indicate disease deterioration. Clinicians should formulate or modify treatment strategies in time according to these specific conditions.


Тема - темы
COVID-19 , Pneumonia , COVID-19/diagnostic imaging , Humans , Lung/diagnostic imaging , Lung/pathology , Pneumonia/pathology , Retrospective Studies , SARS-CoV-2 , Tomography, X-Ray Computed/methods
8.
Nat Commun ; 13(1): 6792, 2022 Nov 10.
Статья в английский | MEDLINE | ID: covidwho-2117248

Реферат

Few live attenuated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are in pre-clinical or clinical development. We seek to attenuate SARS-CoV-2 (isolate WA1/2020) by removing the polybasic insert within the spike protein and the open reading frames (ORFs) 6-8, and by introducing mutations that abolish non-structural protein 1 (Nsp1)-mediated toxicity. The derived virus (WA1-ΔPRRA-ΔORF6-8-Nsp1K164A/H165A) replicates to 100- to 1000-fold-lower titers than the ancestral virus and induces little lung pathology in both K18-human ACE2 (hACE2) transgenic mice and Syrian hamsters. Immunofluorescence and transcriptomic analyses of infected hamsters confirm that three-pronged genetic modifications attenuate the proinflammatory pathways more than the removal of the polybasic cleavage site alone. Finally, intranasal administration of just 100 PFU of the WA1-ΔPRRA-ΔORF6-8-Nsp1K164A/H165A elicits robust antibody responses in Syrian hamsters and protects against SARS-CoV-2-induced weight loss and pneumonia. As a proof-of-concept study, we demonstrate that live but sufficiently attenuated SARS-CoV-2 vaccines may be attainable by rational design.


Тема - темы
COVID-19 , SARS-CoV-2 , Cricetinae , Mice , Animals , Humans , SARS-CoV-2/genetics , Mesocricetus , Antibody Formation , Administration, Intranasal , COVID-19 Vaccines , COVID-19/prevention & control , Lung/pathology , Mice, Transgenic , Spike Glycoprotein, Coronavirus/genetics
9.
Dis Model Mech ; 15(11)2022 11 01.
Статья в английский | MEDLINE | ID: covidwho-2117037

Реферат

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, causes life-threatening disease. This novel coronavirus enters host cells via the respiratory tract, promoting the formation of severe pulmonary lesions and systemic disease. Few animal models can simulate the clinical signs and pathology of COVID-19 patients. Diverse preclinical studies using K18-hACE2 mice and Syrian golden hamsters, which are highly permissive to SARS-CoV-2 in the respiratory tract, are emerging; however, the systemic pathogenesis and cellular tropism of these models remain obscure. We intranasally infected K18-hACE2 mice and Syrian golden hamsters with SARS-CoV-2, and compared the clinical features, pathogenesis, cellular tropism and infiltrated immune-cell subsets. In K18-hACE2 mice, SARS-CoV-2 persistently replicated in alveolar cells and caused pulmonary and extrapulmonary disease, resulting in fatal outcomes. Conversely, in Syrian golden hamsters, transient SARS-CoV-2 infection in bronchial cells caused reversible pulmonary disease, without mortality. Our findings provide comprehensive insights into the pathogenic spectrum of COVID-19 using preclinical models.


Тема - темы
COVID-19 , Cricetinae , Mice , Animals , Mesocricetus , SARS-CoV-2 , Disease Models, Animal , Lung/pathology , Mice, Transgenic
10.
Sci Rep ; 12(1): 18694, 2022 Nov 04.
Статья в английский | MEDLINE | ID: covidwho-2106469

Реферат

SARS-CoV-2 exhibits a diverse host species range with variable outcomes, enabling differential host susceptibility studies to assess suitability for pre-clinical countermeasure and pathogenesis studies. Baseline virological, molecular and pathological outcomes were determined among multiple species-one Old World non-human primate (NHP) species (cynomolgus macaques), two New World NHP species (red-bellied tamarins; common marmosets) and Syrian hamsters-following single-dose, atraumatic intranasal administration of SARS-CoV-2/Victoria-01. After serial sacrifice 2, 10 and 28-days post-infection (dpi), hamsters and cynomolgus macaques displayed differential virus biodistribution across respiratory, gastrointestinal and cardiovascular systems. Uniquely, New World tamarins, unlike marmosets, exhibited high levels of acute upper airway infection, infectious virus recovery associated with mild lung pathology representing a host previously unrecognized as susceptible to SARS-CoV-2. Across all species, lung pathology was identified post-clearance of virus shedding (antigen/RNA), with an association of virus particles within replication organelles in lung sections analysed by electron microscopy. Disrupted cell ultrastructure and lung architecture, including abnormal morphology of mitochondria 10-28 dpi, represented on-going pathophysiological consequences of SARS-CoV-2 in predominantly asymptomatic hosts. Infection kinetics and host pathology comparators using standardized methodologies enables model selection to bridge differential outcomes within upper and lower respiratory tracts and elucidate longer-term consequences of asymptomatic SARS-CoV-2 infection.


Тема - темы
COVID-19 , SARS-CoV-2 , Cricetinae , Animals , Tissue Distribution , Administration, Intranasal , Disease Models, Animal , Lung/pathology , Mesocricetus , Macaca fascicularis
11.
Cell Mol Life Sci ; 79(11): 582, 2022 Nov 05.
Статья в английский | MEDLINE | ID: covidwho-2103840

Реферат

The non-classical human leukocyte antigen (HLA)-G exerts immune-suppressive properties modulating both NK and T cell responses. While it is physiologically expressed at the maternal-fetal interface and in immune-privileged organs, HLA-G expression is found in tumors and in virus-infected cells. So far, there exists little information about the role of HLA-G and its interplay with immune cells in biopsies, surgical specimen or autopsy tissues of lung, kidney and/or heart muscle from SARS-CoV-2-infected patients compared to control tissues. Heterogeneous, but higher HLA-G protein expression levels were detected in lung alveolar epithelial cells of SARS-CoV-2-infected patients compared to lung epithelial cells from influenza-infected patients, but not in other organs or lung epithelia from non-viral-infected patients, which was not accompanied by high levels of SARS-CoV-2 nucleocapsid antigen and spike protein, but inversely correlated to the HLA-G-specific miRNA expression. High HLA-G expression levels not only in SARS-CoV-2-, but also in influenza-infected lung tissues were associated with a high frequency of tissue-infiltrating immune cells, but low numbers of CD8+ cells and an altered expression of hyperactivation and exhaustion markers in the lung epithelia combined with changes in the spatial distribution of macrophages and T cells. Thus, our data provide evidence for an involvement of HLA-G and HLA-G-specific miRNAs in immune escape and as suitable therapeutic targets for the treatment of SARS-CoV-2 infections.


Тема - темы
COVID-19 , Influenza, Human , Humans , COVID-19/genetics , SARS-CoV-2 , HLA-G Antigens/genetics , Influenza, Human/pathology , Lung/pathology
12.
J Allergy Clin Immunol ; 147(1): 81-91, 2021 01.
Статья в английский | MEDLINE | ID: covidwho-2095538

Реферат

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.


Тема - темы
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
13.
EMBO Mol Med ; 14(11): e16283, 2022 Nov 08.
Статья в английский | MEDLINE | ID: covidwho-2091043

Реферат

Our current understanding of the spectrum of TB and COVID-19 lesions in the human lung is limited by a reliance on low-resolution imaging platforms that cannot provide accurate 3D representations of lesion types within the context of the whole lung. To characterize TB and COVID-19 lesions in 3D, we applied micro/nanocomputed tomography to surgically resected, postmortem, and paraffin-embedded human lung tissue. We define a spectrum of TB pathologies, including cavitary lesions, calcium deposits outside and inside necrotic granulomas and mycetomas, and vascular rearrangement. We identified an unusual spatial arrangement of vasculature within an entire COVID-19 lobe, and 3D segmentation of blood vessels revealed microangiopathy associated with hemorrhage. Notably, segmentation of pathological anomalies reveals hidden pathological structures that might otherwise be disregarded, demonstrating a powerful method to visualize pathologies in 3D in TB lung tissue and whole COVID-19 lobes. These findings provide unexpected new insight into the spatial organization of the spectrum of TB and COVID-19 lesions within the framework of the entire lung.


Тема - темы
COVID-19 , Mycobacterium tuberculosis , Tuberculosis , Humans , Lung/diagnostic imaging , Lung/pathology , Tomography, X-Ray Computed
14.
Korean J Radiol ; 21(5): 541-544, 2020 05.
Статья в английский | MEDLINE | ID: covidwho-2089767

Реферат

The coronavirus disease 2019 (COVID-19) pneumonia is a recent outbreak in mainland China and has rapidly spread to multiple countries worldwide. Pulmonary parenchymal opacities are often observed during chest radiography. Currently, few cases have reported the complications of severe COVID-19 pneumonia. We report a case where serial follow-up chest computed tomography revealed progression of pulmonary lesions into confluent bilateral consolidation with lower lung predominance, thereby confirming COVID-19 pneumonia. Furthermore, complications such as mediastinal emphysema, giant bulla, and pneumothorax were also observed during the course of the disease.


Тема - темы
Coronavirus Infections/complications , Mediastinal Emphysema/etiology , Pneumonia, Viral/complications , Pneumothorax/etiology , Adult , Betacoronavirus , Blister , COVID-19 , COVID-19 Testing , China , Clinical Laboratory Techniques , Coronavirus , Coronavirus Infections/diagnosis , Coronavirus Infections/diagnostic imaging , Disease Progression , Humans , Lung/pathology , Male , Pandemics , Pneumonia, Viral/diagnostic imaging , SARS-CoV-2 , Tomography, X-Ray Computed
15.
Front Cell Infect Microbiol ; 12: 971933, 2022.
Статья в английский | MEDLINE | ID: covidwho-2083090

Реферат

During the COVID-19 pandemic, there have been an increasing number of COVID-19 patients with cavitary or cystic lung lesions, re-positive or long-term positive nucleic acid tests, but the mechanism is still unclear. Lung cavities may appear at long time interval from initial onset of coronavirus infection, generally during the absorption phase of the disease. The main histopathological characteristic is diffuse alveolar damage and may have more severe symptoms after initial recovery from COVID-19 and an increased mortality rate. There are many possible etiologies of pulmonary cavities in COVID-19 patients and we hypothesize that occult SARS-CoV-2, in the form of biofilm, is harbored in the airway lacuna with other pathogenic microorganisms, which may be the cause of pulmonary cavities and repeated and long-term positive nucleic acid tests.


Тема - темы
COVID-19 , Nucleic Acids , Tuberculosis, Pleural , Tuberculosis, Pulmonary , Biofilms , Humans , Lung/pathology , Pandemics , SARS-CoV-2 , Tuberculosis, Pulmonary/pathology
16.
Medicina (Kaunas) ; 58(10)2022 Oct 11.
Статья в английский | MEDLINE | ID: covidwho-2071631

Реферат

Background and Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection represents a pathology with primary pulmonary involvement and multisystemic impact, including cardiovascular injuries. The present study aimed to assess the value of clinical, biochemical, and imaging factors in COVID-19 patients in determining the severity of myocardial involvement, and to create a model that can be used toevaluate myocardial injury risk based on clinical, biochemical and imaging factors. Materials and Methods: We performed an observational cohort study on 150 consecutive patients, evaluating their age, sex, hospitalization period, peripheral oxygen saturation (SpO2) in ambient air, systolic and diastolic blood pressure, heart rate, respiratory rate, biochemical markers of cardiac dysfunction (TnI, and NT-proBNP), inflammatory markers (C reactive protein (CRP), fibrinogen, serum ferritin, interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα)), D-dimers, lactate dehydrogenase (LDH), myoglobin and radio-imaging parameters. All patients underwent computerized tomography chest scan in the first two days following admission. Results: We observed elevated heart and respiratory rates, higher systolic blood pressure, and a lower diastolic blood pressure in the patients with cardiac injury; significant differences between groups were registered in TnI, NT-proBNP, LDH, CRP, and D-dimers. For the radiological parameters, we found proportional correlations with the myocardial injury for the severity of lung disease, number of pulmonary segments with alveolar consolidation, number of pulmonary lobes with pneumonia, crazy paving pattern, type of lung involvement, the extent of fibroatelectatic lesions and the mediastinal adenopathies. Conclusions: Myocardial injury occurred in 12% of patients in the study group. Ground glass opacities, interstitial interlobular septal thickening (crazy paving pattern), fibroatelectasic lesions and alveolar consolidations on CT scan were correlated with myocardial injury. Routine lung sectional imaging along with non-specific biomarkers (LDH, D-dimers, and CRP) can be further valuable in the characterization of the disease burden, thus impacting patient care.


Тема - темы
COVID-19 , Humans , COVID-19/complications , SARS-CoV-2 , Interleukin-6 , Tumor Necrosis Factor-alpha , C-Reactive Protein , Myoglobin , Lung/pathology , Biomarkers , Lactate Dehydrogenases , Ferritins , Retrospective Studies
17.
Int J Mol Sci ; 23(19)2022 Sep 23.
Статья в английский | MEDLINE | ID: covidwho-2066119

Реферат

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial fibrotic disease that leads to disability and death within 5 years of diagnosis. Pulmonary fibrosis is a disease with a multifactorial etiology. The concept of aberrant regeneration of the pulmonary epithelium reveals the pathogenesis of IPF, according to which repeated damage and death of alveolar epithelial cells is the main mechanism leading to the development of progressive IPF. Cell death provokes the migration, proliferation and activation of fibroblasts, which overproduce extracellular matrix, resulting in fibrotic deformity of the lung tissue. Mesenchymal stem cells (MSCs) and extracellular vesicles (EVs) are promising therapies for pulmonary fibrosis. MSCs, and EVs derived from MSCs, modulate the activity of immune cells, inhibit the expression of profibrotic genes, reduce collagen deposition and promote the repair of damaged lung tissue. This review considers the molecular mechanisms of the development of IPF and the multifaceted role of MSCs in the therapy of IPF. Currently, EVs-MSCs are regarded as a promising cell-free therapy tool, so in this review we discuss the results available to date of the use of EVs-MSCs for lung tissue repair.


Тема - темы
Extracellular Vesicles , Idiopathic Pulmonary Fibrosis , Mesenchymal Stem Cells , Extracellular Vesicles/metabolism , Fibroblasts/metabolism , Humans , Idiopathic Pulmonary Fibrosis/genetics , Idiopathic Pulmonary Fibrosis/therapy , Lung/pathology , Mesenchymal Stem Cells/metabolism
18.
Cells ; 11(19)2022 10 04.
Статья в английский | MEDLINE | ID: covidwho-2065731

Реферат

Here, we aim to describe COVID-19 pathology across different tissues to clarify the disease's pathophysiology. Lungs, kidneys, hearts, and brains from nine COVID-19 autopsies were compared by using antibodies against SARS-CoV-2, macrophages-microglia, T-lymphocytes, B-lymphocytes, and activated platelets. Alzheimer's Disease pathology was also assessed. PCR techniques were used to verify the presence of viral RNA. COVID-19 cases had a short clinical course (0-32 days) and their mean age was 77.4 y/o. Hypoxic changes and inflammatory infiltrates were present across all tissues. The lymphocytic component in the lungs and kidneys was predominant over that of other tissues (p < 0.001), with a significantly greater presence of T-lymphocytes in the lungs (p = 0.020), which showed the greatest presence of viral antigens. The heart showed scant SARS-CoV-2 traces in the endothelium-endocardium, foci of activated macrophages, and rare lymphocytes. The brain showed scarce SARS-CoV-2 traces, prominent microglial activation, and rare lymphocytes. The pons exhibited the highest microglial activation (p = 0.017). Microthrombosis was significantly higher in COVID-19 lungs (p = 0.023) compared with controls. The most characteristic pathological features of COVID-19 were an abundance of T-lymphocytes and microthrombosis in the lung and relevant microglial hyperactivation in the brainstem. This study suggests that the long-term sequelae of COVID-19 derive from persistent inflammation, rather than persistent viral replication.


Тема - темы
COVID-19 , Thrombosis , Aged , Antigens, Viral , Brain/pathology , Humans , Kidney , Lung/pathology , Macrophages , RNA, Viral , SARS-CoV-2 , T-Lymphocytes , Thrombosis/pathology
19.
Mol Microbiol ; 117(3): 578-588, 2022 03.
Статья в английский | MEDLINE | ID: covidwho-2063875

Реферат

Respiratory infections are a leading cause of mortality worldwide. Most of the research on the underlying disease mechanisms is based on cell culture, organoid, or surrogate animal models. Although these provide important insights, they have limitations. Cell culture models fail to recapitulate cellular interactions in the lung and animal models often do not permit high-throughput analysis of drugs or pathogen isolates; hence, there is a need for improved, scalable models. Precision-cut lung slices (PCLS), small, uniform tissue slices generated from animal or human lungs are increasingly recognized and employed as an ex vivo organotypic model. PCLS retain remarkable cellular complexity and the architecture of the lung, providing a platform to investigate respiratory pathogens in a near-native environment. Here, we review the generation and features of PCLS, their use to investigate the pathogenesis of viral and bacterial pathogens, and highlight their potential to advance respiratory infection research in the future.


Тема - темы
Communicable Diseases , Lung , Animals , Communicable Diseases/pathology , Lung/microbiology , Lung/pathology
20.
Sci Rep ; 12(1): 16956, 2022 Oct 10.
Статья в английский | MEDLINE | ID: covidwho-2062264

Реферат

In late 2019 the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus emerged in China and quickly spread into a worldwide pandemic. It has caused millions of hospitalizations and deaths, despite the use of COVID-19 vaccines. Convalescent plasma and monoclonal antibodies emerged as major therapeutic options for treatment of COVID-19. We have developed an anti-SARS-CoV-2 immunoglobulin intravenous (Human) (COVID-HIGIV), a potential improvement from using convalescent plasma. In this report the efficacy of COVID-HIGIV was evaluated in hamster and mouse models of SARS-CoV-2 infection. COVID-HIGIV treatment in both mice and hamsters significantly reduced the viral load in the lungs. Among COVID-HIGIV treated animals, infection-related body weight loss was reduced and the animals regained their baseline body weight faster than the PBS controls. In hamsters, COVID-HIGIV treatment reduced infection-associated lung pathology including lung inflammation, and pneumocyte hypertrophy in the lungs. These results support ongoing trials for outpatient treatment with COVID-HIGIV for safety and efficacy evaluation (NCT04910269, NCT04546581).


Тема - темы
COVID-19 , Animals , Antibodies, Monoclonal , COVID-19/therapy , COVID-19 Vaccines , Clinical Trials as Topic , Cricetinae , Disease Models, Animal , Humans , Immunization, Passive , Lung/pathology , Mice , SARS-CoV-2
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