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1.
Bratisl Lek Listy ; 123(9): 653-6958, 2022.
Статья в английский | MEDLINE | ID: covidwho-2024875

Реферат

PURPOSE: In addition to the highly variable clinical presentation of acute COVID-19 infection, it can also cause various post-acute signs and symptoms. In our study, we aimed to examine the efficacy of anti-fibrotic therapy in patients who developed pulmonary fibrosis after COVID-19. METHODS: In total, 15 patients who applied to the Post-Covid Outpatient Clinic between May 2021 and August 2021 and were diagnosed with COVID-19 pneumonia, and whose cough, dyspnea, exertional dyspnea and low saturation continued to be present at least 12 weeks after the diagnosis, were included in the study. Off-label pirfenidone treatment was started according to the radiological findings, pulmonary function test parameters (PFT) and 6-minute walking test (6MWT) results. The patients were followed up for 12 weeks. RESULTS: While all of the FVC, FVC%, FEV1, FEV1%, DLCO%, DLCO/VA%, 6MWT, and room air saturation levels were observed to increase statistically significantly in the patients at the 12th week, it was determined that there was a statistically significant decrease in the pulse level in room air (p = 0.01, 0.01, 0.01, 0.01, 0.004, 0.001, 0.002, 0.001, and 0.002, respectively). In regression analysis based on radiological scoring, it was observed that the DLCO and room air saturation levels at the 12th week of the treatment were statistically significantly higher in patients with lower scores at the beginning (p = 0.04, 0.03). In addition, it was observed that anti-fibrotic treatment, which was started in the earliest period, i.e., 12 weeks after the diagnosis, resulted in an improvement in radiological, PFT and 6MWT parameters. CONCLUSION: Patients who still had dyspnea and low saturation 12 weeks after the diagnosis, defined as chronic COVID-19, should be evaluated for anti-fibrotic therapy after the necessary radiological and PFT evaluation. Early treatment commencement brings about, besides radiological improvement, a better response obtained in PFT and 6MWT (Tab. 2, Fig. 2, Ref. 21).


Тема - темы
COVID-19 , Pulmonary Fibrosis , COVID-19/drug therapy , Dyspnea/etiology , Humans , Pulmonary Fibrosis/complications , Pulmonary Fibrosis/drug therapy , Respiratory Function Tests/adverse effects
2.
Int J Mol Sci ; 23(17)2022 Aug 26.
Статья в английский | MEDLINE | ID: covidwho-2023746

Реферат

Although interstitial lung disease (ILD) is a life-threatening pathological condition that causes respiratory failure, the efficiency of current therapies is limited. This study aimed to investigate the effects of human MIKO-1 (hMIKO-1), a hybrid protein that suppresses the abnormal activation of macrophages, on murine macrophage function and its therapeutic effect in a mouse model of bleomycin-induced ILD (BLM-ILD). To this end, the phenotype of thioglycolate-induced murine peritoneal macrophages co-cultured with hMIKO-1 was examined. The mice were assigned to normal, BLM-alone, or BLM + hMIKO-1 groups, and hMIKO-1 (0.1 mg/mouse) was administered intraperitoneally from day 0 to 14. The mice were sacrificed on day 28, and their lungs were evaluated by histological examination, collagen content, and gene expression levels. hMIKO-1 suppressed the polarization of murine macrophages to M2 predominance in vitro. The fibrosis score of lung pathology and lung collagen content of the BLM + hMIKO-1 group were significantly lower than those in the BLM-alone group. The expression levels of TNF-α, IL-6, IL-1ß, F4/80, and TIMP-1 in the lungs of the BLM + hMIKO-1 group were significantly lower than those in the BLM-alone group. These findings indicate that hMIKO-1 reduces lung fibrosis and may be a future therapeutic candidate for ILD treatment.


Тема - темы
Lung Diseases, Interstitial , Pulmonary Fibrosis , Animals , Bleomycin/toxicity , Collagen/metabolism , Disease Models, Animal , Humans , Lung/pathology , Lung Diseases, Interstitial/chemically induced , Lung Diseases, Interstitial/drug therapy , Lung Diseases, Interstitial/metabolism , Macrophages/metabolism , Mice , Mice, Inbred C57BL , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/metabolism
3.
Respir Res ; 23(1): 233, 2022 Sep 06.
Статья в английский | MEDLINE | ID: covidwho-2009402

Реферат

BACKGROUND: Some coronavirus disease 2019 (COVID-19) survivors experience prolonged and varying symptoms, a condition termed post-acute COVID-19 syndrome (PACS). However, the prevalence of chronic pulmonary sequelae of PACS during long-term follow-up remains unclear. Several studies have examined this issue and reported heterogeneous results. METHODS: We conducted a systematic review and meta-analysis using a random-effects model to estimate the pooled prevalence of the pulmonary sequelae of COVID-19, as demonstrated by pulmonary function testing (PFT) and chest computed tomography (CT) performed at least 6 months after initial infection. PubMed, Embase, and Cochrane Library databases were searched from January 1, 2020 to December 31, 2021 to identify related studies. We investigated whether the prevalence of pulmonary sequelae decreased over time and attempted to identify the factors associated with their development by performing multiple subgroup and meta-regression analyses. RESULTS: Of the 18,062 studies identified, 30 met our eligibility criteria. Among these studies, 25 and 22 had follow-up PFT and chest CT data, respectively. The follow-up durations were approximately 6 and 12 months in 18 and 12 studies, respectively. Impaired diffusion capacity was the most common abnormality on PFT (pooled prevalence 35%, 95% confidence interval [CI] 30-41%) with a prevalence of 39% (95% CI 34-45%) and 31% (95% CI 21-40%) in the 6-month and 12-month follow-up studies, respectively (P = 0.115). Restrictive pulmonary dysfunction evident as reduced forced vital capacity was less frequent (pooled prevalence 8%, 95% CI 6-11%); however, its prevalence was lower in the 12-month follow-up studies than in the 6-month follow-up studies (5% [95% CI 3-7%] vs. 13% [95% CI 8-19%], P = 0.006). On follow-up chest CT, the pooled prevalence of persistent ground-glass opacities and pulmonary fibrosis was 34% (95% CI 24-44%) and 32% (95% CI 23-40%), respectively, and the prevalence did not decrease over time. As every meta-analysis showed significant between-study heterogeneity, subgroup and meta-regression analyses were performed to identify potential effect modifiers; the severity of index infection was associated with the prevalence of impaired diffusion capacity and pulmonary fibrosis. CONCLUSIONS: A substantial number of COVID-19 survivors displayed pulmonary sequelae as part of PACS. Except for restrictive pulmonary dysfunction, the prevalence of these sequelae did not decrease until 1 year after initial infection. Considering the association between the severity of acute COVID-19 and risk of pulmonary sequelae, patients who recover from severe COVID-19 require close respiratory follow-up. Systematic review registration number PROSPERO CRD42021234357.


Тема - темы
COVID-19 , Pulmonary Fibrosis , COVID-19/complications , COVID-19/diagnostic imaging , Humans , SARS-CoV-2 , Tomography, X-Ray Computed/methods
4.
Medicine (Baltimore) ; 101(35): e30146, 2022 Sep 02.
Статья в английский | MEDLINE | ID: covidwho-2008664

Реферат

BACKGROUND: There is currently no objective computed tomography (CT)-defined grading system for coronavirus disease (COVID-19)-related pulmonary fibrosis. We propose a CT-based radiological scale that adapts the histological fibrosis scale to pulmonary fibrosis CT findings, to evaluate possible predictive factors for the degree of fibrosis in these patients. METHODS: A new radiological fibrosis grading system was created based on existing histological fibrosis scales. One hundred forty-seven COVID-19 patients with any degree of fibrosis on CT were evaluated. Smoking status, the presence of hypertension, the duration of hospital stays, the presence of comorbid diseases, and the levels of prognostic and predictive factors for COVID-19 were evaluated, and how these parameters affected the fibrosis scores was examined. RESULTS: Of 147 patients, 17.7% had grade 1, 17% had grade 2, 51.7% had grade 3, and 13.6% had grade 4 fibrosis. ANOVA revealed statistically significant relationships between the fibrosis scores and lactate dehydrogenase values, lymphocyte count, C-reactive protein level, and length of hospital stay. Smoking, advanced age, hypertension, and male sex showed significantly higher scores for fibrosis. CONCLUSIONS: Using our CT-defined lung fibrosis grading system, we could predict the severity of fibrosis as well as the resultant lung pathology in COVID-19 patients. Thus, disease exacerbation and development of permanent severe fibrosis can be prevented using the appropriate treatment methods in high-risk patients.


Тема - темы
COVID-19 , Hypertension , Pulmonary Fibrosis , C-Reactive Protein , COVID-19/diagnostic imaging , Fibrosis , Humans , Lactate Dehydrogenases , Male , Pulmonary Fibrosis/diagnostic imaging , Pulmonary Fibrosis/etiology , Tomography, X-Ray Computed/methods
5.
Comput Methods Programs Biomed ; 225: 107094, 2022 Oct.
Статья в английский | MEDLINE | ID: covidwho-2007619

Реферат

BACKGROUND AND OBJECTIVE: Pulmonary fibrosis (PF) is a chronic progressive disease with an extremely high mortality rate and is a complication of COVID-19. Inhalable microspheres have been increasingly used in the treatment of lung diseases such as PF in recent years. Compared to the direct inhalation of drugs, a larger particle size is required to ensure the sustained release of microspheres. However, the clinical symptoms of PF may lead to the easier deposition of microspheres in the upper respiratory tract. Therefore, it is necessary to understand the effects of PF on the deposition of microspheres in the respiratory tract. METHODS: In this study, airway models with different degrees of PF in humans and mice were established, and the transport and deposition of microspheres in the airway were simulated using computational fluid dynamics. RESULTS: The simulation results showed that PF increases microsphere deposition in the upper respiratory tract and decreases bronchial deposition in both humans and mice. Porous microspheres with low density can ensure deposition in the lower respiratory tract and larger particle size. In healthy and PF humans, porous microspheres of 10 µm with densities of 700 and 400 kg/m³ were deposited most in the bronchi. Unlike in humans, microspheres larger than 4 µm are completely deposited in the upper respiratory tract of mice owing to their high inhalation velocity. For healthy and PF mice, microspheres of 6 µm with densities of and 100 kg/m³ are recommended. CONCLUSIONS: The results showed that with the exacerbation of PF, it is more difficult for microsphere particles to deposit in the subsequent airway. In addition, there were significant differences in the deposition patterns among the different species. Therefore, it is necessary to process specific microspheres from different individuals. Our study can guide the processing of microspheres and achieve differentiated drug delivery in different subjects to maximize therapeutic effects.


Тема - темы
COVID-19 , Pulmonary Fibrosis , Animals , Computer Simulation , Delayed-Action Preparations , Humans , Lung , Mice , Microspheres , Models, Biological , Particle Size , Porosity , Pulmonary Fibrosis/drug therapy , Respiratory Aerosols and Droplets , Trachea
6.
J R Coll Physicians Edinb ; 52(2): 90-92, 2022 Jun.
Статья в английский | MEDLINE | ID: covidwho-2005573
7.
Viruses ; 14(9)2022 08 23.
Статья в английский | MEDLINE | ID: covidwho-1997804

Реферат

BACKGROUND: Infection by SARS-CoV-2 has been associated with multiple symptoms; however, still, little is known about persistent symptoms and their probable association with the risk of developing pulmonary fibrosis in patients post-COVID-19. METHODS: A longitudinal prospective study on health workers infected by SARS-CoV-2 was conducted. In this work, signs and symptoms were recorded of 149 health workers with a positive PCR test for SARS-CoV-2 at the beginning of the diagnosis, during the active infection, and during post-COVID-19 follow-up. The McNemar chi-square test was used to compare the proportions and percentages of symptoms between the baseline and each follow-up period. RESULTS: The signs and symptoms after follow-up were cardiorespiratory, neurological, and inflammatory. Gastrointestinal symptoms were unusual at the disease onset, but unexpectedly, their frequency was higher in the post-infection stage. The multivariate analysis showed that pneumonia (HR 2.4, IC95%: 1.5-3.8, p < 0.001) and positive PCR tests still after four weeks (HR 5.3, IC95%: 2.3-12.3, p < 0.001) were factors associated with the diagnosis of post-COVID-19 pulmonary fibrosis in this study group. CONCLUSIONS: Our results showed that pneumonia and virus infection persistence were risk factors for developing pulmonary fibrosis post-COVID-19, after months of initial infection.


Тема - темы
COVID-19 , Pulmonary Fibrosis , COVID-19/complications , Humans , Outpatients , Prospective Studies , Pulmonary Fibrosis/epidemiology , SARS-CoV-2
8.
Aging Cell ; 21(8): e13680, 2022 Aug.
Статья в английский | MEDLINE | ID: covidwho-1992692

Реферат

Determining the mechanism of senescence-associated pulmonary fibrosis is crucial for designing more effective treatments for chronic lung diseases. This study aimed to determine the following: whether Sirt1 and serum vitamin D decreased with physiological aging, promoting senescence-associated pulmonary fibrosis by activating TGF-ß1/IL-11/MEK/ERK signaling, whether Sirt1 overexpression prevented TGF-ß1/IL-11/MEK/ERK signaling-mediated senescence-associated pulmonary fibrosis in vitamin D-deficient (Cyp27b1-/- ) mice, and whether Sirt1 downregulated IL-11 expression transcribed by TGF-ß1/Smad2 signaling through deacetylating histone at the IL-11 promoter in pulmonary fibroblasts. Bioinformatics analysis with RNA sequencing data from pulmonary fibroblasts of physiologically aged mice was conducted for correlation analysis. Lungs from young and physiologically aged wild-type (WT) mice were examined for cell senescence, fibrosis markers, and TGF-ß1/IL-11/MEK/ERK signaling proteins, and 1,25(OH)2 D3 and IL-11 levels were detected in serum. Nine-week-old WT, Sirt1 mesenchymal transgene (Sirt1Tg ), Cyp27b1-/- , and Sirt1Tg Cyp27b1-/- mice were observed the pulmonary function, aging, and senescence-associated secretory phenotype and TGF-ß1/IL-11/MEK/ERK signaling. We found that pulmonary Sirt1 and serum vitamin D decreased with physiological aging, activating TGF-ß1/IL-11/MEK/ERK signaling, and promoting senescence-associated pulmonary fibrosis. Sirt1 overexpression improved pulmonary dysfunction, aging, DNA damage, senescence-associated secretory phenotype, and fibrosis through downregulating TGF-ß1/IL-11/MEK/ERK signaling in Cyp27b1-/- mice. Sirt1 negatively regulated IL-11 expression through deacetylating H3K9/14ac mainly at the region from -871 to -724 of IL-11 promoter, also the major binding region of Smad2 which regulated IL-11 expression at the transcriptional level, and subsequently inhibiting TGF-ß1/IL-11/MEK/ERK signaling in pulmonary fibroblasts. This signaling in aging fibroblasts could be a therapeutic target for preventing senescence-associated pulmonary fibrosis induced by vitamin D deficiency.


Тема - темы
Interleukin-11/metabolism , Pulmonary Fibrosis , Sirtuin 1/metabolism , Vitamin D Deficiency , 25-Hydroxyvitamin D3 1-alpha-Hydroxylase , Animals , Fibrosis , Mice , Mitogen-Activated Protein Kinase Kinases/adverse effects , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/genetics , Sirtuin 1/genetics , Transforming Growth Factor beta1/metabolism , Vitamin D , Vitamin D Deficiency/complications , Vitamin D Deficiency/genetics
9.
Cells ; 11(16)2022 Aug 11.
Статья в английский | MEDLINE | ID: covidwho-1987666

Реферат

Pulmonary fibrosis (PF) is a feared outcome of many pulmonary diseases which results in a reduction in lung compliance and capacity. The development of PF is relatively rare, but it can occur secondary to viral pneumonia, especially COVID-19 infection. While COVID-19 infection and its complications are still under investigation, we can look at a similar outbreak in the past to gain better insight as to the expected long-term outcomes of COVID-19 patient lung function. In the current article, we review the literature relative to PF via PubMed. We also performed a literature search for COVID-related pathological changes in the lungs. Finally, the paper was reviewed and summarized based on the studies' integrity, relative, or power calculations. This article provides a narrative review that endeavors to elucidate the current understanding of the pathophysiological mechanisms underlying PF and therapeutic strategies. We also discussed the potential for preventing progression to the fibrotic state within the context of the COVID-19 pandemic. With the massive scale of the COVID-19 pandemic, we expect there should more instances of PF due to COVID-19 infection. Patients who survive severe COVID-19 infection may suffer from a high incidence of PF.


Тема - темы
COVID-19 , Pneumonia, Viral , Pulmonary Fibrosis , Humans , Lung/pathology , Pandemics , Pneumonia, Viral/pathology , Pulmonary Fibrosis/complications , Pulmonary Fibrosis/drug therapy
10.
J Nanobiotechnology ; 20(1): 272, 2022 Jun 11.
Статья в английский | MEDLINE | ID: covidwho-1940509

Реферат

BACKGROUND: Acute lung injury (ALI), a severe health-threatening disease, has a risk of causing chronic pulmonary fibrosis. Informative and powerful evidence suggests that inflammation and oxidative stress play a central role in the pathogenesis of ALI. Quercetin is well recognized for its excellent antioxidant and anti-inflammatory properties, which showed great potential for ALI treatment. However, the application of quercetin is often hindered by its low solubility and bioavailability. Therefore, to overcome these challenges, an inhalable quercetin-alginate nanogel (QU-Nanogel) was fabricated, and by this special "material-drug" structure, the solubility and bioavailability of quercetin were significantly enhanced, which could further increase the activity of quercetin and provide a promising therapy for ALI. RESULTS: QU-Nanogel is a novel alginate and quercetin based "material-drug" structural inhalable nanogel, in which quercetin was stabilized by hydrogen bonding to obtain a "co-construct" water-soluble nanogel system, showing antioxidant and anti-inflammatory properties. QU-Nanogel has an even distribution in size of less than 100 nm and good biocompatibility, which shows a stronger protective and antioxidant effect in vitro. Tissue distribution results provided evidence that the QU-Nanogel by ultrasonic aerosol inhalation is a feasible approach to targeted pulmonary drug delivery. Moreover, QU-Nanogel was remarkably reversed ALI rats by relieving oxidative stress damage and acting the down-regulation effects of mRNA and protein expression of inflammation cytokines via ultrasonic aerosol inhalation administration. CONCLUSIONS: In the ALI rat model, this novel nanogel showed an excellent therapeutic effect by ultrasonic aerosol inhalation administration by protecting and reducing pulmonary inflammation, thereby preventing subsequent pulmonary fibrosis. This work demonstrates that this inhalable QU-Nanogel may function as a promising drug delivery strategy in treating ALI.


Тема - темы
Acute Lung Injury , Pulmonary Fibrosis , Acute Lung Injury/drug therapy , Alginates , Animals , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Antioxidants/chemistry , Inflammation , Nanogels , Particle Size , Quercetin/pharmacology , Quercetin/therapeutic use , Rats
11.
Int J Mol Sci ; 23(15)2022 Jul 26.
Статья в английский | MEDLINE | ID: covidwho-1957349

Реферат

Pulmonary fibrosis is a consequence of the pathological accumulation of extracellular matrix (ECM), which finally leads to lung scarring. Although the pulmonary fibrogenesis is almost known, the last two years of the COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its post effects added new particularities which need to be explored. Many questions remain about how pulmonary fibrotic changes occur within the lungs of COVID-19 patients, and whether the changes will persist long term or are capable of resolving. This review brings together existing knowledge on both COVID-19 and pulmonary fibrosis, starting with the main key players in promoting pulmonary fibrosis, such as alveolar and endothelial cells, fibroblasts, lipofibroblasts, and macrophages. Further, we provide an overview of the main molecular mechanisms driving the fibrotic process in connection with Galactin-1, -3, -8, and -9, together with the currently approved and newly proposed clinical therapeutic solutions given for the treatment of fibrosis, based on their inhibition. The work underlines the particular pathways and processes that may be implicated in pulmonary fibrosis pathogenesis post-SARS-CoV-2 viral infection. The recent data suggest that galectin-1, -3, -8, and -9 could become valuable biomarkers for the diagnosis and prognosis of lung fibrosis post-COVID-19 and promising molecular targets for the development of new and original therapeutic tools to treat the disease.


Тема - темы
COVID-19 , Pulmonary Fibrosis , COVID-19/complications , Endothelial Cells/metabolism , Galectin 1 , Humans , Pandemics , Pulmonary Fibrosis/metabolism , SARS-CoV-2
12.
Eur Rev Med Pharmacol Sci ; 26(13): 4872-4880, 2022 07.
Статья в английский | MEDLINE | ID: covidwho-1955404

Реферат

OBJECTIVE: Growing interest is directed to the outcomes of COVID-19 in survivors, both in the convalescent period and in the long-term, which are responsible for morbidity and quality of life deterioration. This article aims to describe the mechanisms supporting the possible use of NAC as an adjuvant treatment for post-COVID-19 pulmonary fibrosis. MATERIALS AND METHODS: A search was performed in PubMed/MEDLINE. RESULTS: Interstitial changes have been observed in the CT scan of COVID-19 pneumonia. In patients with respiratory outcomes in the post-COVID-19 stage, glutathione (GSH) deficiency was found and interpreted as a reaction to the inflammatory cascade caused by the viral infection, while the pathophysiological process of pulmonary fibrosis involves numerous cytokines, such as TGF-ß, TNF-α, IL-1, PDGF and VEGF. NAC has a good tolerability profile, is easily administered orally and inexpensively, and has antioxidant and anti-inflammatory effects that may target the pathophysiologic mechanisms involved in pulmonary fibrosis. It may revert GSH deficiency, exerts direct and indirect antioxidant activity, anti-inflammatory activity and improves immune T-cell response. CONCLUSIONS: The mechanism of action of NAC suggests a role in the treatment of pulmonary fibrosis induced by COVID-19.


Тема - темы
COVID-19 , Pulmonary Fibrosis , Acetylcysteine/pharmacology , Acetylcysteine/therapeutic use , Anti-Inflammatory Agents , Antioxidants/pharmacology , COVID-19/drug therapy , Glutathione , Humans , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/drug therapy , Quality of Life
13.
Front Immunol ; 13: 934264, 2022.
Статья в английский | MEDLINE | ID: covidwho-1952335

Реферат

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), responsible for COVID-19, has caused a global pandemic. Observational studies revealed a condition, herein called as Long-COVID syndrome (PC), that affects both moderately and severely infected patients, reducing quality-of-life. The mechanism/s underlying the onset of fibrotic-like changes in PC are still not well defined. The goal of this study was to understand the involvement of the Absent in melanoma-2 (AIM2) inflammasome in PC-associated lung fibrosis-like changes revealed by chest CT scans. Peripheral blood mononuclear cells (PBMCs) obtained from PC patients who did not develop signs of lung fibrosis were not responsive to AIM2 activation by Poly dA:dT. In sharp contrast, PBMCs from PC patients with signs of lung fibrosis were highly responsive to AIM2 activation, which induced the release of IL-1α, IFN-α and TGF-ß. The recognition of Poly dA:dT was not due to the activation of cyclic GMP-AMP (cGAMP) synthase, a stimulator of interferon response (cGAS-STING) pathways, implying a role for AIM2 in PC conditions. The release of IFN-α was caspase-1- and caspase-4-dependent when AIM2 was triggered. Instead, the release of pro-inflammatory IL-1α and pro-fibrogenic TGF-ß were inflammasome independent because the inhibition of caspase-1 and caspase-4 did not alter the levels of the two cytokines. Moreover, the responsiveness of AIM2 correlated with higher expression of the receptor in circulating CD14+ cells in PBMCs from patients with signs of lung fibrosis.


Тема - темы
COVID-19 , DNA-Binding Proteins , Pulmonary Fibrosis , COVID-19/blood , COVID-19/immunology , COVID-19/pathology , Carrier Proteins , Caspase 1/immunology , DNA-Binding Proteins/blood , DNA-Binding Proteins/immunology , Humans , Inflammasomes/blood , Inflammasomes/immunology , Interferon-alpha/metabolism , Leukocytes, Mononuclear/immunology , Pulmonary Fibrosis/blood , Pulmonary Fibrosis/immunology , Pulmonary Fibrosis/pathology , Pulmonary Fibrosis/virology , SARS-CoV-2 , Transforming Growth Factor beta/metabolism
14.
Front Immunol ; 13: 831194, 2022.
Статья в английский | MEDLINE | ID: covidwho-1952320

Реферат

Resulting from severe inflammation and cell destruction, COVID-19 patients could develop pulmonary fibrosis (PF), which remains in the convalescent stage. Nevertheless, how immune response participates in the pathogenesis of PF progression is not well defined. To investigate that question, 12 patients with severe COVID-19 were included in the study. Peripheral mononuclear cell (PBMC) samples were collected shortly after their admission and proceeded for single-cell RNA sequencing (scRNA-seq). After 14 days of discharge, the patients were revisited for chest CT scan. PF index (FI) was computed by AI-assisted CT images. Patients were categorized into FIhi and FIlo based on median of FI. By scRNA-seq analysis, our data demonstrated that frequency of CD4+ activated T cells and Treg cells were approximately 3-fold higher in FIhi patients compared with FIlo ones (p < 0.034 for all). By dissecting the differentially expressed genes, we found an overall downregulation of IFN-responsive genes (STAT1, IRF7, ISG15, ISG20, IFIs, and IFITMs) and S100s alarmins (S100A8, S100A9, S100A12, etc.) in all T-cell clusters, and cytotoxicity-related genes (GZMB, PRF1, and GNLY) in CTLs and γδ T cells in the FIhi cohort, compared with FIlo subjects. The GSEA analysis illustrated decreased expression of genes enriched in IFN signaling, innate immune response, adaptive immune response in T cells, NK cells, and monocytes in FIhi patients compared with FIlo ones. In conclusion, these data indicated that the attenuated IFN-responsive genes and their related signaling pathways could be critical for PF progression in COVID-19 patients.


Тема - темы
COVID-19 , Pulmonary Fibrosis , Adaptive Immunity , Humans , Leukocytes , Leukocytes, Mononuclear , Pulmonary Fibrosis/genetics
15.
Hum Genomics ; 16(1): 20, 2022 06 13.
Статья в английский | MEDLINE | ID: covidwho-1951361

Реферат

The increased resolution of single-cell RNA-sequencing technologies has led to major breakthroughs and improved our understanding of the normal and pathologic conditions of multiple tissues and organs. In the study of parenchymal lung disease, single-cell RNA-sequencing has better delineated known cell populations and identified novel cells and changes in cellular phenotypes and gene expression patterns associated with disease. In this review, we aim to highlight the advances and insights that have been made possible by applying these technologies to two seemingly very different lung diseases: fibrotic interstitial lung diseases, a group of relentlessly progressive lung diseases leading to pulmonary fibrosis, and COVID-19 pneumonia, an acute viral disease with life-threatening complications, including pulmonary fibrosis. We discuss changes in cell populations and gene expression, highlighting potential common features, such as alveolar cell epithelial injury and aberrant repair and monocyte-derived macrophage populations, as well as relevance and implications to mechanisms of disease and future directions.


Тема - темы
COVID-19 , Pulmonary Fibrosis , COVID-19/genetics , Humans , Lung/pathology , Pulmonary Fibrosis/genetics , Pulmonary Fibrosis/pathology , RNA , Single-Cell Analysis
16.
Tuberk Toraks ; 70(2): 203-205, 2022 06.
Статья в английский | MEDLINE | ID: covidwho-1934520
17.
Tuberk Toraks ; 70(2): 179-186, 2022 Jun.
Статья в английский | MEDLINE | ID: covidwho-1934519

Реферат

Introduction: Although the epidemiological and clinical characteristics of COVID-19 patients have been described; the pathogenesis of the disease and its long-term consequences are still unclear. Pulmonary fibrosis is one of these late outcomes. In this study we evaluated Interleukin-17 (IL-17), vascular endothelial growth factor (VEGF), and immunoglobulin G4 (IgG4) levels of COVID-19 infected patients with different clinical course and their effect on pulmonary fibrosis in post-COVID period. Materials and Methods: In total, 90 patients were evaluated. Among the patients who presented for a control visit between 3-12 weeks after acute infection; patients with signs of pulmonary sequelae radiologically (traction bronchiectasis, interseptal thickening, disorders in parenchyma architecture) were classified as Group I (n= 32), patients who recovered without sequelae radiologically as Group II (n= 32). The Control group included healthy individuals who did not have COVID-19, and was classified as Group III (n= 26). Result: The mean age in Group I was significantly higher than Group II and III (p<0.001). There was a statistically significant difference between the VEGF and IL-17 values based on the patient group they are in (p<0.05). Vascular endothelial growth factor values of Group I and III were significantly lower than the patients in Group II (p<0.001). IL-17 values of Group I and II were found to be significantly lower than Group III (p= 0.005). There was no statistically significant relationship between groups in terms of IgG4 values. Conclusions: In our study, it was observed that the profibrotic effects of VEGF, IL-17, and IgG4 were not dominant in patients who recovered with pulmonary sequelae after COVID; therefore, it is thought that different mechanisms mentioned or not yet revealed may cause this outcome.


Тема - темы
COVID-19 , Pulmonary Fibrosis , Disease Progression , Humans , Immunoglobulin G , Interleukin-17 , Lung/diagnostic imaging , Pulmonary Fibrosis/etiology , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factors
18.
Biomed Res Int ; 2022: 9346939, 2022.
Статья в английский | MEDLINE | ID: covidwho-1909925

Реферат

Background: The novel coronavirus first emerged in Wuhan, China, and quickly spread across the globe, spanning various countries and resulting in a worldwide pandemic by the end of December 2019. Given the current advances in treatments available for COVID-19, mesenchymal stem cell (MSC) therapy seems to be a prospective option for management of ARDS observed in COVID-19 patients. This present study is aimed at exploring the therapeutic potential and safety of using MSC obtained by isolation from health cord tissues in the treatment of patients with COVID-19. Methods: A systematic search was done based on the guidelines of the PRISMA 2020 statement. A literature search was executed using controlled vocabulary and indexing of trials to evaluate all the relevant studies involving the use of medical subject headings (MeSH) in electronic databases like PubMed, Embase, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and clinicaltrials.gov up to 31 December 2021. The protocol was registered in the PROSPERO register with ID CRD42022301666. Findings. After screening finally, 22 remaining articles were included in this systematic review. The studies revealed that MSC exosomes are found to be superior to MSC alone in terms of safety owing to being smaller with a lesser immunological response which leads to free movement in blood capillaries without clumping and also cannot further divide, thus reducing the oncogenic potential of MSC-derived exosomes as compared to MSC only. The studies demonstrated that the lungs healed with the use of exosomes compared to how they presented initially at the hospital. MSCs are found to increase the angiogenesis process and alveolar reepithelization, reducing markers like TNF alpha, TGF beta, and COL I and III, reducing the growth of myofibroblasts and increasing survivability of endothelium leading to attenuated pulmonary fibrosis and even reversing them. Interpretation. We can conclude that the use of mesenchymal stem cells or their derived exosomes is safe and well-tolerated in patients with COVID-19. It improves different parameters of oxygenation and helps in the healing of the lungs. The viral load along with different inflammatory cells and biomarkers of inflammation tend to decrease. Chest X-ray, CT scan, and different radiological tools are used to show improvement and reduced ongoing destructive processes.


Тема - темы
COVID-19 , Exosomes , Mesenchymal Stem Cells , Pulmonary Fibrosis , COVID-19/therapy , Humans , Prospective Studies
19.
Am J Respir Crit Care Med ; 205(5): 495-506, 2022 03 01.
Статья в английский | MEDLINE | ID: covidwho-1816972

Реферат

The term "advanced sarcoidosis" is used for forms of sarcoidosis with a significant risk of loss of organ function or death. Advanced sarcoidosis often involves the lung and is described as "advanced pulmonary sarcoidosis" (APS), which includes advanced pulmonary fibrosis, associated complications such as bronchiectasis and infections, and pulmonary hypertension. Although APS affects a small proportion of patients with sarcoidosis, it is the leading cause of poor outcomes, including death. Here we review the major patterns of APS with a focus on the current management as well as potential approaches for improved outcomes for this most serious sarcoidosis phenotype.


Тема - темы
Bronchiectasis , Pulmonary Fibrosis , Sarcoidosis, Pulmonary , Sarcoidosis , Humans , Lung , Sarcoidosis, Pulmonary/complications , Sarcoidosis, Pulmonary/drug therapy
20.
Int Immunopharmacol ; 109: 108805, 2022 Aug.
Статья в английский | MEDLINE | ID: covidwho-1814595

Реферат

Pulmonary vascular endothelial dysfunction is a key pathogenic mechanism in acute respiratory distress syndrome (ARDS), resulting in fibrosis in lung tissues, including in the context of COVID-19. Pirfenidone (PFD) has become a novel therapeutic agent for treating idiopathic pulmonary fibrosis (IPF) and can improve lung function, inhibit fibrosis and inhibit inflammation. Recently, endothelial-to-mesenchymal transition (EndMT) was shown to play a crucial role in various respiratory diseases. However, the role of PFD in the course of EndMT in LPS-induced ARDS remains poorly understood. The purpose of this study was to explore the anti-EndMT effects of PFD on pulmonary fibrosis after LPS-induced ARDS. First, we determined that PFD significantly reduced LPS-induced ARDS, as shown by significant pathological alterations, and alleviated the oxidative stress and inflammatory response in vitro and in vivo. Furthermore, PFD decreased pulmonary fibrosis in LPS-induced ARDS by inhibiting EndMT and reduced the expression levels of Hedgehog (HH) pathway target genes, such as Gli1 and α-SMA, after LPS induction. In summary, this study confirmed that inhibiting the HH pathway by PFD could decrease pulmonary fibrosis by downregulating EndMT in LPS-induced ARDS. In conclusion, we demonstrate that PFD is a promising agent to attenuate pulmonary fibrosis following ARDS in the future.


Тема - темы
Hedgehog Proteins , Pulmonary Fibrosis , Pyridones , Respiratory Distress Syndrome , Animals , Hedgehog Proteins/metabolism , Lipopolysaccharides , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/drug therapy , Pyridones/pharmacology , Respiratory Distress Syndrome/chemically induced , Respiratory Distress Syndrome/drug therapy , Signal Transduction
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