Pulmonary fibrosis from molecular mechanisms to therapeutic interventions: lessons from post-COVID-19 patients
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ABSTRACT:
SUBMITTER: Giacomelli C
PROVIDER: S-EPMC8546906 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundCoronavirus disease 2019 (COVID-19) patients can develop pulmonary fibrosis (PF), which is associated with impaired outcome. We assessed specific leukocytic transcriptome profiles associated with PF and the influence of early dexamethasone (DEXA) treatment on the clinical course of PF in critically ill COVID-19 patients.MethodsWe performed a pre-post design study in 191 COVID-19 patients admitted to the Intensive Care Unit (ICU) spanning two treatment cohorts: the pre-DEXA- (n = 67) and the DEXA-cohort (n = 124). PF was identified based on radiological findings, worsening of ventilatory parameters and elevated circulating PIIINP levels. Longitudinal transcriptome profiles of 52 pre-DEXA patients were determined using RNA sequencing. Effects of prednisone treatment on clinical fibrosis parameters and outcomes were analyzed between PF- and no-PF-patients within both cohorts.ResultsTranscriptome analyses revealed upregulation of inflammatory, coagulation and neutrophil extracellular trap-related pathways in PF-patients compared to no-PF patients. Key genes involved included PADI4, PDE4D, MMP8, CRISP3, and BCL2L15. Enrichment of several identified pathways was associated with impaired survival in a external cohort of patients with idiopathic pulmonary fibrosis. Following prednisone treatment, PF-related profiles reverted towards those observed in the no-PF-group. Likewise, PIIINP levels decreased significantly following prednisone treatment. PF incidence was 28% and 25% in the pre-DEXA- and DEXA-cohort, respectively (p = 0.61). ICU length-of-stay (pre-DEXA: 42 [29-49] vs. 18 [13-27] days, p < 0.001; DEXA: 42 [28-57] vs. 13 [7-24] days, p < 0.001) and mortality (pre-DEXA: 47% vs. 15%, p = 0.009; DEXA: 61% vs. 19%, p < 0.001) were higher in the PF-groups compared to the no-PF-groups within both cohorts. Early dexamethasone therapy did not influence these outcomes.ConclusionsICU patients with COVID-19 who develop PF exhibit upregulated coagulation, inflammation, and neutrophil extracellular trap-related pathways as well as prolonged ICU length-of-stay and mortality. This study indicates that early dexamethasone treatment neither influences the incidence or clinical course of PF, nor clinical outcomes.
| S-EPMC10413531 | biostudies-literature
Project description:Introduction; Pulmonary fibrosis is a frequently reported COVID-19 sequela in which the exact prevalence and risk factors are yet to be established. This meta-analysis aims to investigate the prevalence of post-COVID-19 pulmonary fibrosis (PCPF) and the potential risk factors. Methods; CINAHL, PubMed/MEDLINE, Cochrane Library, Web of Science, and EMBASE databases were searched to identify English language studies published up to December 3, 2021. Results; The systematic search initially revealed a total of 618 articles - of which only 13 studies reporting 2018 patients were included in this study. Among the patients, 1047 (51.9%) were male and 971 (48.1%) were female. The mean age was 54.5 years (15-94). The prevalence of PCPF was 44.9%. The mean age was 59 years in fibrotic patients and 48.5 years in non-fibrotic patients. Chronic obstructive pulmonary disease was the only comorbidity associated with PCPF. Fibrotic patients more commonly suffered from persistent symptoms of dyspnea, cough, chest pain, fatigue, and myalgia (p-value < 0.05). Factors related to COVID-19 severity that were associated with PCPF development included computed tomography score of ≥18, ICU admission, invasive/non-invasive mechanical ventilation, longer hospitalization period, and steroid, antibiotic and immunoglobulin treatments (p-value < 0.05). Parenchymal bands (284/341), ground-glass opacities (552/753), interlobular septal thickening (220/381), and consolidation (197/319) were the most common lung abnormalities found in fibrotic patients. Conclusion, About 44.9% of COVID-19 survivors appear to have developed pulmonary fibrosis. Factors related to COVID-19 severity were significantly associated with PCPF development.
| S-EPMC8983072 | biostudies-literature
Project description:BackgroundPulmonary fibrosis is one of the sequelae of the COVID-19, which seriously affects the quality of life of survivors. Currently, there are no optimal evidence based guidelines targeting this population.Case presentationWe report a 66-year-old female patient without underlying comorbidities admitted to Changsha Public Health Center because of COVID-19. During hospitalization, she developed co-bacterial infection and acute respiratory distress syndrome, and received broad-spectrum antibacterial therapy, invasive mechanical ventilation and extracorporeal membrane oxygenation. After the acute phase, she developed post-COVID-19 pulmonary fibrosis subsequently treated with pirfenidone. Over 96 weeks after pirfenidone treatment, her modified Medical Research Council Dyspnea level improved to 2 from 4 at discharge. Her 6 minutes walk test distance, total lung capacity, and diffusion capacity for carbon monoxide all increased. Chest CT performed on 2 years after illness onset showed regressing fibrosis. The Hospital Anxiety and Depression Scale, Athens Insomnia Scale, and 36-Item Short Form Health Survey questionnaire all improved.ConclusionPost-COVID-19 pulmonary fibrosis is a challenging consequence of COVID-19, and our case suggests that pirfenidone may be an effective treatment option.
| S-EPMC9207265 | biostudies-literature
Project description:RationalePulmonary fibrosis is an infamous sequela of coronavirus disease 2019 (COVID-19) pneumonia leading to long-lasting respiratory problems and activity limitations. Pulmonary rehabilitation is beneficial to improve the symptoms of lung fibrosis. We experienced a post-COVID-19 pulmonary fibrosis patient who received a structured exercise-based pulmonary rehabilitation program.Patient concernsThis article presents a case of successful pulmonary rehabilitation of a patient with post-COVID-19 pulmonary fibrosis. The patient could not cut off the oxygen supplement even after a successful recovery from COVID-19.DiagnosisDiagnosis of COVID-19 was based on the reverse transcription-polymerase chain reaction (RT-PCR). Pulmonary fibrosis was diagnosed by patient's complaint, clinical appearance, and computed tomography (CT) on chest.InterventionThe patient underwent ten sessions of exercise-based rehabilitation program according to Consensus Document on Pulmonary Rehabilitation in Korea, 2015.OutcomeOn the 8th day, he could cut off the oxygen supplementation and complete the one-hour exercise without oxygen. He was discharged after completing the 10-session program without any activity limitations.LessonsExercise-based pulmonary rehabilitation will help the post-COVID-19 pulmonary fibrosis patients. This case suggested the importance of pulmonary rehabilitation program to the post-COVID-19 pulmonary fibrosis patient.
| S-EPMC8615350 | biostudies-literature
Project description:Pulmonary fibrosis (PF) is a disease-refractive lung condition with an increased rate of mortality. The potential factors causing PF include viral infections, radiation exposure, and toxic airborne chemicals. Idiopathic PF (IPF) is related to pneumonia affecting the elderly and is characterized by recurring scar formation in the lungs. An impaired wound healing process, defined by the dysregulated aggregation of extracellular matrix components, triggers fibrotic scar formation in the lungs. The potential pathogenesis includes oxidative stress, altered cell signaling, inflammation, etc. Nintedanib and pirfenidone have been approved with a conditional endorsement for the management of IPF. In addition, natural product-based treatment strategies have shown promising results in treating PF. In this study, we reviewed the recently published literature and discussed the potential uses of natural products, classified into three types-isolated active compounds, crude extracts of plants, and traditional medicine, consisting of mixtures of different plant products-in treating PF. These natural products are promising in the treatment of PF via inhibiting inflammation, oxidative stress, and endothelial mesenchymal transition, as well as affecting TGF-β-mediated cell signaling, etc. Based on the current review, we have revealed the signaling mechanisms of PF pathogenesis and the potential opportunities offered by natural product-based medicine in treating PF.
| S-EPMC8911636 | biostudies-literature
Project description:Vascular calcification (VC) is recognized as a pathological vascular disorder associated with various diseases, such as atherosclerosis, hypertension, aortic valve stenosis, coronary artery disease, diabetes mellitus, as well as chronic kidney disease. Therefore, it is a life-threatening state for human health. There were several studies targeting mechanisms of VC that revealed the importance of vascular smooth muscle cells transdifferentiating, phosphorous and calcium milieu, as well as matrix vesicles on the progress of VC. However, the underlying molecular mechanisms of VC need to be elucidated. Though there is no acknowledged effective therapeutic strategy to reverse or cure VC clinically, recent evidence has proved that VC is not a passive irreversible comorbidity but an active process regulated by many factors. Some available approaches targeting the underlying molecular mechanism provide promising prospects for the therapy of VC. This review aims to summarize the novel findings on molecular mechanisms and therapeutic interventions of VC, including the role of inflammatory responses, endoplasmic reticulum stress, mitochondrial dysfunction, iron homeostasis, metabolic imbalance, and some related signaling pathways on VC progression. We also conclude some recent studies on controversial interventions in the clinical practice of VC, such as calcium channel blockers, renin-angiotensin system inhibitions, statins, bisphosphonates, denosumab, vitamins, and ion conditioning agents.
| S-EPMC9811665 | biostudies-literature
Project description:The COVID-19 pandemic has triggered intensive research and development of drugs and vaccines against SARS-CoV-2 during the last two years. The major success was especially observed with development of vaccines based on viral vectors, nucleic acids and whole viral particles, which have received emergent authorization leading to global mass vaccinations. Although the vaccine programs have made a big impact on COVID-19 spread and severity, emerging novel variants have raised serious concerns about vaccine efficacy. Due to the urgent demand, drug development had originally to rely on repurposing of antiviral drugs developed against other infectious diseases. For both drug and vaccine development the focus has been mainly on SARS-CoV-2 surface proteins and host cell receptors involved in viral attachment and entry. In this review, we expand the spectrum of SARS-CoV-2 targets by investigating the COVID-19 signalome. In addition to the SARS-CoV-2 Spike protein, the envelope, membrane, and nucleoprotein targets have been subjected to research. Moreover, viral proteases have presented the possibility to develop different strategies for the inhibition of SARS-CoV-2 replication and spread. Several signaling pathways involving the renin-angiotensin system, angiotensin-converting enzymes, immune pathways, hypoxia, and calcium signaling have provided attractive alternative targets for more efficient drug development.
| S-EPMC9744501 | biostudies-literature
Project description:The diverse bacterial populations within the symbiotic microbiota play a pivotal role in both health and disease. Microbiota modulates critical aspects of tumor biology including cell proliferation, invasion, and metastasis. This regulation occurs through mechanisms like enhancing genomic damage, hindering gene repair, activating aberrant cell signaling pathways, influencing tumor cell metabolism, promoting revascularization, and remodeling the tumor immune microenvironment. These microbiota-mediated effects significantly impact overall survival and the recurrence of tumors after surgery by affecting the efficacy of chemoradiotherapy. Moreover, leveraging the microbiota for the development of biovectors, probiotics, prebiotics, and synbiotics, in addition to utilizing antibiotics, dietary adjustments, defensins, oncolytic virotherapy, and fecal microbiota transplantation, offers promising alternatives for cancer treatment. Nonetheless, due to the extensive and diverse nature of the microbiota, along with tumor heterogeneity, the molecular mechanisms underlying the role of microbiota in cancer remain a subject of intense debate. In this context, we refocus on various cancers, delving into the molecular signaling pathways associated with the microbiota and its derivatives, the reshaping of the tumor microenvironmental matrix, and the impact on tolerance to tumor treatments such as chemotherapy and radiotherapy. This exploration aims to shed light on novel perspectives and potential applications in the field.
| S-EPMC10626288 | biostudies-literature
Project description:Spinal cord injury (SCI) remains a severe condition with an extremely high disability rate. The challenges of SCI repair include its complex pathological mechanisms and the difficulties of neural regeneration in the central nervous system. In the past few decades, researchers have attempted to completely elucidate the pathological mechanism of SCI and identify effective strategies to promote axon regeneration and neural circuit remodeling, but the results have not been ideal. Recently, new pathological mechanisms of SCI, especially the interactions between immune and neural cell responses, have been revealed by single-cell sequencing and spatial transcriptome analysis. With the development of bioactive materials and stem cells, more attention has been focused on forming intermediate neural networks to promote neural regeneration and neural circuit reconstruction than on promoting axonal regeneration in the corticospinal tract. Furthermore, technologies to control physical parameters such as electricity, magnetism and ultrasound have been constantly innovated and applied in neural cell fate regulation. Among these advanced novel strategies and technologies, stem cell therapy, biomaterial transplantation, and electromagnetic stimulation have entered into the stage of clinical trials, and some of them have already been applied in clinical treatment. In this review, we outline the overall epidemiology and pathophysiology of SCI, expound on the latest research progress related to neural regeneration and circuit reconstruction in detail, and propose future directions for SCI repair and clinical applications.
| S-EPMC10291001 | biostudies-literature
Project description:Aims: SARS-CoV-2 infection causes COVID-19, which in severe cases evokes life-threatening acute respiratory distress syndrome (ARDS). Transcriptome signatures and the functional relevance of non-vascular cell types (e.g. immune and epithelial cells) in COVID-19 are becoming increasingly evident. However, despite its known contribution to vascular inflammation, recruitment/invasion of immune cells, vascular leakage and perturbed hemostasis in the lungs of severe COVID-19 patients, an in-depth interrogation of the endothelial cell (EC) compartment in lethal COVID-19 is lacking. Moreover, progressive fibrotic lung disease represents one of the complications of COVID-19 pneumonia and ARDS. Analogous features between idiopathic pulmonary fibrosis (IPF) and COVID-19 suggest partial similarities in their pathophysiology, yet, a head-to-head comparison of pulmonary cell transcriptomes between both conditions has not been implemented to date.
2022-08-28 | GSE159585 | GEO