Phase 1 trial for treatment of COVID-19 patients with pulmonary fibrosis using hESC-IMRCs.
Ontology highlight
ABSTRACT:
SUBMITTER: Wu J
PROVIDER: S-EPMC7645925 | biostudies-literature | 2020 Dec
REPOSITORIES: biostudies-literature
Publications
Phase 1 trial for treatment of COVID-19 patients with pulmonary fibrosis using hESC-IMRCs.
Wu Jun J Zhou Xing X Tan Yuanqing Y Wang Liu L Li Tianda T Li Zhongwen Z Gao Tingting T Fan Jiaqi J Guo Baojie B Li Wei W Hao Jie J Wang Xianguang X Hu Baoyang B
Cell proliferation 20201026 12
Similar Datasets
Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions worldwide with a high mortality rate due to a lack of definitive treatment. Despite having a wide range of clinical features, acute respiratory distress syndrome (ARDS) has emerged as the primary cause of mortality in these patients. Risk factors and comorbidities like advanced age with limited lung function, pre-existing diabetes, hypertension, cardiovascular diseases, and obesity have increased the risk for severe COVID-19 infection. Rise in inflammatory markers like transforming growth factor β (TGF-β), interleukin-6 (IL-6), and expression of matrix metalloproteinase 1 and 7 (MMP-1, MMP-7), along with collagen deposition at the site of lung injury, results in extensive lung scarring and fibrosis. Anti-fibrotic drugs, such as Pirfenidone and Nintedanib, have emerged as potential treatment options for post-COVID-19 pulmonary fibrosis. A lung transplant might be the only life-saving treatment. Despite the current advances in the management of COVID-19, there is still a considerable knowledge gap in the management of long-term sequelae in such patients, especially concerning pulmonary fibrosis. Follow up on the current clinical trials and research to test the efficacy of various anti-inflammatory drugs is needed to prevent long-term sequelae early mortality in these patients.
| S-EPMC8974316 | biostudies-literature
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: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:This phase 2, randomised, double-blind, placebo-controlled trial evaluated the efficacy and safety of lebrikizumab, an interleukin (IL)-13 monoclonal antibody, alone or with background pirfenidone therapy, in patients with idiopathic pulmonary fibrosis (IPF).Patients with IPF aged ≥40 years with forced vital capacity (FVC) of 40%-100% predicted and diffusing capacity for carbon monoxide of 25%-90% predicted and who were treatment-naïve (cohort A) or receiving pirfenidone (2403 mg·day-1; cohort B) were randomised 1:1 to receive lebrikizumab 250 mg or placebo subcutaneously every 4 weeks. The primary endpoint was annualised rate of FVC % predicted decline over 52 weeks.In cohort A, 154 patients were randomised to receive lebrikizumab (n=78) or placebo (n=76). In cohort B, 351 patients receiving pirfenidone were randomised to receive lebrikizumab (n=174) or placebo (n=177). Baseline demographics were balanced across treatment arms in both cohorts. The primary endpoint (annualised rate of FVC % predicted decline) was not met in cohort A (lebrikizumab versus placebo, -5.2% versus -6.2%; p=0.456) or cohort B (lebrikizumab versus placebo, -5.5% versus -6.0%; p=0.557). In cohort B, a non-statistically significant imbalance in mortality favouring combination therapy was observed (hazard ratio 0.42 (95% CI 0.17-1.04)). Pharmacodynamic biomarkers indicated lebrikizumab activity. The safety profile was consistent with that in previous studies of lebrikizumab and pirfenidone as monotherapies.Lebrikizumab alone or with pirfenidone was not associated with reduced FVC % predicted decline over 52 weeks despite evidence of pharmacodynamic activity. Lebrikizumab was well tolerated with a favourable safety profile. These findings suggest that blocking IL-13 may not be sufficient to achieve a lung function benefit in patients with IPF.
| S-EPMC7859504 | 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
Project description:How to cite this article: B, Khanna P, Sarkar S. Pulmonary Fibrosis in COVID-19 Recovered Patients: Problem and Potential Management. Indian J Crit Care Med 2021;25(2):242-244.
| S-EPMC7922461 | biostudies-literature
Project description:PBI-4050 is a novel orally active small-molecule compound with demonstrated anti-fibrotic activity in several models of fibrosis, including lung fibrosis. We present results from our first clinical study of PBI-4050 in patients with idiopathic pulmonary fibrosis (IPF).This 12-week open-label study explored the safety, efficacy and pharmacokinetics of daily oral doses of 800 mg PBI-4050 alone and in combination with nintedanib or pirfenidone in patients with predominantly mild or moderate IPF. Nine patients received PBI-4050 alone, 16 patients received PBI-4050 with nintedanib and 16 patients received PBI-4050 with pirfenidone.PBI-4050 alone or in combination with nintedanib or pirfenidone was well tolerated. Pharmacokinetic profiles for PBI-4050 were similar in the PBI-4050 alone and PBI-4050+nintedanib groups but reduced in the PBI-4050+pirfenidone group, suggesting a drug-drug interaction. There were no significant changes in forced vital capacity (FVC), either in % predicted or mL, from baseline to week 12 for PBI-4050 alone or PBI-4050+nintedanib. In contrast, a statistically significant reduction (p<0.024) in FVC % pred was seen for PBI-4050+pirfenidone after 12 weeks.There were no safety concerns with PBI-4050 alone or in combination with nintedanib or pirfenidone in IPF patients. The stability of FVC between baseline and week 12 looked encouraging for PBI-4050 alone and in combination with nintedanib.
| S-EPMC6422836 | biostudies-literature
Project description:This review brings together the current knowledge regarding the risk factors and the clinical, radiologic, and histological features of both post-COVID-19 pulmonary fibrosis (PCPF) and idiopathic pulmonary fibrosis (IPF), describing the similarities and the disparities between these two diseases, using numerous databases to identify relevant articles published in English through October 2022. This review would help clinicians, pathologists, and researchers make an accurate diagnosis, which can help identify the group of patients selected for anti-fibrotic therapies and future therapeutic perspectives.
| S-EPMC10296314 | biostudies-literature
Project description:BackgroundPost-COVID-19 pulmonary fibrosis is a significant long-term respiratory morbidity affecting patients' respiratory health. This exploratory study aims to investigate the incidence, clinical characteristics, and acute-phase risk factors for pulmonary fibrosis in COVID-19 patients. Additionally, it evaluates pulmonary function and chest CT outcomes to provide clinical evidence for the early identification of high-risk patients and the prevention of post-COVID-19 pulmonary fibrosis.MethodsWe retrospectively analyzed 595 patients hospitalized for COVID-19 from January 2022 to July 2023. Patients were divided into fibrosis and nonfibrosis groups on the basis of imaging changes. Baseline data, including demographics, disease severity, laboratory indicators, and chest imaging characteristics, were collected. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for pulmonary fibrosis. Pulmonary function and chest CT follow-ups were conducted for the fibrosis group. The data were processed via SPSS 26.0, with P < 0.05 considered statistically significant.ResultsThe incidence of pulmonary fibrosis was 4.37%, with 2.08% in moderate cases and 8.22% in severe cases. Significant differences were found between the fibrosis and nonfibrosis groups in sex; disease severity; NLR; ALB and LDH levels; and percentages of lung reticular lesions, consolidations, and GGOs (P < 0.05). Multivariate analysis revealed LDH (OR = 1.004, 95% CI 1.000-1.007, P = 0.035), ALB (OR = 0.871, 95% CI 0.778-0.974, P = 0.015), lung reticular lesion volume (OR = 1.116, 95% CI 1.040-1.199, P = 0.002), and lung consolidation volume (OR = 1.131, 95% CI 1.012-1.264, P = 0.030) as independent risk factors. The follow-up results revealed significant improvements in pulmonary function, specifically in the FVC%, FEV1%, and DLCO%, but not in the FEV1/FVC. Quantitative chest CT analysis revealed significant differences in lung reticular lesions, consolidation, and GGO volumes but no significant difference in honeycomb volume.ConclusionsThe incidence of pulmonary fibrosis post-COVID-19 increases with disease severity. LDH, ALB, lung reticular lesions, and consolidation volume are independent risk factors for patients with fibrosis.
| S-EPMC11657883 | biostudies-literature
Project description:In December 2019, a novel coronavirus, SARS-CoV-2, appeared, causing a wide range of symptoms, mainly respiratory infection. In March 2020, the World Health Organization (WHO) declared Coronavirus Disease 2019 (COVID-19) a pandemic, therefore the efforts of scientists around the world are focused on finding the right treatment and vaccine for the novel disease. COVID-19 has spread rapidly over several months, affecting patients across all age groups and geographic areas. The disease has a diverse course; patients may range from asymptomatic to those with respiratory failure, complicated by acute respiratory distress syndrome (ARDS). One possible complication of pulmonary involvement in COVID-19 is pulmonary fibrosis, which leads to chronic breathing difficulties, long-term disability and affects patients' quality of life. There are no specific mechanisms that lead to this phenomenon in COVID-19, but some information arises from previous severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS) epidemics. The aim of this narrative review is to present the possible causes and pathophysiology of pulmonary fibrosis associated with COVID-19 based on the mechanisms of the immune response, to suggest possible ways of prevention and treatment.
| S-EPMC7356800 | biostudies-literature