The potential indicators for pulmonary fibrosis in survivors of severe COVID-19.
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ABSTRACT:
SUBMITTER: Huang W
PROVIDER: S-EPMC7521372 | biostudies-literature | 2021 Feb
REPOSITORIES: biostudies-literature
Publications
The potential indicators for pulmonary fibrosis in survivors of severe COVID-19.
Huang Wenhui W Wu Qingxia Q Chen Zhuozhi Z Xiong Zhiyuan Z Wang Kun K Tian Jie J Zhang Shuixing S
The Journal of infection 20200928 2
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Project description:Although pulmonary fibrosis can occur in the absence of a clear-cut inciting agent, and without a clinically clear initial acute inflammatory phase, it is more commonly associated with severe lung injury. This may be due to respiratory infections, chronic granulomatous diseases, medications, and connective tissue disorders. Pulmonary fibrosis is associated with permanent pulmonary architectural distortion and irreversible lung dysfunction. Available clinical, radiographic, and autopsy data has indicated that pulmonary fibrosis is central to severe acute respiratory distress syndrome (SARS) and MERS pathology, and current evidence suggests that pulmonary fibrosis could also complicate infection by SARS-CoV-2. The aim of this review is to explore the current literature on the pathogenesis of lung injury in COVID-19 infection. We evaluate the evidence in support of the putative risk factors for the development of lung fibrosis in the disease and propose risk mitigation strategies. We conclude that, from the available literature, the predictors of pulmonary fibrosis in COVID-19 infection are advanced age, illness severity, length of ICU stay and mechanical ventilation, smoking and chronic alcoholism. With no proven effective targeted therapy against pulmonary fibrosis, risk reduction measures should be directed at limiting the severity of the disease and protecting the lungs from other incidental injuries.
| S-EPMC7439160 | 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:The pandemic of coronavirus disease 2019 (COVID‑19), caused by a novel severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), has caused an enormous impact on the global healthcare. SARS-CoV-2 infection primarily targets the respiratory system. Although most individuals testing positive for SARS-CoV-2 present mild or no upper respiratory tract symptoms, patients with severe COVID-19 can rapidly progress to acute respiratory distress syndrome (ARDS). ARDS-related pulmonary fibrosis is a recognized sequelae of COVID-19. Whether post-COVID-19 lung fibrosis is resolvable, persistent, or even becomes progressive as seen in human idiopathic pulmonary fibrosis (IPF) is currently not known and remains a matter of debate. With the emergence of effective vaccines and treatments against COVID-19, it is now important to build our understanding of the long-term sequela of SARS-CoV-2 infection, to identify COVID-19 survivors who are at risk of developing chronic pulmonary fibrosis, and to develop effective anti-fibrotic therapies. The current review aims to summarize the pathogenesis of COVID-19 in the respiratory system and highlights ARDS-related lung fibrosis in severe COVID-19 and the potential mechanisms. It envisions the long-term fibrotic lung complication in COVID-19 survivors, in particular in the aged population. The early identification of patients at risk of developing chronic lung fibrosis and the development of anti-fibrotic therapies are discussed.
| S-EPMC9988550 | biostudies-literature
Project description:Dexamethasone is the standard of care for critically ill patients with COVID-19, but its immunological effects in this setting and the mechanisms by which it decreases mortality are not understood. We performed bulk and single-cell RNA sequencing of the lower respiratory tract and blood, and plasma cytokine profiling to study the effect of dexamethasone on systemic and pulmonary immune cells. We find signatures of decreased viral injury, antigen presentation, and T cell recruitment in patients treated with dexamethasone. We identify compartment- and cell- specific differences in the effect of dexamethasone in patients with severe COVID that are reproducible in publicly available datasets. Our results highlight the importance of studying compartmentalized inflammation in critically ill patients.
2024-05-05 | GSE236030 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-05-05 | GSE237180 | GEO
Project description:Dexamethasone is the standard of care for critically ill patients with COVID-19, but its immunological effects in this setting and the mechanisms by which it decreases mortality are not understood. We performed bulk and single-cell RNA sequencing of the lower respiratory tract and blood, and plasma cytokine profiling to study the effect of dexamethasone on systemic and pulmonary immune cells. We find signatures of decreased viral injury, antigen presentation, and T cell recruitment in patients treated with dexamethasone. We identify compartment- and cell- specific differences in the effect of dexamethasone in patients with severe COVID that are reproducible in publicly available datasets. Our results highlight the importance of studying compartmentalized inflammation in critically ill patients.
2024-05-05 | GSE237109 | 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:In December, 2019, reports emerged from Wuhan, China, of a severe acute respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). By the end of April, 2020, over 3 million people had been confirmed infected, with over 1 million in the USA alone, and over 215 000 deaths. The symptoms associated with COVID-19 are diverse, ranging from mild upper respiratory tract symptoms to severe acute respiratory distress syndrome. The major risk factors for severe COVID-19 are shared with idiopathic pulmonary fibrosis (IPF), namely increasing age, male sex, and comorbidities such as hypertension and diabetes. However, the role of antifibrotic therapy in patients with IPF who contract SARS-CoV-2 infection, and the scientific rationale for their continuation or cessation, is poorly defined. Furthermore, several licensed and potential antifibrotic compounds have been assessed in models of acute lung injury and viral pneumonia. Data from previous coronavirus infections such as severe acute respiratory syndrome and Middle East respiratory syndrome, as well as emerging data from the COVID-19 pandemic, suggest there could be substantial fibrotic consequences following SARS-CoV-2 infection. Antifibrotic therapies that are available or in development could have value in preventing severe COVID-19 in patients with IPF, have the potential to treat severe COVID-19 in patients without IPF, and might have a role in preventing fibrosis after SARS-CoV-2 infection.
| S-EPMC7228727 | biostudies-literature
Project description:BackgroundAir pollution exposure and idiopathic pulmonary fibrosis (IPF) cause a poor prognosis after SARS-CoV-2 infection, but the underlying mechanisms are not well explored. Angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) are the keys to the entry of SARS-CoV-2. We therefore hypothesized that air pollution exposure and IPF may increase the expression of ACE2 and TMPRSS2 in the lung alveolar region. We measured their expression levels in lung tissues of control non-IPF and IPF patients, and used murine animal models to study the deterioration of IPF caused by particulate matter (PM) and the molecular pathways involved in the expression of ACE2 and TMPRSS2.ResultsIn non-IPF patients, cells expressing ACE2 and TMPRSS2 were limited to human alveolar cells. ACE2 and TMPRSS2 were largely upregulated in IPF patients, and were co-expressed by fibroblast specific protein 1 (FSP-1) + lung fibroblasts in human pulmonary fibrotic tissue. In animal models, PM exposure increased the severity of bleomycin-induced pulmonary fibrosis. ACE2 and TMPRSS2 were also expressed in FSP-1+ lung fibroblasts in bleomycin-induced pulmonary fibrosis, and when combined with PM exposure, they were further upregulated. The severity of pulmonary fibrosis and the expression of ACE2 and TMPRSS2 caused by PM exposure were blocked by deletion of KC, a murine homologue of IL-8, or treatment with reparixin, an inhibitor of IL-8 receptors CXCR1/2.ConclusionsThese data suggested that risk of SARS-CoV-2 infection and COVID-19 disease severity increased by air pollution exposure and underlying IPF. It can be mediated through upregulating ACE2 and TMPRSS2 in pulmonary fibroblasts, and prevented by blocking the IL-8/CXCR1/2 pathway.
| S-EPMC7948665 | biostudies-literature
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