Lung fibrosis: an undervalued finding in COVID-19 pathological series.
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ABSTRACT:
SUBMITTER: Grillo F
PROVIDER: S-EPMC7386839 | biostudies-literature | 2021 Apr
REPOSITORIES: biostudies-literature
Publications
Lung fibrosis: an undervalued finding in COVID-19 pathological series.
Grillo Federica F Barisione Emanuela E Ball Lorenzo L Mastracci Luca L Fiocca Roberto R
The Lancet. Infectious diseases 20200728 4
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Project description:Fibrotic lung changes are well-known complications of SARS, MERS, and ARDS from other causes and are anticipated in recovered COVID patients. However, there is limited data so far showing a temporal relationship between lung changes on imaging in the acute phase and follow-up imaging after recovery from the infection. We present 12 patients who demonstrate the development of interstitial lung changes and pulmonary fibrosis in the same distribution and pattern as the acute phase findings, up to 6 months after the acute infection, demonstrating a direct relationship between these changes and COVID-19 pneumonia.
| S-EPMC8005381 | biostudies-literature
Project description:At the end of 2019, a highly contagious infection began its ominous conquest of the world. It was soon discovered that the disease was caused by a novel coronavirus designated as SARS-CoV-2, and the disease was thus abbreviated to COVID-19 (COVID). The global medical community has directed its efforts not only to find effective therapies against the deadly pathogen but also to combat the concomitant complications. Two of the most common respiratory manifestations of COVID are a significant reduction in the diffusing capacity of the lungs (DLCO) and the associated pulmonary interstitial damage. One year after moderate COVID, the incidence rate of impaired DLCO and persistent lung damage still exceeds 30%, and one-third of the patients have severe DLCO impairment and fibrotic lung damage. The persistent respiratory complications may cause substantial population morbidity, long-term disability, and even death due to the lung fibrosis progression. The incidence of COVID-induced pulmonary fibrosis caused by COVID can be estimated based on a 15-year observational study of lung pathology after SARS. Most SARS patients with fibrotic lung damage recovered within the first year and then remained healthy; however, in 20% of the cases, significant fibrosis progression was found in 5-10 years. Based on these data, the incidence rate of post-COVID lung fibrosis can be estimated at 2-6% after moderate illness. What is worse, there are reasons to believe that fibrosis may become one of the major long-term complications of COVID, even in asymptomatic individuals. Currently, despite the best efforts of the global medical community, there are no treatments for COVID-induced pulmonary fibrosis. In this review, we analyze the latest data from ongoing clinical trials aimed at treating post-COVID lung fibrosis and analyze the rationale for the current drug candidates. We discuss the use of antifibrotic therapy for idiopathic pulmonary fibrosis, the IN01 vaccine, glucocorticosteroids as well as the stromal vascular fraction for the treatment and rehabilitation of patients with COVID-associated pulmonary damage.
| S-EPMC8398080 | biostudies-literature
Project description:Severe COVID-19 may progress into acute respiratory distress syndrome (ARDS) with high mortality risk. Its exact pathological mechanism, therapeutic obstacles and the clinical sequelae are critical and unresolved issues. Here, we reported a representative COVID-19 induced ARDS case experienced initially stable, then suddenly deteriorating up to final respiratory failure courses, until his death despite of lung transplantation. His lung pathology showed necrosis of parenchymal tissues, extensive immune cell infiltration and lung fibrosis. Single-cell RNA sequencing revealed various immune cell populations were largely expanded in his lung, and manifested inflammatory/activated functions. We also showed that cell-crosstalk between lung macrophages and fibroblasts promoted pulmonary fibrosis through IL-1B and TGF-Β signaling pathways. Although SARS-CoV-2 RNA remained undetectable in his respiratory tract specimens including BALF at the later stage of his disease, the presence of SARS-CoV-2 was definitely confirmed in his lung tissues. Thus, this case indicates the pathological mechanism of severe COVID-19 includes pulmonary SARS-CoV-2 persistence, deranged inflammation and the extensive lung fibrosis which set the barriers for effective treatments and indicate potential health complications for severe COVID-19 patients.
2020-12-01 | GSE149878 | GEO
Project description:AimCoronavirus disease (COVID-19) is characterized by pneumonia with secondary damage to multiple organs including the liver. Liver injury (elevated alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) often correlates with disease severity in COVID-19 patients. The aim of this study is to identify pathological microthrombi in COVID-19 patient livers by correlating their morphology with liver injury, and examine hyperfibrinogenemia and von Willebrand factor (vWF) as mechanisms of their formation.MethodsForty-three post-mortem liver biopsy samples from COVID-19 patients were obtained from Papa Giovanni XXIII Hospital in Bergamo, Italy. Three morphological features of microthrombosis (sinusoidal erythrocyte aggregation [SEA], platelet microthrombi [PMT], and fibrous thrombi) were evaluated.ResultsWe found liver sinusoidal microthrombosis in 23 COVID-19 patients (53%) was associated with a higher serum ALT and AST level compared to those without (ALT: 10-fold, p = 0.04; AST: 11-fold, p = 0.08). Of 43 livers, PMT and SEA were observed in 14 (33%) and 19 (44%) cases, respectively. Fibrous thrombi were not observed. Platelet microthrombi were associated with increased ALT (p < 0.01), whereas SEA was not (p = 0.73). In COVID-19 livers, strong vWF staining in liver sinusoidal endothelial cells was associated with significantly increased platelet adhesion (1.7-fold, p = 0.0016), compared to those with weak sinusoidal vWF (2-fold, p < 0.0001). Sinusoidal erythrocyte aggregation in 19 (83%) liver samples was mainly seen in zone 2. Livers with SEA had significantly higher fibrinogen (1.6-fold, p = 0.031) compared to those without SEA in COVID-19 patients.ConclusionsLiver PMT is a pathologically important thrombosis associated with liver injury in COVID-19, while SEA is a unique morphological feature of COVID-19 patient livers. Sinusoidal vWF and hyperfibrinogenemia could contribute to PMT and SEA formation.
| S-EPMC8444906 | biostudies-literature
Project description:BackgroundCoronavirus Disease 2019 (COVID-19) can lead to the development of acute respiratory distress syndrome (ARDS). In some patients with non-resolvable (NR) COVID-19, lung injury can progress rapidly to the point that lung transplantation is the only viable option for survival. This fatal progression of lung injury involves a rapid fibroproliferative response and takes on average 15 weeks from initial symptom presentation. Little is known about the mechanisms that lead to this fulminant lung fibrosis (FLF) in NR-COVID-19.MethodsUsing a pre-designed unbiased PCR array for fibrotic markers, we analyzed the fibrotic signature in a subset of NR-COVID-19 lungs. We compared the expression profile against control lungs (donor lungs discarded for transplantation), and explanted tissue from patients with idiopathic pulmonary fibrosis (IPF). Subsequently, RT-qPCR, Western blots and immunohistochemistry were conducted to validate and localize selected pro-fibrotic targets. A total of 23 NR-COVID-19 lungs were used for RT-qPCR validation.FindingsWe revealed a unique fibrotic gene signature in NR-COVID-19 that is dominated by a hyper-expression of pro-fibrotic genes, including collagens and periostin. Our results also show a significantly increased expression of Collagen Triple Helix Repeat Containing 1(CTHRC1) which co-localized in areas rich in alpha smooth muscle expression, denoting myofibroblasts. We also show a significant increase in cytokeratin (KRT) 5 and 8 expressing cells adjacent to fibroblastic areas and in areas of apparent epithelial bronchiolization.InterpretationOur studies may provide insights into potential cellular mechanisms that lead to a fulminant presentation of lung fibrosis in NR-COVID-19.FundingNational Institute of Health (NIH) Grants R01HL154720, R01DK122796, R01DK109574, R01HL133900, and Department of Defense (DoD) Grant W81XWH2110032 to H.K.E. NIH Grants: R01HL138510 and R01HL157100, DoD Grant W81XWH-19-1-0007, and American Heart Association Grant: 18IPA34170220 to H.K.-Q. American Heart Association: 19CDA34660279, American Lung Association: CA-622265, Parker B. Francis Fellowship, 1UL1TR003167-01 and The Center for Clinical and Translational Sciences, McGovern Medical School to X.Y.
| S-EPMC9667270 | biostudies-literature
Project description: Not available
| S-EPMC6890405 | biostudies-literature
Project description:We profiled 116,314 cells using snRNA-seq of 20 frozen lungs obtained from 19 COVID-19 decedents and seven control patients with short postmortem interval (PMI) autopsies. The COVID-19 cohort comprises seven female and 12 male decedents, including 13 patients of Hispanic ethnicity, with an age range from 58 to >89 years who had acquired SARS-CoV-2 infection and succumbed to the disease. The average time from symptom onset to death was 27.5 days (range, 4–63 days). After rapid autopsy with a median PMI of 4 hours (range 2–9 hours) collected tissues were either flash-frozen or frozen following OCT (optimal cutting temperature) embedment and subjected to snRNA-seq using a droplet-based platform (10x Genomics). All included patients had underlying hypertensive disorder and frequently one or more additional co-morbidities associated with increased risk for severe COVID-19.
2021-04-29 | GSE171524 | GEO
Project description:Here we report single-cell RNA-sequencing generated from one COVID-19 lung removed at the time of organ transplant.
2020-12-29 | GSE163919 | GEO
Project description:BackgroundCardiomyopathy is a leading cause of sudden out-of-hospital death after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) vaccination. Such unexpected COVID-19-related cardiomyopathies are challenging to diagnose as specific pathological findings are not always identified.Case summaryWe reported the autopsy findings of two cases of sudden death due to COVID-19-related cardiomyopathies. In one case, death occurred after SARS-CoV-2 infection, while in the other, after COVID-19 vaccination. We found common pathological findings in both hearts: decreased staining intensity with special stains, loss of rhabdomeres, and multivacuolation in cardiomyocytes without inflammatory cell infiltration. The remaining organs showed no findings that could have contributed to the deaths.ConclusionIn cases of sudden death after SARS-CoV-2 infection or COVID-19 vaccination, the decreased staining intensity with special stains may aid the diagnosis of sudden death due to COVID-19-related cardiomyopathy, even when H&E staining shows few findings.
| S-EPMC10568345 | biostudies-literature
Project description:BackgroundPulmonary involvement in COVID-19 is characterized pathologically by diffuse alveolar damage (DAD) and thrombosis, leading to the clinical picture of Acute Respiratory Distress Syndrome. The direct action of SARS-CoV-2 in lung cells and the dysregulated immuno-coagulative pathways activated in ARDS influence pulmonary involvement in severe COVID, that might be modulated by disease duration and individual factors. In this study we assessed the proportions of different lung pathology patterns in severe COVID-19 patients along the disease evolution and individual characteristics.MethodsWe analysed lung tissue from 41 COVID-19 patients that died in the period March-June 2020 and were submitted to a minimally invasive autopsy. Eight pulmonary regions were sampled. Pulmonary pathologists analysed the H&E stained slides, performing semiquantitative scores on the following parameters: exudative, intermediate or advanced DAD, bronchopneumonia, alveolar haemorrhage, infarct (%), arteriolar (number) or capillary thrombosis (yes/no). Histopathological data were correlated with demographic-clinical variables and periods of symptoms-hospital stay.ResultsPatient´s age varied from 22 to 88 years (18f/23 m), with hospital admission varying from 0 to 40 days. All patients had different proportions of DAD in their biopsies. Ninety percent of the patients presented pulmonary microthrombosis. The proportion of exudative DAD was higher in the period 0-8 days of hospital admission till death, whereas advanced DAD was higher after 17 days of hospital admission. In the group of patients that died within eight days of hospital admission, elderly patients had less proportion of the exudative pattern and increased proportions of the intermediate patterns. Obese patients had lower proportion of advanced DAD pattern in their biopsies, and lower than patients with overweight. Clustering analysis showed that patterns of vascular lesions (microthrombosis, infarction) clustered together, but not the other patterns. The vascular pattern was not influenced by demographic or clinical parameters, including time of disease progression.ConclusionPatients with severe COVID-19 present different proportions of DAD patterns over time, with advanced DAD being more prevalent after 17 days, which seems to be influenced by age and weight. Vascular involvement is present in a large proportion of patients, occurs early in disease progression, and does not change over time.
| S-EPMC7844838 | biostudies-literature