scholarly journals Histopathological features of multiorgan percutaneous tissue core biopsy in patients with COVID-19

2020 ◽  
pp. jclinpath-2020-206623
Author(s):  
Xin-xin Wang ◽  
Chen Shao ◽  
Xiao-jie Huang ◽  
Lin Sun ◽  
Ling-jia Meng ◽  
...  
Keyword(s):  
Cardiac Tissue ◽  
Diffuse Alveolar Damage ◽  
In Situ Hybridisation ◽  
Underlying Disease ◽  
Hepatic Tissue ◽  
Lymphoid Tissues ◽  
Pulmonary Tissue ◽  
Multiple Organs ◽  
Bronchiolar Epithelium ◽  
Immunohistochemistry Stain

AimsThe global outbreak of COVID-19 has resulted in an increased mortality. However, whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect multiple organs is still unclear. In this study, postmortem percutaneous biopsies of multiple organs from deceased patients were performed to understand the histopathological changes caused by COVID-19.MethodsBiopsy specimens of pulmonary, cardiac, hepatic and lymphoid tissues were obtained from three patients, who died due to COVID-19 pneumonia. H&E stain, Masson trichrome stain, immunohistochemistry stain and in-situ hybridisation were used.ResultsPulmonary damages caused by SARS-CoV-2 infection was diffuse alveolar damage (DAD). In the early phase, the histological findings were mainly those of exudative features of DAD. The later phase was characterised by organisation of DAD combined with bacterial pneumonia. No serious damage was found in the bronchiolar epithelium and submucosal glands. The hepatic tissue revealed features of ischaemic necrosis, but findings suggestive of mild lobular hepatitis were also observed. The lymphoid tissue revealed features of non-specific acute lymphadenitis. The cardiac tissue revealed changes of underlying disease. SARS-CoV-2 RNAs were not detected in hepatocytes, cholangiocytes and lymphocytes of lymph nodes.ConclusionsCOVID-19 predominantly involves the pulmonary tissue, causes DAD and aggravates the cardiovascular disease. However, other extrapulmonary tissues did not reveal any virus-specific findings, but were affected by multiple factors. The findings in this report caution the pathologists that they should not mistakenly attribute all the histological features to CoV infection. Moreover, the clinicians should pay attention to the potentially injurious and correctable causes.

scholarly journals Pathological Study of the 2019 Novel Coronavirus Disease (COVID-19) through Post-Mortem Core Biopsies

2020 ◽  
Author(s):  
Sufang Tian ◽  
Yong Xiong ◽  
Huan Liu ◽  
Li Niu ◽  
Jianchun Guo ◽  
...  
Keyword(s):  
Diffuse Alveolar Damage ◽  
Disease Onset ◽  
Underlying Disease ◽  
Significant Rise ◽  
Lymphocytic Leukemia ◽  
Alveolar Epithelial Cells ◽  
Post Mortem ◽  
Alveolar Epithelial ◽  
Cell Counts ◽  
Novel Coronavirus

Data on pathologic changes of the 2019 novel coronavirus disease (COVID-19) are scarce. To gain knowledge about the pathology that may contribute to disease progression and fatality, we performed post-mortem needle core biopsies of lung, liver, and heart in four patients who died of COVID-19 pneumonia. The patients’ ages ranged from 59 to 81, including 3 males and 1 female. Each patient had at least one underlying disease, including immunocompromised status (chronic lymphocytic leukemia and renal transplantation) or other conditions (cirrhosis, hypertension, and diabetes). Time from disease onset to death ranged from 15 to 52 days. All patients had elevated white blood cell counts, with significant rise toward the end, and all had lymphocytopenia except for the patient with leukemia. Histologically, the main findings are in the lungs, including injury to the alveolar epithelial cells, hyaline membrane formation, and hyperplasia of type II pneumocytes, all components of diffuse alveolar damage. Consolidation by fibroblastic proliferation with extracellular matrix and fibrin forming clusters in airspaces is evident. In one patient, the consolidation consists of abundant intra-alveolar neutrophilic infiltration, consistent with superimposed bacterial bronchopneumonia. The liver exhibits mild lobular infiltration by small lymphocytes, and centrilobular sinusoidal dilation. Patchy necrosis is also seen. The heart shows only focal mild fibrosis and mild myocardial hypertrophy, changes likely related to the underlying conditions. In conclusion, the post-mortem examinations show advanced diffuse alveolar damage, as well as superimposed bacterial pneumonia in some patients. Changes in the liver and heart are likely secondary or related to the underlying diseases.

scholarly journals Detection of enterovirus protein and RNA in multiple tissues from nPOD organ donors with type 1 diabetes

2018 ◽  
Author(s):  
Maarit Oikarinen ◽  
Jutta E Laiho ◽  
Sami Oikarinen ◽  
Sarah J Richardson ◽  
Irina Kusmartseva ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Lymph Nodes ◽  
Pancreatic Islets ◽  
Lymphoid Tissues ◽  
Small Intestinal Mucosa ◽  
Organ Donors ◽  
Tissue Samples ◽  
Multiple Organs ◽  
Pancreatic Lymph Nodes

AbstractEpidemiological studies have shown an association between enterovirus (EV) infections and type 1 diabetes (T1D), and EV protein has been detected in the pancreatic islets of T1D patients. Here we correlated the detection of EVs in lymphoid tissues (spleen and pancreatic lymph nodes) and small intestinal mucosa to the virus detection in the pancreas of T1D, autoantibody-positive (aab+) and non-diabetic control organ donors of the Network for Pancreatic Organ Donors with Diabetes (nPOD) study. Formalin-fixed paraffin-embedded tissue samples were screened for insulin and EV protein using immunohistochemistry, and frozen tissue for EV genome using RT-PCR. The presence of EV protein in the pancreatic islets correlated with the presence of insulin-positive cells. Altogether 62 % of T1D and aab+ donors were positive for EV protein in pancreatic islets (only insulin-positive donors included), 40 % in duodenum and 32 % in spleen, compared to 33 %, 14 %, and 27 % of non-diabetic controls. Pancreatic lymph nodes were positive for EV protein in 60 % of T1D and aab+ cases. T1D and aab+ donors were more frequently VP1-positive in multiple organs than control donors (39 % vs. 11 %; including only insulin-positive donors). EV RNA was found in selected donors and from multiple tissue types except for duodenum, and individual T1D and aab+ donors were EV RNA-positive in multiple organs. The role of extra-pancreatic organs and their interplay with EV in T1D pathogenesis remains to be solved, but we hypothesize that these organs may serve as a reservoir for the virus which may reside in these tissues in a slow-replicating persistent form.

Hypoxia stimulates human preproendothelin-1 promoter activity in transgenic mice

1997 ◽  
Vol 273 (4) ◽  
pp. L848-L855 ◽  
Author(s):  
Catherine R. Aversa ◽  
Suzanne Oparil ◽  
Jaime Caro ◽  
Huaibin Li ◽  
Shuang-Dan Sun ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Transgene Expression ◽  
Regulatory Mechanisms ◽  
Pulmonary Vasculature ◽  
Pulmonary Tissue ◽  
Hypoxic Induction ◽  
Flanking Sequences ◽  
Bronchiolar Epithelium

Significant elevations in endothelin (ET)-1 levels accompany many diseases, but the underlying regulatory mechanisms are unclear. To investigate the in vivo regulation of human preproendothelin-1 (PPET-1), we examined the activity of the PPET-1 promoter in transgenic mice exposed to hypoxia. Mice expressing one of three PPET-1 promoter-luciferase (PPET-1/LUC) reporter transgenes (≈2.5 kb, 138 bp, or none of the 5′-flanking sequences of the PPET-1 gene) were generated. LUC expression was reduced in mice with a truncated 138-bp PPET-1 promoter. Exposure of mice bearing the 2.5-kb PPET-1/LUC transgene to hypoxia (10% O2for 24 h) increased LUC expression sixfold in pulmonary tissue but only twofold in other tissues. In situ hybridization revealed the strongest transgene expression in the pulmonary vasculature and bronchiolar epithelium. These data are consistent with the hypothesis that hypoxic induction of the PPET-1 gene leads to increased pulmonary production of ET-1 in diseases associated with low O2tension.

scholarly journals Postmortem Biopsies of the Lung, Heart, Liver, and Spleen of COVID-19 Patients

2021 ◽  
Author(s):  
Isil Yurdaisik ◽  
Ahu Senem Demiroz ◽  
Aysim Buge Oz ◽  
Mustafa Akker ◽  
Ayse Gul Agirman ◽  
...  
Keyword(s):  
Histopathological Examination ◽  
Diffuse Alveolar Damage ◽  
Case Series ◽  
Neutrophil Infiltration ◽  
Underlying Disease ◽  
Heart Tissue ◽  
Ct Images ◽  
Tissue Samples ◽  
Tissue Acquisition ◽  
Lung Biopsies

Objective: We aimed to evaluate histopathologic alterations in the lung, heart, liver, and spleen of coronavirus disease 2019 (COVID-19) decedents through postmortem core needle biopsies. Materials and Methods: Patients who died of reverse transcription-polymerase chain reaction-proven COVID-19 were included in this postmortem case series. Postmortem percutaneous ultrasound-guided biopsies using 14- and 16-gauge needles were performed in the lungs, heart, liver, and spleen. Biopsy samples were stained with hematoxylin-eosin and examined under a light microscope. Clinicodemographic characteristics, chest computed tomography (CT) images, and COVID-19-related treatments of the patients were also collected. Results: Seven patients were included in this study. Liver and heart tissue samples were available from all patients, and lung and spleen tissues were available from five and three patients, respectively. Chest CT images predominantly revealed bibasilar ground-glass opacities. Lung biopsies showed diffuse alveolar damage in all biopsy specimens. Heart findings were nonspecific and largely compatible with the underlying disease. Patchy necrosis, steatosis, and mononuclear cellular infiltration were the main findings in the liver biopsies. Splenic histopathological examination showed that splenic necrosis and neutrophil infiltration were the common findings in all patients. Conclusion: Tissue acquisition was complete for the heart and liver and acceptable for lungs. The amount of tissue was sufficient for a proper histopathologic examination. The histopathological findings were generally in accordance with previous autopsy studies. The lung radiological findings were also correlated with the histopathologic findings. We consider that a postmortem biopsy is a feasible alternative for histopathological examinations in COVID-19 decedents.

scholarly journals Histopathology and Ultrastructural Findings of Fatal COVID-19 Infections

2020 ◽  
Author(s):  
Benjamin T. Bradley ◽  
Heather Maioli ◽  
Robert Johnston ◽  
Irfan Chaudhry ◽  
Susan L. Fink ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Cardiac Tissue ◽  
Diffuse Alveolar Damage ◽  
Small Sample Size ◽  
Laboratory Data ◽  
Small Sample ◽  
Viral Rna ◽  
Type I ◽  
Rt Pcr ◽  
Viral Particles

BackgroundSARS-CoV-2 is the cause of an ongoing pandemic with a projected 100,000 to 240,000 U.S. deaths. To date, documentation of histopathologic features in fatal cases of COVID-19 has been limited due to small sample size and incomplete organ sampling.MethodsPost-mortem examinations were performed on 12 fatal COVID-19 cases in Washington State during February-March 2020. Clinical and laboratory data were reviewed. Tissue examination of all major organs was performed by light microscopy and electron microscopy. The presence of viral RNA in sampled tissues was tested by RT-PCR.ResultsAll 12 patients were older with significant preexisting comorbidities. The major pulmonary finding was diffuse alveolar damage in the acute and/or organizing phases with virus identified in type I and II pneumocytes by electron microscopy. The kidney demonstrated viral particles in the tubular epithelium, endothelium, and podocytes without significant inflammation. Viral particles were also observed in the trachea and large intestines. SARS-CoV-2 RNA was detected in the cardiac tissue of a patient with lymphocytic myocarditis. RT-PCR also detected viral RNA in the subcarinal lymph nodes, liver, spleen, and large intestines.ConclusionSARS-CoV-2 represents the third novel coronavirus to cause widespread human disease since 2002. Similar to SARS and MERS, the primary pathology was diffuse alveolar damage with virus located in the pneumocytes. However, other major organs including the heart and kidneys may be susceptible to viral replication and damage leading to increased mortality in those with disseminated disease. Understanding the pathology of SARS-CoV-2 will be essential to design effective therapies.

scholarly journals Attenuation of oxidative stress and cardioprotective effects of zinc supplementation in experimental diabetic rats

2017 ◽  
Vol 117 (3) ◽  
pp. 335-350 ◽  
Author(s):  
Susmita Barman ◽  
Krishnapura Srinivasan
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzyme ◽  
Enzyme Activities ◽  
Cardiac Tissue ◽  
Diabetic Rats ◽  
Hepatic Tissue ◽  
Antioxidant Enzyme Activities ◽  
Markers Of Oxidative Stress ◽  
Cardioprotective Effects ◽  
Apoptotic Factors

AbstractOxidative stress plays a major role in the pathogenesis of diabetes mellitus, which further exacerbates damage of cardiac, hepatic and other tissues. We have recently reported that Zn supplementation beneficially modulates hyperglycaemia and hypoinsulinaemia, with attendant reduction of associated metabolic abnormalities in diabetic rats. The present study assessed the potential of Zn supplementation in modulating oxidative stress and cardioprotective effects in diabetic rats. Diabetes was induced in Wistar rats with streptozotocin, and groups of diabetic rats were treated with 5- and 10-fold dietary Zn interventions (0·19 and 0·38 g Zn/kg diet) for 6 weeks. The markers of oxidative stress, antioxidant enzyme activities and concentrations of antioxidant molecules, lipid profile, and expressions of fibrosis and pro-apoptotic factors in the cardiac tissue were particularly assessed. Supplemental Zn showed significant attenuation of diabetes-induced oxidative stress in terms of altered antioxidant enzyme activities and increased the concentrations of antioxidant molecules. Hypercholesterolaemia and hyperlipidaemia were also significantly countered by Zn supplementation. Along with attenuated oxidative stress, Zn supplementation also showed significant cardioprotective effects by altering the mRNA expressions of fibrosis and pro-apoptotic factors (by >50 %). The expression of lipid oxidative marker 4-hydroxy-2-nonenal (4-HNE) protein in cardiac tissue of diabetic animals was rectified (68 %) by Zn supplementation. Elevated cardiac and hepatic markers in circulation and pathological abnormalities in cardiac and hepatic tissue architecture of diabetic animals were ameliorated by dietary Zn intervention. The present study indicates that Zn supplementation can attenuate diabetes-induced oxidative stress in circulation as well as in cardiac and hepatic tissues.

scholarly journals Increased number of pulmonary megakaryocytes in COVID-19 patients with diffuse alveolar damage. An autopsy study with clinical correlation and review of the literature.

2020 ◽  
Author(s):  
Mariel F. Valdivia-Mazeyra ◽  
Clara Salas ◽  
Jesús M. Nieves-Alonso ◽  
Luz Martín-Fragueiro ◽  
Carmen Bárcena ◽  
...  
Keyword(s):  
Diffuse Alveolar Damage ◽  
Lung Damage ◽  
Pulmonary Injury ◽  
Autopsy Study ◽  
Pulmonary Tissue ◽  
Tissue Samples ◽  
Future Studies ◽  
Pulmonary Response ◽  
Histopathologic Finding ◽  
Pulmonary Microcirculation

Abstract Megakaryocytes are normally present in the lung where they play a role in platelet homeostasis. The latter are well known to participate in the pathogenesis of lung damage, particularly in acute lung injury. Although megakaryocytes are usually not mentioned as a characteristic histopathologic finding associated to acute pulmonary injury, a few studies point out that their number is increased in the lungs of patients with diffuse alveolar damage. In this autopsy study we have observed a relevant number of pulmonary megakaryocytes in COVID-19 patients dying with acute respiratory distress syndrome. We have studied pulmonary tissue samples of 18 patients most of which died after prolonged disease and use of mechanical ventilation. Most samples showed fibroproliferative or fibrotic diffuse alveolar damage and an increased number of megakaryocytes. In six, thrombi of the pulmonary microcirculation were seen. We compare our findings with previous published autopsy reports, mainly focusing on the description of megakaryocytes. Our patients showed abnormal coagulation parameters with high levels of fibrinogen, D-dimers and variable thrombocytopenia. Since the lung is considered an active site of megakariopoiesis, a prothrombotic status leading to platelet activation, aggregation and consumption may trigger a compensatory pulmonary response. An increased number of pulmonary megakaryocytes suggests and supports a relation with the thrombotic events so often seen in COVID-19. Regardless of its etiology, future studies of patients dying with acute pulmonary injury should include pulmonary megakaryocytes as a histologic variable of interest.

A novel Notch ligand, Dll4, induces T-cell leukemia/lymphoma when overexpressed in mice by retroviral-mediated gene transfer

Blood ◽  
2001 ◽  
Vol 98 (13) ◽  
pp. 3793-3799 ◽  
Author(s):  
Xiao-Qiang Yan ◽  
Ulla Sarmiento ◽  
Yu Sun ◽  
Guo Huang ◽  
Jane Guo ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Fate ◽  
Early Stage ◽  
Lymphoproliferative Disease ◽  
Lymphoid Tissues ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Notch Ligand ◽  
Cell Fate Decisions ◽  
Multiple Organs

Abstract Notch receptors mediate cell-fate decisions through interaction with specific ligands during development. The biological role of a novel Notch ligand, Dll4, in mice was explored by reconstituting lethally irradiated mice with bone marrow (BM) cells transduced with Dll4 retroviral vector. White blood cell and lymphocyte counts in Dll4-overexpressing mice were reduced at the early stage of reconstitution but increased significantly at approximately 10 weeks after BM transplantation. BM, spleen, lymph nodes, and peripheral blood ofDll4-overexpressing mice contained predominantly CD4+CD8+ T cells and virtually lacked B cells. The Dll4-overexpressing mice eventually developed a lethal phenotype that was characterized by the progression of a T-cell lymphoproliferative disease (restricted to BM and lymphoid tissues) to transplantable monoclonal T-cell leukemia/lymphoma scattered to multiple organs. Results suggest that the interaction of Dll4with Notch1 may provide key signals for T-cell development.

scholarly journals Exophytic primary gastric squamous cell carcinoma and H. pylori gastritis

2019 ◽  
Vol 12 (7) ◽  
pp. e230310 ◽  
Author(s):  
Kehua Zhou ◽  
Aniqa Faraz ◽  
Minoti Magotra ◽  
Muhammad Tahir
Keyword(s):  
Weight Loss ◽  
Squamous Cell Carcinoma ◽  
Helicobacter Pylori ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Abdominal Ct ◽  
Multiple Organs ◽  
Night Sweats ◽  
H Pylori ◽  
Immunohistochemistry Stain

Primary gastric squamous cell carcinoma (SCC) is rare, and the simultaneous Helicobacter pylori infection has not been reported in the literature. Here, we presented a patient with concurrent H. pylori gastritis and primary gastric SCC. A 54-year-old Hispanic man presented with diarrhoea, chills, night sweats and weight loss of 16 lbs for the previous 6 weeks. Abdominal CT revealed large exophytic mass from the stomach infiltrating multiple organs. Biopsy was performed and histology showed squamoid features. Immunohistochemistry stain was positive for p40, CK5/6, CK7 and Helicobacter type organisms. Patient was diagnosed with primary gastric SCC and has been receiving chemotherapy. We also reviewed the diagnosis, prognosis and treatment of primary gastric SCC.

scholarly journals SARS-CoV-2 Causes a Systemically Multiple Organs Damages and Dissemination in Hamsters

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhiqi Song ◽  
Linlin Bao ◽  
Pin Yu ◽  
Feifei Qi ◽  
Shuran Gong ◽  
...  
Keyword(s):  
Adrenal Gland ◽  
Lymph Nodes ◽  
Diffuse Alveolar Damage ◽  
Systemic Disease ◽  
Treatment Strategies ◽  
Antigen Expression ◽  
Viral Rna ◽  
Post Inoculation ◽  
Focal Lesions ◽  
Multiple Organs

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has spread across the world and impacted global healthcare systems. For clinical patients, COVID-19 not only induces pulmonary lesions but also affects extrapulmonary organs. An ideal animal model that mimics COVID-19 in humans in terms of the induced systematic lesions is urgently needed. Here, we report that Syrian hamster is highly permissive to SARS-CoV-2 and exhibit diffuse alveolar damage and induced extrapulmonary multi-organs damage, including spleen, lymph nodes, different segments of alimentary tract, kidney, adrenal gland, ovary, vesicular gland and prostate damage, at 3–7 days post inoculation (dpi), based on qRT-PCR, in situ hybridization and immunohistochemistry detection. Notably, the adrenal gland is a novel target organ, with abundant viral RNA and antigen expression detected, accompanied by focal to diffuse inflammation. Additionally, viral RNA was also detected in the corpus luteum of the ovary, vesicular gland and prostate. Focal lesions in liver, gallbladder, myocardium, and lymph nodes were still present at 18 dpi, suggesting potential damage after disease. Our findings illustrate systemic histological observations and the viral RNA and antigen distribution in infected hamsters during disease and convalescence to recapitulate those observed in humans with COVID-19, providing helpful data to the pathophysiologic characterization of SARS-CoV-2-induced systemic disease and the development of effective treatment strategies.

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