Corpus overview


MeSH Disease

Human Phenotype


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    Acute Lung injury MESHD evolution in Covid-19

    Authors: Claudio Doglioni; Claudia Ravaglia; Giulio Rossi; Alessandra Dubini; Federica Pedica; Sara Piciucchi; Antonio Vizzuso; Lorenza Pecciarini; Franco Stella; Stefano Maitan; Vanni Agnoletti; Emiliano Gamberini; Emanuele Russo; Silvia Puglisi; Antonella Arcadu; Luca Donati; Simona Di Cesare; Carmela Grosso; Giovanni Poletti; Vittorio Sambri; Elisabetta Fabbri; Giovanni Pizzolo; Stefano Ugel; Vincenzo Bronte; Athol U Wells; Marco Chilosi; Venerino Poletti; Tobias Boettler; Bertram Bengsch; Robert Thimme; Maike Hofmann; Christoph Neumann-Haefelin

    doi:10.1101/2020.08.09.20170910 Date: 2020-08-13 Source: medRxiv

    BACKGROUND Pathogenesis of Coronavirus disease MESHD 2019 (Covid-19) is poorly understood. Most histologic studies come from post-mortem analysis, with existing data indicating that histologic features of acute respiratory distress syndrome MESHD respiratory distress HP syndrome are typically present in fatal cases. However, this observation may be misleading, due to confounding factors in pre-terminal disease, including injury resulting from prolonged mechanical ventilation. Ante-mortem lung biopsy may provide major pathogenetic insights, potentially providing a basis for novel treatment approaches. AIM This comparative, multicenter, prospective, observational study was planned to identify ante-mortem histological profile and immunohistochemical features of lung tissue in patients with Covid-19 in early and late phases of the disease, including markers of inflammatory cells and major pathways involved in the cytokine storm triggering. METHODS Enrolled patients underwent lung biopsy, according to the study protocol approved by local Ethical Committee, either within 15 days of the first symptoms appearing (early phase) or after > 15 days (more advanced disease). Key exclusion criteria were excessive or uncorrectable bleeding MESHD risk and cardiovascular disease MESHD with heart failure MESHD. Lung samples were obtained by conventional trans-bronchialbiopsy, trans-bronchial lung cryobiopsy or surgical lung biopsy. RESULTS 23 patients were enrolled: 12 patients underwent lung biopsy within 15 days and 11 patients more than 15 days after the onset of symptoms TRANS. Early biopsies were characterized by spots of patchy acute lung injury MESHD ( ALI MESHD) with alveolar type II MESHD cells hyperplasia MESHD and significant vascular abnormalities MESHD (disordered angiogenesis with alveolar capillary hyperplasia, luminal enlargement MESHD and thickened walls of pulmonary venules, perivascularCD4-T-cell infiltration), with no hyaline membranes. In the later stages, the alveolar architecture MESHD appeared disrupted, with areas of organizing ALI MESHD, venular congestion and capillary thromboembolic microangiopathy MESHD. Striking phenotypic features were demonstrated in hyper plastic pneumocytes MESHD and endothelial cells, including the expression of phospho-STAT3 and molecules involved in immunoinhibitory signals (PD-L1 and IDO1). Alveolar MESHD macrophages exhibited macrophage-related markers (CD68, CD11c, CD14) together with unusual markers, such as DC-Lamp/CD208, CD206, CD123/IL3AR. CONCLUSION A morphologically distinct Covid pattern was identified in the earlier stages of the disease, with prominent epithelial and endothelial cell abnormalities, that may be potentially reversible, differing strikingly from findings in classical diffuse alveolar damage MESHD. These observations may have major therapeutic implications, justifying studies of early interventions aimed at mitigating inflammatory organ injury.

    Vascular Obliteration Due To Endothelial And Myointimal Growth In COVID-19

    Authors: Jara Valtueña; Gerardo Martínez-García; Daniel Ruiz-Sánchez; María Garayar-Cantero; Carlos Dueñas; Ángel Aguado-García; Jose María Prieto de Paula; Pilar Manchado López

    doi:10.21203/ Date: 2020-05-28 Source: ResearchSquare

    Background: Severe coronavirus disease MESHD 2019 (Covid-19) is a systemic multi-organ viral invasion. Previous studies found that many patients had a procoagulant state and/or severe hypoxemia HP hypoxemia MESHD with relatively well-preserved lung mechanics. Mechanisms underlying the vascular and its surrounding tissue are not well known yet.  Histological data in Covid-19 tissues´ patients are still limited and mainly focused on post-mortem analysis. Since SARS-CoV-2 largely affects cutaneous tissue, we aim to examine in depth skin lesions MESHD related to Covid-19 in order to understand better how the disease might affect living tissue.Methods: Five skin lesions from Covid-19 adult TRANS patients were selected for histological tissue examination. Vast amount of data of immunohistochemistry (IHC) and direct immunofluorescent (DIF) were part of the assessment. Results: A common strong vasculopathic reaction pattern based on prominent vascular endothelial and myointimal cellgrowth was identified. Endothelial cell distortion generated vascular lumen obliteration and a strike erythrocyte and serum SERO extravasation. Extensive significant vascular C4d and C3 deposition throughout vascular cell wall was also identified. A regenerative epidermal hyperplasia MESHD with tissue structure preservation was found. Conclusions: Covid-19 could comprise an obliterative micro-angiopathy consisting on endothelial and myointimal intensive growth with complement activation. This mechanism, together with increased vascular permeability identified, could contribute to obliterative vascular lumen and hemorrhage MESHD in Covid-19. Activation of the complement and angiogenic pathways could have an important role in inducing and maintaining this vasculopathic reaction pattern. Thus, anticoagulation by itself could not completely reverse vascular lumen obliteration, with consequent hemorrhagic increased risk associated. Skin is the largest organ in the body, the most accessible one and can mirror other organs of the body. Findings of this study could contribute to a better understanding of physio-pathological mechanisms underlying SARS-CoV-2 infection MESHD on living tissue and could help further studies find potential targets for specific therapeutic interventions in Covid-19 severe patients. 

    The Novel Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2) Directly MESHD Decimates Human Spleens and Lymph Nodes

    Authors: yongwen chen; Zeqing Feng; Bo Diao; Rongshuai Wang; Gang Wang; Chenhui Wang; Yingjun Tan; Liang Liu; Changsong Wang; Ying Liu; Yueping Liu; Zilin Yuan; Liang Ren; Yuzhang Wu

    doi:10.1101/2020.03.27.20045427 Date: 2020-03-31 Source: medRxiv

    While lymphocytopenia MESHD is a common characteristic of patients infected by the novel severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), the mechanisms responsible for this depletion are unclear. Through careful inspection of the spleens and lymph nodes (LNs) from six cases with postmortem examinations, we observed that SARS-CoV-2 could directly infect secondary lymphoid organs to induce cell death. Immunohistochemistry demonstrated ACE2 (angiotensin-converting enzyme 2), the potential receptor of SARS-CoV-2, expresses on tissue-resident CD169+ macrophages in spleens and LNs. Immunofluorescent staining confirmed that viral nucleocaspid protein (NP) can be found in ACE2+ cells, CD169+ macrophages, but not in CD3+ T cells or B220+ B cells in spleens and LNs. SARS-CoV-2 infection MESHD induces severe tissue damage including lymph follicle depletion, splenic nodule atrophy MESHD, histiocyte hyperplasia MESHD and lymphocyte reductions. Moreover, in situ TUNEL staining illustrated that viral infection MESHD leads to severe lymphocyte apoptosis, which might be mediated by viral antigens inducing Fas upregulation. Furthermore, SARS-CoV-2 also triggers macrophages to produce IL-6, a proinflammatory cytokine that directly promotes lymphocyte necrosis MESHD. Collectively, these results demonstrate that SARS-CoV-2 directly neutralizes human spleens and LNs through infecting tissue- resident CD169+ macrophages.

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

    Authors: Sufang Tian; Yong Xiong; Huan Liu; Li Niu; Jianchun Guo; Meiyan Liao; Shu-Yuan Xiao

    id:10.20944/preprints202003.0311.v1 Date: 2020-03-20 Source:

    Data on pathologic changes of the 2019 novel coronavirus disease MESHD (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 HP pneumonia MESHD. The patients’ ages TRANS ranged from 59 to 81, including 3 males TRANS and 1 female TRANS. Each patient had at least one underlying disease, including immunocompromised status ( chronic lymphocytic leukemia MESHD leukemia HP and renal transplantation) or other conditions ( cirrhosis HP cirrhosis MESHD, hypertension HP hypertension MESHD, and diabetes MESHD). Time from disease onset to death ranged from 15 to 52 days. All patients had elevated white blood SERO cell counts, with significant rise toward the end, and all had lymphocytopenia MESHD except for the patient with leukemia HP leukemia MESHD. Histologically, the main findings are in the lungs, including injury to the alveolar MESHD epithelial cells, hyaline membrane formation, and hyperplasia of type II pneumocytes MESHD, all components of diffuse alveolar damage MESHD. 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 MESHD, consistent with superimposed bacterial bronchopneumonia MESHD. 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 MESHD and mild myocardial hypertrophy MESHD, changes likely related to the underlying conditions. In conclusion, the post-mortem examinations show advanced diffuse alveolar damage MESHD, as well as superimposed bacterial pneumonia HP pneumonia MESHD in some patients. Changes in the liver and heart are likely secondary or related to the underlying diseases.

    Clinical Pathology of Critical Patient with Novel Coronavirus Pneumonia HP (COVID-19)

    Authors: Weiren Luo; Hong Yu; Jizhou Gou; Xiaoxing Li; Yan Sun; Jinxiu Li; Lei Liu

    id:202002.0407/v4 Date: 2020-03-09 Source:

    Background Critical patients with novel coronavirus pneumonia MESHD pneumonia HP ( COVID-19) have worse outcome and high mortality. However, the histopathology of critical patient with COVID-19 remains undisclosed. Methods We performed the whole lung biopsy, and described the pathological changes of critical COVID-19 patient done with transplant by HE staining, immunohistochemistry and special staining observed under the microscopy. Findings The whole lungs displayed diffuse congestive appearance and partly haemorrhagic necrosis MESHD on gross examination. The haemorrhagic necrosis MESHD was prominently present in outer edge of the right lower lung. The cut surfaces of the lung displayed severe congestive and haemorrhagic changes. The main pathological changes showed massive pulmonary interstitial fibrosis MESHD, and partly hyaline degeneration MESHD, variable degrees of hemorrhagic pulmonary infarction MESHD. Small vessels hyperplasia MESHD, vessel wall thickening, lumen stenosis, occlusion and microthrombosis MESHD formation. Focal monocytes, lymphocytes and plasma SERO cells infiltrating into pulmonary HP interstitium. Bronchiolitis HP Bronchiolitis MESHD and alveolitis with proliferation, atrophy MESHD, desquamation MESHD and squamous MESHD metaplasia of epithelial cells. Atrophy MESHD, vacuolar degeneration, proliferation, desquamation MESHD and squamous MESHD metaplasia in alveolar epithelial MESHD cells. Alveolar MESHD cavity congestion was prominent, and contained mucus, edema HP edema MESHD fluid, desquamated epithelial cells, and inflammatory cells. We also found several multinucleate giant cells and intracytoplasmic viral inclusion bodies. Special stains including Masson stain, sirius red staining, reticular fibers staining indicated massive pulmonary interstitial fibrosis MESHD. Immunohistochemistry showed positive for immunity cells including CD3, CD4, CD8, CD20, CD79a, CD5, CD38 and CD68. Interpretation We demonstrate the pathological findings of critical patient with COVID-19, which might provide a deep insight of the pathogenesis and severity of this disease.

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MeSH Disease
Human Phenotype

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