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MeSH Disease

Human Phenotype

Transmission

Seroprevalence
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    Confirmed central olfactory system lesions on brain MRI in COVID-19 patients with anosmia HP: a case-series

    Authors: Yannick Girardeau; Yoan GALLOIS; Guillaume DE BONNECAZE; Bernard ESCUDE; Clarisse LAFONT; Gilles CHATELLIER; Mathieu MARX

    doi:10.1101/2020.07.08.20148692 Date: 2020-07-17 Source: medRxiv

    Objective: Anosmia HP has been listed as a key-symptom associated with the COVID-19 infection MESHD. Because it often occurs without any sign of rhinitis MESHD rhinitis HP, lesions of the central olfactory system have been suspected. To date, however, there is no evidence that anosmia HP caused by SARS-CoV2 could be the result of brain damage. Methods: We conducted a case-series on 10 consecutive COVID-19 patients who reported anosmia HP. Each patient prospectively underwent a validated olfactory test (Sniffin Sticks test) and a brain MRI. Results: Hypersignal intensity lesions of the central olfactory system were found in 3 subjects on 3D T2 FLAIR and 2D T2 High Resolution images with a lesion involving the olfactory bulbs and/or the orbitofrontal cortex. These 3 subjects showed a severe and persistent loss of smell on the olfactory test. Mucosal hyperplasia MESHD of the upper nasal cavities was found in two other subjects with significant smell disorders. There was no MRI anomaly in two subjects with good smell restoration. Conclusions: Anomalies of the central olfactory system could be responsible for anosmia HP in patients with COVID-19 infection MESHD. Further studies are needed to assess the impact on long-term functional prognosis of these lesions.

    Structure of human steroid 5α-reductase 2 with anti-androgen drug finasteride

    Authors: Qingpin Xiao; Lei Wang; Shreyas Supekar; Tao Shen; Heng Liu; Fei Ye; Junzhou Huang; Hao Fan; Zhiyi Wei; Cheng Zhang

    doi:10.21203/rs.3.rs-40159/v1 Date: 2020-07-04 Source: ResearchSquare

    Human steroid 5α-reductase 2 (SRD5α2) as a critical integral membrane enzyme in steroid metabolism catalyzes testosterone to dihydrotestosterone. Mutations on its gene have been linked to 5α-reductase deficiency and prostate cancer HP. Finasteride and dutasteride as SRD5α2 inhibitors are widely used anti-androgen drugs for benign prostate hyperplasia MESHD, which have recently been indicated in the treatment of COVID-19. The molecular mechanisms underlying enzyme catalysis and inhibition remained elusive for SRD5α2 and other eukaryotic integral membrane steroid reductases due to a lack of structural information. Here, we report a crystal structure of human SRD5α2 at 2.8 Å revealing a unique 7-TM structural topology and an intermediate adduct of finasteride and NADPH as NADP-dihydrofinasteride in a largely enclosed binding cavity inside the membrane. Structural analysis together with computational and mutagenesis studies reveals molecular mechanisms for the 5α-reduction of testosterone and the finasteride inhibition involving residues E57 and Y91. Molecular dynamics simulation results indicate high conformational dynamics of the cytosolic region regulating the NADPH/NADP+ exchange. Mapping disease MESHD-causing mutations of SRD5α2 to our structure suggests molecular mechanisms for their pathological effects. Our results offer critical structural insights into the function of integral membrane steroid reductases and will facilitate drug development.

    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/rs.3.rs-32241/v2 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 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 related to Covid-19 in order to understand better how the disease MESHD 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. 

    Pulmonary post-mortem findings in a large series of COVID-19 cases from Northern Italy

    Authors: Luca Carsana; Aurelio Sonzogni; Ahmed Nasr; Roberta Rossi; Alessandro Pellegrinelli; Pietro Zerbi; Roberto Rech; Riccardo Colombo; Spinello Antinori; Mario Corbellino; Massimo Galli; Emanuele Catena; Antonella Tosoni; Andrea Gianatti; Manuela Nebuloni

    doi:10.1101/2020.04.19.20054262 Date: 2020-04-22 Source: medRxiv

    Importance. The analysis of lung tissues of patients with COVID-19 may help understand pathogenesis and clinical outcomes in this life-threatening respiratory illness. Objective. To determine the histological patterns in lung tissue of patients with severe COVID-19. Design and participants. Lungs tissues of 38 cases who died for COVID-19 in two hospital of Northern Italy were systematically analysed. Hematoxylin-eosin staining, immunohistochemistry for the inflammatory infiltrate and cellular components, electron microscopy were performed. Results. The features of the exudative and proliferative phases of Diffuse Alveolar Disease MESHD (DAD) were found: capillary congestion, necrosis MESHD of pneumocytes, hyaline membrane, interstitial oedema, pneumocyte hyperplasia MESHD and reactive atypia, platelet-fibrin thrombi. The inflammatory infiltrate was composed by macrophages in alveolar lumens and lymphocytes mainly in the interstitium. Electron microscopy revealed viral particles within cytoplasmic vacuoles of pneumocytes. Conclusions and relevance. The predominant pattern of lung lesions in COVID-19 patients is DAD, as described for the other two coronavirus that infect humans, SARS-CoV and MERS-CoV. Hyaline membrane formation and pneumocyte atypical hyperplasia MESHD are frequently found. The main relevant finding is the presence of platelet-fibrin thrombi in small arterial vessels; this important observation fits into the clinical context of coagulopathy which dominates in these patients and which is one of the main targets of therapy.

    The Novel Severe Acute Respiratory Syndrome MESHD Coronavirus 2(SARS-CoV-2) Directly 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 is a common characteristic of patients infected by the novel severe acute respiratory syndrome MESHD coronavirus 2 (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 MESHD. 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: Preprints.org

    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 MESHD and fatality, we performed post-mortem needle core biopsies of lung, liver, and heart in four patients who died of COVID-19 pneumonia MESHD pneumonia HP. 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 MESHD, including immunocompromised status (chronic lymphocytic leukemia MESHD leukemia HP and renal transplantation) or other conditions ( cirrhosis HP, hypertension MESHD hypertension HP, and diabetes). Time from disease MESHD onset to death MESHD 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 except for the patient with leukemia MESHD leukemia HP. Histologically, the main findings are in the lungs, including injury to the alveolar epithelial cells, hyaline membrane formation, and hyperplasia MESHD 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 MESHD. The liver exhibits mild lobular infiltration by small lymphocytes, and centrilobular sinusoidal dilation. Patchy necrosis MESHD 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, as well as superimposed bacterial pneumonia MESHD pneumonia HP in some patients. Changes in the liver and heart are likely secondary or related to the underlying diseases MESHD.

    Clinical Pathology of Critical Patient with Novel Coronavirus Pneumonia MESHD 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: Preprints.org

    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, variable degrees of hemorrhagic pulmonary infarction MESHD. Small vessels hyperplasia MESHD, vessel wall thickening, lumen stenosis, occlusion and microthrombosis formation. Focal monocytes, lymphocytes and plasma SERO cells infiltrating into pulmonary HP interstitium. Bronchiolitis MESHD Bronchiolitis HP and alveolitis with proliferation, atrophy MESHD, desquamation and squamous metaplasia MESHD of epithelial cells. Atrophy MESHD, vacuolar degeneration, proliferation, desquamation and squamous metaplasia MESHD in alveolar epithelial cells. Alveolar cavity congestion was prominent, and contained mucus, edema MESHD edema HP 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 MESHD.

    Pulmonary Pathology of Early Phase 2019 Novel Coronavirus (COVID-19) Pneumonia MESHD Pneumonia HP in Two Patients with Lung Cancer

    Authors: Sufang Tian; Weidong Hu; Li Niu; Huan Liu; Haibo Xu; Shu-Yuan Xiao

    id:10.20944/preprints202002.0220.v2 Date: 2020-03-02 Source: Preprints.org

    There is currently a lack of pathologic data on the novel coronavirus (SARS-CoV-2) pneumonia MESHD pneumonia HP, or COVID-19, from autopsy or biopsy. Two patients who recently underwent lung lobectomies for adenocarcinoma MESHD were retrospectively found to have had COVID-19 at the time of surgery. These two cases thus provide important first opportunities to study the pathology of COVID-19. Pathologic examinations revealed that, apart from the tumors, the lungs of both patients exhibited edema MESHD edema HP, proteinaceous exudate, focal reactive hyperplasia MESHD of pneumocytes with patchy inflammatory cellular infiltration, and multinucleated giant cells. Hyaline membranes were not prominent. Since both patients did not exhibit symptoms of pneumonia MESHD pneumonia HP at the time of surgery, these changes likely represent an early phase of the lung pathology of COVID-19 pneumonia MESHD pneumonia HP.

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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