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.

    Methods of An Open-Label Proof-Of-Concept Trial of Intravenous Valproic Acid for Severe COVID-19

    Authors: Erwin Chiquete; Liz Toapanta-Yanchapaxi; Carlos Cantu-Brito

    doi:10.1101/2020.04.26.20079988 Date: 2020-05-01 Source: medRxiv

    Background: Coronavirus disease 2019 (COVID-19) is the systemic entity caused by the severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) that may cause death MESHD through severe atypical pneumonia HP pneumonia MESHD and acute lung injury MESHD. Valproic acid (VPA) has shown anti-inflammatory activity and mild intrinsic antiviral effect. These properties warrant the study of VPA as a possible active treatment in persons with severe COVID-19. Methods: Consecutive adult TRANS patients needing invasive mechanical ventilation (IMV) will be given intravenous (i.v.) VPA at a starting dose of 20 mg/kg/day and up to 60/kg/day (in 60 min i.v. infusions in 250 mL normal saline) as needed to reach plasma SERO VPA concentrations of 50-100 mcg/mL (measured every 72 h). These patients will be followed-up for 10 days for the primary outcome and for a further period of 30 days after treatment completion for the secondary outcome of recurrence. The primary study outcome is the reduction in the case fatality rate of at least 50% after 10 days of treatment (as compared with natural history). Secondary outcomes are the reduction of length of stay (LOS) of at least 50%, as well as COVID-19 recurrence at 30-day follow-up. The most important safety outcomes are acute liver failure MESHD, acute pancreatitis HP acute pancreatitis MESHD, and thrombocytopenia HP thrombocytopenia MESHD. Conclusion: Although long-term adverse effects and even pro-inflammatory consequences have been reported with the chronic use of VPA, given the urgent need for a drug against COVID-19 to shorten the high mortality and LOS, the study of VPA is justified from a scientific standpoint.

    Network-Based Analysis of Fatal Comorbidities of COVID-19 and Potential Therapeutics

    Authors: Broto Chakrabarty; Dibyajyoti Das; Gopalakrishnan Bulusu; Arijit Roy

    doi:10.26434/chemrxiv.12136470.v1 Date: 2020-04-20 Source: ChemRxiv

    Coronavirus disease MESHD 2019 (COVID-19) is a highly contagious disease MESHD caused by severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2). The case fatality rate is significantly higher in older patients and those with diabetes MESHD, cancer MESHD or cardiovascular disorders MESHD. The human proteins, angiotensin-converting enzyme 2 (ACE2) and basigin (BSG), are involved in high-confidence host-pathogen interactions with proteins from SARS-CoV-2. We applied the random walk with restart method on the human interactome to construct a significant sub-network around these two proteins. The protein-protein interaction sub-network captures the effects of viral invasion on fatal comorbidities through critical pathways. The ‘insulin resistance’, ‘AGE-RAGE signaling pathway in diabetic complications MESHD’ and ‘adipocytokine signaling pathway’ were found in all fatal comorbidities. The association of these critical pathways with aging and its related diseases explains the molecular basis of COVID-19 fatality. We further investigated the critical proteins and corresponding pathways, and identified drugs that have effects on these proteins/pathways based on gene expression studies. We particularly focused on drugs that significantly downregulate ACE2 along with other critical proteins identified by the network-based approach. Among them, COL-3 (also known as incyclinide) had earlier shown activity against acute lung injury MESHD and acute respiratory distress MESHD respiratory distress HP, while entinostat and mocetinostat have been investigated for non-small-cell lung cancer MESHD. We propose that these drugs can be repurposed for COVID-19.

    A retrospective study of the clinical characteristics of COVID-19 infection MESHD in 26 children TRANS

    Authors: Anjue Tang; Wenhui Xu; min shen; Peifen Chen; Guobao Li; Yingxia Liu; Lei Liu

    doi:10.1101/2020.03.08.20029710 Date: 2020-03-10 Source: medRxiv

    Background: The outbreak of novel coronavirus pneumonia MESHD pneumonia HP in China began in December 2019. Studies on novel coronavirus disease MESHD (COVID-19) were less based on pediatric patients. This study aimed to reveal the clinical characteristics of COVID-19 in children TRANS. Method: This study retrospectively analyzed the clinical symptoms, laboratory results, chest CT, and treatment of children TRANS with laboratory-confirmed COVID-19(ie, with samples that were positive for 2019 novel coronavirus[2019-nCoV]) who were admitted to Shenzhen Center of National Infectious Disease MESHD Clinical Medical Research from January 16 to February 8, 2020. Result: Nine patients had no obvious clinical symptom. 11 patients developed fever HP fever MESHD. Other symptoms, including cough HP(in eleven of seventeen patients), rhinorrhea HP rhinorrhea MESHD(in two), diarrhea HP diarrhea MESHD(in two), vomiting HP vomiting MESHD(in two), were also observed. A small minority of patients had lymphocytopenia MESHD. Alanine transaminase or transaminase increased in three cases. According to chest CT scan, 11 patients showed unilateral pneumonia MESHD pneumonia HP, 8 patients had no pulmonary infiltration. No serious complications such as acute respiratory syndrome MESHD and acute lung injury MESHD occurred in all patients. Conclusion: The clinical characteristics of 2019-nCoV infection MESHD in children TRANS were different from adult TRANS. The overall condition of children TRANS were mild and have a good prognosis.

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MeSH Disease
Human Phenotype

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