Corpus overview


MeSH Disease

Human Phenotype


    displaying 1 - 10 records in total 295
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    Clinical and intestinal histopathological findings in SARS-CoV-2/COVID-19 patients with hematochezia HP

    Authors: Margaret Cho; Weiguo Liu; Sophie Balzora; Yvelisse Suarez; Deepthi Hoskoppal; Neil D Theise; Wenqing Cao; Suparna A Sarkar

    doi:10.1101/2020.07.29.20164558 Date: 2020-08-07 Source: medRxiv

    Gastrointestinal (GI) symptoms of SARS-CoV2/COVID-19 in the form of anorexia MESHD anorexia HP, nausea MESHD nausea, vomiting HP, vomiting MESHD, abdominal pain MESHD abdominal pain HP and diarrhea MESHD diarrhea HP are usually preceeded by respiratory manifestations and are associated with a poor prognosis. Hematochezia HP is an uncommon clinical presentation of COVID-19 disease MESHD and we hypothesize that older patients with significant comorbidites ( obesity MESHD obesity HP and cardiovascular) and prolonged hospitalization are suspectible to ischemic injury to the bowel. We reviewed the clinical course, key laboratory data including acute phase reactants, drug/medication history in two elderly TRANS male TRANS patients admitted for COVID-19 respiratory failure HP. Both patients had a complicated clinical course and suffered from hematochezia HP and acute blood SERO loss anemia MESHD anemia HP requiring blood SERO transfusion around day 40 of their hospitalization. Colonoscopic impressions were correlated with the histopathological findings in the colonic biopies and changes compatible with ischemia MESHD to nonspecific acute inflammation MESHD, edema MESHD edema HP and increased eosinophils in the lamina propria were noted.Both patients were on anticoagulants, multiple antibiotics and antifungal agents due to respiratory infections MESHD at the time of lower GI bleeding. Hematochezia HP resolved spontaneously with supportive care. Both patients eventually recovered and were discharged. Elderly TRANS patients with significant comorbid conditions are uniquely at risk for ischemic injury to the bowel. Hypoxic conditions due to COVID-19 pneumonia MESHD pneumonia HP and respiratory failure HP, compounded by preexisting cardiovascular complications, and/or cytokine storm orchestrated by the viral infection MESHD leading to alteration in coagulation profile and/or drug/medication injury can be difficult to distinguish in these critically ill patients. Presentation of hematochezia HP may further increase the mortality and morbidity of COVID-19 patients, and prompt consultation and management by gastroenterology is therefore warranted.

    Paracetamol use in COVID-19: friend TRANS or enemy?

    Authors: Piero Sestili; Carmela Fimognari

    id:202008.0186/v1 Date: 2020-08-07 Source:

    COVID-19 pandemic represents an unprecedented sanitary threat: antiviral and host-directed medications to treat the disease MESHD are still urgently needed.A great effort has been paid to find drugs and treatments for hospitalized, severely ill patients. However, medications used for the domiciliary management of initial symptoms, notwithstanding their importance, have not been and are not presently regarded with the same attention. In analogy with other respiratory viral infections MESHD, COVID-19 patients in the early phase require specific antivirals (still lacking) and non-etiotropic drugs to lower pain MESHD pain HP, fever MESHD fever HP and control inflammation MESHD. Non-steroidal antinflammatory drugs (NSAIDs) and paracetamol (PAC) are widely used as non-etiotropic agents in these conditions and hence are both theoretically repurposable for COVID-19. However, a warning from some research reports and National Authorities raised NSAIDs safety concerns because of the supposed induction of ACE2 protein levels (the receptor used by SARS-CoV2 to enter host airways cells), the risk of bacterial superinfections MESHD and masking of disease MESHD symptoms. As a consequence, the use of NSAIDs was, and is, strongly discouraged while the alternative adoption of paracetamol is still preferred.On the basis of novel data and hypothesis on the possible role of scarce glutathione (GSH) levels in the exacerbation of COVID-19 and of the GSH depleting activity of PAC, this commentary raises the question of whether PAC may produce an oxidative imbalance which could be detrimental in COVID-19 clinical outcomes.

    Inflammasome activation in COVID-19 patients

    Authors: Tamara S Rodrigues; Keyla SG Sa; Adriene Y Ishimoto; Amanda Becerra; Samuel Oliveira; Leticia Almeida; Augusto V Goncalves; Debora B Perucello; Warrison A Andrade; Ricardo Castro; Flavio P Veras; Juliana E Toller-Kawahisa; Daniele C Nascimento; Mikhael HF de Lima; Camila MS Silva; Diego B Caetite; Ronaldo B Martins; Italo A Castro; Marjorie C Pontelli; Fabio C de Barros; Natalia B do Amaral; Marcela C Giannini; Leticia P Bonjorno; Maria Isabel F Lopes; Maira N Benatti; Rodrigo C Santana; Fernando C Vilar; Maria Auxiliadora-Martins; Rodrigo Luppino-Assad; Sergio CL de Almeida; Fabiola R de Oliveira; Sabrina S Batah; Li Siyuan; Maira N Benatti; Thiago M Cunha; Jose C Alves-Filho; Fernando Q Cunha; Larissa D Cunha; Fabiani G Frantz; Tiana Kohlsdorf; Alexandre T Fabro; Eurico Arruda; Rene DR de Oliveira; Paulo Louzada-Junior; Dario S Zamboni

    doi:10.1101/2020.08.05.20168872 Date: 2020-08-06 Source: medRxiv

    Severe cases of COVID-19 are characterized by a strong inflammatory process that may ultimately lead to organ failure and patient death MESHD. The NLRP3 inflammasome is a molecular platform that promotes inflammation MESHD via cleavage and activation of key inflammatory molecules including active caspase-1 (Casp1p20), IL-1{beta} and IL-18. Although the participation of the inflammasome in COVID-19 has been highly speculated, the inflammasome activation and participation in the outcome of the disease MESHD is unknown. Here we demonstrate that the NLRP3 inflammasome is activated in response to SARS-CoV-2 infection MESHD and it is active in COVID-19, influencing the clinical outcome of the disease MESHD. Studying moderate and severe COVID-19 patients, we found active NLRP3 inflammasome in PBMCs and tissues of post-mortem patients upon autopsy. Inflammasome-derived products such as Casp1p20 and IL-18 in the sera correlated with the markers of COVID-19 severity, including IL-6 and LDH. Moreover, higher levels of IL-18 and Casp1p20 are associated with disease MESHD severity and poor clinical outcome. Our results suggest that the inflammasome is key in the pathophysiology of the disease MESHD, indicating this platform as a marker of disease MESHD severity and a potential therapeutic target for COVID-19.

    Predictive Parameters for the Worsening Clinical Course of Mild COVID-19 Pneumonia MESHD Pneumonia HP

    Authors: Cho Rom Hahm; Young Kyung Lee; Dong Hyun Oh; Mi Young Ahn; Jae-Phil Choi; Na Ree Kang; Jungkyun Oh; Hanzo Choi; Suhyun Kim

    doi:10.21203/ Date: 2020-08-06 Source: ResearchSquare

    Background: This study aimed to determine parameters for worsening oxygenation in mild COVID-19 pneumonia MESHD pneumonia HP.Methods: This retrospective cohort study included confirmed COVID-19 pneumonia MESHD pneumonia HP in a single public hospital in South Korea from January to April 2020. Parameters were compared between the two groups on the basis of clinical course: the desaturation group was defined as those with oxygen saturation ≤ 94% on ambient air, or received oxygen or mechanical ventilation (MV) throughout the clinical course versus the nonevent group who were without any respiratory event up to 28 days. The severity and extent of viral pneumonia MESHD pneumonia HP from an initial single chest CT were calculated using artificial intelligence (AI) algorithms and measured visually by a radiologist. Results: We included 136 patients with 32 (23.5%) in the desaturation group, of whom two needed MV and one died. Initial vital signs and duration of symptoms showed no difference between the two groups, however, univariate logistic regression analysis revealed that a variety of parameters at admission were associated with an increased risk of a desaturation event. In a sex-, age TRANS-, and comorbid illness-matched case-control study, ferritin ≥ 280 μg/L (OR 3.600, 95% CI 1.142-11.346; p=0.029), LDH≥ 240 U/L (OR 3.600, 95% CI 1.142-11.346; p=0.029), pneumonia MESHD pneumonia HP burden (OR 1.010, 95% CI 1.002-1.019; p=0.021), and extent (OR 1.194, 95% CI 1.017-1.401; p=0.030) by AI, and visual severity scores (OR 1.146, 95% CI 1.005-1.307; p=0.042) were the predictive parameters for worsening clinical course with desaturation. Conclusion: Our study presents initial CT parameters measured by AI or visual severity scoring as well as serum SERO markers of inflammation MESHD at admission as the best parameters for predicting worsening oxygenation in the COVID-19 pneumonia MESHD pneumonia HP cohort. Initial chest CT scans may help clinicians diagnose viral pneumonia MESHD pneumonia HP and evaluate the prognosis in mild COVID-19. 

    Alveolitis in severe SARS-CoV-2 pneumonia MESHD pneumonia HP is driven by self-sustaining circuits between infected alveolar macrophages and T cells

    Authors: Rogan A Grant; Luisa Morales-Nebreda; Nikolay S Markov; Suchitra Swaminathan; Estefany R Guzman; Darryl A Abbott; Helen K Donnelly; Alvaro Donayre; Isaac A Goldberg; Zasu M Klug; Nicole Borkowski; Ziyan Lu; Hermon Kihshen; Yuliya Politanska; Lango Sichizya; Mengjia Kang; Ali Shilatifard; Chao Qi; A Christine Argento; Jacqueline M Kruser; Elizabeth S Malsin; Chiagozie O Pickens; Sean Smith; James M Walter; Anna E Pawlowski; Daniel Schneider; Prasanth Nannapaneni; Hiam Abdala-Valencia; Ankit Bharat; Cara J Gottardi; GR Scott Budinger; Alexander A Misharin; Benjamin David Singer; Richard G Wunderink; - The NU SCRIPT Study Investigators

    doi:10.1101/2020.08.05.238188 Date: 2020-08-05 Source: bioRxiv

    Some patients infected with Severe Acute Respiratory Syndrome MESHD Coronavirus-2 (SARS-CoV-2) develop severe pneumonia MESHD pneumonia HP and the acute respiratory distress HP syndrome MESHD (ARDS). Distinct clinical features in these patients have led to speculation that the immune response to virus in the SARS-CoV-2-infected alveolus differs from other types of pneumonia MESHD pneumonia HP. We collected bronchoalveolar lavage fluid samples from 86 patients with SARS-CoV-2-induced respiratory failure HP and 252 patients with known or suspected pneumonia MESHD pneumonia HP from other pathogens and subjected them to flow cytometry and bulk transcriptomic profiling. We performed single cell RNA-Seq in 5 bronchoalveolar lavage fluid samples collected from patients with severe COVID-19 within 48 hours of intubation. In the majority of patients with SARS-CoV-2 infection MESHD at the onset of mechanical ventilation, the alveolar space is persistently enriched in alveolar macrophages and T cells without neutrophilia HP. Bulk and single cell transcriptomic profiling suggest SARS-CoV-2 infects alveolar macrophages that respond by recruiting T cells. These T cells release interferon-gamma to induce inflammatory cytokine release from alveolar macrophages and further promote T cell recruitment. Our results suggest SARS-CoV-2 causes a slowly unfolding, spatially-limited alveolitis in which alveolar macrophages harboring SARS-CoV-2 transcripts and T cells form a positive feedback loop that drives progressive alveolar inflammation MESHD.

    IFN-γ and TNF-α drive a CXCL10+ CCL2+ macrophage phenotype expanded in severe COVID-19 and other diseases MESHD with tissue inflammation MESHD

    Authors: Lorien Shakib; Sara Shanaj; Aparna Nathan; - Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus; Laura T. Donlin

    doi:10.1101/2020.08.05.238360 Date: 2020-08-05 Source: bioRxiv

    Immunosuppressive and anti-cytokine treatment may have a protective effect for patients with COVID-19. Understanding the immune cell states shared between COVID-19 and other inflammatory diseases MESHD with established therapies may help nominate immunomodulatory therapies. Using an integrative strategy, we built a reference by meta-analyzing > 300,000 immune cells from COVID-19 and 5 inflammatory diseases MESHD including rheumatoid arthritis MESHD rheumatoid arthritis HP (RA), Crohn disease MESHD (CD), ulcerative colitis MESHD ulcerative colitis HP (UC), lupus, and interstitial lung disease MESHD. Our cross- disease MESHD analysis revealed that an FCN1+ inflammatory macrophage state is common to COVID-19 bronchoalveolar lavage samples, RA synovium, CD ileum, and UC colon. We also observed that a CXCL10+ CCL2+ inflammatory macrophage state is abundant in severe COVID-19, inflamed CD and RA, and expresses inflammatory genes such as GBP1, STAT1, and IL1B. We found that the CXCL10+ CCL2+ macrophages are transcriptionally similar to blood SERO-derived macrophages stimulated with TNF- and IFN-{gamma} ex vivo. Our findings suggest that IFN-{gamma}, alongside TNF-, might be a key driver of this abundant inflammatory macrophage phenotype in severe COVID-19 and other inflammatory diseases MESHD, which may be targeted by existing immunomodulatory therapies.

    Varicella Zoster Virus Induced Acute Retinal Necrosis MESHD Following Acute Meningoencephalitis MESHD in a Patient with Presumed COVID-19

    Authors: Kiana Hassanpour; Faezeh Khorasanizadeh; Hamid Ahmadieh; Mahmood Nabavi; Narsis Daftarian; Alireza Ramezani

    doi:10.21203/ Date: 2020-08-05 Source: ResearchSquare

    Background: To report the coincidence of acute retinal necrosis syndrome MESHD (ARN) following acute meningoencephalitis MESHD and presumed coronavirus disease MESHD 2019 (COVID-19) in an immunocompetent patient. Case presentation: A 58-year old female TRANS presented to our emergency MESHD department complaining of sudden unilateral visual loss HP following a recent hospitalization for a viral meningoencephalitis MESHD. Magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, polymerase chain reaction (PCR) of the aqueous humor, reverse transcriptase polymerase chain reaction (RT-PCR) of the nasopharyngeal swab specimen, chest computed tomography (CT), and fundus photography were performed for the patient. Ophthalmic examination revealed severe ocular inflammation MESHD and yellowish patches of necrotizing retinitis MESHD retinitis HP in the right eye compatible with the diagnosis of ARN. The result of PCR on the aqueous humor was positive for VZV. The patient received one intravitreal ganciclovir injection and 10 days intravenous ganciclovir followed by oral acyclovir. The patient underwent COVID-19 screening tests; chest CT-scan showed the features highly suggestive for COVID-19 while the RT-PCR was negative two times. Two months later, BCVA reached 20/70 in the right eye. The anterior chamber reaction and KPs resolved and the vitreous haziness significantly decreased Conclusion: A case of VZV induced ARN following acute meningoencephalitis MESHD was observed in association with presumed COVID-19. This could be an incidental finding in the pandemic era of COVID-19; however, it could also suggest that COVID-19 might trigger ARN in cases having latent herpes family viruses. 

    The DHODH Inhibitor PTC299 Arrests SARS-CoV-2 Replication and Suppresses Induction of Inflammatory Cytokines

    Authors: Jeremy Luban; Rachel Sattler; Elke Muhlberger; Jason D. Graci; Liangxian Cao; Marla Weetall; Christopher Trotta; Joseph M. Colacino; Sina Bavari; Caterina Strambio-De-Castillia; Ellen L. Suder; Yetao Wang; Veronica Soloveva; Katherine Cintron-Lue; Nikolai A. Naryshkin; Mark Pykett; Ellen M. Welch; Ronald Kong; Elizabeth Goodwin; Allan Jacobson; Slobodan Paessler; Stuart Peltz

    doi:10.1101/2020.08.05.238394 Date: 2020-08-05 Source: bioRxiv

    The coronavirus disease MESHD 2019 (COVID-19) pandemic has created an urgent need for therapeutics that inhibit the SARS-CoV-2 virus and suppress the fulminant inflammation MESHD characteristic of advanced illness. Here, we describe the anti-COVID-19 potential of PTC299, an orally available compound that is a potent inhibitor of dihydroorotate dehydrogenase (DHODH), the rate-limiting enzyme of the de novo pyrimidine biosynthesis pathway. In tissue culture, PTC299 manifests robust, dose-dependent, and DHODH-dependent inhibition of SARS CoV-2 replication (EC50 range, 2.0 to 31.6 nM) with a selectivity index >3,800. PTC299 also blocked replication of other RNA viruses, including Ebola virus. Consistent with known DHODH requirements for immunomodulatory cytokine production, PTC299 inhibited the production of interleukin (IL)-6, IL-17A (also called IL-17), IL-17F, and vascular endothelial growth factor (VEGF) in tissue culture models. The combination of anti-SARS-CoV-2 activity, cytokine inhibitory activity, and previously established favorable pharmacokinetic and human safety profiles render PTC299 a promising therapeutic for COVID-19.

    Aprepitant as a combinant with Dexamethasone reduces the inflammation MESHD via Neurokinin 1 Receptor Antagonism in severe to critical Covid-19 patients and potentiates respiratory recovery: A novel therapeutic approach

    Authors: Riffat Mehboob; Fridoon Ahmad; Ahad Qayyum; Muhammad Asim Rana; Muhammad Akram Tariq; Javed Akram

    doi:10.1101/2020.08.01.20166678 Date: 2020-08-04 Source: medRxiv

    Background: Corona virus infection MESHD is a respiratory infection MESHD, compromising the normal breathing in critical patients by damaging the lungs. Researches are ongoing to find an efficient treatment strategy for this disease MESHD by either inactivating the virus or boosting the immune system of patient or by managing the cytokine storm. Aim: To evaluate the clinical outcomes of Substance P receptor Neurokinin 1 antagonist in Covid 19 patients against the usual treatments as controls. Patients and Methods: It is a randomized clinical trial, open label, having two arms, one receiving normal management and care while other receiving Neurokinin 1 Receptor antagonist, Aprepitant, in addition. Dexamethasone, a corticosteroid is also administered orally to both the groups. PCR positive, hospitalized patients with more than 18 years of age TRANS, both genders TRANS, moderate to critical phase were included. 18 patients were randomly allocated in both arms, having 10 in group A and 8 in group B. Lab investigations were performed in both the groups before and after the intervention. We report preliminary results for the comparison of Aprepitant 80 mg given once daily for 3 to 5 days vs routine management. The primary outcome was total in hospital days and duration of disease MESHD. Results: Mean age TRANS of patients in group A was 47.63 +12.07years while 60.90+ 9.75 years in group TRANS B. There were 3 males TRANS in group A and 8 in group B. There were 2 critical patients in group A and 5 in group B. Biochemical and hematological parameters in both groups didnot show much difference except the C reactive protein reduction in the intervention group, indicative of a reduced inflammation MESHD. Oxygen saturation also improved but more patients should be enrolled to get a statistically significant data. One patient was discharged from each group within 5 days and one patient expired in each. Conclusions: It is a pilot study but the findings give a strong clue for the therapeutic potential of Aprepitant. Patients who received a combination therapy of Aprepitant and Dexamethasone were recovered earlier and showed improved clinical outcomes, laboratory findings and reduced C reactive protein which is an inflammatory marker. We suggest here a study on larger sample size to get a deeper insight of its potential and efficacy. It may be more effective in severe to critical patients having respiratory difficulties.

    Decreased Eosinophil Counts HP and Elevated Lactate Dehydrogenase Predict Severe COVID-19 Patients with Underlying Chronic Airway Diseases MESHD

    Authors: Lingling Yi; Dian Chen; Shuchen Zhang; Yuchen Feng; Wenliang Wu; Chenli Chang; Shengchong Chen; Guohua Zhen

    doi:10.21203/ Date: 2020-08-04 Source: ResearchSquare

    Background: Several predictors for the severity of coronavirus disease MESHD 2019 (COVID-19) have been reported, including decreased circulating lymphocytes and eosinophil counts. However, chronic airway inflammation MESHD characterized by accumulated lymphocytes or eosinophils may affect the pathogenesis of COVID-19. We aimed to investigate the predictors for the severity of COVID-19 in patients with chronic airway diseases MESHD.Methods: In this retrospective cohort study, we reviewed medical records of all laboratory-confirmed COVID-19 patients with chronic bronchitis MESHD chronic bronchitis HP, chronic obstructive pulmonary disease MESHD chronic obstructive pulmonary disease HP (COPD) and asthma MESHD asthma HP admitted in Sino-French New City Branch of Tongji Hospital, a large regional hospital in Wuhan, China, from January 26th to April 3rd. The Tongji Hospital ethics committee approved this study.Results: There were 59 patients with underlying chronic airway inflammation MESHD including chronic bronchitis MESHD chronic bronchitis HP, COPD, and asthma MESHD asthma HP. When compared with non-severe patients, severe patients were more likely to have decreased lymphocyte counts (0.6 vs. 1.1× 10⁹/L, p < 0.001), eosinopenia (< 0.02 × 10⁹/L, 73% vs. 24%, p < 0.001), increased lactate dehydrogenase (LDH) (471.0 vs. 230.0 U/L, p < 0.001) and elevated IL-6 level (47.4 vs. 5.7 pg/ml, p = 0.002) on admission. Eosinopenia and elevated LDH were significantly associated with disease MESHD severity in both univariate and multivariate regression models included the above variables. Eosinopenia was also an independent risk factor for mortality of this cohort in a multivariate model included the above variables. Moreover, eosinophil counts and LDH levels tended to return to normal range over time in both groups after treatment and severe patients recovered slower than non-severe patients, especially eosinophil counts.Conclusions: Eosinopenia and elevated LDH are potential predictors of disease MESHD severity in COVID-19 patients with underlying chronic airway diseases MESHD. Theses predictors may help clinicians identify the severe COVID-19 patients with chronic bronchitis MESHD chronic bronchitis HP, COPD, and asthma MESHD asthma HP.

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MeSH Disease
Human Phenotype

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