Corpus overview


MeSH Disease

Human Phenotype


    displaying 1 - 10 records in total 14
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    Lack of Tocilizumab effect on mortality in COVID19 patients

    Authors: Holt, Gregory E; Batra, Mayank; Murthi, Mukunthan; Kambali, Shweta; Santos, Kayo; Perez Bastidas, Maria Virginia; Asif, Huda; Haddadi, Sara; Arias, Sixto; Mirsaeidi, Mehdi

    doi:10.21203/ Date: 2020-07-01 Source: ResearchSquare

    Off-label tocilizumab use in COVID-19 patients reflects concern for cytokine release syndrome MESHD. Comparison of matched COVID-19 pneumonia MESHD pneumonia HP patients found elevated IL-6 levels correlated with mortality that did not change with tocilizumab administration. Correlating mortality with increased IL-6 doesn’t imply causality however lack of improvement by tocilizumab requires clinical trial alterations.

    Pulse Therapy with Corticosteroids and Intravenous Immunoglobulin in the Management of Severe Tocilizumab-Resistant COVID-19: A Report of Three Clinical Cases

    Authors: Mikhail V. Sheianov; Yurii D. Udalov; Sergei S. Ochkin; Andrei N. Bashkov; Dmitrii N. Shikunov; Aleksandra P. Netrebina; Artem I. Kryntsilov; Aleksandr E. Ozerov; Aleksandr S. Samoilov

    id:10.20944/preprints202006.0260.v1 Date: 2020-06-21 Source:

    Three patients with severe life-threatening COVID-19 who failed to achieve substantial improvement on tocilizumab, received pulse therapy with corticosteroids (methylprednisolone, 1000 mg/day IV for three consecutive days) and intravenous immunoglobulin (20 g/day IV). This was associated with a prompt resolution of respiratory failure HP, elimination of cytokine release syndrome MESHD, and reversal of pulmonary CT changes. The treatment was generally safe and well tolerated. There was no evidence of protracted persistence of the virus in the patients who received pulse therapy. Randomized controlled trials are necessary to specify the efficacy and safety of high-dose methylprednisolone and intravenous immunoglobulin in the treatment of severe life-threatening COVID-19 separately or in combination.

    Life-threatening cardiogenic shock MESHD cardiogenic shock HP in a pediatric patient with SARS-CoV-2-associated myocarditis MESHD myocarditis HP treated with remdesivir: a case description and report of similar cases from the Literature

    Authors: Silvia Molinari; Lucia M.D. Colasanto; Maria L. Melzi; Alessandro Cattoni; Roberto Panceri; Michela Bombino; Giuseppe Lapadula; Andrea Biondi

    doi:10.21203/ Date: 2020-06-12 Source: ResearchSquare

    BackgroundChildren are relatively spared from Coronavirus disease MESHD 2019 (COVID-19), but some severe cases have been reported. Severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) infection MESHD in children TRANS may affect the cardiovascular system. We hereby report about a case of myocarditis MESHD myocarditis HP evolving to cardiogenic shock MESHD cardiogenic shock HP in a SARS-CoV-2 positive child TRANS.Case presentationAn otherwise healthy 12-year-old patient was admitted with fever MESHD fever HP, vomiting MESHD vomiting HP, diarrhoea and drowsiness HP, without any respiratory symptoms. He was diagnosed with COVID-19 on nasopharyngeal swab. He developed hypotension MESHD hypotension HP and cardiogenic shock MESHD cardiogenic shock HP. Bedside echocardiography revealed left ventricular impairment with an ejection fraction (LVEF) below 25%. Plasmatic markers of myocardial injury were remarkably raised, as well as inflammatory biomarkers, including procalcitonin (highest recorded value: 66 ng/mL) and interleukin-6 (8209 pg/mL). The child TRANS was transferred to Intensive Care Unit and he was treated with catecholamine support, mechanical ventilation and empiric anti-infectious therapy, including broad spectrum antibiotics and the antiviral agent remdesivir. All additional microbiological investigations yielded negative results. We observed a gradual improvement of LVEF within 5 days. A cardiac magnetic resonance confirmed the suspicion of myocarditis MESHD myocarditis HP. After 21 days of hospitalisation, the child TRANS was discharged without sequelae.ConclusionsOur hypothesis is that the child TRANS suffered from SARS-CoV-2-induced fulminant myocarditis MESHD myocarditis HP, probably in the setting of cytokine release syndrome MESHD (CRS). The peculiarity of this SARS-CoV-2 infection MESHD is the presence of cardiac failure in a previously healthy child TRANS without a respiratory illness. The positive outcome is in line with published Literature about the overall better prognosis of COVID-19 children TRANS compared to adults TRANS. Remdesivir, an investigational antiviral therapy, may have played a role on the clinical improvement of the child TRANS.

    Cytokine Release Syndrome MESHD-Associated Encephalopathy HP in Patients with COVID-19

    Authors: Peggy Perrin; Nicolas Collongues; Seyyid Baloglu; Dimitri Bedo; Xavier Bassand; Thomas Lavaux; Gabriela Gautier; Nicolas Keller; Stephane Kremer; Samira Fafi-Kremer; Bruno Moulin; Ilies Benotmane; Sophie Caillard

    id:10.20944/preprints202006.0103.v1 Date: 2020-06-07 Source:

    Severe disease MESHD and uremia MESHD are risk factors for neurological complications of coronavirus disease MESHD-2019 (COVID-19). An in-depth analysis of a case series was conducted to describe the neurological manifestations of patients with COVID-19 and gain pathophysiological insights that may guide clinical decision-making – especially with respect to the cytokine release syndrome MESHD (CRS). Extensive clinical, laboratory, and imaging phenotyping was performed in five patients. Neurological presentation included confusion MESHD confusion HP, tremor MESHD tremor HP, cerebellar ataxia MESHD ataxia HP, behavioral alterations, aphasia MESHD aphasia HP, pyramidal syndrome MESHD, coma MESHD coma HP, cranial nerve palsy, dysautonomia, and central hypothyroidism HP hypothyroidism MESHD. Neurological disturbances were remarkably accompanied by laboratory evidence of CRS. SARS-CoV-2 was undetectable in the cerebrospinal fluid. Hyperalbuminorachy and increased levels of the astroglial protein S100B were suggestive of blood SERO-brain barrier (BBB) dysfunction. Brain MRI findings comprised evidence of acute leukoencephalitis (n = 3, of whom one with a hemorrhagic form), cytotoxic edema MESHD edema HP mimicking ischemic stroke HP stroke MESHD (n = 1), or normal results (n = 2). Treatment with corticosteroids and/or intravenous immunoglobulins was attempted – resulting in rapid recovery from neurological disturbances in two cases. Patients with COVID-19 can develop neurological manifestations that share clinical, laboratory, and imaging similarities with those of chimeric antigen receptor-T cell-related encephalopathy HP. The pathophysiological underpinnings appear to involve CRS, endothelial activation, BBB dysfunction, and immune-mediated mechanisms.

    COVID-19 pathophysiology may be driven by a loss of inhibition of the Renin-Angiotensin-Aldosterone System

    Authors: Susanne Rysz; Jonathan Al-Saadi; Anna Sjöström; Maria Farm; Francesca Campoccia Jalde; Michael Plattén; Helen Eriksson; Margareta Klein; Roberto Vargas-Paris; Sven Nyrén; Goran Abdula; Russell Ouellette; Tobias Granberg; Malin Jonsson Fagerlund; Johan Lundberg

    doi:10.21203/ Date: 2020-05-29 Source: ResearchSquare

    SARS-CoV-2 enters the cell through the ACE2 receptor, which is considered one of the main inhibitors in the Renin-Angiotensin-Aldosterone System (RAAS).1​ ,2 The virus has been shown to downregulate the ACE2 receptor, leading to a subsequent increase in the vasopressoragentangiotensinII.3​ Evidently,criticalcoronavirusdisease2019(COVID-19)is thought to be due to a dysregulated immune response, causing a cytokine-release syndrome MESHD eventually leading to acute respiratory distress HP syndrome MESHD (ARDS).4​ ,5 ​However, several reports on clinical laboratory features and case-descriptions of critically ill patients with COVID-19 show discrepancies compared to typical ARDS. Here, we show that infusing swines with angiotensin II induces a pathophysiological syndrome MESHD closely resembling that of patients with RT-PCR-positive COVID-19. By using multimodal clinical imaging of patients, comparing laboratory data and translational histological features, we show that it is highly likely that an increase in RAAS is one, if not the main, pathogenic feature in critical COVID-19. Furthermore, it is plausible that this large animal model can be used to screen for potential new treatments for patients with severe COVID-19 and that MRI lung perfusion can be used to evaluate the outcome of potential treatments targeting the pathophysiological syndrome MESHD

    Cytokine release syndrome MESHD is not usually caused by secondary hemophagocytic lymphohistiocytosis MESHD in a cohort of 19 critically ill COVID-19 patients

    Authors: Georg Lorenz; Philipp Moog; Quirin Bachmann; Paul La Rosee; Heike Schneider; Michaela Schlegl; Christoph Spinner; Uwe Heemann; Roland M Schmid; Hana Algül; Tobias Lahmer; Wolfgang Huber; Christoph Schmaderer

    doi:10.21203/ Date: 2020-05-27 Source: ResearchSquare

    Background: Severe COVID-19 associated respiratory failure HP, poses the one challenge of our days. Assessment and treatment of COVID-19 associated hyperinflammation may be key to improve outcomes. It was speculated that in subgroups of patients secondary hemophagocytic lymphohistiocytosis MESHD (sHLH) or cytokine release syndrome MESHD (CRS) with features of macrophage activation syndrome MESHD might drive severe disease MESHD trajectories. If confirmed, profound immunosuppressive therapy would be a rationale treatment approach.Methods: Over a median observation period of 11 (IQR: 8; 16) days, 19 consecutive confirmed severe COVID-19-patients admitted to our intensive-care-unit were tested for presence of sHLH by two independent experts. HScores and 2004-HLH diagnostic criteria were assessed. Patients were grouped according to short-term clinical courses: discharge from ICU versus ongoing ARDS or death MESHD at time of analysis.Results: The median HScore at admission was 157 (IQR: 98;180), without the key clinical triad of HLH, i.e. progressive cytopenia, persistent fever MESHD fever HP and organomegaly. Independent expert chart review revealed the absence of sHLH in all cases. No patient reached more than 3/6 of modified HLH 2004 criteria. Nevertheless, patients presented hyperinflammation with peripheral neutrophilic signatures (neutrophil/lymphocyte-ratio>3.5). The latter best paralleled their short-term clinical courses, with declining relative neutrophil numbers prior to extubation (4.4, [IQR: 2.5;6.3]; n=8) versus those with unfavourable courses (7.6, [IQR: 5.2;31], n=9).Conclusion: Our study rules out virus induced sHLH as the leading cause of most severe-COVID-19 trajectories. Instead, an associated innate neutrophilic hyperinflammatory response or virus-associated-CRS appears dominant in patients with an unfavourable clinical course. Therapeutic implications are discussed.

    COVID-19 Perfect Storm (Part I): Cytokine Release Syndrome MESHD in Aged TRANS People

    Authors: Sirio Fiorino; Claudio Gallo; Maddalena Zippi; Sergio Sabbatani; Roberto Manfredi; Renzo Moretti; Elisa Fogacci; Caterina Maggioli; Francesca Travasoni Loffredo; Enrico Giampieri; Ivan Corazza; Christoph Dickmans; Claudio Denitto; Michele Cammarosano; Michele Battilana; Paolo Emilio Orlandi; Francesco Del Forno; Francesco Miceli; Michela Visani; Giorgia Acquaviva; Paolo Leandri; Elio Jovine; Roberto Jovine; Dario de Biase

    id:202005.0303/v1 Date: 2020-05-18 Source:

    Objectives: In December 2019 a novel human-infecting coronavirus, SARS-CoV-2, has emerged. The WHO has stated the epidemic as a “public health emergency MESHD of international concern”. A drammatic situation has emerged with thousands of deaths MESHD, occurring mainly in the aged TRANS and very ill people. Epidemiological studies suggest that immune system function is impaired in elderly TRANS individuals and these subjects often present a severe deficiency in nutrients as fatsoluble and hydrosoluble vitamins. Design: In this first part of the review about Cov2 in aged TRANS people, we searched for reviews describing the characteristics of autoimmune diseases MESHD and the available therapeutic protocols for their treatment. We sed them as a paradigm with the purpose to retrieve pathogenetic mechanisms in common among these pathological conditions and SARS-CoV-2 infection MESHD, as well as the alteration induced in immune system function by this virus, or by its homologous SARS-CoV. Results: SARS-CoV-2 infection MESHD induces an important immune system dysfunction with the development of an exhuberant proinflammatory response in the host, and with the development of a life-threatening condition defined as Cytokine Release Syndrome MESHD (CRS). This leads to the Acute Respiratory Syndrome MESHD (ARDS), mainly in the aged TRANS people. High mortality and lethality rates have been observed in the elderly TRANS subjects with CoV-2-related infection MESHD. Conclusion: These diseases MESHD may serve as a paradigm for the study of CRS emerging in the course of SARS CoV-2 infection MESHD. This review discusses about the possible activity of Vitamin A, D, E and C in restoring normal antiviral Immune System function or the potential therapeutic role of these micronutrients as a part of a multi-treatment strategy against SARS- CoV-2 infection MESHD.

    Lysosomotropic Active Compounds—Hidden Protection against COVID-19 / SARS-CoV-2 Infection MESHD?

    Authors: Markus Blaess; Lars Kaiser; Martin Sauer; Hans-Peter Deigner

    id:10.20944/preprints202005.0061.v1 Date: 2020-05-05 Source:

    The COVID-19 pandemic is one of the largest challenges in medicine and health care worldwide in recent decades, and it is infecting and killing increasing numbers of people every day. In this paper, we discuss the possible relationships among lysosomotropism, increasing lysosomal pH, and the SARS-CoV-2 infection MESHD and disease MESHD process, and we deduce a possible approach for treatment and prophylaxis. Lysosomotropism is a biological characteristic of small molecules, such as (hydroxyl)chloroquine, amitriptyline, NB 06, or sertraline, which is present in addition to intrinsic receptor-mediated or enzymatic pharmacological effects. Lysosomotropic compounds affect prominent inflammatory messengers, such as IL1B, CCL4, CCL20, and IL6, as well as cathepsin L dependent viral entry (fusion) into host cells. Therefore, this heterogeneous group of compounds is a promising candidate for the prevention and treatment of SARS-CoV-2 infections MESHD, as well as influenza A infections MESHD and cytokine release syndrome MESHD (CRS) triggered by bacterial or viral infections MESHD. Patients who have already taken medications with lysosomotropic compounds for other pre-existing conditions may benefit from this treatment in the COVID-19 pandemic. Increased lysosomal pH levels play an important role in the disease MESHD process in common skin disorders, such as psoriasis MESHD and atopic dermatitis MESHD atopic dermatitis HP, thus suggesting that affected individuals might benefit from their particular conditions in the COVID-19 pandemic. We suggest data analysis of patients with these diseases MESHD, and who are treated with lysosomotropic compounds, and, if the results are promising, subsequent clinical testing of off-label therapy with clinically approved lysosomotropic compounds in the current COVID-19 pandemic and future influenza A pandemics.

    Disruption of the CCL5/RANTES-CCR5 Pathway Restores Immune Homeostasis and Reduces Plasma SERO Viral Load in Critical COVID-19

    Authors: Bruce Pattterson; Harish Seetthamraju; Kush Dhody; Michael Corley; Kazem Kazempour; Jay Lalezari; Alina Pang; Christopher Sugai; Edgar Francisco; Amruta Pise; Hallison Rodrigues; Matthew Ryou; Helen Wu; Gabriela Webb; Byung Park; Scott Kelly; Nader Pourhassan; Alena Lelic; Lama Kdouh; Monica Herrera; Eric Hall; Enver Aklin; Lishomwa Ndhlovu; Jonah Sacha

    doi:10.21203/ Date: 2020-05-02 Source: ResearchSquare

    Severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease MESHD 2019 (COVID-19), is now pandemic with nearly three million cases reported to date1. Although the majority of COVID-19 patients experience only mild or moderate symptoms, a subset will progress to severe disease MESHD with pneumonia MESHD pneumonia HP and acute respiratory distress HP syndrome MESHD (ARDS) requiring mechanical ventilation2. Emerging results indicate a dysregulated immune response characterized by runaway inflammation MESHD, including cytokine release syndrome MESHD (CRS), as the major driver of pathology in severe COVID-193,4. With no treatments currently approved for COVID-19, therapeutics to prevent or treat the excessive inflammation MESHD in severe disease MESHD caused by SARS-CoV-2 infection MESHD are urgently needed. Here, in 10 terminally-ill, critical COVID-19 patients we report profound elevation of plasma SERO IL-6 and CCL5 (RANTES), decreased CD8+ T cell levels, and SARS-CoV-2 plasma SERO viremia MESHD viremia HP. Following compassionate care treatment with the CCR5 blocking antibody SERO leronlimab, we observed complete CCR5 receptor occupancy on macrophage and T cells, rapid reduction of plasma SERO IL-6, restoration of the CD4/CD8 ratio, and a significant decrease in SARS-CoV-2 plasma SERO viremia MESHD viremia HP. Consistent with reduction of plasma SERO IL-6, single-cell RNA-sequencing revealed declines in transcriptomic myeloid cell clusters expressing IL-6 and interferon-related genes. These results demonstrate a novel approach to resolving unchecked inflammation MESHD, restoring immunologic deficiencies, and reducing SARS-CoV-2 plasma SERO viral load via disruption of the CCL5-CCR5 axis, and support randomized clinical trials to assess clinical efficacy of leronlimab-mediated inhibition of CCR5 for COVID-19.

    Potential of natural astaxanthin in alleviating the risk of cytokine storm and improve health in COVID-19: A scoping review

    Authors: Jayanta Talukdar; Bhaskar Bhadra; Santanu Dasgupta; Vinod Nagle

    doi:10.21203/ Date: 2020-05-02 Source: ResearchSquare

    Background: Natural astaxanthin as a potent anti-oxidant and broad-spectrum anti-inflammatory bioactive molecule plays important role in modulating the immune response, speculated to be a potential supplement to alleviate cytokine release storm in COVID-19. Objective: Review of published literature to summarize the rationale for possible benefits of natural astaxanthin to support COVID-19 patients. Methods: Retrieved relevant literature from electronic databases including Google scholar, PubMed, Scopus, etc. and reviewed following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Statement. We adapted the article as scoping review. Results: Cytokine release syndrome MESHD (CRS) is reported as a common feature in COVID-19, which can lead to potentially fatal, hyper-inflammatory acute respiratory distress HP condition, diagnosed with elevated serum SERO level of pro-inflammatory cytokines like IL-6, CRP, etc. that positively correlated with disease MESHD severity. Anti-inflammatory drug, like tocilizumab, etc. are under clinical trials as anti-CRS therapy. Astaxanthin can potentially alleviate CRS by regulating inflammatory cytokines by inhibiting the activities of NF-kB, TNF-α, JAK/STAT-3, etc. Available pre-clinical and clinical trials data support its excellent safety, and potential therapeutic and health benefits. Conclusions: Natural astaxanthin has tremendous potential as co-adjunctive supplement, desiring necessary clinical supports on its efficacy and beneficial against COVID-19.

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MeSH Disease
Human Phenotype

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