Corpus overview


MeSH Disease

Human Phenotype


    displaying 21 - 30 records in total 258
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    Increased number of pulmonary megakaryocytes in COVID-19 patients with diffuse alveolar damage. An autopsy study with clinical correlation and review of the literature.

    Authors: Mariel F. Valdivia-Mazeyra; Clara Salas; Jesús M. Nieves-Alonso; Luz Martín-Fragueiro; Carmen Bárcena; Patricia Muñoz-Hernández; Karen Villar-Zarra; Javier Martín-López; Fernando Ramasco-Rueda; Javier Fraga; José A. Jiménez-Heffernan

    doi:10.21203/ Date: 2020-07-25 Source: ResearchSquare

    Megakaryocytes are normally present in the lung where they play a role in platelet homeostasis. The latter are well known to participate in the pathogenesis of lung damage, particularly in acute lung injury MESHD. Although megakaryocytes are usually not mentioned as a characteristic histopathologic finding associated to acute pulmonary injury, a few studies point out that their number is increased in the lungs of patients with diffuse alveolar damage. In this autopsy study we have observed a relevant number of pulmonary megakaryocytes in COVID-19 patients dying with acute respiratory distress HP syndrome MESHD. We have studied pulmonary tissue samples of 18 patients most of which died after prolonged disease MESHD and use of mechanical ventilation. Most samples showed fibroproliferative or fibrotic diffuse alveolar damage and an increased number of megakaryocytes. In six, thrombi of the pulmonary microcirculation were seen. We compare our findings with previous published autopsy reports, mainly focusing on the description of megakaryocytes. Our patients showed abnormal coagulation parameters with high levels of fibrinogen, D-dimers and variable thrombocytopenia MESHD thrombocytopenia HP. Since the lung is considered an active site of megakariopoiesis, a prothrombotic status leading to platelet activation, aggregation and consumption may trigger a compensatory pulmonary response. An increased number of pulmonary megakaryocytes suggests and supports a relation with the thrombotic events so often seen in COVID-19. Regardless of its etiology, future studies of patients dying with acute pulmonary injury should include pulmonary megakaryocytes as a histologic variable of interest.

    Chronic Hemodialysis Patients have better outcomes with COVID-19 - a retrospective cohort study

    Authors: Ashutossh Naaraayan; Abhishek Nimkar; Amrah Hasan; Sushil Pant; Momcilo Durdevic; Henrik Elenius; Corina Nava Suarez; Prasanta Basak; Kameswari Lakshmi; Michael Mandel; Stephen Jesmajian

    doi:10.1101/2020.07.22.20159202 Date: 2020-07-24 Source: medRxiv

    Introduction Several comorbid conditions, have been identified as risk factors in patients with COVID-19. However, there is a dearth of data describing the impact of COVID-19 infection MESHD in patients with end-stage renal disease MESHD on hemodialysis (ESRD-HD). Methods This retrospective case series analyzed 362 adult TRANS patients consecutively hospitalized with confirmed COVID-19 illness between March 12, 2020 and May 13, 2020, at a teaching hospital in the New York City metropolitan area. Primary outcome was severe pneumonia MESHD pneumonia HP as defined by the World Health Organization. Secondary outcomes were: 1) the Combined Outcome of Acute respiratory distress HP syndrome MESHD or in-hospital Death MESHD (COAD), and 2) the need for High-levels of Oxygen supplementation (HiO2). Results Patients with ESRD-HD had lower odds for poor outcomes including severe pneumonia MESHD pneumonia HP [Odds Ratio (OR) 0.4, Confidence Interval (CI) (0.2-0.9) p=.04], HiO2 [OR 0.3, CI (0.1-0.8) p=.02] and COAD [OR 0.4, CI (0.2-1.05) p=.06], when compared to patients without ESRD. In contrast, higher odds for severe pneumonia MESHD pneumonia HP, COAD and HiO2 were seen with advancing age TRANS. African-Americans were over-represented in the hospitalized patient cohort, when compared to their representation in the community (35% vs 18%). Hispanics had higher odds for severe-illness and HiO2 when compared to Caucasians. Conclusions Patients with ESRD-HD had a milder course of illness with a lower likelihood of severe pneumonia MESHD pneumonia HP and a lesser need for aggressive oxygen supplementation when compared to patients not on chronic dialysis. This protective effect, might have a pathophysiologic basis and needs to be further explored.

    Cell type-specific immune dysregulation HP in severely ill COVID-19 patients

    Authors: Changfu Yao; Stephanie A Bora; Tanyalak Parimon; Tanzira Zaman; Oren A Friedman; Joseph A Palatinus; Nirmala S Surapaneni; Yuri P Matusov; Giuliana Cerro Chiang; Alexander G Kassar; Nayan Patel; Chelsi ER Green; Adam W Aziz; Harshpreet Suri; Jo Suda; Andres A Lopez; Gislaine A Martins; Barry R Stripp; Sina A Gharib; Helen S Goodridge; Peter Chen

    doi:10.1101/2020.07.23.20161182 Date: 2020-07-24 Source: medRxiv

    Coronavirus disease MESHD 2019 (COVID-19) has quickly become the most serious pandemic since the 1918 flu pandemic. In extreme situations, patients develop a dysregulated inflammatory lung injury MESHD called acute respiratory distress HP syndrome MESHD (ARDS) that causes progressive respiratory failure HP requiring mechanical ventilatory support. Recent studies have demonstrated immunologic dysfunction in severely ill COVID-19 patients. To further delineate the dysregulated immune response driving more severe clinical course from SARS-CoV-2 infection MESHD, we used single-cell RNA sequencing (scRNAseq) to analyze the transcriptome of peripheral blood SERO mononuclear cells (PBMC) from hospitalized COVID-19 patients having mild disease MESHD (n = 5), developing ARDS (n = 6), and recovering from ARDS (n = 6). Our data demonstrated an overwhelming inflammatory response with select immunodeficiencies HP within various immune populations in ARDS patients. Specifically, their monocytes had defects in antigen presentation and deficiencies in interferon responsiveness that contrasted the higher interferon signals in lymphocytes. Furthermore, cytotoxic activity was suppressed in both NK and CD8 lymphocytes whereas B cell activation was deficient, which is consistent with the delayed viral clearance in severely ill COVID-19 patients. Finally, we identified altered signaling pathways in the severe group that suggests immunosenescence and immunometabolic changes could be contributing to the dysfunctional immune response. Our study demonstrates that COVID-19 patients with ARDS have an immunologically distinct response when compared to those with a more innocuous disease MESHD course and show a state of immune imbalance in which deficiencies in both the innate and adaptive immune response may be contributing to a more severe disease MESHD course in COVID-19.

    Sequential use of hemadsorption using Cytosorb® and Biosky® filter- technology in a COVID-19 patient suffering from severe ARDS 

    Authors: Matthias Mezger; Ingo Eitel; Stephan Ensminger; Dirk Pogorzalek; Zhipan Huang; Tobias Graf

    doi:10.21203/ Date: 2020-07-22 Source: ResearchSquare

    In March 2020, the World Health Organization (WHO) declared the novel coronavirus disease MESHD (COVID- 19) pandemic. Here, we present the case of a patient who was admitted to our hospital with acute respiratory distress HP syndrome MESHD (ARDS) following infection MESHD with COVID-19. After initial stabilization through restrictive fluid management, hemadsorption using Cytosorb® was performed and finally temporary extubation of the patient was possible. However, the patient again clinically deteriorated and needed ventilation and finally ECMO-support and high catecholamine application. Whilst being on VV- ECMO, hemadsorption using Biosky® MG 350 filter was performed. In this manuscript, after a brief overview of the role of hemadsorption in ARDS, a detailed case presentation is followed by a critical discussion of the current literature.

    In-silico modeling of COVID-19 ARDS: pathophysiological insights and potential management implications

    Authors: Anup Das; Sina Saffaran; Marc Chikhani; Timothy Scott; Marianna Laviola; Nadir Yehya; John Laffey; Jonathan G. Hardman; Declan G. Bates

    doi:10.1101/2020.07.21.20158659 Date: 2020-07-22 Source: medRxiv

    Objectives: Patients with COVID-19 Acute Respiratory Distress HP Syndrome MESHD (CARDS) appear to present with at least two distinct phenotypes: severe hypoxemia HP with relatively well-preserved lung compliance and lung gas volumes (Type 1) and a more conventional ARDS phenotype displaying the typical characteristics of the baby lung (Type 2). We aimed to test plausible hypotheses regarding the pathophysiological mechanisms underlying CARDS, and to evaluate the resulting implications for ventilatory management. Design: We adapted a high-fidelity computational simulator, previously validated in several studies of ARDS, to (a) develop quantitative insights into the key pathophysiologic differences between CARDS and conventional ARDS, and (b) assess the impact of different PEEP, FiO2 and tidal volume settings. Setting: Interdisciplinary Collaboration in Systems Medicine Research Network. Subjects: The simulator was calibrated to represent CARDS patients with both normal and elevated body mass indices undergoing invasive mechanical ventilation. Measurements and Main Results: An ARDS model implementing disruption of hypoxic pulmonary vasoconstriction and vasodilation leading to hyperperfusion of collapsed lung regions failed to replicate clinical data on Type 1 CARDS patients. Adding mechanisms to reflect disruption of alveolar gas-exchange due to the effects of pneumonitis, and heightened vascular resistance due to the emergence of microthrombi, produced levels of V/Q mismatch and hypoxemia HP consistent with data from Type 1 CARDS patients, while preserving close to normal lung compliance and gas volumes. Atypical responses to PEEP increments between 5 and 15 cmH2O were observed for this Type 1 CARDS model across a range of measures: increasing PEEP resulted in reduced lung compliance and no improvement in oxygenation, while Mechanical Power, Driving Pressure and Plateau Pressure all increased. FiO2 settings based on ARDSnet protocols at different PEEP levels were insufficient to achieve adequate oxygenation. Incrementing tidal volumes from 5 to 10 ml/kg produced similar increases in multiple indicators of ventilator induced lung injury MESHD in the Type 1 CARDS model to those seen in a conventional ARDS model. Conclusions: Our model suggests that use of standard PEEP/ FiO2 tables, higher PEEP strategies, and higher tidal volumes, may all be potentially deleterious in Type 1 CARDS patients, and that a highly personalized approach to treatment is advisable.

    The folate antagonist methotrexate diminishes replication of the coronavirus SARS-CoV-2 and enhances the antiviral efficacy of remdesivir in cell culture models

    Authors: Kim M Stegmann; Antje Dickmanns; Sabrina Gerber; Vella Nikolova; Luisa Klemke; Valentina Manzini; Denise Schloesser; Cathrin Bierwirth; Julia Freund; Maren Sitte; Raimond Lugert; Gabriela Salinas; Dirk Goerlich; Bernd Wollnik; Uwe Gross; Matthias Dobbelstein

    doi:10.1101/2020.07.18.210013 Date: 2020-07-20 Source: bioRxiv

    The search for successful therapies of infections MESHD with the coronavirus SARS-CoV-2 is ongoing. We tested inhibition of host cell nucleotide synthesis as a promising strategy to decrease the replication of SARS-CoV-2-RNA, thus diminishing the formation of virus progeny. Methotrexate (MTX) is an established drug for cancer therapy and to induce immunosuppression. The drug inhibits dihydrofolate reductase and other enzymes required for the synthesis of nucleotides. Strikingly, the replication of SARS-CoV-2 was inhibited by MTX in therapeutic concentrations around 1 M, leading to more than 1000-fold reductions in virus progeny in Vero C1008 (Vero E6) as well as Calu-3 cells. Virus replication was more sensitive to equivalent concentrations of MTX than of the established antiviral agent remdesivir. MTX strongly diminished the synthesis of viral structural proteins and the amount of released virus RNA. Virus replication and protein synthesis were rescued by folinic acid (leucovorin) and also by inosine, indicating that purine depletion is the principal mechanism that allows MTX to reduce virus RNA synthesis. The combination of MTX with remdesivir led to synergistic impairment of virus replication, even at 300 nM MTX. The use of MTX in treating SARS-CoV-2 infections MESHD still awaits further evaluation regarding toxicity and efficacy in infected organisms, rather than cultured cells. Within the frame of these caveats, however, our results raise the perspective of a two-fold benefit from repurposing MTX for treating COVID-19. Firstly, its previously known ability to reduce aberrant inflammatory responses might dampen respiratory distress HP. In addition, its direct antiviral activity described here would limit the dissemination of the virus. SIGNIFICANCEO_LIMTX is one of the earliest cancer drugs to be developed, giving rise to seven decades of clinical experience. It is on the World Health Organizations List of Essential Medicines, can be administered orally or parenterally, and its costs are at single digit {euro} or $ amounts/day for standard treatment. In case of its successful further preclinical evaluation for treating SARS-CoV-2 infections MESHD, its repurposing to treat COVID-19 would thus be feasible, especially under low-resource conditions. C_LIO_LIAdditional drugs exist to interfere with the synthesis of nucleotides, e.g. additional folate antagonists, inhibitors of GMP synthetase, or inhibitors of dihydroorotate dehydrogenase (DHODH). Such inhibitors have been approved as drugs for different purposes and might represent further therapeutic options against infections MESHD with SARS-CoV-2 C_LIO_LIRemdesivir is currently the most established drug for treating COVID-19. Our results argue that MTX and remdesivir, even at moderate concentrations, can act in a synergistic fashion to repress virus replication to a considerably greater extent than either drug alone. C_LIO_LICOVID-19, in its severe forms, is characterized by pneumonia MESHD pneumonia HP and acute respiratory distress HP syndrome MESHD, and additional organ involvements. These manifestations are not necessarily a direct consequence of virus replication and cytopathic effects, but rather a result of an uncontrolled inflammatory and immune response. Anti-inflammatory drugs such as glucocorticoids are thus being evaluated for treating COVID-19. However, this bears the risk of re-activating virus spread by suppressing a sufficient and specific immune response. In this situation, it is tempting to speculate that MTX might suppress both excessive inflammation MESHD as well as virus replication at the same time, thus limiting both the pathogenesis of pneumonia MESHD pneumonia HP and also the spread of virus within a patient. C_LI

    Can Adenosine Fight COVID-19 Acute Respiratory Distress HP Syndrome MESHD?

    Authors: Carmela Falcone; Massimo Caracciolo; Pierpaolo Correale; Sebastiano Macheda; Eugenio Giuseppe Vadalà; Stefano La Scala; Marco Tescione; Roberta Danieli; Anna Ferrarelli; Maria Grazia Tarsitano; Lorenzo Romano; Antonino De Lorenzo

    id:10.20944/preprints202007.0426.v1 Date: 2020-07-19 Source:

    Some COVID-19 patients develop interstitial pneumonia MESHD pneumonia HP that can evolve into Acute Respiratory Distress HP Syndrome MESHD (ARDS). This is accompanied by an inflammatory cytokine storm. SarS-CoV has proteins capable of promoting cytokine storm, especially in patients with comorbidities, including obesity MESHD obesity HP. Since there is currently no resolutive therapy for ARDS and given the scientific literature regarding the use of adenosine, its application has been hypothesized. Adenosine through its receptors is able to inhibit the acute inflammatory process, increase the protection capacity of the epithelial barrier and reduce the damage due to an overactivation of the immune system, such as in cytokine storms. These features are known in ischemia MESHD / reperfusion models and could also be exploited in acute lung injury MESHD, with hypoxia MESHD. In light of these hypotheses, for compassionate use, a COVID-19 patient, with unresponsive respiratory failure HP, was treated with adenosine. The results showed a rapid and clear improvement in clinical conditions, with the negative effect of detection of SarS-CoV2.

    Identifying organ dysfunction trajectory-based subphenotypes in critically ill patients with COVID-19

    Authors: Chang Su; Zhenxing Xu; Katherine Hoffman; Parag Goyal; Monika M Safford; Jerry Lee; Sergio Alvarez-Mulett; Luis Gomez-Escobar; David R Price; John S Harrington; Lisa K Torres; Fernando J Martinez; Thomas R Campion Jr.; Rainu Kaushal; Augustine M.K. Choi; Fei Wang; Edward J Schenck

    doi:10.1101/2020.07.16.20155382 Date: 2020-07-18 Source: medRxiv

    Rationale. COVID-19-associated respiratory failure HP offers the unprecedented opportunity to evaluate the differential host response to a uniform pathogenic insult. Prior studies of Acute Respiratory Distress HP Syndrome MESHD (ARDS) have identified subphenotypes with differential outcomes. Understanding whether there are distinct subphenotypes of severe COVID-19 may offer insight into its pathophysiology. Objectives. To identify and characterize distinct subphenotypes of COVID-19 critical illness MESHD defined by the post-intubation trajectory of Sequential Organ Failure Assessment (SOFA) score. Methods. Intubated COVID-19 patients at two hospitals in New York city were leveraged as development and validation cohorts. Patients were grouped into mild, intermediate, and severe strata by their baseline post-intubation SOFA. Hierarchical agglomerative clustering was performed within each stratum to detect subphenotypes based on similarities amongst SOFA score trajectories evaluated by Dynamic Time Warping. Statistical tests defined trajectory subphenotype predictive markers. Measurements and Main Results. Distinct worsening and recovering subphenotypes were identified within each stratum, which had distinct 7-day post-intubation SOFA progression trends. Patients in the worsening suphenotypes had a higher mortality than those in the recovering subphenotypes within each stratum (mild stratum, 29.7% vs. 10.3%, p=0.033; intermediate stratum, 29.3% vs. 8.0%, p=0.002; severe stratum, 53.7% vs. 22.2%, p<0.001). Worsening and recovering subphenotypes were replicated in the validation cohort. Routine laboratory tests, vital signs, and respiratory variables rather than demographics and comorbidities were predictive of the worsening and recovering subphenotypes. Conclusions. There are clear worsening and recovering subphenotypes of COVID-19 respiratory failure HP after intubation, which are more predictive of outcomes than baseline severity of illness. Organ dysfunction trajectory may be well suited as a surrogate for research in COVID-19 respiratory failure HP.


    Authors: Enric Monreal; Susana Sainz de la Maza; Elena Natera-Villalba; Alvaro Beltran-Corbellini; Fernando Rodriguez-Jorge; Jose Ignacio Fernandez-Velasco; Paulette Walo-Delgado; Alfonso Muriel; Javier Zamora; Araceli Alonso-Canovas; Jesus Fortun; Luis Manzano; Beatriz Montero-Errasquin; Lucienne Costa-Frossard; Jaime Masjuan; Luisa Maria Villar

    doi:10.1101/2020.07.17.20156315 Date: 2020-07-17 Source: medRxiv

    INTRODUCTION: Despite the increasing evidence of the benefit of corticosteroids for the treatment of moderate-severe Coronavirus disease MESHD 2019 (COVID-19) patients, no data are available about the potential role of high doses of steroids for these patients. METHODS: All consecutive confirmed COVID-19 patients admitted to a single center were selected, including those treated with steroids and an acute respiratory distress HP syndrome MESHD (ARDS). Patients were allocated to the high doses (HD, 250mg/day or more of methylprednisolone) of corticosteroids or the standard doses (SD, 1.5mg/kg/day or more of methylprednisolone) at discretion of treating physician. The primary endpoint was the mortality between both cohorts and secondary endpoints were the risk of need for mechanical ventilation (MV) or death MESHD and the risk of developing a severe ARDS. RESULTS: 573 patients were included: 428 (74.7%) men, with a median (IQR) age TRANS of 64 (54-73) years. In HD cohort, a worse baseline respiratory situation was observed and male TRANS sex, older age TRANS and comorbidities were significantly more common. After adjusting by baseline characteristics, HD were associated with a higher mortality than SD (adjusted-OR 2.46, 95% CI 1.58-3.83, p<0.001) and with an increased risk of needing MV or death MESHD (adjusted-OR 2.50, p=0.001). Conversely, the risk of developing a severe ARDS was similar between groups. Interaction analysis showed that HD increased mortality exclusively in elderly TRANS patients. CONCLUSION: Our real-world experience advises against exceeding 1-1.5mg/kg/day of corticosteroids for severe COVID-19 with an ARDS, especially in older subjects. This reinforces the rationale of modulating rather than suppressing immune responses in these patients.

    Lung ultrasound and computed tomography to monitor COVID-19 pneumonia MESHD pneumonia HP in critically ill patients: a two-center prospective cohort study

    Authors: Micah Heldeweg; Jorge A. Lopez Matta; Mark E. Haaksma; Jasper M. Smit; Carlos V. Elzo Kraemer; Harm-Jan S. de Grooth; E. de Jonge; L.J. Meijboom; Leo M.A. Heunks; David J. van Westerloo; Pieter Roel Tuinman

    doi:10.21203/ Date: 2020-07-17 Source: ResearchSquare

    Background: Lung ultrasound can adequately monitor disease MESHD severity in pneumonia MESHD pneumonia HP and acute respiratory distress HP syndrome MESHD. We hypothesize lung ultrasound can adequately monitor COVID-19 pneumonia MESHD pneumonia HP in critically ill patients. Methods: Adult TRANS patients with COVID-19 pneumonia MESHD pneumonia HP admitted to the intensive care unit of two academic hospitals who underwent a 12-zone lung ultrasound and a chest CT examination were included. Baseline characteristics, and outcomes including composite endpoint death MESHD or ICU stay >30 days were recorded. Lung ultrasound and CT images were quantified as a Lung Ultrasound Score Involvement index (LUSI) and CT Severity Involvement index (CTSI). Primary outcome was the correlation, agreement, and concordance between LUSI and CTSI. Secondary outcome was the association of LUSI and CTSI with the composite endpoints.Results: We included 55 ultrasound examinations in 34 patients, which were 88% were male TRANS, with a mean age TRANS of 63 years and mean P/F ratio of 151. The correlation between LUSI and CTSI was strong (r=0.795), with an overall 15% bias, and limits of agreement ranging -40 to 9.7. Concordance between changes in sequentially measured LUSI and CTSI was 81%. In the univariate model, high involvement on LUSI and CTSI were associated with a composite endpoint. In the multivariate model, LUSI was the only remaining independent predictor.Conclusions: Lung ultrasound can be used as an alternative for chest CT in monitoring COVID-19 pneumonia MESHD pneumonia HP in critically ill patients as it can quantify pulmonary involvement, register changes over the course of the disease MESHD, and predict death MESHD or ICU stay >30 days.Trial registration: NTR, NL8584. registered 01 May 2020 - retrospectively registered,

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MeSH Disease
Human Phenotype

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