Corpus overview


MeSH Disease

Human Phenotype


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    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.

    Elevated oxygen demand in a case of COVID-19 with severe ARDS: a point for optimal oxygenation therapy including ECMO management

    Authors: Taku Oshima; Takehiko Oami; Mana Yamashiro; Akiko Higashi; Yosuke Hayashi; Natsumi Suga; Shin Takayanagi; Seiichiro Sakao; Taka-aki Nakada

    doi:10.21203/ Date: 2020-07-30 Source: ResearchSquare

    Background: Coronavirus disease MESHD 2019 (COVID-19) caused by SARS-CoV-2 has become a global pandemic, and those developing critically ill conditions have been reported to have mortality in the range of 39% to 61%. Due to the lack of definitive treatments, mechanical ventilation and supportive oxygenation therapy are key management strategies for the survival of patients with acute respiratory distress HP syndrome MESHD (ARDS). Optimizing oxygenation therapy is mandatory to treat patients with severe respiratory failure HP, to sufficiently compensate for the oxygen (O2) demand. We experienced a case of severe ARDS due to COVID-19 successfully treated with extracorporeal membrane oxygenation (ECMO) after increasing oxygen delivery according to O2 consumption measurement by indirect calorimetryCase Presentation: A 29-year-old obese but otherwise healthy man was hospitalized for treatment of COVID-19 pneumonia MESHD pneumonia HP presenting with a 4-day history of persisting cough MESHD cough HP, high fever MESHD fever HP, and dyspnea MESHD dyspnea HP. Mechanical ventilation, nitric oxide inhalation, and prone positioning were initiated in the ICU against severe respiratory dysfunction. Indirect calorimetry on the 3rd and 6th ICU days revealed persistent elevation of oxygen consumption (VO2) of 380 mL/min. Veno-venous ECMO was initiated on the 7th ICU day after further deterioration of respiratory failure HP. Periodic events of SpO2 decline due to effortful breathing was not resolved by neuromuscular blockade in attempt to reduce O2 consumption. Increasing the ECMO flow induced hemolysis MESHD and hyperkalemia MESHD hyperkalemia HP despite the use of large bore cannulas and ECMO circuit free of clots and defects. The hemoglobin management level was elevated from 10 g/dL to 13 g/dL to increase blood SERO oxygen capacity, enabling the reduction of ECMO flow while attenuating respiratory effort and maintaining SpO2. Lung protective ventilation strategy and prone positioning were continued for successful weaning from ECMO on the 16th ICU day, and the ventilator on the 18th ICU day.Conclusion: The present case of severe ARDS due to COVID-19 was successfully treated with ECMO. Enhancing oxygen delivery was crucial to compensate for the elevated O2 demand. Measuring O2 consumption by indirect calorimetry can elucidate the oxygen demand for optimizing the oxygenation therapy for successful management and survival of critically ill COVID-19 patients. 

    60-day survival of critically ill COVID-19 first comers

    Authors: Corinna N. Lang; V. Zotzmann; B. Schmid; M. Berchtold-Herz; S. Utzolino; P.M. Biever; T. Pottgießer; D. Duerschmied; C. Bode; T. Wengenmayer; D.L. Staudacher

    doi:10.21203/ Date: 2020-07-29 Source: ResearchSquare

    Background: Germany reported sufficient intensive care unit (ICU) resources throughout the first wave of coronavirus disease MESHD 2019 (COVID-19). The treatment of critically ill COVID-19 patients without rationing may improve the outcome. We therefore analyzed resources allocated to critically ill COVID-19 patients and their outcomes. Methods: Retrospectively, we enrolled SARS-CoV2 PCR positive patients with respiratory failure HP from 03/08/2020 to 04/08/2020 and followed until 05/28/2020 in the university hospital of Freiburg, Germany. Results: Thirty-four COVID-19 patients were admitted to the ICU in the defined interval with medium age TRANS of 67±13 (31-86) years. 6/34 (17.6%) were female TRANS. All patients suffered from moderate or severe acute respiratory distress HP syndrome MESHD (ARDS), 91.2% of the patients were intubated and 23.5% required extracorporeal membrane oxygenation (ECMO). Proning was performed in 67.6%, renal replacement therapy (RRT) was required in 35.3%. 96% required more than 20 nursing hours per day. Mean ICU stay was 21±19 (1-81) days. 60-day survival of critically ill COVID-19 patients was 50.0% (17/34). Causes of death MESHD were multi-organ failure (52.9%), refractory ARDS (17.6%) and intracerebral hemorrhage MESHD (17.6%). Conclusions: Treatment of critically ill COVID-19 patients is protracted and resource intense. In a context without resources shortage, 50% of critically ill COVID-19 survived up to 60 days.

    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.

    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.

    Early initiation of Extracorporeal Blood SERO Purification using the AN69ST (oXiris®) hemofilter as a treatment modality for COVID - 19 patients: a single-centre case series

    Authors: Petar Ugurov; Dijana Popevski; Tanja Gramosli; Dashurie Neziri; Dragica Vuckova; Emil Stoicovski; Lidija Veljanovska-Kiridjievska; Katerina Ignevska; Sanja Mehandziska; Elena Ambarkova; Rodney Alexander Rosalia; Zan Mitrev

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

    Introduction: Our understanding of the COVID-19 disease MESHD has been steadily evolving since the original outbreak in December 2019. Advanced disease MESHD is characterised by a hyperinflammatory state, systemic coagulopathies and multiorgan involvement, in particular respiratory distress HP. We here describe our initial experience with treating of COVID-19 patients based on early initiation of extracorporeal blood SERO purification, systemic heparinisation and respiratory support.Methods: 15 patients were included; 2 were females TRANS. We monitored real-time several biochemical, immunological and coagulation biomarkers associated with disease MESHD severity following admission to our dedicated COVID-19 intensive care unit. To guide personalised treatment, we monitored among others levels of IL-6, IL-8, TNF-α, C-Reactive Protein (CRP), Neutrophil-to-Lymphocyte ratios, Thrombocyte counts, D-Dimers, Fibrinogen, and Activation Clotting time (ACT).Treatment consisted of individualised respiratory support supplemented with 1 - 4 cycles of 24-hour Extracorporeal Organ Support (ECOS) and Blood SERO Purification using the AN69ST (oXiris®) hemofilter. We administered heparin (300 U/kg) to counter suspected hypercoagulability HP (= elevated Fibrinogen or D-dimers) states to maintain ACT ≥ 180 seconds.Results: N = 10 presented with severe to critical disease MESHD (= dyspnoea, hypoxia MESHD, respiratory rate > 30/min, peripheral oxygen saturation < 90%, or > 50% lung involvement on X-ray imaging). A single case was admitted with a critical condition (= respiratory failure HP). One patient died after 5 days of hospitalisation after developing Acute Respiratory Syndrome MESHD. 8 Patients have been discharged - average ICU length-of-stay was 9.9 ± 2.4 days. Clinical improvement was associated with normalisation (increase) of thrombocytes, white blood SERO cells, stable levels of IL-6 (< 50 ng/mL) and a decrease of CRP and Fibrinogen. Conclusion: Means to monitor COVID-19 disease MESHD severity during hospitalisation are crucial to control disease progression MESHD and prevent hyperinflammation and irreversible multiorgan failure. We present here a real-time monitoring system accounting for biochemical, immunological, coagulation parameters and radiological imaging. The combination of systemic heparin anticoagulation regimens and blood SERO purification may prevent hyperinflammation, thromboembolism MESHD thromboembolism HP during hospitalisation and thus support clinical recovery. 

    Identification of Risk Factors for in-hospital Death MESHD of COVID - 19 Pneumonia MESHD Pneumonia HP

    Authors: Zhigang Wang; Zhiqiang Wang

    doi:10.21203/ Date: 2020-07-13 Source: ResearchSquare

    Objective: To examine the clinical characteristics and identify independent risk factors for in-hospital mortality of 2019 novel coronavirus (COVID-19) pneumonia MESHD pneumonia HP.Methods: A total of 156 patients diagnosed with COVID-19 pneumonia MESHD pneumonia HP at the central Hospital of Wuhan from January 29, 2020, to March 20, 2020 were enrolled in this single-centered retrospective study. Their epidemiological parameters, clinical presentations, underlying diseases MESHD, laboratory test results and disease MESHD outcomes were collected and analyzed. Results: The median age TRANS of enrolled patients was 66. Underlying diseases MESHD were identified in 101 patients, with hypertension MESHD hypertension HP being the most common one, followed by cardiovascular disease MESHD and diabetes. The most common symptoms identified upon admission were fever MESHD fever HP, cough MESHD cough HP, dyspnea MESHD dyspnea HP and fatigue MESHD fatigue HP. Compared to survival cases, patients who dead during hospitalization had higher plasma SERO levels of D-dimer, creatinine, creatine kinase, lactate dehydrogenase, lactate and lower percentage of lymphocytes (LYM [%]), platelet count and albumin levels. Most enrolled patients received anti-biotics and anti-viral treatment. In addition, 60 patients received corticosteroid and 51 received intravenous immunoglobulin infusion. 44 patients received noninvasive ventilation, 19 received invasive ventilation. Respiratory failure HP was the most frequently observed complication (106 [67.9%]), followed by sepsis MESHD sepsis HP (103 [66.0%]), acute respiratory distress HP syndrome MESHD (ARDS) (67 [42.9%]) and septic shock MESHD shock HP (50 [32.1%]). Multivariable regression suggested that advanced age TRANS (OR [odds ratio]= 1.059, 95% CI [confidence interval]: 1.011-1.110, P= 0.016) and elevated lactate level upon admission (OR= 2.411, 95% CI: 1.177-4.941, P= 0.016) were independent risk factors for in-hospital mortality for COVID-19 infection MESHD. Meanwhile, increased LYM (%) at admission (OR= 0.798, 95% CI: 0.728-0.876, P< 0.001) indicated a better prognosis. Conclusions: In this study, we discovered that age TRANS, LYM (%) and lactate level upon admission were independent factors that could influence in-hospital mortality rate.

    Disease MESHD severity-specific neutrophil signatures in blood SERO transcriptomes stratify COVID-19 patients

    Authors: Anna C. Aschenbrenner; Maria Mouktaroudi; Benjamin Kraemer; Nikolaos Antonakos; Marie Oestreich; Konstantina Gkizeli; Melanie Nuesch-Germano; Maria Saridaki; Lorenzo Bonaguro; Nico Reusch; Kevin Bassler; Sarantia Doulou; Rainer Knoll; Tal Pecht; Theodore S. Kapellos; Nikoletta Rovina; Charlotte Kroeger; Miriam Herbert; Lisa Holsten; Arik Horne; Ioanna D. Gemuend; Shobhit Agrawal; Kilian Dahm; Martina van Uelft; Anna Drews; Lena Lenkeit; Niklas Bruse; Jelle Gerretsen; Jannik Gierlich; Matthias Becker; Kristian Haendler; Michael Kraut; Heidi Theis; Simachew Mengiste; Elena De Domenico; Jonas Schulte-Schrepping; Lea Seep; Jan Raabe; Christoph Hoffmeister; Michael ToVinh; Verena Keitel; Gereon J. Rieke; Valentina Talevi; Ahmad N. Aziz; Peter Pickkers; Frank van de Veerdonk; Mihai G. Netea; Joachim L. Schultze; Matthijs Kox; Monique M.B. Breteler; Jacob Nattermann; Antonia Koutsoukou; Evangelos J. Giamarellos-Bourboulis; Thomas Ulas

    doi:10.1101/2020.07.07.20148395 Date: 2020-07-08 Source: medRxiv

    The SARS-CoV-2 pandemic is currently leading to increasing numbers of COVID-19 patients all over the world. Clinical presentations range from asymptomatic TRANS, mild respiratory tract infection MESHD respiratory tract infection HP, to severe cases with acute respiratory distress HP syndrome MESHD, respiratory failure HP, and death MESHD. Reports on a dysregulated immune system in the severe cases calls for a better characterization and understanding of the changes in the immune system. Here, we profiled whole blood SERO transcriptomes of 39 COVID-19 patients and 10 control donors enabling a data-driven stratification based on molecular phenotype. Neutrophil activation-associated signatures were prominently enriched in severe patient groups, which was corroborated in whole blood SERO transcriptomes from an independent second cohort of 30 as well as in granulocyte samples from a third cohort of 11 COVID-19 patients. Comparison of COVID-19 blood SERO transcriptomes with those of a collection of over 2,600 samples derived from 11 different viral infections MESHD, inflammatory diseases MESHD and independent control samples revealed highly specific transcriptome signatures for COVID-19. Further, stratified transcriptomes predicted patient subgroup-specific drug candidates targeting the dysregulated systemic immune response of the host.

    Plasma SERO IL-6 Levels following Corticosteroid Therapy as an Indicator of ICU Length of Stay in Critically ill COVID-19 Patients

    Authors: Samir Awasthi; Tyler Wagner; AJ Venkatakrishnan; Arjun Puranik; Matthew Hurchik; Vineet Agarwal; Ian Conrad; Christian Kirkup; Raman Arunachalam; John O'Horo; Walter Kremers; Rahul Kashyap; William Morice; John Halamka; Amy W Williams; William A Faubion; Andrew D Badley; Gregory J Gores; Venky Soundararajan

    doi:10.1101/2020.07.02.20144733 Date: 2020-07-03 Source: medRxiv

    Intensive Care Unit (ICU) admissions and mortality in severe COVID-19 patients are driven by cytokine storms and acute respiratory distress HP syndrome MESHD (ARDS). Interim clinical trial results suggest that the corticosteroid dexamethasone displays superior 28-day survival in severe COVID-19 patients requiring ventilation or oxygen. Among 16 patients with plasma SERO IL-6 measurement post-corticosteroid administration, a higher proportion of patients with an IL-6 value over 10 pg/mL have worse outcomes (i.e. ICU Length of Stay > 15 days or death MESHD) when compared to 41 patients treated with non-corticosteroid drugs including antivirals, tocilizumab, azithromycin, and hydroxychloroquine (p-value = 0.0024). Given this unexpected clinical association between post-corticosteroid IL-6 levels and COVID-19 severity, we hypothesized that the Glucocorticoid Receptor (GR or NR3C1) may be coupled to IL-6 expression in specific cell types that govern cytokine release syndrome MESHD (CRS). Examining single cell RNA-seq data from bronchoalveolar lavage fluid of severe COVID-19 patients and nearly 2 million human cells from a pan-tissue scan shows that alveolar macrophages, smooth muscle cells, and endothelial cells co-express both NR3C1 and IL-6. The mechanism of Glucocorticoid Receptor (GR) agonists mitigating pulmonary and multi-organ inflammation MESHD in some COVID-19 patients with respiratory failure HP, may be in part due to their successful antagonism of IL-6 production within lung macrophages and vasculature.

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MeSH Disease
Human Phenotype

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