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.

    Rationale for the Use of Radiation-Activated Mesenchymal Stem Cells in Acute Respiratory Distress HP Syndrome MESHD

    Authors: Isabel Tovar Martín; Rosa Guerrero; Jesús Joaquín Lopez-Peñalver; José Expósito; José Mariano Ruiz de Almodóvar

    id:10.20944/preprints202008.0035.v1 Date: 2020-08-02 Source:

    Previously we have shown that the combination of radiotherapy with human-umbilical-cord-derived mesenchymal stem-cell therapy significantly reduces the size of the xenotumours in mice, both in the directly irradiated tumour and in the distant non-irradiated tumour or in its metastasis. We have also shown that exosomes secreted from mesenchymal stem-cells pre-irradiated with 2 Gy are quantitatively, functionally and qualitatively different from the exosomes secreted from non-irradiated mesenchymal cells and also that proteins, exosomes and microvesicles secreted by mesenchymal cells suffer a dramatic change when cells are activated or non-activated, with the amount of protein present in the exosomes of the pre-irradiated cells being 1.5-fold times greater compared to those from non-irradiated cells. This finding correlates with a dramatic increase in the anti-tumour activity of the exosomes secreted by pre-irradiated mesenchymal-cells. After the proteomic analysis of the load of the exosomes released from both irradiated and non-irradiated cells, we conclude that annexin A1 is the most important and significant difference between the exosomes released by the cells in either status. Knowing the role of annexin A1 in the control of hypoxia MESHD and inflammation MESHD which is characteristic of acute- distress-respiratory HP syndrome MESHD, we have designed a hypothetical therapeutic strategy, based on the transplantation of mesenchymal stem cells stimulated with radiation, to alleviate the symptoms of patients who, due to pneumonia MESHD pneumonia HP caused by COVID-19, require the care of an intensive care unit for patients with life-threatening conditions. With this hypothesis, we would seek to improve the patients’ respiratory capacity and increase the expectations of their cure.

    Treatment of sepsis MESHD sepsis HP-related Acute Respiratory Distress HP Syndrome MESHD with Vasoactive Intestinal Peptide

    Authors: Jihad G. Youssef; Sami Said; George Youssef; Matthew J. Javitt; Jonathan C Javitt

    doi:10.21203/ Date: 2020-08-01 Source: ResearchSquare

    Purpose: To assess the clinical safety and possible effectiveness of Vasoactive Intestinal Peptide in the treatment of Acute Respiratory Distress HP Syndrome MESHD (ARDS) related to sepsisMethods: Under FDA Investigational New Drug clearance, 8 patients with ARDS related to sepsis MESHD sepsis HP were treated with 50 pmole/kg/hr – 100 pmole/kg/hr of Vasoactive Intestinal Peptide by intravenous infusion for 12 hours. All patients were on mechanical ventilation and full telemetery.Results: No drug-related serious adverse events were seen. Hypotension was seen in association with two infusions and diarrhea MESHD diarrhea HP in association with one, but did not necessitate cessation of therapy. Bigeminy was seen in association with one infusion without sequelae. Seven of eight patients demonstrated a successful course during intensive care and were successfully removed from mechanical ventilation and discharged from intensive care. The eighth patient succumbed to purulent secretions in the lungs. Of those who were discharged from the ICU, six demonstrated successful 30 day survival. The seventh died from a cerebral infract at day 30, deemed unrelated to treatment with VIP. Serum levels of Tumor Necrosis MESHD Factor α were obtained in 6 patients at baseline and 24 hours and were seen to decrease with treatment in five patients.Conclusions: Initial clinical results of treatment with VIP in patients with ARDS demonstrated a safety profile consistent with previous studies in normal volunteers. The successful clinical course seen in 7 of 8 patients in the setting of an expected 50% survival may suggest that VIP shows promise in the treatment of other infectious conditions that damage the pulmonary epithelium, particularly COVID-19.Registration: This clinical trial was registered with under NCT00004494. Trial was registered before the first patient was enrolled.

    Mortality rate among critically ill patients with COVID-19 in a medical system with adequate hospital resources: a prospective observational study

    Authors: Christina Routsi; Eleni Magira; Stelios Kokkoris; Ilias Siembos; Charikleia Vrettou; Dimitris Zervakis; Eleni Ischaki; Sotiris Malahias; Ioanna Sigala; Andreas Asimakos; Theodora Daidou; Panagiotis Kaltsas; Evangelia Douka; Adamandia Sotiriou; Vassiliki Markaki; Prodromos Temberikidis; Apostolos Koroneos; Panagiotis Politis; Zafiria Mastora; Efrosini Dima; Theodoros Tsoutsouras; Ioannis Papahatzakis; Panagiota Gioni; Athina Strilakou; Aikaterini Maraguti; Eleftheria Mizi; Ageliki Kanavou; Aikaterini Sarri; Evdokia Gavrielatou; Spyros Mentzelopoulos; Ioannis Kalomenidis; Vassilios Papastamopoulos; Anastasia Kotanidou; Spyros G Zakynthinos

    doi:10.21203/ Date: 2020-08-01 Source: ResearchSquare

    Background: For critically ill patients with coronavirus disease MESHD 2019 (COVID-19) who require intensive care unit (ICU) admission, mortality rates vary widely depending on many factors, among which hospital resources and clinical setting seem important. We sought to determine the outcome of critically ill patients admitted in the usual multidisciplinary ICUs of a big referral for COVID-19 tertiary-care hospital with adequate resources.Methods: We performed a prospective observational study of all adult TRANS patients with COVID-19 consecutively admitted to four COVID-designated ICUs at Evangelismos Hospital, Athens, Greece, from March 11 to April 27, 2020.Results: Among 50 critically ill patients, ICU and hospital mortality for the entire cohort was 32% (16/50), whereas 66% (33/50) of patients were discharged alive from the ICU and 2% (1/50) were still treated in the ICU until June 16, 2020. ICU and hospital mortality for those who received invasive mechanical ventilation was 39% (16/41). Patients who eventually died had already increased risk of death MESHD on ICU admission, as suggested by the high values of the Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores, the presence of current malignancy and occurrence of cardiac arrest HP in 44% (7/16) of patients, and the general need for circulatory support by noradrenaline. Median PaO2/FiO2 on ICU admission for the entire cohort was 121 mmHg [interquartile range (IQR), 86-171 mmHg] and most patients had moderate and severe acute respiratory distress HP syndrome MESHD (ARDS) according to the Berlin Definition. The primary cause of death MESHD of all patients was multi-organ failure, most commonly due to sepsis MESHD sepsis HP, whereas none died from refractory hypoxemia HP, neurologic dysfunction or withdrawal of life support. Hospital stay was long in patients who survived [median 24 days (IQR, 15-35 days)] and was frequently complicated by bacteremias MESHD bacteremias HP [36% (12/33)].Conclusion: Severely ill COVID-19 patients with moderate and severe ARDS may have equal or even lower mortality rates compared to ARDS due to other causes, when they are admitted in general ICUs with experienced and adequate staff without limitations in hospital resources, where established ARDS therapies are used. 

    Montelukast in Hospitalized Patients Diagnosed with COVID-19

    Authors: Ahsan Khan; Christian Misdary; Nikhil Yegya-Raman; Sinae Kim; Navaneeth Narayanan; Sheraz Siddiqui; Padmini Salgame; Jared Radbel; Frank De Groote; Carl Michel; Janice Mehnert; Caleb Hernandez; Thomas Braciale; Jyoti Malhotra; Michael A. Gentile; Salma K. Jabbour

    doi:10.21203/ Date: 2020-08-01 Source: ResearchSquare

    Background Several therapeutic agents have been assessed for the treatment of COVID-19, but few approaches have been proven efficacious. Because leukotriene receptor antagonists such as montelukast have been shown to reduce both cytokine release and lung inflammation MESHD in preclinical models of viral influenza and acute respiratory distress HP syndrome MESHD, we hypothesized that therapy with montelukast would reduce clinical deterioration MESHD as measured by the COVID-19 Ordinal Scale.Methods We performed a retrospective analysis of COVID-19 confirmed hospitalized patients treated with or without montelukast. We used “clinical deterioration” as the primary endpoint, a binary outcome defined as any increase in the Ordinal Scale value from Day 1 to Day 3 of hospital stay, as these data were uniformly available for all admitted patients before hospital discharge. Rates of clinical deterioration MESHD between the montelukast and non-montelukast groups were compared using the Fisher’s exact test. Univariate logistic regression was also used to assess the association between montelukast use and clinical deterioration MESHD.Results A total of 92 patients were analyzed, 30 received montelukast at the discretion of the treating physician and 62 patients who did not receive montelukast. Patients receiving montelukast experienced significantly fewer events of clinical deterioration MESHD compared to patients not receiving montelukast (10% vs 32%, p = 0.022). Sensitivity SERO analysis among those without asthma MESHD asthma HP showed a trend toward fewer clinical deterioration MESHD events in the montelukast group than non-montelukast groups (11% vs 33%, p = 0.077). Sensitivity SERO analysis among those who did not receive azithromycin showed fewer clinical deterioration MESHD events in the montelukast group vs. non-montelukast groups (8% vs 32%, p = 0.030).Conclusions Our findings suggest that montelukast associates with a reduction in clinical deterioration MESHD for COVID-19 confirmed patients as measured on the COVID-19 Ordinal Scale. Montelukast may have activity in COVID-19 infection MESHD, and future efforts should evaluate this potential therapy.

    Intravenous immunoglobulin treatment for patients with severe COVID-19: a retrospective multi-center study

    Authors: Jiao Liu; Yizhu Chen; Ranran Li; Xuan Dong; Yizhong Li; Qianghong Xu; Huibin Feng; Sisi Huang; Jun Guo; Lidi Zhang; Xiaofei Ye; Wei Zhu; Hangxiang Du; Yong’an Liu; Tao Wang; Limin Chen; Zhenliang Wen; Jean-Louis Teboul; Dechang Chen

    doi:10.21203/ Date: 2020-08-01 Source: ResearchSquare

    Background: Intravenous immunoglobulin (IVIG) is commonly used to treat severe COVID-19, although the clinical outcomes remain unclear. This study evaluated the effectiveness of IVIG treatment for severe COVID-19.Methods: This retrospective multi-center study evaluated 28-day mortality and time for SARS-CoV-2 RNA clearance in severe COVID-19 patients with or without IVIG treatment. Propensity score matching was used to control confounding factors. Logistic regression and competing risk analyses were performed.Results: The study included 850 patients (421 patients received IVIG). No significant differences in 28-day mortality or time for SARS-CoV-2 RNA clearance were observed (p=0.357 and p=0.123, respectively). High-dose of IVIG treatment (>10 g/day) (n=27) was associated with decreased 28-day mortality (OR: 0.33, 95% CI: 0.14–0.77; p=0.011). The IVIG group had prolonged median hospitalization, less shock MESHD shock HP, and higher incidences of acute respiratory distress HP syndrome MESHD, myocardial injury. Furthermore, IVIG-treated patients were more likely to require non-invasive mechanical ventilation and less likely to require invasive mechanical ventilation.Conclusions: IVIG treatment for severe COVID-19 patients was not associated with significant improvements in 28-day mortality or time for SARS-CoV-2 RNA clearance. However, some improvements in 28-day survival were observed for high-dose IVIG treatment (>10 g/day).

    Covid-19-associated coagulopathy (CoAC): thrombin burst and insufficient fibrinolysis leading to bad outcome.

    Authors: Marco Ranucci; Clementina Sitzia; Ekaterina Baryshnikova; Umberto Di Dedda; Rosanna Cardani; Fabio Martelli; Massimiliano Corsi Romanelli

    doi:10.21203/ Date: 2020-08-01 Source: ResearchSquare

    Background: COVID-19 associated coagulopathy is characterized by a pro-thrombotic state. However, the nature of this pattern has not been comprehensively studied. We investigated the coagulation pattern of patients with COVID-19 acute respiratory distress HP syndrome MESHD (ARDS) comparing survivors to not survivors. Methods: Prospective cohort study conducted in the Intensive Care Unit (ICU) of a University Hospital . Twenty COVID-19 ARDS patients received measurements of markers of thrombin generation (prothrombin fragment 1+2, PF 1+2); fibrinolysis activation (tissue plasminogen activator, tPA) and inhibition (plasminogen activator inhibitor-2, PAI-2); fibrin synthesis (fibrinopeptide A) and fibrinolysis magnitude (plasmin-antiplasmin complex, PAP, and D-dimers). Measurements were done at the ICU admission and after 10-14 days. Results: The general pattern showed an increased thrombin generation, modest or null release of t-PA, and increased levels of PAI-2, Fibrinopeptide A, PAP and D-dimers. At baseline, non survivors had a significantly (P=0.014) higher PAI-2/PAP ratio than survivors (109, interquartile range [IQR] 18.1-216, vs. 8.7, IQR 2.9-12.6). At follow-up, thrombin generation was significantly (P=0.025) reduced in survivors (PF 1+2 from 396 pg/mL, IQR 185-585 to 237 pg/mL, IQR 120-393), whereas it increased in non-survivors. Fibrinolysis inhibition at follow-up remained stable in survivors, and increased in non-survivors, leading to a significant (P=0.026) difference in PAI-2 levels (161 pg/mL, IQR 50-334, vs. 1,088 pg/mL, IQR 177-1,565). Conclusions: Severe patterns of COVID-19 infection MESHD (ARDS) are characterized by a thrombin burst, triggered by the release of IL-6 and other cytokines, and the consequent release of Tissue Factor. Mechanisms of fibrinolysis regulation appear unbalanced toward fibrinolysis inhibition. In survivors, this pattern ameliorates, whereas in non-survivors it worsens, leading to the environment for clinically relevant thrombi generation, that was found in 58% of non-surviving patients. Trial registration: (NCT04441502).

    Corticosteroid therapy for corona virus disease MESHD 2019-related acute respiratory distress HP syndrome MESHD: a cohort study with propensity score analysis

    Authors: Chaomin Wu; Dongni Hou; Chunling Du; Yanping Cai; Junhua Zheng; Jie Xu; Xiaoyan Chen; Cuicui Chen; Xianglin Hu; Yuye Zhang; Juan Song; Lu Wang; Yen-cheng Chao; Yun Feng; Weining Xiong; Dechang Chen; Ming Zhong; Jie Hu; Jinjun Jiang; Chunxue Bai; Xin Zhou; Jinfu Xu; Fengyun Gong; Yuanlin Song

    doi:10.21203/ Date: 2020-08-01 Source: ResearchSquare

    Background The impact of corticosteroid therapy on outcomes of patients with Coronavirus disease MESHD-2019 (COVID-19) is highly controversial. We aimed to compare the risk of death MESHD between COVID-19-related ARDS patients with corticosteroid treatment and those without.Methods In this single-centre retrospective observational study, patients with ARDS caused by COVID-19 between 24 December 2019 and 24 February 2020 were enrolled. The primary outcome was 60-day in-hospital death MESHD. The exposure was prescribed systemic corticosteroids or not. Time-dependent Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for 60-day in-hospital mortality.Results A total of 382 patients including 226 (59.2%) patients who received systemic corticosteroids and 156 (40.8%) patients with standard treatment were analyzed. The maximum dose of corticosteroids was 80.0 (IQR 40.0–80.0) mg equivalent methylprednisolone per day, and duration of corticosteroid treatment was 7.0 (4.0–12.0) days in total. In Cox regression analysis using corticosteroid treatment as a time-varying variable, corticosteroid treatment was associated with a significant reduction in risk of in-hospital death MESHD within 60 days (HR, 0.48; 95% CI, 0.25, 0.93; p = 0.0285). The association remained significantly after adjusting for age TRANS, sex, Sequential Organ Failure Assessment score at hospital admission, propensity score of corticosteroid treatment, and comorbidities (HR: 0.51; CI: 0.27, 0.99; p = 0.0471). Corticosteroids were not associated with delayed viral RNA clearance in our cohort.Conclusion In this clinical practice setting, low-to-moderate dose corticosteroid treatment was associated with reduced risk of death MESHD in COVID-19 patients who developed ARDS.

    Clinical features and disease MESHD severity in an Iranian population of COVID-19 patients

    Authors: Shima Nabavi; Zahra Javidarabshahi; Abolghasem Allahyari; Mohammad Ramezani; Mohsen Seddigh-Shamsi; Sahar Ravanshad; Mina AkbariRad; Farnoosh Ebrahimzadeh; Shohre Khatami; Maryam Emadzadeh; Neda Saeedian; Ahmadreza Zarifian; Maryam Miri; Fariba Rezaeetalab; Sepide Hejazi; Reza Basiri; Mahnaz Mozdourian

    doi:10.21203/ Date: 2020-07-31 Source: ResearchSquare

    Objectives: Coronavirus disease MESHD 2019 (COVID-19) can present with a variety of symptoms. Severity of the disease MESHD may be associated with several factors. Here, we review clinical features of COVID-19 patients with different severities.Methods: This cross-sectional study was performed in Imam Reza hospital, Mashhad, Iran, during February-April 2020. COVID-19 patients with typical computed tomography (CT) patterns and/or positive reverse-transcriptase polymerase chain reaction (RT-PCR) were included. The patients were classified into three groups of moderate, severe, and critical based on disease MESHD severity. Demographic, clinical, laboratory, and radiologic findings were collected and compared. P<0.05 was considered statistically significant.Results: Overall, 200 patients with mean age TRANS of 69.75±6.39 years, of whom 82 (41%) were female TRANS were studied. Disease MESHD was severe/critical in the majority of patients (167, 83.5%). Disease MESHD severity was significantly associated with age TRANS, malignant comorbidities, dyspnea MESHD dyspnea HP, nausea MESHD nausea/vomiting HP/ vomiting MESHD, confusion MESHD confusion HP, respiratory rate, pulse rate, O2 saturation, extent of CT involvement, serum SERO C-reactive protein (CRP), pH, pO2, and aspartate transaminase (P<0.05). Moreover, complications including shock MESHD shock HP, coagulopathy, acidosis MESHD acidosis HP, sepsis MESHD sepsis HP, acute respiratory distress HP syndrome MESHD (ARDS), intensive care unit (ICU) admission, and intubation were significantly higher in patients with higher severities. O2 saturation, nausea MESHD nausea/vomiting HP/ vomiting MESHD, and extent of lung CT involvement were independent predictors of severe/critical COVID-19 (OR=0.342, 45.93, and 25.48, respectively; P<0.05).Conclusions: Our results indicate O2 saturation, nausea MESHD nausea/vomiting HP/ vomiting MESHD, and extent of lung CT involvement as independent predictors of severe COVID-19 conditions. Serum SERO CRP levels and pO2 were also considerably higher patients with higher severity and can be used along with other factors as possible predictors of severe disease MESHD in COVID-19 patients.

    Tocilizumab shortens time on mechanical ventilation and length of hospital stay in patients with severe COVID-19: a retrospective cohort study.

    Authors: Johannes Eimer; Jan Vesterbacka; Anna-Karin Svensson; Bertil Stojanovic; Charlotta Wagrell; Anders Sonnerborg; Piotr Nowak

    doi:10.1101/2020.07.29.20164160 Date: 2020-07-30 Source: medRxiv

    Background: Hyperinflammation is a key feature of the pathogenesis of COVID-19 with a central role of the interleukin-6 pathway. We aimed to study the impact of the IL-6 receptor antagonist tocilizumab on the outcome of patients admitted to the intensive care unit (ICU) with acute respiratory distress HP syndrome MESHD (ARDS) related to COVID-19. Methods: Eighty-seven patients with confirmed SARS-CoV-2 infection MESHD and moderate to severe ARDS were included (n tocilizumab = 29, n controls = 58). A matched cohort was created using a propensity score. The primary endpoint was 30-day all-cause mortality, secondary endpoints included ventilation-free days and length of stay. Results: No difference was found in 30-day all-cause mortality in patients treated with tocilizumab compared to controls (17.2% vs. 32.8%, p = 0.2; HR = 0.52 [0.19 - 1.39], p = 0.19). Ventilator-free days were 19.0 (IQR 12.5 - 20.0) versus 9 (IQR 0.0 - 18.5; p = 0.04), respectively. A higher rate of freedom from mechanical ventilation at 30 days was achieved in patients receiving tocilizumab (HR 2.83 [1.48 - 5.40], p < 0.002). Median length of stay in ICU and total length of stay were reduced by 8 and 9.5 days in patients treated with tocilizumab. Similar results were obtained in the analysis of the propensity score matched cohort. Conclusions: Treatment of critically ill patients with ARDS due to COVID-19 with tocilizumab was not associated with reduced 30-day all-cause mortality, but shorter duration on ventilatory support as well as shorter overall length of stay in hospital and in ICU.

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MeSH Disease
Human Phenotype

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