Corpus overview


MeSH Disease

Human Phenotype


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    Identification of Three Endotypes in Pediatric Acute Respiratory Distress Syndrome MESHD Respiratory Distress HP Syndrome by Nasal Transcriptomic Profiling

    Authors: James "Garrett" Williams; Rashika Joshi; Rhonda Jones; Aditi Paranjpe; Mario Pujato; Krishna Roskin; Toni Yunger; Erin Stoneman; Patrick Lahni; Hector R Wong; Brian Michael Varisco

    doi:10.1101/2020.04.28.20083451 Date: 2020-05-02 Source: medRxiv

    Acute respiratory distress HP respiratory distress MESHD syndrome ( ARDS MESHD) and pediatric ARDS (PARDS) can be triggered by multiple pulmonary and non-pulmonary insults and are the source of substantial morbidity and mortality. The nasal and lower conducting airways have similar cell composition and nasal transcriptomes identify disease state and sub-classes in lung cancer MESHD, COPD MESHD, and asthma HP asthma MESHD. We conducted an observational, prospective trial to determine whether this technique could identify PARDS endotypes in 26 control and 25 PARDS subjects <18 admitted to the pediatric ICU. RNA from inferior turbinate brushing was collected on days 1, 3, 7, and 14. Standard RNA-processing yielded 29% usable specimens by mRNA-Seq, and a low-input protocol increased yield to 95% usable specimens. 64 low-input specimens from 10 control and 15 PARDS subjects were used for model development. Control and some PARDS subjects clustered together in Group A while some day 1, 3, and 7 specimens clustered into Groups B and C with specimens from these subjects moving to Group A with PARDS resolution. In multivariate analysis, the only clinical variables associated with specimen Group B or C assignment was severity of lung injury MESHD or viral PARDS trigger. Compared to Group A, Group B had upregulation of innate immune processes and Group C had upregulation of ciliary and microtuble processes. Analysis of the 15 standard processing specimens identified the same grouping. Mortality trended higher in group B (25%) and C subjects (28.6%) compared to A (5%, p=0.1). Comparison of groups with 16 PARDS-associated serum SERO biomarkers identified correlation of Endotype B with Tumor Necrosis MESHD Factor-alpha, but not other inflammatory cytokines and Endotype C with Surfactant Protein D. We identified three nasal transcriptomic PARDS endotypes. A is similar to control. B is marked by an innate immune signature only weakly reflected in the serum SERO. C may be associated with loss of epithelial barrier integrity. Nasal transcriptomics may be useful for prognostic and predictive enrichment in future PARDS trials. Identifier NCT03539783

    SARS-CoV-2 receptor mutation in Egyptian population

    Authors: Mohamed Abouelhoda; Abdel-Rahman N. Zekri; Mohammed M Hafez

    doi:10.1101/2020.04.27.20082206 Date: 2020-05-02 Source: medRxiv

    The Coronavirus disease 2019 (COVID-19) is a respiratory tract infectious disease MESHD caused by Severe Acute Respiratory Syndrome coronavirus 2 MESHD (SARS-CoV-2). SARS-CoV-2 triggers severe pneumonia HP pneumonia MESHD leading to acute respiratory distress HP respiratory distress MESHD syndrome and death MESHD in severe cases. According to WHO reported, Egypt is among the countries with low confirmed SARS CoV2 infected symptomatic cases and death MESHD. We postulate that one of the reasons for this may be due mutations in the viral receptor. Therefore this study was conducted to confirm or reject this postulation.

    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 (CRS) is reported as a common feature in COVID-19, which can lead to potentially fatal, hyper-inflammatory acute respiratory distress condition MESHD respiratory distress HP condition, diagnosed with elevated serum SERO level of pro-inflammatory cytokines like IL-6, CRP, etc. that positively correlated with disease 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.

    Favorable outcomes of elderly TRANS COVID-19 patients in Guangzhou, China: a retrospective, observational study

    Authors: Gang Xu; Jun Zhao; Fuchun Zhang; Feng Liu; Congrui Feng; Yudong Hu; Yuluo Chen; Liuqian Wang; Yuwei Tong; Yueping Li; Haiyan Shi; Wei Ma

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

    Objective: To clarify the outcomes of elderly TRANS patients with COVID-19.Methods: All 265 confirmed adult TRANS patients with COVID-19 were included in this retrospective study, 43 (16.2%) of whom were 65 years and older. Electronic medical records of the subjects were reviewed to obtain information on clinical characteristics and outcomes. The allocations of medical resource were also recorded.Results: Only one death case occurred in the elderly TRANS. The mortality of elderly TRANS patients was no higher than that of young patients (2.3% vs. 0%, P = 0.126). The cure rate was 95.3% in elderly TRANS patients and 99.5% in young patients (P = 0.067), and the duration of hospitalization is 27 days in elderly TRANS patients and 18 days in young patients (P = 0.001). The elderly TRANS suffered from more comorbidities (67.4% vs. 24.8%, P < 0.001), most of which is hypertension HP hypertension MESHD. Significantly more severe cases occurred in elderly TRANS patients compared with young patients (37.2% vs. 16.7%, P = 0.004). The elderly TRANS were more likely to present with complications including acute respiratory distress HP respiratory distress MESHD syndrome, acute myocardial injury MESHD, septic shock MESHD shock HP and acute kidney injury HP acute kidney injury MESHD (all P < 0.05), respectively. No medical staffs were infected during the treatment of COVID-19.Conclusion: The cure rate and the mortality of the elderly TRANS seemed to be no worse than that of the young, though the elderly TRANS were with longer hospitalization. Elderly TRANS patients with COVID-19 could be treatable if handled properly. More severe cases and complications in elderly TRANS patients should prompt for more complex treatment and special considerations.

    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 coronavirus 2 MESHD (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 with pneumonia HP pneumonia MESHD and acute respiratory distress syndrome MESHD respiratory distress HP syndrome ( ARDS MESHD) requiring mechanical ventilation2. Emerging results indicate a dysregulated MESHD immune response characterized by runaway inflammation MESHD, including cytokine release syndrome (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 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 viremia MESHD plasma SERO 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 viremia MESHD plasma SERO viremia HP. Consistent with reduction of plasma SERO IL-6, single-cell RNA-sequencing revealed declines MESHD 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 MESHD, 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.

    Identification of Drugs Blocking SARS-CoV-2 Infection MESHD using Human Pluripotent Stem Cell-derived Colonic MESHD Organoids

    Authors: Xiaohua Duan; Yuling Han; Liuliu Yang; Benjamin Nilsson; Pengfei Wang; Tuo Zhang; Xing Wang; Dong Xu; Jenny Zhaoying Xiang; skyler uhl; Yaoxing Huang; Huanhuan Chen; Hui Wang; Benjamin R. tenOever; Robert E. Schwartz; David D Ho; Fong Cheng Pan; Shuibing Chen; Todd R. Evans

    doi:10.1101/2020.05.02.073320 Date: 2020-05-02 Source: bioRxiv

    Summary ParagraphThe current COVID-19 pandemic is caused by SARS-coronavirus MESHD 2 (SARS-CoV-2). There are currently no therapeutic options for mitigating this disease due to lack of a vaccine and limited knowledge of SARS-CoV-2 biology. As a result, there is an urgent need to create new disease models to study SARS-CoV-2 biology and to screen for therapeutics using human disease-relevant tissues. COVID-19 patients typically present with respiratory symptoms including cough HP, dyspnea HP dyspnea MESHD, and respiratory distress HP, but nearly 25% of patients have gastrointestinal indications including anorexia HP anorexia MESHD, diarrhea HP diarrhea MESHD, vomiting HP vomiting MESHD, and abdominal pain HP abdominal pain MESHD. Moreover, these symptoms are associated with worse COVID-19 outcomes1. Here, we report using human pluripotent stem cell-derived colonic MESHD organoids (hPSC-COs) to explore the permissiveness of colonic cell types to SARS-CoV-2 infection MESHD. Single cell RNA-seq and immunostaining showed that the putative viral entry receptor ACE2 is expressed in multiple hESC-derived colonic cell types, but highly enriched in enterocytes. Multiple cell types in the COs can be infected by a SARS-CoV-2 pseudo-entry virus, which was further validated in vivo using a humanized mouse model. We used hPSC-derived COs in a high throughput platform to screen 1280 FDA-approved drugs against viral infection MESHD. Mycophenolic acid and quinacrine dihydrochloride were found to block the infection of SARS-CoV-2 pseudo-entry virus in COs both in vitro and in vivo, and confirmed to block infection of SARS-CoV-2 MESHD virus. This study established both in vitro and in vivo organoid models to investigate infection of SARS-CoV-2 disease MESHD-relevant human colonic cell types and identified drugs that blocks SARS-CoV-2 infection MESHD, suitable for rapid clinical testing.

    Release of potential pro-inflammatory peptides from SARS-CoV-2 spike glycoproteins in neutrophil-extracellular traps

    Authors: Aitor Blanco-Miguez; Borja Sanchez

    doi:10.1101/2020.05.02.072439 Date: 2020-05-02 Source: bioRxiv

    COVID-2019 has progressed in around 10-15% of patients to an acute respiratory distress HP respiratory distress MESHD syndrome characterized by extensive pulmonary inflammation MESHD and elevated production of pro-inflammatory cytokines. Neutrophil activation seems to be crucial in the initiation and perpetuation of this exacerbated lung inflammation MESHD. However, the precise mechanisms by which this activation occurs remain yet elusive. To this end, this in silico study tried to identify potential proinflammatory inducing peptides (PIPs) produced by the action of the elastase released in neutrophil-extracellular traps over SARS-CoV-2 particles. We found nine potential PIPs exclusive from the SARS-CoV-2, showing homology against T cell recognition epitopes. Moreover, 78 percent of these exclusive PIPs were found produced by the enzymatic cleavage on the spike glycoproteins, suggesting that high PIP concentrations might be released following SARS-CoV-2 huge replication rate. Therefore, these PIPs might play a role in the exacerbated inflammatory response observed in some patients. HighlightsO_LINine potential PIPs were predicted exclusive from the SARS-CoV-2. C_LIO_LISARS-CoV-2 PIPs showed homology against T cell recognition epitopes. C_LIO_LIMost of PIPs were produced by enzymatic cleavage of the spike glycoproteins. C_LIO_LIThe release of these PIPs might be related to the increased inflammatory response HP observed in the patients. C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=189 SRC="FIGDIR/small/072439v1_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@1cd2c3forg.highwire.dtl.DTLVardef@113f8b7org.highwire.dtl.DTLVardef@2df78eorg.highwire.dtl.DTLVardef@1d7c946_HPS_FORMAT_FIGEXP M_FIG C_FIG

    Hydroxychloroquine application is associated with a decreased mortality in critically ill MESHD patients with COVID-19

    Authors: Bo Yu; Dao Wen Wang; Chenze Li

    doi:10.1101/2020.04.27.20073379 Date: 2020-05-01 Source: medRxiv

    Importance: Coronavirus disease 2019 (COVID-19) is a pandemic with no specific drugs and high mortality. The most urgent thing is to find effective treatments. Objective: To determine whether hydroxychloroquine application may be associated with a decreased risk of death MESHD in critically ill COVID-19 patients and what is potential mechanism. Design, Setting and Patients: This retrospective study included all 568 critically ill COVID-19 patients who were confirmed by pathogen laboratory tests despite antiviral treatment and had severe acute respiratory distress syndrome MESHD respiratory distress HP syndrome, PAO2/FIO2 <300 with need of mechanical ventilation in Tongji Hospital, Wuhan, between February 1 of 2020 to April 8 of 2020. All 568 patients received comparable basic treatments including antiviral drugs and antibiotics, and 48 of them additionally received oral hydroxychloroquine (HCQ) treatment (200 mg twice a day for 7-10 days). Primary endpoint is mortality of patients, and inflammatory cytokines levels were compared between hydroxychloroquine and non-hydroxychloroquine (NHCQ) treatments. MAIN OUTCOMES AND MEASURES: In-hospital death MESHD and hospital stay time (day) were obtained, level of inflammatory cytokine (IL-6) was measured and compared between HCQ and NHCQ treatments. RESULTS: The median age TRANS of 568 critically ill MESHD patients is 68 (57, 76) years old with 37.0% being female TRANS. Mortalities are 18.8% (9/48) in HCQ group and 45.8% (238/520) in NHCQ group (p<0.001). The time of hospital stay before patient death is 15 (10-21) days and 8 (4 - 14) days for the HCQ and NHCQ groups, respectively (p<0.05). The level of inflammatory cytokine IL-6 was significantly lowered from 22.2 (8.3-118.9) pg/mL at the beginning of the treatment to 5.2 (3.0-23.4) pg/ml (p<0.05) at the end of the treatment in the HCQ group but there is no change in the NHCQ group. CONCLUSIONS AND RELEVANCE: Hydroxychloroquine treatment is significantly associated with a decreased mortality in critically ill MESHD patients with COVID-19 through attenuation of inflammatory cytokine storm. Therefore, hydroxychloroquine should be prescribed for treatment of critically ill COVID-19 patients to save lives.

    Systematic review of international guidelines for tracheostomy in COVID-19 patients.

    Authors: Carlos M Chiesa-Estomba; Jerome R Lechien; Christian Calvo-Henriquez; Nicolas Fakhry; Petros D Karkos; Shazia Peer; Jon A Sistiaga-Suarez; Jose A Gonzalez-Garcia; Giovanni Cammaroto; Miguel Mayo; Pablo Parente-Arias; Sven Saussez; Tareck Ayad

    doi:10.1101/2020.04.26.20080242 Date: 2020-04-29 Source: medRxiv

    At this moment, the world leaves under the SARS-CoV-2 outbreak pandemic. As Otolaryngologists - Head & Neck Surgeons, we need to perform and participate in examinations and procedures within the head and neck region and airway that are at particularly high risk of exposure and infection because of aerosol and droplet contamination. One of those surgical procedures on demand at this moment is tracheostomy, due the increasing admission in ICU departments and the increased need of ventilatory support secondary to respiratory distress HP respiratory distress MESHD syndrome. This review of international guidelines for tracheostomy in COVID-19 infected MESHD patients, aiming to summarize in a systematic way the available recommendations from 18 guidelines from all over the world.

    Menstrual blood SERO-derived mesenchymal stem cells provide new insights into the treatment of coronavirus disease MESHD 2019 (COVID-19)

    Authors: Xin Chen; Liang Yu; Lijun Chen; Xiaoqin Zheng; Lingling Tang; Kaijin Xu; Hongliu Cai; Yu Chen; Shufa Zheng; Juan Lu; Zhenyu Xu; Qiang Zhang; Hainv Gao; Yifei Li; Jingjing Qu; Yingan Jiang; Xiaowei Xu; Charlie Xiang; Lanjuan Li

    doi:10.21203/ Date: 2020-04-29 Source: ResearchSquare

    Background: The coronavirus disease MESHD 2019 (COVID-19) causing a cluster of respiratory infections MESHD in Wuhan, China, is identified in December 2019. The main symptoms are defined as fever HP fever MESHD, cough HP cough MESHD, shortness of breath MESHD, with early symptom of sputum, acute respiratory distress syndrome MESHD respiratory distress HP syndrome ( ARDS MESHD), and the final lung injury MESHD and pulmonary fibrosis HP pulmonary fibrosis MESHD. Currently, there is no effective method to cure it. Mesenchymal stem cell (MSC) therapy is an immediate need for treating COVID-19 especially severe patients at present.Methods: We describe the two confirmed case TRANS of COVID-19 severe patients in Hangzhou, China to explore the role of menstrual blood SERO-derived MSC in the treatment of SARS-CoV-2 infection MESHD. Furthermore, we mimic disease model of pulmonary fibrosis HP pulmonary fibrosis MESHD in mice to assess the role of MSC. Then, a co-culture system to investigate the underlying mechanism between MSC and pulmonary-associated cells by a series of Physiological, biochemical, bioinformatics analysis.Results: MSC transplantation increases the immune indicators (including lymphocytes) and decreases inflammatory indicators (such as IL-6, IL-10, TNF, and IFN). More importantly, the two patients alleviated symptom and discharged after 3 weeks’ treatment with MSC MESHD. Additionally, MSCs exhibit an anti-inflammatory role through suppressing some inflammatory factors (RANTES, GM-CSF, MIG-1g, MCP-5, Eotaxin), which is anastomotic to current clinical study using MSC to treat COVID-19. Conclusions: This is the first report using menstrual blood SERO-derived MSC in treating COVID-19 patients. From our clinical results, we hold one idea that MSCs reduced inflammatory effect to defend cytokine storm. The underlying mechanism is probably that MSCs inhibit epithelia cell apoptosis and reduce the secretion of inflammatory factors to prevent myofibroblasts activity. MSC provides an alternative method for treating COVID-19 particularly some patients with ARDS MESHD or subsequent pulmonary fibrosis HP pulmonary fibrosis MESHD.Trial registration: This clinical trial was submitted to and approved by the Ethics Committee of the First Affiliated Hospital, Collage of Medicine, Zhejiang University. MSC administration in patient with COVID-19 was conducted in a single center and open-label clinical trial (ChiCTR2000029606).

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MeSH Disease
Human Phenotype

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