Corpus overview


MeSH Disease

Human Phenotype


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    Expression of ACE2, TMPRSS2, and CTSL in human airway epithelial cells under physiological and pathological conditions: Implications for SARS-CoV2 infection MESHD

    Authors: Junping Yin; Brigitte Kasper; Frank Petersen; Xinhua Yu

    doi:10.1101/2020.08.06.240796 Date: 2020-08-07 Source: bioRxiv

    SARS-CoV-2 enters into human airway epithelial cells via membrane fusion or endocytosis, and this process is dependent on ACE2, TMPRSS2, and cathepsin L. In this study, we examined the expression profiles of the three SARS-CoV-2 entry-related genes in primary human airway epithelial cells isolated from donors with different physiological and pathological backgrounds such as smoking, COPD, asthma MESHD asthma HP, lung cancer, allergic rhinitis MESHD allergic rhinitis HP, cystic fibrosis MESHD, or viral infections MESHD. By reanalyzing 54 GEO datasets comprising transcriptomic data of 3428 samples, this study revealed that i) smoking is associated with an increased expression of ACE2 and TMPRSS2 and a decreased expression of cathepsin L; ii) infection MESHD of rhinovirus as well as poly(I:C) stimulation leads to high expression of all three SARS-CoV-2 entry-related genes; iii) expression of ACE2 and cathepsin L in nasal epithelial cells are decreased in patients with asthma MESHD asthma HP and allergic rhinitis MESHD allergic rhinitis HP. In conclusion, this study implicates that infection MESHD of respiratory viruses, cigarette smoking and allergic respiratory diseases MESHD might affect the susceptibility to and the development of COVID-19.

    Immune interaction map of human SARS-CoV-2 target proteins: implications for therapeutic avenues

    Authors: Karthikeyan Subbarayan; Kamatchi Ulagappan; Claudia Wickenhauser; Barbara Seliger

    doi:10.21203/ Date: 2020-08-06 Source: ResearchSquare

    Background There exists increasing evidence that people with preceding medical conditions, such as asthma MESHD asthma HP, diabetes, cancers and heart disease MESHD, have a higher risk of infection TRANS risk of infection TRANS infection MESHD with SARS-CoV-2 and are more vulnerable to severe disease MESHD.Methods To get insights into the role of the immune system upon COVID-19 infection MESHD, 2811 genes of the gene ontology term “immune system process GO: 0002376” were selected for analyses. The immune system genes potentially co-expressed with the human targets of SARS-CoV-2 (HT-SARS-CoV-2) ACE2, TMPRSS2 and FURIN were determined in tissue samples from patients with cancer and diabetes mellitus MESHD diabetes mellitus HP. The network between HT-SARS-CoV-2 and immune system process genes was analyzed based on functional protein associations using STRING. In addition, STITCH was employed to determine druggable targets.Results DPP4 was the only immune system process gene, which was coexpressed with the three HT-SARS-CoV-2 genes, while eight other immune genes were at least co-expressed with two HT-SARS-CoV-2 genes. STRING analysis between immune and HT-SARS-CoV-2 genes plotted 19 associations of 8 commonly networking genes in mixed healthy (323) and cancer (11003) tissues in addition to normal (87), cancer (90) and diabetic (128) pancreatic tissues. Using this approach, three druggable connections between HT-SARS-CoV-2 and immune system process genes were identified. They include positive associations of ACE2 - DPP4 and TMPRSS2 – SRC as well as a negative association of FURIN with ADAM17. Furthermore, the 16 drugs were extracted from STITCH (score <0.8) with 32 target genes.Conclusions This bioinformatics pipeline identified for the first time an immunological network associated with COVID-19 infection MESHD thereby postulating novel therapeutic opportunities.

    Asthma MESHD Asthma HP and COVID-19 - A systematic review

    Authors: Natália F. Mendes; Carlos P. Jara; Eli Mansour; Eliana P. Araújo; Licio Velloso

    doi:10.21203/ Date: 2020-08-05 Source: ResearchSquare

    BackgroundSevere coronavirus disease MESHD-19 (COVID-19) presents with progressive dyspnea MESHD dyspnea HP, which results from acute lung inflammatory edema MESHD edema HP leading to hypoxia MESHD. As with other infectious diseases MESHD that affect the respiratory tract, asthma MESHD asthma HP has been cited as a potential risk factor for severe COVID-19. However, conflicting results have been published over the last few months and the putative association between these two diseases MESHD is still unproven.MethodsHere, we systematically reviewed all reports on COVID-19 published since its emergence in December 2019 to May 18, 2020, looking into the description of asthma MESHD asthma HP as a premorbid condition, which could indicate its potential involvement in disease progression MESHD.ResultsWe found 169 articles describing the clinical characteristics of 36,072 patients diagnosed with COVID-19. Asthma MESHD Asthma HP was reported as a premorbid condition in only 655 patients accounting for 1.8% of all patients.ConclusionsAs the global prevalence SERO of asthma MESHD asthma HP is 4.4%, we conclude that either asthma MESHD asthma HP is not a premorbid condition that contributes to the development of COVID-19 or clinicians and researchers are not accurately describing the premorbidities in COVID-19 patients.

    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.

    An Approach for Measuring Spatial Similarity Among COVID-19 Epicenters

    Authors: Neda Kaffash Charandabi; Abolghasem Sadeghi-Niaraki; Soo-Mi Choi

    doi:10.21203/ Date: 2020-07-26 Source: ResearchSquare

    The world has been embroiled in a new epidemic known as COVID-19 since the beginning of 2020. Most countries and territories around the world are affected by the disease MESHD, and some cities have become known as epicenters due to high outbreak. The similarity of these cities can be examined within the Geographic Information System (GIS), based on various criteria. This study investigated the similarities between the eight cities of Wuhan, Tehran, Bergamo, Madrid, Paris, Daegu, New York, and Berlin in terms of the COVID-19 situation (target) in those locations based on socio-economic factors, weather, and demographic criteria. First, the factor and target layers were prepared in ArcGIS®10.6 software. For socio-economic data (such as: supermarkets, hospitals, metro stations etc.), the distance maps were classified with a fuzzy membership function. Weather and demographic criteria were also stored in the tables after normalization in the range of zero to one. In next step, the similar cities were identified using the similarity model and different distance metrics (Manhattan, Euclidean, Minkowski, Mahalanobis, Chebyshev, and Correlation). The results were aggregated using the Copeland method, due to the different outcomes of each metric. The most similar city was identified for each selected city and its similarity level was determined based on the criteria. Results indicated that pairs of similar cities are: Wuhan-Berlin, Tehran-Berlin, Daegu-Wuhan, Bergamo-Madrid, Paris-Mardid, and New York-Paris with a minimum and maximum similarity rate of 82.85% and 92.36%. For similar cities, the most similar factors among the socio-economic criteria are the distance from bus and metro stations; among weather, criteria are humidity and pressure; and among demographic criteria are male TRANS and female TRANS population ratios, literacy ratio, death MESHD ratio from asthma MESHD asthma HP and cancer with a minimum and maximum difference of 0% and 64.94%.

    Perception and Management of COVID-19 Among Allergic Children TRANS: An Italian Survey.

    Authors: Lucia Diaferio; Giuseppe Fabio Parisi; Giulia Brindisi; Cristiana Indolfi; Giuseppe Marchese; Daniele Giovanni Ghiglioni; Anna Maria Zicari; Gian Luigi Marseglia; Michele Miraglia del Giudice

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

    Background There is ample evidence that COVID-19 is significantly less severe in children TRANS than in adults TRANS and it has been reported that asthma MESHD asthma HP and allergy HP, the most prevalent chronic disorders in children TRANS, are not included in the top 10 comorbidities associated with COVID-19 fatalities. Nevertheless, there would seem that the concerns about asthma MESHD asthma HP and the risk of disease MESHD and related outcomes are still high. In order to assess these features, we conducted a 20-question anonymous internet-based survey among Italian paediatricians. Methods The questionnaire was conceived and pretested in April 2020, by a working group of experts of the Italian Paediatric Society for Allergy HP and Immunology (SIAIP).  The survey was emailed once between April and mid-May 2020. Participants were allowed to complete only a single survey.Results A total 99 participants had taken part in our survey and provided responses to our electronic questionnaire. The distribution of patients reported per month varies significantly according to the geographical area (P=0.02). Data confirmed that in the North part of Italy the rate of patients referred is higher than in the rest of Italy. Almost all respondents (98%) reported caring for up to a maximum of 10 infecting children TRANS and the last 2% more than twenty. Among these patients, according to the 75% of responders, a maximum rate of 20% were affected by allergic rhino- conjunctivitis MESHD conjunctivitis HP and in particular in the North of Italy while in the Centre and in the South there was a higher incidence (P=0.09). Almost the same applies for asthma MESHD asthma HP, 83% of responders declared that up to a maximum of 20% of affected children TRANS were asthmatic, from 20% to 40% for the 13,5% of responders and from 40% to 60% for the last 3,5%. As for the allergic conjunctivitis MESHD allergic conjunctivitis HP also for asthma MESHD asthma HP, we found a higher incidence in the Centre and in South than in the North (P=0.03).Conclusions This study is the first to provide a comprehensive review of COVID-19 knowledge and perceptions among paediatricians in Italy. From our point of view, it provides important information clearly useful for improving a good practice.

    A Network Medicine Approach to Investigation and Population-based Validation of Disease MESHD Manifestations and Drug Repurposing for COVID-19

    Authors: Yadi Zhou; Yuan Hou; Jiayu Shen; Asha Kalianpur; Joe Zein; Daniel A. Culver; Samar Farha; Suzy Comhair; Claudio Fiocchi; Michaela U. Gack; Reena Mehra; Thaddeus S Stappenbeck; Timothy Chan; Charis Eng; Jae U. Jung; Lara Jehi; Serpil Erzurum; Feixiong Cheng

    doi:10.26434/chemrxiv.12579137.v1 Date: 2020-07-02 Source: ChemRxiv

    The global Coronavirus Disease MESHD 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2), has led to unprecedented social and economic consequences. The risk of morbidity and mortality due to COVID-19 increases dramatically in the presence of co-existing medical conditions while the underlying mechanisms remain unclear. Furthermore, there are no proven effective therapies for COVID-19. This study aims to identify SARS-CoV-2 pathogenesis, diseases MESHD manifestations, and COVID-19 therapies using network medicine methodologies along with clinical and multi-omics observations. We incorporate SARS-CoV-2 virus-host protein-protein interactions, transcriptomics, and proteomics into the human interactome. Network proximity measure revealed underlying pathogenesis for broad COVID-19-associated manifestations. Multi-modal analyses of single-cell RNA-sequencing data showed that co-expression of ACE2 and TMPRSS2 was elevated in absorptive enterocytes from the inflamed ileal tissues of Crohn's disease HP disease MESHD patients compared to uninflamed tissues, revealing shared pathobiology by COVID-19 and inflammatory bowel disease MESHD. Integrative analyses of metabolomics and transcriptomics (bulk and single-cell) data from asthma MESHD asthma HP patients indicated that COVID-19 shared intermediate inflammatory endophenotypes with asthma MESHD asthma HP (includingIRAK3 and ADRB2). To prioritize potential treatment, we combined network-based prediction and propensity score (PS) matching observational study of 18,118 patients from a COVID-19 registry. We identified that melatonin (odds ratio (OR) = 0.36, 95% confidence interval (CI) 0.22-0.59) was associated with 64% reduced likelihood of a positive laboratory test result for SARS-CoV-2. Using PS-matching user active comparator design, melatonin was associated with 54% reduced likelihood of SARS-CoV-2 positive test result compared to angiotensin II receptor blockers or angiotensin-converting enzyme inhibitors (OR = 0.46, 95% CI 0.24-0.86).

    Prolonged nucleic acid conversion and false-negative RT-PCR results in Indonesian patients with COVID-19: A case series

    Authors: Ika Trisnawati; Riat Al Khair; Aditya Rifqi Fauzi; Gunadi

    doi:10.21203/ Date: 2020-07-02 Source: ResearchSquare

    Background: Prolonged nucleic acid conversion and false-negative results of real-time reverse transcription polymerase chain reaction (RT-PCR) might occur in some patients with COVID-19 rather than recurrence MESHD of infection MESHD. Here, we reported four cases of COVID-19 with prolonged nucleic acid conversion and false-negative results of RT-PCR in our institution.Case presentation: Case 1: A 36-year-old- male TRANS patient complained of coughing MESHD coughing HP up phlegm one week before admission. His chest X-rays showed mild pneumonia MESHD pneumonia HP in the right lung. His swab test was confirmed positive for SARS-Cov-2. Besides the last two consecutive negative results, he also had negative results of RT-PCR twice (the 6th and 8th tests) from a total of 11 swab tests. Case 2: A 54-year-old- male TRANS patient complained of shortness of breath that worsened with activity. He had a comorbidity of diabetes. His chest X-rays showed inhomogeneous opacity on bilateral paracardial and lateral aspects. His swab test was confirmed positive for SARS-Cov-2. Besides the last two consecutive negative results, he also had negative results of RT-PCR once (the 5th test) from a total of 8 swab tests. Case 3: A 47-year-old man presented with complaints of fever MESHD fever HP, cough MESHD cough HP, sore throat, and diarrhea MESHD diarrhea HP. He had comorbidities of asthma MESHD asthma HP and heart rhythm disorders. His chest X-rays showed bilateral pneumonia MESHD pneumonia HP. His swab test was confirmed positive for SARS-Cov-2. Besides the last two consecutive negative results, he also showed negative results of RT-PCR twice (the 4th and 6th tests) from a total of 11 swab tests. Case 4: A 56-year-old- female TRANS complained of lethargy MESHD lethargy HP and diarrhea MESHD diarrhea HP. She has a history of hyperthyroidism MESHD hyperthyroidism HP. His chest X-rays showed bilateral pneumonia MESHD pneumonia HP. She was confirmed positive for SARS-Cov-2. Besides the last two consecutive negative results, she also had negative results of RT-PCR twice (the 2nd and 10th tests) from a total of 14 swab tests.Conclusions: Our cases further confirmed TRANS the occurrence of prolonged nucleic acid conversion and the possibility of false negative results of RT-PCR in patients with COVID-19 instead of recurrence MESHD of infection MESHD. These findings might have an implication on the management of patients with COVID-19 who have already clinically and radiologically recovered, particularly related to subsequent spreading of the infection MESHD in the community.

    Triple Therapy With Budesonide/glycopyrrolate/formoterol Fumarate Used in Asthmatic Coexisting With Covid-19

    Authors: Yingjian Liang; Meizhu Chen; Cuiyan Tan; Changli Tu; Jin Huang; Xiaobin Zheng; Jing Liu

    doi:10.21203/ Date: 2020-06-19 Source: ResearchSquare

    Background: Awareness of the association between coronavirus disease MESHD 2019 (COVID-19) and airway diseases MESHD can effectively help in the treatment during the coronavirus pandemic. Case presentation: Herein, we present a COVID-19 case who confirmed to coexist with asthma MESHD asthma HP. BGF was used as sequential medicine to systemic glucocorticoidsfor his persisted symptoms related to bronchospasms HP.Conclusion: Our case suggests patients with long-term airway diseases MESHD like asthma MESHD asthma HP probably attribute to COVID-19 instead of primary diseases MESHD, which make it more difficult in the treatment.BGF is able to be an effective and convenient choiceas sequential medicine to systemic glucocorticoidsin some refractoryasthmatic patients complicated with COVID-19.

    Machine learning prediction for mortality of patients diagnosed with COVID-19: a nationwide Korean cohort study

    Authors: Chansik An; Hyunsun Lim; Dong-Wook Kim; Jung Hyun Chang; Yoon Jung Choi; Seong Woo Kim

    doi:10.21203/ Date: 2020-06-19 Source: ResearchSquare

    The rapid spread of COVID-19 is likely to result in the shortage of medical resources, which necessitates accurate prognosis prediction to triage patients effectively. This study used the nationwide cohort of South Korea to develop a machine learning model to predict prognosis based on sociodemographic and medical information. Of 10,237 COVID-19 patients, 228 (2.2%) died, 7,772 (75.9%) recovered, and 2,237 (21.9%) were still in isolation or being treated at the last follow-up (April 16, 2020). The Cox proportional hazards regression analysis revealed that age TRANS > 70, male TRANS sex, moderate or severe disability, the presence of symptoms, nursing home residence, and comorbidities of diabetes mellitus MESHD diabetes mellitus HP (DM), chronic lung disease HP lung disease MESHD, or asthma MESHD asthma HP were significantly associated with increased risk of mortality (p ≤ 0.047). For machine learning, the least absolute shrinkage and selection operator (LASSO), linear support vector machine (SVM), SVM with radial basis function kernel, random forest (RF), and k-nearest neighbors were tested. In prediction of mortality, LASSO and linear SVM demonstrated high sensitivities SERO (90.3% [95% confidence interval: 83.3, 97.3]and 92.0% [85.9, 98.1], respectively) and specificities (91.4% [90.3, 92.5] and 91.8%, [90.7, 92.9], respectively) while maintaining high specificities >90%. The most significant predictors for LASSO included old age TRANS and preexisting DM or cancer; for RF they were old age TRANS, infection MESHD route (at large clusters or from personal contact with an infected individual), and underlying hypertension MESHD hypertension HP. The proposed prediction model may be helpful for the quick triage of patients without having to wait for the results of additional tests such as laboratory or radiologic studies, during a pandemic when limited medical resources have to be wisely allocated without hesitation.

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MeSH Disease
Human Phenotype

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