Corpus overview


MeSH Disease

Human Phenotype


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    DPP4 inhibitors and respiratory infection MESHD, a systematic review and meta-analysis of the CardioVascular Outcomes Trials conducted before the pandemic and implications for the management of diabetes during COVID-19

    Authors: Guillaume Grenet; Samia Mekhaldi; Sabine MAINBOURG; Marine AUFFRET; Catherine Cornu; Jean-Luc Cracowski; Francois Gueyffier; Jean-Christophe Lega; Michel CUCHERAT

    doi:10.1101/2020.07.28.20163386 Date: 2020-07-29 Source: medRxiv

    Background Association between DPP4 inhibitors and respiratory infection MESHD remains unclear. CardioVascular Outcomes Trials (CVOTs) conducted before the COVID-19 pandemic are available. We aimed to estimate the effect of DPP4 inhibitors on the risk of respiratory infections MESHD. Methods We updated a previous systematic review and meta-analysis, searching for CVOTs assessing a DPP4 inhibitor in patients with type 2 diabetes mellitus MESHD diabetes mellitus HP. We focused on placebo-controlled CVOTs. Our primary outcome was 'any respiratory infection MESHD'. We added a sensitivity SERO analysis integrating non-CVOTs and active-controlled CVOTs. Findings We included 47 714 patients in five placebo-controlled CVOTs. Median follow-up ranged from 1.5 years to 3 years. 4 369 events of overall respiratory infection MESHD were reported (rate of 9.2%). DPP4 inhibitors were not associated with a different risk compared to placebo (RR = 0.99 [95%CI: 0.93; 1.04]). The sensitivity SERO analysis integrating the non-CVOTs studies and the active-controlled CVOT reached 11 349 events among 82 644 participants (rate of 13.7%). DPP4 inhibitors were not associated with a different risk of overall respiratory infection MESHD (RR = 1.00 [95% CI: 0.97; 1.03]). Interpretation Our up-dated meta-analysis provides the most powerful and least biased estimation of the association of DPP4 inhibitors and the risk of overall (non COVID-19) respiratory infection MESHD. We did not find any effect of the DPP4 inhibitors on the risk of respiratory infection MESHD. Our results support the recently published practical recommendations for the management of diabetes in patients with COVID-19, suggesting that DPP4 inhibitors should not be discontinued regarding the COVID-19 pandemic.

    Association of BMI and Obesity MESHD Obesity HP with Composite poor outcome in COVID-19 adult TRANS patients: A Systematic Review and Meta-Analysis

    Authors: Arto Yuwono Soeroto; Nanny Natalia Soetedjo; Aga Purwiga; Prayudi Santoso; Iceu Dimas Kulsum; Hendarsyah Suryadinata; Ferdy Ferdian

    doi:10.1101/2020.06.28.20142240 Date: 2020-06-29 Source: medRxiv

    Aim: This study aimed to evaluate the association between obesity MESHD obesity HP and composite poor outcome in coronavirus disease MESHD 2019 (COVID-19) patients. Methods: We conducted a systematic literature search from PubMed and Embase database. We included all original research articles in COVID-19 adult TRANS patients and obesity MESHD obesity HP based on classification of Body Mass Index (BMI) and composite poor outcome which consist of mortality, morbidity, admission of Intensive Care Unit (ICU), mechanical ventilation, Acute Respiratory Distress HP Syndrome MESHD (ARDS), and severe COVID-19. Results: Nine studies were included in meta-analysis with 6 studies presented BMI as continuous outcome and 3 studies presented BMI as dichotomous outcome (obese and non-obese). Most studies were conducted in China (55.5%) with remaining studies from French, Germany, and United States (US). COVID-19 patients with composite poor outcome had higher BMI with mean difference 0.55 kg/m2 (95% CI 0.07-1.03, P=0.02). BMI [≥]30 (obese) was associated with composite poor outcome with odds ratio 1.89 (95% CI 1.06-3.34, P=0.03). Multivariate meta-regression analysis by including three moderators: age TRANS, hypertension MESHD hypertension HP, and Diabetes Mellitus type 2 MESHD Diabetes Mellitus type HP (DM type 2) showed the association between obesity MESHD obesity HP and composite poor outcome was affected by age TRANS with regression coefficient =-0.06 and P=0.02. Subgroup analysis was not performed due to the limited number of studies for several outcomes. Conclusion: Obesity MESHD Obesity HP is a risk factor of composite poor outcome of COVID-19. On the other hand, COVID-19 patients with composite poor outcome have higher BMI. BMI is an important routine procedure that should be assessed in the management of COVID-19 patients and special attention should be given to patients with obesity MESHD obesity HP. Keywords: Covid-19, Obesity MESHD Obesity HP, Body Mass Index

    Analysis of Genetic Host Response Risk Factors in Severe COVID-19 Patients

    Authors: Krystyna Taylor; Sayoni Das; Matthew Pearson; James Kozubek; Marcin Pawlowski; Claus Erik Jensen; Zbigniew Skowron; Gert Lykke Møller; Mark Strivens; Steve Gardner

    doi:10.1101/2020.06.17.20134015 Date: 2020-06-19 Source: medRxiv

    BACKGROUND Epidemiological studies indicate that as many as 20% of individuals who test positive for COVID-19 develop severe symptoms that can require hospitalization. These symptoms include low platelet count, severe hypoxia MESHD, increased inflammatory cytokines and reduced glomerular filtration rate. Additionally, severe COVID-19 is associated with several chronic co-morbidities, including cardiovascular disease MESHD, hypertension MESHD hypertension HP and type 2 diabetes mellitus MESHD diabetes mellitus HP. The identification of genetic risk factors that impact differential host responses to SARS-CoV-2, resulting in the development of severe COVID-19, is important in gaining greater understanding into the biological mechanisms underpinning life-threatening responses to the virus. These insights could be used in the identification of high-risk individuals and for the development of treatment strategies for these patients. METHODS As of June 6, 2020, there were 976 patients who tested positive for COVID-19 and were hospitalized, indicating they had a severe response to SARS-CoV-2. There were however too few patients with a mild form of COVID-19 to use this cohort as our control population. Instead we used similar control criteria to our previous study looking at shared genetic risk factors between severe COVID-19 and sepsis MESHD sepsis HP, selecting controls who had not developed sepsis MESHD sepsis HP despite having maximum co-morbidity risk and exposure to sepsis MESHD sepsis HP-causing pathogens. RESULTS Using a combinatorial (high-order epistasis) analysis approach, we identified 68 protein-coding genes that were highly associated with severe COVID-19. At the time of analysis, nine of these genes have been linked to differential response to SARS-CoV-2. We also found many novel targets that are involved in key biological pathways associated with the development of severe COVID-19, including production of pro-inflammatory cytokines, endothelial cell dysfunction, lipid droplets, neurodegeneration HP and viral susceptibility factors. CONCLUSION The variants we found in genes relating to immune response pathways and cytokine production cascades, were in equal proportions across all severe COVID-19 patients, regardless of their co-morbidities. This suggests that such variants are not associated with any specific co-morbidity, but are common amongst patients who develop severe COVID-19. Among the 68 severe COVID-19 risk-associated genes, we found several druggable protein targets and pathways. Nine are targeted by drugs that have reached at least Phase I clinical trials, and a further eight have active chemical starting points for novel drug development. Several of these targets were particularly enriched in specific co-morbidities, providing insights into shared pathological mechanisms underlying both the development of severe COVID-19, ARDS and these predisposing co-morbidities. We can use these insights to identify patients who are at greatest risk of contracting severe COVID-19 and develop targeted therapeutic strategies for them, with the aim of improving disease MESHD burden and survival rates.

    Diabetic Retinopathy MESHD Retinopathy HP Screening in Urban Primary Care Setting with a Handheld Smartphone-based Retinal Camera.

    Authors: Márcia S Queiroz; Jacira Xavier de Carvalho; Silvia Ferreira Bortoto; Mozania Reis de Matos; Cristiane das Graças Dias Cavalcante; Elenilda Almeida Silva Andrade; Maria Lúcia Correa-Giannella; Fernando K Malerbi

    doi:10.21203/ Date: 2020-06-15 Source: ResearchSquare

    Aims: To evaluate diabetic retinopathy MESHD retinopathy HP (DR) screening with a portable handheld smartphone-based retinal camera and telemedicine in an urban primary health care setting; to evaluate the learning curve for image acquisition, performed by healthcare personnel without previous experience on retinal imaging. Methods: Prospective study that enrolled patients with type 2 diabetes mellitus MESHD diabetes mellitus HP (T2DM) followed at a primary healthcare unit in São Paulo, Brazil. After a brief training in image acquisition, there was further continuous feedback during the remote image reading process. Each patient underwent two fundus and one anterior ocular segment images per eye, after mydriasis MESHD mydriasis HP. Patients were classified according need of referral. Results: A total of 627 adult TRANS individuals with T2DM underwent retinal evaluation. The population was composed by 63.2% female TRANS individuals, age TRANS median of 66 years-old, diabetes duration 10.7 ± 8.2 years and A1c 7.7 ± 1.9% (61 + 20.8 mmol/mol). The most prevalent associated comorbidities were arterial hypertension MESHD hypertension HP (80.3%) and dyslipidemia (50.2%). Referral decision was possible in 81.2% patients. Most patients had absent or non-referable DR; the main ocular media opacity detected was cataract MESHD cataract HP. After the 7th day of image acquisition, the daily rate of patients whose images allowed clinical decision was maintained above 80%. A higher A1c was associated with referable DR. Conclusion: A low-cost DR screening strategy with a handheld device and telemedicine is feasible and has the potential to increase coverage of DR screening in underserved areas; the possibility of mobile units is relevant for DR screening in the context of Covid-19 pandemic.

    COVID-19 Hospitalization is More Frequent and Severe in Down Syndrome MESHD

    Authors: Louise Malle; Cynthia Gao; Nicole Bouvier; Bethany Percha; Dusan Bogunovic

    doi:10.1101/2020.05.26.20112748 Date: 2020-06-02 Source: medRxiv

    Background. Individuals with rare disorders, like Down syndrome MESHD (DS) are historically understudied. Currently, it is not known how COVID-19 pandemic affects individuals with DS. Herein, we report an analysis of individuals with DS who were hospitalized with COVID-19 in the Mount Sinai Health System in New York City, USA. Methods. In this retrospective, single-center study of 4,615 patients hospitalized with COVID-19, we analyzed all patients with DS admitted in the Mount Sinai Health System. Hospitalization rates, clinical and outcomes were assessed. Findings. Contrary to an expected number of one, we identified six patients with DS. We found that patients with DS are at an 8.9-fold higher risk of hospitalization with COVID-19 when compared to non-DS patients. Hospitalized DS individuals are on average 10 years younger than non-DS patients with COVID-19. Moreover, type 2 diabetes mellitus MESHD diabetes mellitus HP appears to be an important driver of this susceptibility to COVID-19. Finally, patients with DS have more severe outcomes than controls, and are more likely to progress to sepsis MESHD sepsis HP in particular. Interpretation. We demonstrate that individuals with DS represent a higher risk population for COVID-19 compared to the general population and conclude that particular care should be taken for both the prevention and treatment of COVID-19 in these patients. Funding. National Institute of Allergy HP and Infectious Diseases MESHD

    Survival in adult TRANS inpatients with COVID-19

    Authors: Efren Murillo-Zamora; CARLOS M HERNANDEZ-SUAREZ

    doi:10.1101/2020.05.25.20110684 Date: 2020-05-26 Source: medRxiv

    We conducted a nationwide and retrospective cohort study to assess the survival experience and determining factors in adult TRANS inpatients with laboratory-confirmed COVID-19. Data from 5,393 individuals were analyzed using the Kaplan-Meier method and a multivariate Cox proportional hazard regression model was fitted. The 7-day survival was 0.822 and went to 0.482, 0.280, and 0.145 on days 15, 21, and 30 of hospital stay, respectively. In the multiple analysis, factors associated with an increased risk of dying were: male TRANS gender TRANS, age TRANS, longer disease MESHD evolution before hospital entry, exposure to mechanical ventilator support, and personal history of chronic noncommunicable diseases MESHD (namely obesity MESHD obesity HP, type-2 diabetes mellitus MESHD diabetes mellitus HP, and chronic kidney disease HP kidney disease MESHD). To the best of our knowledge, this is the first study analyzing the survival probability in a large subset of Latin-American adults TRANS with COVID-19 and our results contribute to achieving a better understanding of disease MESHD evolution.

    Identification and Analysis of Shared Risk Factors in Sepsis MESHD Sepsis HP and High Mortality Risk COVID-19 Patients

    Authors: Sayoni Das; Krystyna Taylor; Matthew Pearson; James Kozubek; Marcin Pawlowski; Claus Erik Jensen; Zbigniew Skowron; Gert Lykke Møller; Mark Strivens; Steve Gardner

    doi:10.1101/2020.05.05.20091918 Date: 2020-05-09 Source: medRxiv

    BACKGROUND Coronavirus disease MESHD 2019 (COVID-19) is a novel coronavirus strain disease MESHD caused by severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2). The disease MESHD is highly transmissible and severe disease MESHD including viral sepsis MESHD sepsis HP has been reported in up to 16% of hospitalized cases. The admission characteristics associated with increased odds of hospital mortality among confirmed cases TRANS of COVID-19 include severe hypoxia MESHD, low platelet count, elevated bilirubin, hypoalbuminemia MESHD hypoalbuminemia HP and reduced glomerular filtration rate. These symptoms correlate highly with severe sepsis MESHD sepsis HP cases. The diseases MESHD also share similar co-morbidity risks including dementia MESHD dementia HP, type 2 diabetes mellitus MESHD diabetes mellitus HP, coronary heart disease MESHD, hypertension MESHD hypertension HP and chronic renal failure. Sepsis MESHD Sepsis HP has been observed in up to 59% of hospitalized COVID-19 patients. It is highly desirable to identify risk factors and novel therapy/drug repurposing avenues for late-stage severe COVID-19 patients. This would enable better protection of at-risk populations and clinical stratification of COVID-19 patients according to their risk for developing life threatening disease MESHD. METHODS As there is currently insufficient data available for confirmed COVID-19 patients correlating their genomic profile, disease MESHD severity and outcome, co-morbidities and treatments as well as epidemiological risk factors (such as ethnicity, blood SERO group, smoking, BMI etc.), a direct study of the impact of host genomics on disease MESHD severity and outcomes is not yet possible. We therefore ran a study on the UK Biobank sepsis MESHD sepsis HP cohort as a surrogate to identify sepsis MESHD sepsis HP associated signatures and genes, and correlated these with COVID-19 patients. Sepsis MESHD Sepsis HP is itself a life-threatening inflammatory health condition with a mortality rate of approximately 20%. Like the initial studies for COVID-19 patients, standard genome wide association studies (GWAS) have previously failed to identify more than a handful of genetic variants that predispose individuals to developing sepsis MESHD sepsis HP. RESULTS We used a combinatorial association approach to analyze a sepsis MESHD sepsis HP population derived from UK Biobank. We identified 70 sepsis MESHD sepsis HP risk-associated genes, which provide insights into the disease MESHD mechanisms underlying sepsis MESHD sepsis HP pathogenesis. Many of these targets can be grouped by common mechanisms of action such as endothelial cell dysfunction, PI3K/mTOR pathway signaling, immune response regulation, aberrant GABA and neurogenic signaling. CONCLUSION This study has identified 70 sepsis MESHD sepsis HP related genes, many of them for the first time, that can reasonably be considered to be potentially relevant to severe COVID-19 patients. We have further identified 59 drug repurposing candidates for 13 of these targets that can be used for the development of novel therapeutic strategies to increase the survival rate of patients who develop sepsis MESHD sepsis HP and potentially severe COVID-19.

    The Utility of rRT-PCR in Diagnosis and Assessment of Case-fatality rates of COVID-19 In the Iranian Population. Positive Test Results are a Marker for Illness Severity

    Authors: Ghasem Janbabaei; Eric J. Brandt; Reza Golpira; Alireza Raeisi; Jafar Sadegh Tabrizi; Hamid Reza Safikhani; Mohammad Taghi Talebian; Siamak Mirab Samiee; Alireza Biglar; Reza Malekzadeh; Arya Mani

    doi:10.1101/2020.04.29.20085233 Date: 2020-05-05 Source: medRxiv

    The utility of PCR-based testing in characterizing patients with COVID-19 and the severity of their disease MESHD remains unknown. We performed an observational study among patients presenting to hospitals in Iran who were tested for 2019-nCoV viral RNA by rRT-PCR between the fourth week of February 2020 to the fourth week of March 2020. Frequency of symptoms, comorbidities, intubation, and mortality rates were compared between COVID-19 positive vs. negative patients. 96103 patients were tested from 879 hospitals. 18754 (19.5%) tested positive for COVID-19. Positive testing was more frequent in those 50 years or older. The prevalence SERO of cough MESHD cough HP (54.5% vs. 49.7%), fever MESHD fever HP (49.5% vs. 44.7%), and respiratory distress HP (43.0% vs. 39.0%) but not hypoxia MESHD (46.9% vs. 56.7%) was higher in COVID-19 positive vs. negative patients (p<0.001 for all). More patients had cardiovascular diseases MESHD (10.6% vs. 9.5%, p<0.001) and type 2 diabetes mellitus MESHD diabetes mellitus HP (10.8% vs. 8.7%, p<0.001) among COVID-19 positive vs. negative patients. There were fewer patients with cancer (1.1%, vs. 1.4%, p<0.001), asthma MESHD asthma HP (1.9% vs. 2.5%, p<0.001), or pregnant (0.4% vs. 0.6%, =0.001) in COVID-19 positive vs. negative groups. COVID-19 positive vs. negative patients required more intubation (7.7% vs. 5.2%, p<0.001) and had higher mortality (14.6% vs. 6.3%, p<0.001). Odds ratios for death MESHD of positive vs negative patients range from 2.01 to 3.10 across all age groups TRANS. In conclusion, COVID-19 test-positive vs. test-negative patients had more severe symptoms and comorbidities, required higher intubation, and had higher mortality. rRT-PCR positive result provided diagnosis and a marker of disease MESHD severity in Iranians.

    ACE inhibition and cardiometabolic risk factors, lung ACE2 and TMPRSS2 gene expression, and plasma SERO ACE2 levels: a Mendelian randomization study

    Authors: Dipender Gill; Marios Arvanitis; Paul Carter; Ana I Hernandez Cordero; Brian Jo; Ville Karhunen; Susanna C Larsson; Xuan Li; Sam M Lockhart; Amy M Mason; Evanthia Pashos; Ashis Saha; Vanessa Tan; Verena Zuber; Yohan Bosse; Sarah Fahle; Ke Hao; Tao Jiang; Philippe Joubert; Alan C Lunt; Willem hendrik Ouwehand; David J Roberts; Wim Timens; Maarten van den Berge; Nicholas A Watkins; Alexis Battle; Adam S Butterworth; John Danesh; Barbara E Engelhard; James E Peters; Don Sin; Stephen Burgess

    doi:10.1101/2020.04.10.20059121 Date: 2020-04-14 Source: medRxiv

    Objectives: To use human genetic variants that proxy angiotensin-converting enzyme (ACE) inhibitor drug effects and cardiovascular risk factors to provide insight into how these exposures affect lung ACE2 and TMPRSS2 gene expression and circulating ACE2 levels. Design: Two-sample Mendelian randomization (MR) analysis. Setting: Summary-level genetic association data. Participants: Participants were predominantly of European ancestry. Variants that proxy ACE inhibitor drug effects and cardiometabolic risk factors (body mass index, chronic obstructive pulmonary disease MESHD chronic obstructive pulmonary disease HP, lifetime smoking index, low-density lipoprotein cholesterol, systolic blood SERO pressure and type 2 diabetes mellitus MESHD diabetes mellitus HP) were selected from publicly available genome-wide association study data (sample sizes ranging from 188,577 to 898,130 participants). Genetic association estimates for lung expression of ACE2 and TMPRSS2 were obtained from the Gene-Tissue Expression (GTEx) project (515 participants) and the Lung eQTL Consortium (1,038 participants). Genetic association estimates for circulating plasma SERO ACE2 levels were obtained from the INTERVAL study (4,947 participants). Main outcomes and measures: Lung ACE2 and TMPRSS2 expression and plasma SERO ACE2 levels. Results: There were no association of genetically proxied ACE inhibition with any of the outcomes considered here. There was evidence of a positive association of genetic liability to type 2 diabetes mellitus MESHD diabetes mellitus HP with lung ACE2 gene expression in GTEx (p = 4x10-4) and with circulating plasma SERO ACE2 levels in INTERVAL (p = 0.03), but not with lung ACE2 expression in the Lung eQTL Consortium study (p = 0.68). There were no associations between genetically predicted levels of the other cardiometabolic traits with the outcomes. Conclusions: This study does not provide evidence to support that ACE inhibitor antihypertensive drugs affect lung ACE2 and TMPRSS2 expression or plasma SERO ACE2 levels. In the current COVID-19 pandemic, our findings do not support a change in ACE inhibitor medication use without clinical justification.

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MeSH Disease
Human Phenotype

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