scholarly journals HLA-A*11:01:01:01, HLA-C*12:02:02:01-HLA-B*52:01:02:02, Age and Sex Are Associated With Severity of Japanese COVID-19 With Respiratory Failure

2021 ◽  
Vol 12 ◽  
Author(s):  
Seik-Soon Khor ◽  
Yosuke Omae ◽  
Nao Nishida ◽  
Masaya Sugiyama ◽  
Noriko Kinoshita ◽  
...  
Keyword(s):  
Prediction Model ◽  
Risk Prediction ◽  
Early Identification ◽  
Association Studies ◽  
Risk Prediction Model ◽  
Age At Diagnosis ◽  
World Health ◽  
Hla Association ◽  
Hla Alleles ◽  
B 52

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing coronavirus disease 2019 (COVID-19) was announced as an outbreak by the World Health Organization (WHO) in January 2020 and as a pandemic in March 2020. The majority of infected individuals have experienced no or only mild symptoms, ranging from fully asymptomatic cases to mild pneumonic disease. However, a minority of infected individuals develop severe respiratory symptoms. The objective of this study was to identify susceptible HLA alleles and clinical markers that can be used in risk prediction model for the early identification of severe COVID-19 among hospitalized COVID-19 patients. A total of 137 patients with mild COVID-19 (mCOVID-19) and 53 patients with severe COVID-19 (sCOVID-19) were recruited from the Center Hospital of the National Center for Global Health and Medicine (NCGM), Tokyo, Japan for the period of February–August 2020. High-resolution sequencing-based typing for eight HLA genes was performed using next-generation sequencing. In the HLA association studies, HLA-A*11:01:01:01 [Pc = 0.013, OR = 2.26 (1.27–3.91)] and HLA-C*12:02:02:01-HLA-B*52:01:01:02 [Pc = 0.020, OR = 2.25 (1.24–3.92)] were found to be significantly associated with the severity of COVID-19. After multivariate analysis controlling for other confounding factors and comorbidities, HLA-A*11:01:01:01 [P = 3.34E-03, OR = 3.41 (1.50–7.73)], age at diagnosis [P = 1.29E-02, OR = 1.04 (1.01–1.07)] and sex at birth [P = 8.88E-03, OR = 2.92 (1.31–6.54)] remained significant. The area under the curve of the risk prediction model utilizing HLA-A*11:01:01:01, age at diagnosis, and sex at birth was 0.772, with sensitivity of 0.715 and specificity of 0.717. To the best of our knowledge, this is the first article that describes associations of HLA alleles with COVID-19 at the 4-field (highest) resolution level. Early identification of potential sCOVID-19 could help clinicians prioritize medical utility and significantly decrease mortality from COVID-19.

scholarly journals HLA-A*11:01:01:01, HLA*C*12:02:02:01-HLA-B*52:01:02:02, age and sex are associated with severity of Japanese COVID-19 with respiratory failure

2021 ◽  
Author(s):  
Seik-Soon Khor ◽  
Yosuke Omae ◽  
Nao Nishida ◽  
Masaya Sugiyama ◽  
Noriko Kinoshita ◽  
...  
Keyword(s):  
Early Identification ◽  
Association Studies ◽  
World Health ◽  
Clinical Markers ◽  
Hla Association ◽  
The World ◽  
Center Hospital ◽  
Health Organization ◽  
B 52 ◽  
Generation Sequencing

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing coronavirus disease 2019 (COVID-19) was announced as an outbreak by the World Health Organization (WHO) in January 2020 and as a pandemic in March 2020. The majority of infected individuals have experienced no or only mild symptoms, ranging from fully asymptomatic cases to mild pneumonic disease. However, a minority of infected individuals develop severe respiratory symptoms. The objective of this study was to identify susceptible HLA alleles and clinical markers for the early identification of severe COVID-19 among hospitalized COVID-19 patients. A total of 137 patients with mild COVID-19 (mCOVID-19) and 53 patients with severe COVID-19 (sCOVID-19) were recruited from the Center Hospital of the National Center for Global Health and Medicine (NCGM), Tokyo, Japan for the period of February–August 2020. High-resolution sequencing-based typing for eight HLA genes was performed using next-generation sequencing. In the HLA association studies, HLA-A*11:01:01:01 [Pc = 0.013, OR = 2.26 (1.27–3.91)] and HLA-C*12:02:02:01-HLA-B*52:01:01:02 [Pc = 0.020, OR = 2.25 (1.24–3.92)] were found to be significantly associated with the severity of COVID-19. After multivariate analysis controlling for other confounding factors and comorbidities, HLA-A*11:01:01:01 [P = 3.34E-03, OR = 3.41 (1.50–7.73)], age at diagnosis [P = 1.29E-02, OR = 1.04 (1.01–1.07)] and sex at birth [P = 8.88E-03, OR = 2.92 (1.31–6.54)] remained significant. Early identification of potential sCOVID-19 could help clinicians prioritize medical utility and significantly decrease mortality from COVID-19.

scholarly journals A multi-locus predictiveness curve and its summary assessment for genetic risk prediction

2019 ◽  
Vol 29 (1) ◽  
pp. 44-56
Author(s):  
Changshuai Wei ◽  
Ming Li ◽  
Yalu Wen ◽  
Chengyin Ye ◽  
Qing Lu
Keyword(s):  
Prediction Model ◽  
Risk Prediction ◽  
Genetic Variants ◽  
Genetic Risk ◽  
Prediction Models ◽  
Association Studies ◽  
Risk Prediction Model ◽  
Substantial Contribution ◽  
Great Promise ◽  
Genetic Risk Prediction

Genetic association studies using high-throughput genotyping and sequencing technologies have identified a large number of genetic variants associated with complex human diseases. These findings have provided an unprecedented opportunity to identify individuals in the population at high risk for disease who carry causal genetic mutations and hold great promise for early intervention and individualized medicine. While interest is high in building risk prediction models based on recent genetic findings, it is crucial to have appropriate statistical measurements to assess the performance of a genetic risk prediction model. Predictiveness curves were recently proposed as a graphic tool for evaluating a risk prediction model on the basis of a single continuous biomarker. The curve evaluates a risk prediction model for classification performance as well as its usefulness when applied to a population. In this article, we extend the predictiveness curve to measure the collective contribution of multiple genetic variants. We further propose a nonparametric, U-statistics-based measurement, referred to as the U-Index, to quantify the performance of a multi-locus predictiveness curve. In particular, a global U-Index and a partial U-Index can be used in the general population and a subpopulation of particular clinical interest, respectively. Through simulation studies, we demonstrate that the proposed U-Index has advantages over several existing summary statistics under various disease models. We also show that the partial U-Index can have its own uniqueness when rare variants have a substantial contribution to disease risk. Finally, we use the proposed predictiveness curve and its corresponding U-Index to evaluate the performance of a genetic risk prediction model for nicotine dependence.

Development of Neurobehavioral Deterioration Risk Prediction Model for Welder: A Proposed Study

2018 ◽  
Vol 10 (5) ◽  
Author(s):  
Nuur Azreen Paiman ◽  
◽  
Azian Hariri ◽  
Ibrahim Masood ◽  
Arma Noor ◽  
...  
Keyword(s):  
Prediction Model ◽  
Risk Prediction ◽  
Risk Prediction Model

Wound dehiscence after radical cystectomy: A novel risk-prediction model

2021 ◽  
Vol 79 ◽  
pp. S1112-S1113
Author(s):  
A.A. Nasrallah ◽  
M. Mansour ◽  
C.H. Ayoub ◽  
N. Abou Heidar ◽  
J.A. Najdi ◽  
...  
Keyword(s):  
Prediction Model ◽  
Radical Cystectomy ◽  
Risk Prediction ◽  
Wound Dehiscence ◽  
Risk Prediction Model

scholarly journals Protocol for the development and validation of a risk prediction model for stillbirths from 35 weeks gestation in Australia

2020 ◽  
Vol 4 (1) ◽  
Author(s):  
Jessica K. Sexton ◽  
Michael Coory ◽  
Sailesh Kumar ◽  
Gordon Smith ◽  
Adrienne Gordon ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Prediction Model ◽  
Risk Prediction ◽  
Late Pregnancy ◽  
Risk Prediction Model ◽  
Past Century ◽  
Reporting Standards ◽  
Robust Method ◽  
Predictive Values ◽  
Multivariable Logistic Regression

Abstract Background Despite advances in the care of women and their babies in the past century, an estimated 1.7 million babies are born still each year throughout the world. A robust method to estimate a pregnant woman’s individualized risk of late-pregnancy stillbirth is needed to inform decision-making around the timing of birth to reduce the risk of stillbirth from 35 weeks of gestation in Australia, a high-resource setting. Methods This is a protocol for a cross-sectional study of all late-pregnancy births in Australia (2005–2015) from 35 weeks of gestation including 5188 stillbirths among 3.1 million births at an estimated rate of 1.7 stillbirths per 1000 births. A multivariable logistic regression model will be developed in line with current TransparentReporting of a multivariable prediction model forIndividualPrognosis orDiagnosis (TRIPOD) guidelines to estimate the gestation-specific probability of stillbirth with prediction intervals. Candidate predictors were identified from systematic reviews and clinical consultation and will be described through univariable regression analysis. To generate a final model, elimination by backward stepwise multivariable logistic regression will be performed. The model will be internally validated using bootstrapping with 1000 repetitions and externally validated using a temporally unique dataset. Overall model performance will be assessed with R2, calibration, and discrimination. Calibration will be reported using a calibration plot with 95% confidence intervals (α = 0.05). Discrimination will be measured by the C-statistic and area underneath the receiver-operator curves. Clinical usefulness will be reported as positive and negative predictive values, and a decision curve analysis will be considered. Discussion A robust method to predict a pregnant woman’s individualized risk of late-pregnancy stillbirth is needed to inform timely, appropriate care to reduce stillbirth. Among existing prediction models designed for obstetric use, few have been subject to internal and external validation and many fail to meet recommended reporting standards. In developing a risk prediction model for late-gestation stillbirth with both providers and pregnant women in mind, we endeavor to develop a validated model for clinical use in Australia that meets current reporting standards.

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