Timely evaluation of the protective effects of Coronavirus Disease 2019 (COVID-19) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern is urgently needed to inform pandemic control planning. Based on 78 vaccine efficacy or effectiveness (VE) data from 49 studies and 1,984,241 SARS-CoV-2 sequences collected from 31 regions, we analyzed the relationship between genetic distance (GD) of circulating viruses against the vaccine strain and VE against symptomatic infection. We found that the GD of the receptor-binding domain of the SARS-CoV-2 spike protein is highly predictive of vaccine protection and accounted for 86.3% (P = 0.038) of the VE change in a vaccine platform-based mixed-effects model and 87.9% (P = 0.006) in a manufacturer-based model. We applied the VE-GD model to predict protection mediated by existing vaccines against new genetic variants and validated the results by published real-world and clinical trial data, finding high concordance of predicted VE with observed VE. We estimated the VE against the Delta variant to be 82.8% (95% prediction interval: 68.7–96.0) using the mRNA vaccine platform, closely matching the reported VE of 83.0% from an observational study. Among the four sublineages of Omicron, the predicted VE varied between 11.9% and 33.3%, with the highest VE predicted against BA.1 and the lowest against BA.2, using the mRNA vaccine platform. The VE-GD framework enables predictions of vaccine protection in real time and offers a rapid evaluation method against novel variants that may inform vaccine deployment and public health responses.
Background: The effects of multiple meteorological factors on influenza activity remain unclear in Chongqing, the largest municipality in China. We aimed to fix this gap in this study.Methods: Weekly meteorological data and influenza surveillance data in Chongqing were collected from 2012 to 2019. Distributed lag nonlinear models (DLNMs) were conducted to estimate the effects of multiple meteorological factors on influenza activity.Results: Inverted J-shaped nonlinear associations between mean temperature, wind speed, sunshine and influenza activity were found. The relative risks (RRs) of influenza activity increased as weekly average mean temperature fell below 18.18℃, average wind speed fell below 1.55 m/s and average sunshine fell below 2.36 hours. Taking the median values as the references, lower temperature and windless could significantly increase the risks of influenza activity and last for 4 weeks. A J-shaped nonlinear association was observed between relative humidity and influenza activity; the risk of influenza activity increased with rising relative humidity with 78.26% as the break point. Taking the median value as the reference, high relative humidity could increase the risk of influenza activity and last for 3 weeks. In addition, we found the relationship between aggregate rainfall and influenza activity could be described with a U-shaped curve. Rainfall effect has significantly higher RR than rainless effect.Conclusions: Our study shows that multiple meteorological factors have strong associations with influenza activity in Chongqing, providing evidence for developing a meteorology-based early warning system for influenza to facilitate timely response to upsurge of influenza activity.
We evaluated and compared humoral immune responses after inactivated coronavirus disease 2019 (COVID‐19) vaccination among naïve individuals, asymptomatically infected individuals, and recovered patients with varying severity. In this multicenter, prospective cohort study, blood samples from 666 participants were collected before and after 2 doses of inactivated COVID‐19 vaccination. Among 392 severe acute respiratory syndrome coronavirus 2‐naïve individuals, the seroconversion rate increased significantly from 51.8% (median antispike protein pan‐immunoglobulins [S‐Igs] titer: 0.8 U/ml) after the first dose to 96% (median S‐Igs titer: 79.5 U/ml) after the second dose. Thirty‐two percent of naïve individuals had detectable neutralizing antibodies (NAbs) against the original strain but all of them lost neutralizing activity against the Omicron variant. In 274 individuals with natural infection, humoral immunity was significantly improved after a single vaccine dose, with median S‐Igs titers of 596.7, 1176, 1086.5, and 1828 U/ml for asymptomatic infections, mild cases, moderate cases, and severe/critical cases, respectively. NAb titers also improved significantly. However, the second dose did not substantially increase antibody levels. Although a booster dose is needed for those without infection, our findings indicate that recovered patients should receive only a single dose of the vaccine, regardless of the clinical severity, until there is sufficient evidence to confirm the benefits of a second dose.
Predictions of cardiovascular disease risks based on health records have long attracted broad research interests. Despite extensive efforts, the prediction accuracy has remained unsatisfactory. This raises the question as to whether the data insufficiency, statistical and machine-learning methods, or intrinsic noise have hindered the performance of previous approaches, and how these issues can be alleviated. Based on a large population of patients with hypertension in Shenzhen, China, we aimed to establish a high-precision coronary heart disease (CHD) prediction model through big data and machine-learning Data from a large cohort of 42,676 patients with hypertension, including 20,156 patients with CHD onset, were investigated from electronic health records (EHRs) 1-3 years prior to CHD onset (for CHD-positive cases) or during a disease-free follow-up period of more than 3 years (for CHD-negative cases). The population was divided evenly into independent training and test datasets. Various machine-learning methods were adopted on the training set to achieve high-accuracy prediction models and the results were compared with traditional statistical methods and well-known risk scales. Comparison analyses were performed to investigate the effects of training sample size, factor sets, and modeling approaches on the prediction performance. An ensemble method, XGBoost, achieved high accuracy in predicting 3-year CHD onset for the independent test dataset with an area under the receiver operating characteristic curve (AUC) value of 0.943. Comparison analysis showed that nonlinear models (K-nearest neighbor AUC 0.908, random forest AUC 0.938) outperform linear models (logistic regression AUC 0.865) on the same datasets, and machine-learning methods significantly surpassed traditional risk scales or fixed models (eg, Framingham cardiovascular disease risk models). Further analyses revealed that using time-dependent features obtained from multiple records, including both statistical variables and changing-trend variables, helped to improve the performance compared to using only static features. Subpopulation analysis showed that the impact of feature design had a more significant effect on model accuracy than the population size. Marginal effect analysis showed that both traditional and EHR factors exhibited highly nonlinear characteristics with respect to the risk scores. We demonstrated that accurate risk prediction of CHD from EHRs is possible given a sufficiently large population of training data. Sophisticated machine-learning methods played an important role in tackling the heterogeneity and nonlinear nature of disease prediction. Moreover, accumulated EHR data over multiple time points provided additional features that were valuable for risk prediction. Our study highlights the importance of accumulating big data from EHRs for accurate disease predictions.
Multi-population cohorts offer unprecedented opportunities for profiling disease risk in large samples, however, heterogeneous risk effects underlying complex traits across populations make integrative prediction challenging. In this study, we propose a novel Bayesian probability framework, the Prism Vote (PV), to construct risk predictions in heterogeneous genetic data. The PV views the trait of an individual as a composite risk from subpopulations, in which stratum-specific predictors can be formed in data of more homogeneous genetic structure. Since each individual is described by a composition of subpopulation memberships, the framework enables individualized risk characterization. Simulations demonstrated that the PV framework applied with alternative prediction methods significantly improved prediction accuracy in mixed and admixed populations. The advantage of PV enlarges as genetic heterogeneity and sample size increase. In two real genome-wide association data consists of multiple populations, we showed that the framework considerably enhanced prediction accuracy of the linear mixed model in five-group cross validations. The proposed method offers a new aspect to analyze individual’s disease risk and improve accuracy for predicting complex traits in genotype data.
Background The effects of multiple meteorological factors on influenza activity remain elusive in Chongqing, the largest municipality in China. We aimed to fix this gap in this study. Methods Weekly meteorological data and influenza surveillance data in Chongqing were collected from 2012 to 2019. Distributed lag nonlinear models (DLNMs) were conducted to estimate the effects of multiple meteorological factors on influenza activity. Results Inverted J-shaped nonlinear associations between mean temperature, wind speed, sunshine and influenza activity were found. The relative risks (RRs) of influenza activity increased as weekly average mean temperature fell below 18.18℃, average wind speed fell below 1.55 m/s and average sunshine fell below 2.36 hours. Taking the median values as the references, lower temperature and windless could significantly increase the risks of influenza activity and last for 4 weeks. A J-shaped nonlinear association was observed between relative humidity and influenza activity; the risk of influenza activity increased with rising relative humidity with 78.26% as the break point. Taking the median value as the reference, high relative humidity could increase the risk of influenza activity and last for 3 weeks. In addition, we found the relationship between aggregate rainfall and influenza activity could be described with a U-shaped curve. The RR for rainfall effect was significantly higher than rainless effect. Conclusions Our study shows that multiple meteorological factors have strong associations with influenza activity in Chongqing, providing evidence for developing a meteorology-based early warning system for influenza to facilitate timely response to upsurge of influenza activity.
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