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Algorithmic bias in COVID-19 detection systems poses aserious threat to equitable pandemic response, asdemographicdisparities in model performance risk worsening healthoutcomes across vulnerable populations. We present anadoptedCausal Concept Bottleneck Model (C2BM) framework thatsystematically addresses fairness in multimodal COVID-19detection by learning interpretable concepts from chest CTscans and patient metadata. Our approach targets theCountry → Institution → COVID causal pathway throughprincipledinterventions, achieving substantial bias reduction: age andgender demographic parity differences decrease from 51.15%to 18.50% (64% reduction), gender disparate impact improvesfrom 0.6475 to 0.9812 (51% improvement), whilepreserving 98.45% diagnostic F1-score. Throughcomprehensive evaluation across four model variants, wedemonstrate that causal interventions enable stable andreproduciblefairness improvements without compromising clinicalutility. Our work establishes that principled causalreasoning canachieve practical fairness-accuracy trade-offs in COVID-19detection systems, providing actionable guidance forequitable healthcare AI deployment. 

Accurate prediction of the transmission fitness of emerging SARS-CoV-2 variants is vital for timely public health responses. In this study, we present a deep learning framework that predicts variant fitness from raw genomic sequences using a convolutional neural network (CNN) trained to regress Differential Population Growth Rate (DPGR) values. Our approach achieves high predictive accuracy R-square value of 0.92 on genomic sequences sampled from the USA and Europe. To interpret the model’s predictions, we apply SHapley Additive exPlanations (SHAP) to identify nucleotide-level contributions to predicted fitness. Our analysis highlights key mutations in ORF9 (nucleocapsid), ORF2 (spike), ORF5 (membrane), and ORF8 that either enhance or reduce predicted DPGR. Notably, we identify amino acid–altering mutations such as D3L, E484K, N501Y, and V97I as strong positive contributors to fitness, while synonymous or non-coding mutations had more subtle or regulatory effects. These findings validate the potential of sequence-based modeling and interpretable AI to support early detection and prioritization of high-risk variants. 

Estimating the transmission fitness of SARS‐CoV‐2 variants and understanding their evolutionary fitness trends are important for epidemiological forecasting. Existing methods are often constrained by their parametric natures and do not satisfactorily align with the observations during COVID‐19. Here, we introduce a sliding‐window data‐driven pairwise comparison method, the differential population growth rate (DPGR) that uses viral strains as internal controls to mitigate sampling biases. DPGR is applicable in time windows in which the logarithmic ratio of two variant subpopulations is approximately linear. We apply DPGR to genomic surveillance data and focus on variants of concern (VOCs) in multiple countries and regions. We found that the log‐linear assumption of DPGR can be reliably found within appropriate time windows in many areas. We show that DPGR estimates of VOCs align well with regional empirical observations in different countries. We show that DPGR estimates agree with another method for estimating pathogenic transmission. Furthermore, DPGR allowed us to construct viral relative fitness landscapes that capture the shifting trends of SARS‐CoV‐2 evolution, reflecting the relative changes of transmission traits for key genotypic changes represented by major variants. The straightforward log‐linear regression approach of DPGR may also facilitate its easy adoption. This study shows that DPGR is a promising new tool in our repertoire for addressing future pandemics. 

The global effort to combat the COVID-19 pandemic faces ongoing uncertainty with the emergence of Variants of Concern featuring numerous mutations on the Spike (S) protein. In particular, the Omicron Variant is distinguished by 32 mutations, including 10 within its receptor-binding domain (RBD). These mutations significantly impact viral infectivity and the efficacy of vaccines and antibodies currently in use for therapeutic purposes. In our study, we employed structure-based computational saturation mutagenesis approaches to predict the effects of Omicron missense mutations on RBD stability and binding affinity, comparing them to the original Wuhan-Hu-1 strain. Our results predict that mutations such as G431W and P507W induce the most substantial destabilizations in the Wuhan-Hu-1-S/Omicron-S RBD. Notably, we postulate that mutations in the Omicron-S exhibit a higher percentage of enhancing binding affinity compared to Wuhan-S. We found that the mutations at residue positions G447, Y449, F456, F486, and S496 led to significant changes in binding affinity. In summary, our findings may shed light on the widespread prevalence of Omicron mutations in human populations. The Omicron mutations that potentially enhance their affinity for human receptors may facilitate increased viral binding and internalization in infected cells, thereby enhancing infectivity. This informs the development of new neutralizing antibodies capable of targeting Omicron’s immune-evading mutations, potentially aiding in the ongoing battle against the COVID-19 pandemic. 

Abstract In this paper, NeuralProphet (NP), an explainable hybrid modular framework, enhances the forecasting performance of pandemics by adding two neural network modules; auto-regressor (AR) and lagged-regressor (LR). An advanced deep auto-regressor neural network (Deep-AR-Net) model is employed to implement these two modules. The enhanced NP is optimized via AdamW and Huber loss function to perform multivariate multi-step forecasting contrast to Prophet. The models are validated with COVID-19 time-series datasets. The NP’s efficiency is studied component-wise for a long-term forecast for India and an overall reduction of 60.36% and individually 34.7% by AR-module, 53.4% by LR-module in MASE compared to Prophet. The Deep-AR-Net model reduces the forecasting error of NP for all five countries, on average, by 49.21% and 46.07% for short-and-long-term, respectively. The visualizations confirm that forecasting curves are closer to the actual cases but significantly different from Prophet. Hence, it can develop a real-time decision-making system for highly infectious diseases. 

The ongoing COVID-19 pandemic continues to infect people worldwide, and the virus continues to evolve in significant ways which can pose challenges to the efficiency of available vaccines and therapeutic drugs and cause future pandemic. Therefore, it is important to investigate the binding and interaction of ACE2 with different RBD variants. A comparative study using all-atom MD simulations was conducted on ACE2 binding with 8 different RBD variants, including N501Y, E484K, P479S, T478I, S477N, N439K, K417N and N501YE484K- K417N on RBD. Based on the RMSD, RMSF, and DSSP results, overall the binding of RBD variants with ACE2 is stable, and the secondary structure of RBD and ACE2 are consistent after the point mutation. Besides that, a similar buried surface area, a consistent binding interface and a similar amount of hydrogen bonds formed between RBD and ACE2 although the exact residue pairs on the binding interface were modified. The change of binding free energy from point mutation was predicted using the free energy perturbation (FEP) method. It is found that N501Y, N439K, and K417N can strengthen the binding of RBD with ACE2, while E484K and P479S weaken the binding, and S477N and T478I have negligible effect on the binding. Point mutations modified the dynamic correlation of residues in RBD based on the dihedral angle covariance matrix calculation. Doing dynamic network analysis, a common intrinsic network community extending from the tail of RBD to central, then to the binding interface region was found, which could communicate the dynamics in the binding interface region to the tail thus to the other sections of S protein. The result can supply unique methodology and molecular insight on studying the molecular structure and dynamics of possible future pandemics and design novel drugs.