SARS-CoV-2 reinfection remains a significant public health challenge that requires accurate risk assessment across populations. Using prospectively collected data from two independent cohorts, we developed and externally validated an interpretable machine learning model for predicting symptomatic SARS-CoV-2 reinfection. The cohort comprised 1,156 adults from Wuxi and Nantong, China, with a median follow-up duration of 10 months. Reinfection occurred in 128 participants (11.1%). The model integrated eighteen clinical and immune features, and ultimately identified spike-specific nasal secretory immunoglobulin A (sIgA) and spike-specific CD4+ central memory T cells (TCM) as key predictors. Developed using the extreme gradient boosting (XGB) algorithm, the prediction model achieved an AUC of 0.835 in the internal validation cohort and demonstrated strong discrimination in the external validation cohort. SHAP analysis revealed that higher nasal spike-specific sIgA was associated with lower risk, while spike-specific CD4+ TCM cells exhibited a non-linear association with reinfection. This interpretable immune-based model provides a framework for immune-informed risk stratification, enabling better prediction and management of SARS-CoV-2 reinfection risk in settings with heterogeneous population immunity.
Elderly individuals with pulmonary fibrosis lesions and latent tuberculosis infection (LTBI) in rural China are high-risk for active tuberculosis (TB), and tuberculosis preventive treatment (TPT) is effective for this group. This study used decision tree-Markov model comparing: targeted CXR_LTBI_6-week H2P2 (6-week rifapentine-isoniazid) and CXR_LTBI_6H (6-month isoniazid) for individuals with chest X-ray (CXR)-detected pulmonary fibrosis lesions and subsequent LTBI positivity, versus non-targeted LTBI_6-week H2P2 and LTBI_6H for elderly LTBI-positive individuals, validated via scenario and sensitivity analyses. Over 5 and 20 year horizons among simulated cohort of 10,000 individuals aged ≥65 years, CXR_LTBI_6-week H₂P₂ served as the only strategy on the cost-effectiveness frontier, with baseline costs of $73,122.83 and $166,058.33, total QALYs of 52,024.52 and 116,650.90, and prevented active TB cases of 40 and 63 respectively. Compared with this strategy, all other strategies were absolutely dominated, presenting fewer prevented active TB cases (1-30), reduced QALYs (0.55-38.39) and elevated total costs ($32,948.71-$1,845,680.24) with CXR_LTBI_6H brought the minimum health loss (0.55 lost QALYs) and cost increment ($32,948.71) among all dominated options. Two scenario analyses regarding the waning long-term protective efficacy of 6-week H2P2 further verified the sustained cost-effectiveness dominance of CXR_LTBI_6-week H2P2. One-way and probabilistic sensitivity analyses consistently confirmed that CXR_LTBI_6-week H2P2 remained the most robust cost-saving strategy regardless of parameter variation and model uncertainty. In conclusion, CXR-guided LTBI TPT is cost-effective among rural elderly Chinese with pulmonary fibrosis lesions, with the 6-week H2P2 regimen as the optimal preventive strategy.
Since 2020, H5Nx high Pathogenicity avian influenza viruses (HPAIVs) belonging to hemagglutinin (HA) clade 2.3.4.4b have undergone widespread dispersal in wild birds, posing substantial threats to global poultry populations and mammals worldwide. In this study, we report the co-circulation of clade 2.3.4.4b H5N1 and H5N6 HPAIVs associated with mortality events in Anseriformes and Charadriiformes at a coastal wintering site in Fujian Province, China. H5N1 and H5N6 viruses were identified in 4 species of waterfowl (Bean Goose, Eastern Spot-billed Duck, Eurasian Wigeon, and Eurasian Curlew). Phylogenetic analysis indicated that these H5N1 and H5N6 isolates were clade 2.3.4.4b strains circulating within Eurasia and lacked known mammalian adaptation markers in key proteins. The infected birds exhibited severe systemic multi-organ pathology, with the most pronounced damage observed in the lungs. H5N6 and H5N1 viruses caused lethal injury in BALB/c mice, with H5N1 leading to systemic infection. Environmental sampling also revealed the presence of H5N1 HPAIVs alongside low-pathogenicity avian influenza viruses (LPAIVs) such as H3N1 and H6N1. Our findings highlight the complex and dynamic transmission patterns of H5 HPAIV in wild bird populations and the substantial threat they pose to mammals, underscoring the critical importance of sustained surveillance for high pathogenicity avian influenza in wild birds.
A novel recombinant strain of Echovirus 11 has recently emerged worldwide and has been associated with increased pathogenicity, particularly causing severe disease in neonates. The enhanced virulence of this variant may be linked to its recombinant nature and the accumulation of mutations in capsid proteins.In this study, we investigated the relationship between genetic variations and virulence using a clinical isolate of the dominant Echovirus 11 D5 genotype, in comparison with the prototype strain. In vitro characterization in A549 human lung epithelial cells revealed that the clinical isolate exhibits significantly greater cytopathic effects than the prototype, as evidenced by increased lytic replication, reduced cell viability, and higher viral loads accompanied by enhanced release of infectious particles. The isolated virus was found to directly bind and activate the Fas receptor as demonstrated by surface plasmon resonance and cross-linking mass spectrometry analyses. This was found to enhance productive viral replication and facilitate the efficient release of newly assembled virions from infected cells, thereby promoting rapid viral dissemination. Collectively, these findings elucidate the mechanism underlying the increased aggressiveness of this emerging Echovirus 11 variant and underscore the importance of heightened surveillance and awareness of its potential clinical impact.
Continued SARS-CoV-2 antigenic drift and the persistent risk of zoonotic sarbecovirus spillover highlight the need for broadly protective countermeasures. Here, we longitudinally profiled the B-cell receptor (BCR) repertoire of a single volunteer who received heterologous booster vaccination followed by Omicron BF.7 breakthrough infection, integrating bulk BCR sequencing with single B-cell culture and antibody binding analysis. Breakthrough infection was associated with broadened serum neutralization across SARS-CoV-2 variants and related sarbecoviruses, consistent with recall of antibodies targeting conserved epitopes. Repertoire analysis revealed stage-specific remodeling, with high-affinity binding antibodies shifting from an IGHV1-46-enriched profile after vaccination to preferential representation of IGHV3-30-3 after infection. Isolated monoclonal antibodies exhibited nanomolar-to-picomolar binding affinities to diverse animal-derived sarbecovirus spikes, with broad binding commonly, but not universally, associated with CDRH3 lengths of 14-16 amino acids. Phylogenetic and sequence analyses defined divergent evolutionary trajectories for IGHV1-46 and IGHV3-30-3 lineages, highlighting candidate genetic features that warrant validation in larger cohorts. Together, these findings describe how sequential heterologous antigen exposures can reshape the humoral repertoire in one individual and generate hypotheses for future pan-sarbecovirus antibody and vaccine studies.
