Background: Functional cure is widely regarded as the optimal therapeutic endpoint in chronic hepatitis B (CHB), yet its long-term impact on overall survival and multisystem health remains insufficiently quantified, limiting its role in clinical decision-making and treatment prioritization. Methods: We analyzed data from a large prospective, multicenter, community-based cohort including 6,024 Chinese CHB patients. To address immortal time bias and confounding, we applied time-dependent Cox proportional hazards models to model functional cure as a time-dependent exposure, combined with propensity score matching. We further quantified population-level impact using population attributable fractions (PAFs) and estimated absolute survival benefits using restricted mean survival time (RMST). Findings: Over a median follow-up of 11.1 years, 1,032 patients achieving functional cure were compared with 2,882 matched patients with persistent infection. Functional cure was associated with significantly lower risks of cirrhosis (adjusted hazard ratio [aHR], 0.44; 95% CI, 0.27-0.73) and hepatocellular carcinoma (aHR, 0.49; 95% CI, 0.32-0.75). It was also associated with a 54% reduction in all-cause mortality (aHR, 0.46; 95% CI, 0.35-0.61), including reductions in liver-related, extrahepatic cancer-related, and cardiovascular mortality. At the population level, functional cure corresponded to an estimated gain of 5.19 years in life expectancy within the observed age range. Interpretation : Functional cure in CHB is associated with substantial gains in life expectancy and broad reductions in both hepatic and extrahepatic mortality. These findings highlight the potential value of functional cure as a clinically meaningful endpoint beyond virological suppression and suggest its relevance for long-term risk stratification and treatment prioritization in CHB management.

OBJECTIVES:This study aimed to investigate the potential for dog-to-human transmission of Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) and characterize viral shedding patterns in naturally infected dogs. METHODS:We conducted genomic analysis of SFTSV strains isolated from an infected dog and its owner using whole-genome sequencing. Viral loads were quantified in canine saliva, urine, and stool samples via qRT-PCR during the acute infection phase. RESULTS:Genomic sequencing revealed 100% identity between viral strains from the dog and owner. The dog exhibited exceptionally high viral loads, particularly in bloody stools (2.2 × 107 copies/mL) and saliva (2.3 × 105 copies/mL), with persistent shedding observed throughout the clinical course. The owner developed SFTSV infection 14 days after the dog's symptom onset. CONCLUSIONS:This study provides the first molecular confirmation of direct SFTSV transmission from dogs to humans, identifying bloody stools and saliva as high-risk transmission sources. These findings underscore the importance of including dogs in SFTSV surveillance systems and implementing protective measures when handling sick pets in endemic areas.

BACKGROUND:Enteroviruses (EVs) are the major pathogens causing viral encephalitis and meningitis and frequently drive outbreaks in high-risk settings such as schools and healthcare facilities. We analyzed outbreaks reported from 1960-2025 to map epidemiology, clinical manifestations, and serotypes, informing prevention and control. METHODS:We systematically searched Web of Science, PubMed, CNKI, and Wanfang from 1960 to July 1, 2025 using the keywords of enterovirus, encephalitis, meningitis and outbreak to assemble a global dataset of enterovirus encephalitis and meningitis outbreaks. Eligible studies must report outbreaks of laboratory-confirmed enterovirus meningitis or encephalitis, while those with unclear outbreak definitions or no laboratory confirmation were excluded. Standardized forms were used to extract information on outbreak characteristics, case demographics, and etiology data. A random-effects model was employed to derive combined estimates of attack rates, hospitalization rates, clinical manifestations and serotype distribution, with subgroup analyzes by geographic region, temporal period, and age group. This research was registered in PROSPERO (CRD420251140412). RESULTS:A total of 56 outbreaks (28,622 cases) across 20 countries were included. Outbreaks were most prevalent in the Western Pacific and Europe, exhibiting seasonal peaks in June-July (Northern Hemisphere) and April-May (Southern Hemisphere), with a median size of 90 cases. Schools and medical institutions were the major outbreak settings. EV-B was the dominant species (94.6%, 53/56), with E30 being the most prevalent serotype. Two decades, 2000-2009 and 2010-2019, saw the highest number of reported outbreaks. The overall attack rate was estimated at 13.2% (95% CI 6.1-22.3). Notably, the pooled hospitalization rate was exceptionally high at 94.0% (95% CI 85.9-99.2). The most frequently reported symptoms were fever, headache, and vomiting. CONCLUSIONS:Enterovirus encephalitis and meningitis outbreaks remain a persistent global concern, marked by high hospitalization rates, summer-autumn peaks and regional patterns. They primarily affect children under 15 years old, with multiple serotypes in circulation. Shifting toward active syndromic and genomic surveillance, alongside targeted prevention in high-risk settings, is urgently needed. FUNDING:This work was supported by the Beijing Natural Science Foundation (L242052) and National Key R&D Program of China (2024YFC2310403); Jiangsu Province 333 Project.

As coronavirus disease 2019 (COVID-19) has transitioned into an endemic phase characterized by sustained transmission and widespread hybrid immunity, understanding region-specific determinants of severe disease remains important for real-world risk stratification and public health planning. A retrospective surveillance study was conducted using 5,072 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) whole-genome sequences linked to clinical metadata from 13 cities in Jiangsu Province (from January 2023 to December 2024). Features derived from clinical, viral genomic, and regional epidemiological domains were evaluated using five machine learning models and assessed on an independent 2024 cohort. Model interpretability was examined using SHapley Additive exPlanations (SHAP) analysis. Key mutations were further examined through epitope prediction, peptide-HLA docking and binding affinity assessments to explore potential immunological implications. Integrated multidimensional features demonstrated superior predictive performance compared with single-domain inputs. In the independent 2024 validation cohort, LightGBM achieved the best overall performance (F1-score = 0.603; AUC = 0.735). SHAP analysis identified age as the dominant model predictor, followed by the age-viral load interaction, regional location, vaccination status, and selected viral genomic features. Epitope prediction and structural analyses suggested L452W-associated changes in predicted peptide-HLA interaction patterns within the evaluated set of high-frequency HLA class I alleles in the Jiangsu population, providing candidate hypotheses for future experimental validation. COVID-19 severity during the endemic phase appeared to reflect interactions among host susceptibility, viral genetic variation, and regional epidemiological context, with age and vaccination emerging as key predictive factors. This population-based, interpretable framework highlights clinically relevant risk-associated features and may support real-world risk stratification in ongoing and future infectious disease surveillance.

OBJECTIVES:To characterize SARS-CoV-2-specific humoral and cellular immunity in a large community cohort, focusing on age-related differences following hybrid immunity from prior infection and vaccination. METHODS:In this cross-sectional study, 1186 adults (median age: 62 years, IQR 43-73) were enrolled from six districts in Jiangsu province, eastern China. Spike-specific immune responses including serum total antibodies (Abs), nasal secretory IgA (sIgA), memory B cells, circulating follicular helper T (cTfh) cells, and CD4⁺/CD8⁺ memory T cell subsets were evaluated. Multivariable logistic regression identified factors associated with immune responses. RESULTS:Compared with younger adults, individuals aged ≥65 years exhibited significantly lower levels of spike-specific serum total Abs, spike-specific memory B cells, spike-specific cTfh cells, and spike-specific CD4+ terminally differentiated effector memory T (TEMRA) cells, but significantly higher levels of spike-specific CD8+ TEMRA cells (all P < 0.05). Spike-specific nasal sIgA, CD4⁺/CD8⁺ TCM and TEM subsets were comparable between age groups. After adjustment for sex, infection history, vaccination status, body mass index (BMI), diabetes, and lifestyle factors, age ≥65 years was associated with reduced spike-specific total Abs (OR 0.653, 95% CI 0.512-0.839), memory B cells (OR 0.780, 95% CI 0.613-0.992), and cTfh cells (OR 0.706, 95% CI 0.554-0.899). In contrast, older age was associated with elevated spike-specific CD8⁺ TEMRA cells (OR 1.396, 95% CI 1.096-1.778). CONCLUSIONS:Despite widespread hybrid immunity, older adults displayed impaired humoral and T-B helper responses alongside selective expansion of spike-specific CD8⁺ TEMRA cells. These findings define an age-associated immune phenotype in the endemic phase and support age-tailored vaccination and immune monitoring strategies.

Background:Hand, foot, and mouth disease (HFMD), a common childhood illness caused by various enteroviruses, poses a significant public health threat in the Asia-Pacific region, where severe cases associated with enterovirus A71 (EV71) are a major concern. The EV71 vaccination program was introduced in China in late 2016. Although randomized controlled trials have established the robust efficacy and safety of these vaccines, assessing their real-world performance remains crucial. Subsequent studies have evaluated its real-world effectiveness in several provinces, including Zhejiang and Guangdong. However, evidence on its real-world impact in reducing EV71-associated HFMD in Jiangsu Province remains limited. Objective:This study aimed to describe HFMD epidemiological characteristics and to evaluate the population-level effectiveness of the EV71 vaccination program in Jiangsu Province. Methods:We characterized the temporal distribution of EV71-related HFMD cases based on longitudinal surveillance data collected through the National Notifiable Diseases Surveillance System in Jiangsu Province from 2012 to 2019 and assessed the impact of vaccination using a Bayesian structural time series model under a counterfactual framework. The intervention effect of the EV71 vaccine was estimated by comparing the observed data with predictions from a counterfactual model scenario without vaccination. Results:A total of 932,274 HFMD cases were reported in Jiangsu from 2012 to 2019, including 5190 (0.56%) severe cases. An estimated 140,876 (15.11%) cases were attributed to EV71. EV71-associated HFMD cases showed a marked decline, with estimated numbers of 22,303, 9796, and 3900 in 2017, 2018, and 2019, respectively. We estimated that 30,117 EV71 cases (95% credible interval -1777 to 93,601) were prevented by the vaccination program from 2017 to 2019, corresponding to a reduction of 45.55% (95% credible interval -5.19% to 72.22%). The effectiveness of vaccination increased annually, with reductions of -1.03% (95% credible interval -94.85% to 48.29%) in 2017, 55.54% (95% credible interval 13.94%-77.56%) in 2018, and 82.28% (95% credible interval 65.77%-90.89%) in 2019. Furthermore, we observed that children younger than 4 years obtained greater benefits compared with those older than 4 years, with the greatest reduction of 57.68% (95% credible interval 13.04%-79.65%) in the 3- to 4-year age group, followed by a 48.09% (95% credible interval 28.00%-62.98%) reduction in the 0- to 2-year age group. In contrast, the reduction was markedly lower, at 16.75 % (95% credible interval -96.53% to 65.47%) in children older than 4 years during the 2017 to 2019 period. Conclusions:EV71 vaccination is an effective measure to prevent HFMD. The sharp decline in EV71-associated HFMD cases following the implementation of the EV71 vaccination program suggests a potential causal relationship. Therefore, strengthening vaccine coverage remains a public health priority.

Background: Meteorological factors influence infectious diarrhea transmission through multiple pathways, yet no composite index exists to quantify their combined effect. We developed and evaluated a Meteorological Risk Index for Infectious Diarrhea (MRIID) integrating multiple meteorological drivers for Jiangsu Province, eastern China. Methods: We analyzed 210,069 infectious diarrhea cases reported across 95 county-level districts during 2015–2024. A time-stratified case-crossover design combined with distributed lag non-linear models (DLNMs) was used to estimate relationships between five meteorological factors (temperature, relative humidity, maximum wind speed, air pressure, and precipitation) and infectious diarrhea risk over lags 0–21 days. A gradient boosting machine (GBM) model was employed to derive data-driven contribution weights for each factor. The MRIID was constructed by combining factor-specific excess risks with GBM-derived weights and standardizing to a 0–100 scale. The association between MRIID and diarrhea risk was further assessed using the case-crossover framework. ​Results: Temperature and relative humidity exhibited inverted J-shaped associations with infectious diarrhea, with greater risk at low exposures, while air pressure and wind speed showed J-shaped associations with greater risk at high exposures. Diarrhea risk decreased with increasing precipitation. The GBM model assigned the highest weights to temperature (0.43) and relative humidity (0.26), followed by maximum wind speed (0.16), air pressure (0.12), and precipitation (0.03). The MRIID demonstrated the strongest effect on the concurrent day, with risk diminishing over approximately three weeks. The cumulative MRIID showed an approximately linear positive association with infectious diarrhea incidence, with each unit increase corresponding to a 1.74% rise in risk (95% CI: 1.58%, 1.89%). Sensitivity analyses confirmed the robustness of these findings. Conclusions: The MRIID effectively synthesizes the combined meteorological risk for infectious diarrhea into a single, interpretable metric. Temperature and relative humidity are the dominant drivers. The index offers a practical tool for integrating meteorological information into diarrhea surveillance and early warning systems, supporting timely public health preparedness. ​

H9N2 avian influenza viruses inherently carry cross-species transmission potential, making continuous surveillance critical for pandemic prevention. This study focused on monitoring the 2024 H9N2 epidemic in Jiangsu Province’s external environment, analyzing its molecular evolution and receptor binding properties, assessing cross-species transmission and pandemic risks, and investigating serological antibody levels across different human populations. Environmental samples were collected from live poultry markets, farms, slaughterhouses, and bird habitats across Jiangsu, screened via quantitative PCR (qPCR), with positive samples used for virus isolation and whole-genome sequencing. Receptor binding properties were tested by hemagglutination assay, and H9N2 antibody levels were measured in 370 occupationally exposed individuals and 240 non-exposed individuals using hemagglutination inhibition (HI) assays. Among the 5779 collected samples, 6.89% tested H9N2-positive, and 12 strains belonging to the Eurasian lineage Y280-like clade G57 genotype were successfully isolated. All strains carried the HA-Q226L mutation, with 11 showing preferential binding to human α-2,6 receptors and one strain possessing dual receptor binding capability. Internal genes harbored mammalian adaptation mutations, and M2 proteins contained mutations conferring complete resistance to amantadine-class antiviral drugs. Serological tests revealed antibody positive rates of 4.05% in exposed populations and 2.5% in non-exposed populations, with no statistically significant difference between groups. These findings confirm that Jiangsu’s circulating H9N2 viruses have acquired human receptor preference and mammalian adaptation, posing silent infection and pandemic risks. Enhanced surveillance and the development of candidate vaccine stockpiles are strongly recommended.

There has been an increasing interest in the association between meteorological risk factors and scarlet fever risk. However, the associations between individual-level exposure to meteorological factors and the scarlet fever risk remain poorly understood. We collected 36, 912 scarlet fever cases in Jiangsu Province, China (2005–2023) from the Nationwide Notifiable Infectious Diseases Reporting Information System. These data were then paired with daily meteorological factors, including temperature, relative humidity, solar radiation, wind speed, surface pressure, and total precipitation, sourced from the ERA5-Land dataset. A time-stratified case-crossover design was applied using conditional logistic regression combined with distributed lag non-linear models to examine both linear and non-linear associations, while adjusting for public holidays and recent outbreaks. Subgroup analyses by age, gender, period, and season were conducted to assess potential heterogeneity. Effect estimates for individual exposures are expressed as odds ratios (ORs), and interactions were evaluated using the relative excess odds due to interaction (REOI), attributable proportion (AP), and the synergy index (S). Significant linear associations (ORs per one-unit increment) were observed for all meteorological variables except wind speed with a 2–5 day lag, peaking at 3 days. Positive associations were found for solar radiation (OR = 1.009, 95 ^2 and surface pressure (OR = 1.088, 95 ^∘ C, relative humidity (OR = 0.995, 95 ^∘ C and fluctuating risk at extreme cold (below −5 ^∘ C). Relative humidity displayed an M-shaped curve, peaking at 56–86 = 0.97). Solar radiation and surface pressure showed overall declining trends, with elevated risks at lower levels (OR = 1.03 at 1.08 MJ/m ^2 ; OR = 1.01 at 99.82 kPa) and fluctuations across their central ranges. Total precipitation and wind speed showed rising trends, with ORs >1 above 15.1 mm and 5.0 m/s. Stronger associations were observed among individuals aged ≥ 6 years (e.g., temperature OR = 0.988, 95

In recent years, resistance of Klebsiella pneumoniae to the clinical last-resort drugs carbapenem and tigecycline has intensified, including Metallo-β-Lactamase-producing K. pneumoniae (MBL-KP), which demonstrated resistance to ceftazidime-avibactam (CZA), posing a significant public health threat. This study focused on the carbapenems, CZA, and tigecycline resistance mechanisms of MBL-producing Carbapenem-resistant K. pneumoniae (MBL-CRKP). A retrospective study and genomic epidemiological analysis of Carbapenem-resistant K. pneumoniae (CRKP) strains isolated from Yangzhou City, Jiangsu Province, China, between 2016 and 2023 was conducted. The detection rate of CRKP in Yangzhou City has increased significantly in recent years, with five strains carrying the Metallo-β-Lactamases (MBLs) gene, all of which exhibited resistance to carbapenems and CZA. Two strains even showed reduced susceptibility to tigecycline, with one harboring tmexCD2-toprJ2. Moreover, three CRKP strains carrying both blaKPC-2 and blaNDM-1/blaNDM-29 genes were identified. Plasmids carrying MBL genes can horizontally transfer, leading to the spread of resistance, thus further exacerbating the difficulty of clinical treatment and the spread of resistance. In conclusion, this study not only revealed the resistance of MBL-CRKP strains to clinical last-resort therapeutic drugs but also explored the resistance mechanism and horizontal transfer through genomic analysis. Moreover, this study also suggested that microbial drug resistance surveillance should be conducted from the perspective of “one health” in the future to combat this global health challenge.

Early diagnosis and differentiating infected from vaccinated animals (DIVA) are the milestone in mitigation, control, and eradication of virus. However, the continuous evolution of new virus strains has hindered the success of many classical techniques, and no DIVA-compatible vaccines are available for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We here develop a universal diagnostic protein-peptide hybrid microarray (PPHM) for different SARS-CoV-2 strains infections and extend the DIVA concept to differentiate recently infected from historically vaccinated/infected hosts (DIVH) in the context of SARS-CoV-2 using in a single sample. First, we analyzed the amino acid sequence identities, which exceeded 96.6%, among the SARS-CoV-2 strains-Delta, Omicron, and New Omicron-and the wild strain. Based on this analysis, we identified a unique diagnostic combination for each of the three SARS-CoV-2 strains using the same peptide probes from the wild strain. Subsequently, we developed a diagnostic combination without regard to strain specificity, PPHMSARS-CoV-2, suitable for all three strains, demonstrating a specificity of 99.0% (99/100) and a sensitivity of 90.2% (175/194). Finally, we successfully achieved DIVH and classified 314 individuals to the classifications of uninfected (57/314, 18.2%), newly vaccinated or infected (5/314, 1.6%), recently infected (78/314, 24.8%), and historically vaccinated or infected (174/314, 55.4%) using PPHMSARS-CoV-2.IMPORTANCESevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused global health concerns and led to economic losses reaching trillion dollars since 2019. Many diagnostic techniques are showing great success; for instance, nucleic acid amplification showed high specificity and sensitivity in SARS-CoV-2 infections. However, the results of these techniques can be affected by the continuous evolution of SARS-CoV-2 strains, and these techniques were not compatible with differentiating infected from vaccinated animals (DIVA). To circumvent these unfavorable outcomes, a novel strategy is imperative. In this study, we made an exciting discovery: transiently produced IgGs can be used not only for diagnosis and DIVA but also for differentiating recent infections from past infections (approximately 70 days after the occurrence of vaccination or infection). This protein-peptide hybrid microarray technique will have a positive impact on the mitigation and eradication of coronaviruses.

Objective:Severe fever with thrombocytopenia syndrome (SFTS), an emerging infectious disease with substantial mortality, was first reported in China in 2009 and subsequently became endemic to South Korea, Japan, Vietnam, and the United Arab Emirates. Despite growing concerns about its transmission dynamics, the potential for human-to-human transmission through close physical contact remains inadequately explored in the literature. Methods:We conducted comprehensive epidemiological investigations of the initial cases of SFTS. In these investigations, real-time fluorescent reverse transcription polymerase chain reaction (RT-PCR) was used to analyze blood samples, followed by whole-genome sequencing (WGS) for phylogenetic tree construction. Results:Our analyses identified one potential index case (Case A) and one confirmed case (Case B), both of which tested positive for SFTS virus (SFTSV) nucleic acid. Notably, we observed an 8.65 % positive rate for SFTSV nucleic acid in Haemaphysalis longicornis ticks near Case A's residence. Additionally, the only potential exposure route for Case B appeared to be close physical contact with Case A. Genetic sequencing indicated high nucleotide homology (ranging from 99.63 % to 99.91 %) between the SFTSV strains isolated from both cases. Conclusions:Collectively, our study further demonstrated that close intimate contact may serve as a significant mode of SFTSV transmission among humans. This finding underscores the importance of enhancing awareness and implementing preventive measures among patients, healthcare providers, and relevant public health personnel regarding the human-to-human transmission of SFTS, contributing to more targeted public health strategies in SFTS-endemic regions, particularly in areas with low endemicity levels.

Over the past decade, multiple outbreaks of hand, foot, and mouth disease (HFMD) have occurred in East Asia, especially in China. It is crucial to understand the distribution pattern and risk factors of HFMD while also studying the corresponding characteristics of reinfections. This paper aims to jointly analyze the spatiotemporal distribution and influential factors of primary infection and reinfection of HFMD in Jiangsu province, China, under the Bayesian framework. Using county-level monthly HFMD counts from 2009 to 2023, we proposed four spatiotemporal hierarchical models with latent effects shared in the reinfection sub-model to evaluate the influence of air pollution, meteorological factors, and demographic characteristics on primary infection and reinfection of HFMD. The integrated nested Laplace approximation (INLA) approach estimated model parameters and quantified the spatial and temporal random effects. The optimal model with spatial, temporal, and spatiotemporal interaction effects indicated a significant positive influence of NO _2 , wind speed, relative humidity, and solar radiation, as well as a significant negative effect of PM _2.5 , O _3 , temperature above 27 °C, precipitation, and COVID-19, on both infections. Scattered status and critical primary infection have a significant positive effect on primary infection and reinfection. Positive sharing coefficients revealed similar spatiotemporal patterns of both types of infection. Beyond these fixed effects, non-linear analyses further highlighted comparable exposure-response patterns for primary infection and reinfection, with notable thresholds around 50–70 g/m ^3 for PM _2.5 , 90 g/m ^3 for O _3 , 80 g/m ^3 for NO _2 , 20 °C for temperature, and 55

In this study, a homogeneous immunoassay based on ortho-touch reaction and graphene oxide (GO) quenched acridine esterification chemiluminescence is developed for sensitive detection of SARS-CoV-2 antigen. The sensitivity and specificity of this method was further evaluated with viral protein, virus strains and clinical samples. Benefiting from strong chemiluminescence signal and good quenching performance of GO, this method allows enhanced signal-to-background ratio, and the limit of detection is down to 0.02 ng/ml of viral protein or equivalently 200 copies/ml of virus strains. In clinical evaluations, our approach demonstrated a high level of agreement with digital RT-PCR, achieving a positive coincidence rate of 90.87 %, a negative coincidence rate of 99.77 %, and an overall concordance of 96.53 %, while showing no cross-reactivity with other prevalent viruses. This method offers a promising, sensitive, rapid, and cost-effective platform for early SARS-CoV-2 diagnosis. Moreover, it can potentially be adapted for detecting other pathogens.

Background:SARS-CoV-2 Omicron lineages continue to evolve, driving recurrent infection waves since 2022 through immune escape in populations with diverse immunological histories. Understanding cross-variant neutralization capacity, especially against emerging variants like JN.1, is critical for optimizing protection strategies. Methods:We conducted genomic surveillance in Jiangsu Province (December 2022-February 2024) to identify circulating variants and stratified 150 participants into six cohorts based on immune histories (BA.5/XBB breakthrough infections, JN.1 infections, and sequential exposures). Pseudovirus neutralization assays were employed to evaluate serum responses against ancestral (WT), early Omicron (BA.4/5, BF.7, BQ.1), recombinant (XBB/XBB.1.5/XBB.1.22/EG.5.1), and JN.1 variants. Results:Sera from BA.5/XBB breakthrough infections showed significantly reduced neutralization against JN.1 and EG.5.1 (vs. WT). In contrast, recent JN.1 infection induced broad-spectrum neutralization, with cross-protection comparable across variants. Sequential Omicron exposures (e.g., BA.5 → JN.1/XBB) enhanced cross-neutralization versus single infections, notably generating potent, broad antibodies even during acute phases-a previously unreported finding. Conclusions:Heterogeneous immune backgrounds necessitate vigilant monitoring of emerging variants, and sequential Omicron exposures confer robust cross-protection that can guide vaccine design and long-term public health strategies-all within a One Health framework that integrates human serosurveillance with animal and environmental monitoring to preempt cross-species transmission and future zoonotic spillover.

ABSTRACTAs the COVID‐19 pandemic continues, increasingly complex vaccination and infection histories have made it urgent to investigate the antibody dynamics in populations with hybrid immunity. This study aimed to explore the multi‐time‐point dynamics of SARS‐CoV‐2 IgG antibody levels in a community‐based population in Jiangsu Province, China, following the Omicron BA.5 wave, as well as the long‐term persistence of IgG antibodies nearly 2 years postinfection. A total of 2737 participants across Jiangsu Province were followed up at three different time points over a 6‐month period (December 2022–June 2023). Additionally, a cross‐sectional serological survey was conducted in October 2024, involving 230 participants to assess long‐term antibody persistence. We used generalized additive models to fit antibody dynamics curves, generalized linear mixed models to explore factors influencing antibody levels, and Kaplan‐Meier survival analysis to estimate cumulative seroreversion rates. Our findings revealed that, following the large‐scale Omicron BA.5 infections, over 85% of the population initially exhibited seropositive IgG levels. Older individuals (> 65 years) had significantly lower antibody levels and faster rates of decline compared to younger participants. Booster immunization reduced the risk of seroreversion by 59.79% (95% CI: 29.63%–76.46%), while individuals with multiple infections experienced slower antibody decay. In the cross‐sectional survey conducted 22 months postinfection, the IgG seropositivity rate remained high, exceeding 98%, indicating sustained immunity at the population level. This study provides valuable insights into the dynamics and persistence of IgG antibody levels following large‐scale infection. The results underscore the importance of tailored booster immunization strategies to sustain long‐term immunity, especially in vulnerable groups like the elderly. Additionally, ongoing serological monitoring is essential for assessing population immunity and informing future vaccination strategies.

SARS-CoV-2 has continued to spread globally since its outbreak. As the virus evolves, new variants affect the efficacy of current vaccines and treatments. Therefore, understanding and explaining the viral prevalence of SARS-CoV-2 is crucial for developing effective public health strategies. Genomic information from the SARS-CoV-2 network surveillance laboratories in Jiangsu Province in 2023 was collected. The impact of private mutations on binding affinity of the spike protein to Angiotensin Converting Enzyme 2 (ACE2) was evaluated by Bioinformatic analyses, pseudovirus infection assays and Bio-Layer Interferometry (BLI). The impact of private mutations on antibody escape capacity was evaluated through Pseudotyped Virus Neutralization Assay (PVNA). The major circulating SARS-CoV-2 sublineages in Jiangsu Province in 2023 included BA.5.2*, XBB.1.5*, XBB.1.16*, XBB.1.22*, and XBB.1.9*. Key private mutations analyzed were E748V in XBB.1.5.24, H146K and I210T in XBB.1.22.1, H146K + I210T, and L455F in EG.5.1/EG.5.1.1. Bioinformatic analyses, pseudovirus infection assays, and BLI results showed that L455F significantly increased the spike protein’s binding affinity to ACE2. PVNA results indicated that H146K and I210T enhance the antibody evasion ability of the XBB.1.22.1 spike protein, while L455F did so for EG.5.1/EG.5.1.1. However, E748V increased antibody neutralization sensitivity for XBB.1.5.24. E748V, I210T, and L455F became characteristic of their respective descent lineages GF.1, FY.3.1, and HK.3. The epidemic durations of FY.3.1 and HK.3 were longer than that of GF.1. Continuous monitoring and functional analysis of SARS-CoV-2 private mutations can be an effective approach for explaining patterns of viral prevalence. This has significant implications for the timely formulation of prevention and control measures.