Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is associated with a high short-term mortality rate. Therefore, early and accurate prognostic prediction is crucial for precise clinical management. This study aims to investigate the expression patterns of intercellular adhesion molecule-1 (ICAM-1) and its predictive value for the short-term prognosis of patients with HBV-ACLF. The Methylight method was used to quantitatively detect ICAM-1 promoter methylation level in peripheral blood mononuclear cells (PMBCs) of 286 participants. Meanwhile, the mRNA and plasma expression levels of ICAM-1 were determined using RT-qPCR and ELISA, respectively. The ICAM-1 promoter methylation levels in PBMCs of HBV-ACLF patients were significantly lower than those in chronic hepatitis B (CHB) patients and healthy controls (HCs), whereas the mRNA and plasma expression levels of ICAM-1 were markedly elevated. The ICAM-1 methylation levels in HBV-ACLF patients correlated with specific clinical parameters. Among HBV-ACLF patients, ICAM-1 methylation levels were significantly lower in the non-survivor groups at both 28 and 90 days. The study further revealed that ICAM-1 methylation level serves as an independent influencing factor for the prognosis of HBV-ACLF patients at 28 and 90 days. Based on ROC curve and Kaplan-Meier curves, ICAM-1 methylation levels demonstrated excellent performance in predicting 28- and 90-day mortality in patients with HBV-ACLF. In conclusion, patients with HBV-ACLF exhibit hypomethylation of the ICAM-1 promoter. The combination of ICAM-1 promoter methylation level and MELD score can effectively enhance the predictive ability for the short-term prognosis of HBV-ACLF patients.
Understanding the transmission routes of avian influenza viruses (AIVs) is critical for outbreak control. Beyond direct contact and aerosol transmission, indirect transmission via contaminated environmental surfaces contributes to exposure risk, particularly in live poultry markets (LPMs). Although previous studies have examined the environmental persistence of individual AIV strains, systematic comparisons among genetically related viruses remain scarce. H9N2, designated by the WHO as a potential "Pathogen X," is of particular concern. Here, we assessed the environmental persistence and indirect transmission potential of four genetically related H9N2 AIVs originating from the same LPM-associated epidemiological context: one human isolate (H19) and three LPM environmental isolates (E01, E02, E03). All viruses exhibited temperature-dependent infectivity decay on four surface materials. Notably, H19 and E01 demonstrated prolonged environmental persistence compared with E02 and E03 under multiple conditions. Moreover, smooth, non-porous surfaces (plastic, glass, stainless steel) generally supported longer viral survival than porous non-woven fabric. In a guinea pig model, H19 and E01 led to detectable indirect transmission, whereas E02 and E03 did not. Comparative sequence analysis revealed differences at NP-346 and PB2-18 between these two phenotypic groups, although the functional relevance of these substitutions remains to be determined. Collectively, these findings reveal that environmental persistence and indirect transmission potential can vary markedly among genetically related LPM-associated H9N2 AIVs, supporting the integration of environmental adaptability into routine risk assessment frameworks.
This retrospective single-center study compared nucleic acid testing (NAT), time-resolved fluorescence immunoassay (TRFIA), and enzyme-linked immunosorbent assay (ELISA) for screening hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), and Treponema pallidum (TP) among 1243 preoperative and pre-transfusion patients. Specimens were detected by pathogen-targeted NAT, serological TRFIA and routine ELISA panels, respectively. HBV positive rates were 2.17% (NAT), 2.09% (TRFIA) and 1.53% (ELISA); HCV positive rates were 0.08%, 0.24% and 0.08%, without statistical intergroup differences (all p > 0.05). TRFIA yielded a significantly higher TP positive rate than ELISA (0.88% versus 0.40%, p < 0.05), while no HIV-positive specimens were identified in this cohort. Kappa tests showed moderate-to-good consistency for HBV (0.711-0.842) and perfect concordance between NAT and ELISA for HCV (Kappa = 1.000). Twenty-three discordant samples were found, including eight NAT-only HBV positives suggestive of potential window-period infections and six TRFIA-only TP positives. Limited by an obstetric-female-dominated cohort, scarce HCV cases, and zero HIV positives, standard diagnostic accuracy metrics could not be comprehensively evaluated. NAT and TRFIA exhibit complementary screening values, yet their combined application may increase false-positive risks and lacks systematic cost-effectiveness evidence to support large-scale clinical implementation.
Hepatitis E virus (HEV) is a significant cause of acute liver failure (ALF). The role of glycogen phosphorylase L (PYGL) in the diagnosis and prognosis of HEV-ALF remains unclear. This study collected clinical data and baseline characteristics from HEV-ALF patients, acute hepatitis E (AHE) patients, and healthy controls (HCs), measuring serum PYGL levels in each group. Methods including Orthogonal partial least squares discriminant analysis (OPLS-DA), receiver operating characteristic (ROC) and decision curve analysis (DCA) were used to evaluate the clinical utility of PYGL. Results showed that PYGL effectively diagnosed HEV-ALF (AUC = 0.911). PYGL levels were significantly higher in HEV-ALF patients than in AHE patients and HCs (p < 0.001). Among HEV-ALF patients, non-survivors exhibited higher PYGL levels than survivors (p < 0.001). PYGL demonstrated good predictive ability for 30-day mortality (AUC = 0.859). OPLS-DA and DCA confirmed its strong decision-making utility. Furthermore, PYGL levels escalated with increasing organ failure and paralleled clinical worsening, being highest in the deterioration group (p < 0.05). PYGL is a potential diagnostic and prognostic biomarker in HEV-ALF patients, where elevated levels indicate poorer outcomes and support early intervention.
Airborne transmission is an important route for the spread of respiratory viruses. To assess the potential for airborne shedding of influenza A virus (IAV) and respiratory syncytial virus (RSV), this study compared the presence of viral RNA in air samples collected near hospitalized patients. Patients with IAV or RSV infection and a nasopharyngeal swab cycle threshold value of 28 or lower were included. Air sampling was performed using a vacuum cleaner equipped with a detachable soluble air filter attached to the hose inlet. For each patient, one sample was collected 50 cm dorsally and one 50 cm ventrally relative to the patient's face, each for 2 min. Filters were dissolved and analyzed for viral RNA by RT-qPCR. In total, 59 patients were included: 39 with IAV infection and 21 with RSV infection, including one patient co-infected with both viruses. Air samples were more frequently positive in RSV-infected patients than in IAV-infected patients (12/21 [57%] vs. 6/39 [15%], p = 0.0012). In multivariable analysis, RSV-infections remained associated with higher rates of air sample positivity after adjustment for nasopharyngeal viral load. These findings suggest different aerosol shedding between RSV and IAV, although differences in infectious potential remain to be determined.
Influenza B viruses contribute substantially to global morbidity and mortality, yet genomic data from the Middle East remain limited. We retrospectively performed whole-genome sequencing of six influenza B virus-positive residual nasopharyngeal specimens collected at King Abdulaziz Medical City, Riyadh, during the 2024-2025 season, including one fatal pediatric case, and described their genomic features alongside clinical outcomes. All six genomes belonged to the B/Victoria lineage and clustered within V1A.3a.2-derived subclades circulating globally during 2024-2025. Five genomes, including the fatal pediatric case, were assigned to subclade C.5.6, whereas one non-fatal case belonged to C.5.7. The Saudi sequences were interspersed among contemporaneous reference strains from Europe, Asia, and North America, without evidence of a distinct local lineage. The fatal isolate did not occupy a distinct phylogenetic position and contained none of the screened virulence-associated markers, including the neuraminidase N342K substitution. These genomes provide regional surveillance data from an underrepresented setting. Given the small sample size and inclusion of a single fatal case, the findings are descriptive and do not permit inference regarding genomic determinants of disease severity. Larger studies integrating viral genomic, clinical, and host data are needed.
Hemophagocytic lymphohistiocytosis (HLH) is a severe, rapidly progressive disease. While viral infection is considered a common etiology of pediatric HLH, specific causative viruses other than the Epstein-Barr virus (EBV) have been rarely identified. This study utilized metagenomic next-generation sequencing (NGS) to identify potential causative pathogens in plasma samples from 17 pediatric patients with suspected HLH. Additionally, one case each of confirmed EBV- and cytomegalovirus (CMV)-associated HLH was analyzed for methodological validation. Plasma cell-free RNA (cfRNA) profiling was performed using NGS data to assess the host transcriptome response. Significant viral reads of human herpesvirus-6B, human herpesvirus-7, and Hubei reo-like virus (HRLV) 14 were detected using metagenomic NGS in one patient each. Plasma cfRNA profiles from five patients with viral infection (including EBV and CMV) were compared to those of 14 patients without viral infection. By comparing the two patient groups, 1053 differentially expressed genes were identified. The gene ontology (GO) term of "adaptive immune response" (GO: 0002250) was significantly enriched among upregulated genes in the virus-positive group. Furthermore, an isolated cluster consisting specifically of mitochondrial RNAs, was identified in the upregulated genes of the virus-positive group. Using metagenomic NGS, several candidate viral pathogens were identified in patients with suspected infection-related HLH. The viral genome of HRLV 14, previously undetected in human clinical samples, was identified in one patient. The results from plasma cfRNA profiling suggest that mitochondrial RNAs may reflect the underlying pathogenesis of virus-associated HLH and have potential utility as disease biomarkers.
Antiretroviral therapy (ART) has markedly improved the prognosis of people living with HIV (PLWH); however, latent viral reservoirs remain a major barrier to a cure. The "Shock and Kill" strategy aims to reactivate latent provirus with latency-reversing agents (LRAs) and subsequently eliminate the infected cells, yet most LRAs characterized to date provide only the "shock" component. Through screening a small-molecule library, we identified 2-hydrido-2,2'-spirobi(1,3,2-benzodioxaphosphole) (2-HSB) as a novel candidate that both reactivates latent HIV provirus and selectively induces cytopathic effects in latently infected reservoir cell lines, thereby exhibiting a dual "Shock and Kill" activity within a single compound. Mechanistically, the HIV-1 tat protein appears to contribute to this selectivity. At the single-cell level, the two effects appeared largely independent, indicating that, under the conditions tested, reactivation was not a consequence of cell death and vice versa. Importantly, 2-HSB induced viral transcription in ex vivo CD4+ T cells from ART-suppressed PLWH. Together, these findings identify 2-HSB as a dual-action candidate that reactivates latent HIV-1 and preferentially induces cytopathic effects in reservoir cell-line models, while supporting further mechanistic and ex vivo validation in primary reservoir-bearing cells.
Thrombotic risk in COVID-19 extends beyond acute illness, including in nonhospitalized individuals, suggesting that thrombo-inflammatory biology may persist during recovery. Longitudinal sampling with pre-infection baselines is needed to distinguish infection-associated signals from inter-individual variability and time-related drift in blood gene expression. To define coordinated, time-resolved whole-blood transcriptomic programs during SARS-CoV-2 convalescence using longitudinal within-person comparisons before and after infection, alongside COVID-19-naïve controls. Adults were sampled longitudinally with specimens collected before SARS-CoV-2 infection (T0) and at ~3 months (T1) and ~6 months (T2) post-infection; COVID-19-naïve controls were sampled across matched timepoints. COVID-19-naïve status was confirmed using a multiplex anti-nucleocapsid IgG assay spanning multiple variant antigens. Whole-blood RNA-seq (PAXgene) was analyzed with DESeq. 2 using models that incorporated time point and participant. To prioritize infection-linked changes, genes differentially expressed over time in controls were identified and excluded from comparisons between COVID-19 time points. Pathways were assessed by pre-ranked GSEA (MSigDB) and clustered with aPEAR. After excluding control-associated genes, COVID-19 convalescence remained associated with marked transcriptional remodeling (T1 vs. T0: 782 genes; T2 vs. T0: 655 genes; p < 0.05) and persistent pathway-level changes. Interferon-α and interferon-γ signatures were enriched at both T1 and T2, and a core set of interferon-associated genes remained elevated across convalescence. SARS-CoV-2 infection is followed by durable whole-blood immune-defense programs, including persistent interferon signaling, detectable up to 6 months post-infection. These sustained signatures support a model of prolonged post-infectious immune activation that may contribute to extended thromboinflammatory risk.
Molecular point-of-care testing (POCT) platforms have demonstrated considerable utility in rapid and accurate influenza diagnostics. Among them, the Cepheid Xpert is widely used in clinical practice, while Coyote Flash10 and Genewise NAT-3000 were recently approved, with few performance data available. Performances of Flash10 and NAT-3000 were evaluated in parallel with the Xpert assay. The limits of detection (LoDs) were determined using serially diluted standard reference materials of inactivated influenza virus A and B (FluA/B). Clinical performance was assessed using 200 remnant nasopharyngeal swab specimens. Other assay features were also compared. All three platforms featured comparable hands-on procedures and turnaround times ranging from 26 to 33 min. The Xpert assay was more sensitive than the other two, with the lowest LoDs at 72.6, 49.3, 213.2, and 66.8 copies/mL for FluA H1N1, FluA H3N2, FluB Victoria, and FluB Yamagata, respectively. The Flash10 and NAT-3000 assays showed similar LoDs for FluA, ranging from 483.4 to 576.8 copies/mL; for Victoria and Yamagata, their LoDs were 296.4 and 92.7 copies/mL for Flash10 and 1419.1 and 591.0 copies/mL for NAT-3000. Clinical performance revealed high concordance across assays. Positive and negative percentage agreements ranged from 93.33% to 100.00%, along with high Kappa values ranging from 0.94 to 0.95. Linear regression analysis showed moderate to strong associations between the cycle threshold values of positive specimens. The two new molecular POCT platforms were similarly user-friendly and showed comparable performance to the Xpert platform for FluA/B detection, despite their higher LoDs, indicating they are potential alternatives for rapid respiratory virus detection.
Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne pathogen that causes severe fever with thrombocytopenia syndrome and posed a severe threat to public health. Our study panned and screened the phage-display antibody library constructed from the peripheral blood mononuclear cell (PBMC) from three SFTSV-infected convalescent patients. Human monoclonal antibodies (hmAbs) targeting SFTSV glycoprotein N (Gn) were isolated from the library and evaluated for binding, affinity, and neutralizing activities in vitro. Epitope identification was performed by structural model analysis, immunofluorescence and RT-qPCR. The results showed that hmAb B36 is a Gn-binding, moderately high affinity, neutralizing antibody. Moreover, hmAb B36 recognizes a conformational epitope formed by six residues on the domainⅠof the SFTSV Gn, which differs from the epitope previously reported. Among these residues, G114, L155, and S158 were identified as key sites for hmAb B36-mediated recognition. This study performed isolation and identification of a novel neutralizing antibody, offering insights for the future development of therapeutic antibody cocktails and vaccines against SFTSV.
International guidelines require that human papillomavirus (HPV) assays intended for primary cervical cancer screening demonstrate adequate reproducibility and non-inferior clinical accuracy compared with validated comparator assays. The clinical performance of the Sansure Human Papillomavirus DNA Diagnostic Kit (Sansure HPV Kit), a multiplex real-time PCR assay detecting HPV16 and HPV18 individually and 13 additional HPV types in aggregate, was evaluated according to the Meijer study design. The applied Ct cut-off for HPV-positivity was ≤ 39. A panel of 890 clinician-collected cervical samples from women aged ≥ 30 years participating in routine screening in Belgium, including 90 histologically confirmed CIN2+ cases and 800 ≤ CIN1 controls was collated. The Abbott RealTime High Risk HPV assay served as the comparator test. Non-inferiority margins were ≥ 0.90 for relative sensitivity and ≥ 0.98 for relative specificity. Reproducibility was assessed through re-analysis of previously published data. After exclusion of four invalid samples, 886 samples were included in the accuracy analysis. Relative sensitivity compared with Abbott RealTime was 0.978 (95% CI: 0.947-1.009; pnon-inferiority = 0.007) for CIN2+ and 0.966 (95% CI: 0.921-1.013; pnon-inferiority = 0.045) for CIN3+. Relative specificity for ≤ CIN1 was 1.003 (95% CI: 0.991-1.014; pnon-inferiority = 0.0006). Reproducibility data demonstrated intra-laboratory agreement of 93.8% (κ = 0.842) and inter-laboratory agreement of 94.4% (κ = 0.856), exceeding the Meijer reproducibility thresholds. Considering the Ct clinical cutoff (≤ 39.0), the Sansure HPV Kit fulfils the established international validation criteria for clinical sensitivity, specificity, and reproducibility for use in primary cervical cancer screening using PreservCyt as storage medium for cervical samples. Consideration of genotype composition, including detection of HPV53 within a pooled channel, is warranted in the context of organised screening programmes.
Hepatitis C virus (HCV) remains a major global public health concern due to the absence of an effective vaccine and its diversity, which complicate diagnosis, genotyping, and clinical management despite the widespread use of direct-acting antivirals (DAAs). In regions where multiple HCV genotypes co-circulate, inter-genotypic recombination represents an additional challenge for accurate classification and molecular surveillance. In this study, we investigate the presence and characterize inter-genotypic recombinant strains of HCV in Cameroon. Among 512 chronically infected patients initially genotyped by Sanger sequencing of Core and NS5B regions, 10 samples (1.9%) showed genotypic discordance, suggesting putative recombination. Whole-genome sequencing using Oxford Nanopore technology, combined with phylogenomic and recombinant analysis, confirmed the recombinant nature of all 10 isolates. Most recombinant (7/10) shared a unique breakpoint in the NS2/NS3 region, primarily displaying a genotype 2/1 genomic profile, while one group had a breakpoint in the E2/p7 region (genotype 4/1 genomic profile). One isolate exhibited a more complex structure with two successive breakpoints (4/2 followed by 2/1). Genotypes 1 and 2 were the most frequently involved parental lineages. These findings demonstrate the ongoing circulation of diverse natural HCV recombinant forms in Cameroon and identify genomic regions that appear preferentially involved in recombination events. Our results highlight the limitations of genotypic approaches based on partial genomes and underscore the importance of comprehensive genomic characterization to improve HCV genotype classification, surveillance, and therapeutic strategies in Central Africa.
This study aimed to compare the prognostic performances of individual laboratory parameters and biomarker ratios derived from them formortality in patients with Crimean-Congo Hemorrhagic Fever (CCHF), and to examine the temporal stability of the strongest index. A total of 1171 adult patients with laboratory-confirmed CCHF followed between 2014 and 2024 were retrospectively included in the study. Admission data were recorded, and the mortality discriminative performances of individual and derived biomarkers (interleukin-6-to-platelet ratio [IL-6/PLT], interleukin-6-to-calcium ratio [IL-6/Ca], ferritin-to-platelet ratio [Ferritin/PLT], and ferritin-to-calcium ratio [Ferritin/Ca]) for mortality were compared using ROC analysis. Ninety-seven patients (8.3%) resulted in mortality. Among the individual parameters, IL-6 demonstrated the highest discriminative ability for mortality (AUC: 0.887). Among the derived indices, the IL-6/PLT ratio demonstrated the highest overall performance with an AUC value of 0.920 (95% CI: 0.871-0.969; p < 0.001). The optimal cut-off value for the IL-6/PLT ratio was determined as 0.78 (88% sensitivity, 81% specificity). Mortality reached 100% in all patients with a ratio of ≥ 16. Sequential ROC analyzes demonstrated that the IL-6/PLT ratio maintained high prognostic stability throughout the course of infection. The IL-6/PLT ratio, a combined indicator of inflammatory response and hemostatic dysfunction, is a powerful biomarker candidate for the early and dynamic monitoring of mortality risk in CCHF.
After the COVID-19 emergency, respiratory viruses have re-emerged with changing and region-specific patterns. We aimed to characterize how these shifts affected viral circulation, clinical severity, and management of pediatric viral-associated lower respiratory tract disease (LRTD)across two post-pandemic seasons in Rome, Italy. We conducted a retrospective observational study of children (< 6 years) hospitalized with PCR-confirmed viral LRTDs during the 2022-2023 and 2023-2024 seasons. Of the 1,249 children hospitalized for LRTD, 49.08% were admitted during the 2022-2023 season and 50.92% during the 2023-2024 season. Clinical severity at presentation (PRESS ≥ 4) did not differ between the two seasons; however, a severe in-hospital course (CSS > 3) was more frequent in 2023-2024 (8.96% vs. 4.24%; p = 0.001). In 2023-2024, the corticosteroid use increased (77.20% vs. 72.43%; p = 0.05), whereas antibiotic use decreased (47.80% vs. 39.78%; p = 0.004). Respiratory syncytial virus remained the most common pathogen in both seasons, with no significant variation between them. Similarly, influenza showed no significant difference in prevalence. Compared with 2022-2023, 2023-2024 showed a higher prevalence of rhinovirus (50.31% vs. 37.36%), enterovirus (24.53% vs. 15.82%), bocavirus (13.99% vs. 8.16%) and viral codetection (51.89% vs. 45.02%) while adenovirus was more frequent in 2022-2023 (7.39% vs. 13.21%). Multivariable analysis identified the 2023-2024 season (OR 2.37; 95% CI 1.45-3.87), younger age (OR 0.96 per month; 95% CI 0.94-0.98), and comorbidities (OR 2.91; 95% CI 1.66-5.11) as independent predictors of severe in-hospital course. Male sex, viral codetection, and viral clinical categories were not associated with severity. In conclusion, in Rome's regional context, the evolving viral ecology highlights the need for continued local surveillance to guide clinical preparedness and optimize management in forthcoming seasons.
ABSTRACT This study aimed to compare the prognostic performances of individual laboratory parameters and biomarker ratios derived from them formortality in patients with Crimean‐Congo Hemorrhagic Fever (CCHF), and to examine the temporal stability of the strongest index. A total of 1171 adult patients with laboratory‐confirmed CCHF followed between 2014 and 2024 were retrospectively included in the study. Admission data were recorded, and the mortality discriminative performances of individual and derived biomarkers (interleukin‐6‐to‐platelet ratio [IL‐6/PLT], interleukin‐6‐to‐calcium ratio [IL‐6/Ca], ferritin‐to‐platelet ratio [Ferritin/PLT], and ferritin‐to‐calcium ratio [Ferritin/Ca]) for mortality were compared using ROC analysis. Ninety‐seven patients (8.3%) resulted in mortality. Among the individual parameters, IL‐6 demonstrated the highest discriminative ability for mortality (AUC: 0.887). Among the derived indices, the IL‐6/PLT ratio demonstrated the highest overall performance with an AUC value of 0.920 (95% CI: 0.871–0.969; p < 0.001). The optimal cut‐off value for the IL‐6/PLT ratio was determined as 0.78 (88% sensitivity, 81% specificity). Mortality reached 100% in all patients with a ratio of ≥ 16. Sequential ROC analyzes demonstrated that the IL‐6/PLT ratio maintained high prognostic stability throughout the course of infection. The IL‐6/PLT ratio, a combined indicator of inflammatory response and hemostatic dysfunction, is a powerful biomarker candidate for the early and dynamic monitoring of mortality risk in CCHF.
The 2025-2026 Northern Hemisphere influenza season was characterised globally by rapid expansion of A(H3N2) subclade K. Saudi Arabia reported an A(H3N2)-dominant epidemic peaking in epidemiological Weeks 43-46 (20 October-16 November 2025), with national test positivity reaching 36.8%. To characterise circulating H3N2 viruses and assess divergence from the vaccine reference strain, we performed amplicon-based whole-genome Oxford Nanopore sequencing of 149 residual A(H3N2)-positive respiratory specimens collected in Riyadh between August and December 2025 (one specimen in August and the remainder during October-December, reflecting the epidemic curve). We recovered 81 haemagglutinin (HA) and 71 neuraminidase (NA) high-quality consensus sequences. Nextclade classified 64 HA sequences (79.0%) as subclade K and 17 (21.0%) as the parental clade J.2.4; NA sequences segregated into B.4.2.2 (61, 85.9%) and B.4.2 (10, 14.1%). Among 69 isolates with paired HA and NA, the two clade assignments were strongly non-independent (Fisher exact two-sided p = 8.4 × 10-4; odds ratio 0.077, 95% CI: 0.011-0.436), with the K + B.4.2.2 constellation predominating (50/69, 72.5%). Twelve of 69 isolates (17.4%) showed an HA-NA clade mismatch (nine J.2.4-HA + B.4.2.2-NA; three K-HA + B.4.2-NA), consistent with within-season reassortment. Whole-genome maximum-likelihood phylogenies of all eight gene segments showed that the K and J.2.4 lineages remained largely coherent across the genome, with the internal segments broadly co-segregating (pairwise topological concordance, Spearman ρ 0.18-0.71); the reassortment signal was therefore concentrated at the HA-NA surface-gene pairing. Six HA1 substitutions (K2N, S144N, N158D, I160K, Q173R, T328A) discriminated subclade K from J.2.4 at high statistical significance and mapped to antigenic sites A, B, C, and D and the protein N-terminus. No neuraminidase-inhibitor or baloxavir resistance markers were detected. These data document a K-clade-predominant epidemic with persistent J.2.4 co-circulation, within-season HA-NA reassortment, and marked HA1 divergence from the vaccine reference, against a background of fully susceptible antiviral genotypes.
Hyperactive immune responses are implicated in the disease severity, prognosis, and complications of Severe Fever with Thrombocytopenia Syndrome (SFTS). In this study, we analyzed the differences in cytokine levels and clinical characteristics between severe and non-severe SFTS patients, aiming to assess the validity of interleukin-6 (IL-6), interleukin-8 (IL-8), interferon-α (IFN-α), and interferon-γ (IFN-γ) as predictors of disease severity and clinical outcomes in patients with SFTS. We retrospectively analyzed the demographic characteristics, clinical features, and the aforementioned four cytokines in a cohort of 110 laboratory-confirmed SFTS patients between July 2024 and August 2025. A total of 110 patients with SFTS were enrolled in this study. According to our grouping criteria, 52 patients (47.27%) were classified into the severe group, and 58 patients (52.73%) were classified into the non-severe group. Serum samples from patients with severe and non-severe SFTS were analyzed to compare differences in some routine hematological parameters, liver function, cardiac enzymes, acute-phase proteins and viral load. We further analyzed the correlation between the serum levels of IL-6, IL-8, IFN-α and IFN-γ and the aforementioned clinical laboratory parameters in patients with SFTS. Receiver operating characteristic (ROC) curve analysis demonstrated that serum levels of IL-6 and IFN-γ have predictive value for the severity of SFTS (p < 0.05). As the cut-off value of IL-8 remained within the normal range, it was not predictive of disease severity. We evaluated the potential of IL-6 and IFN-γ as diagnostic and prognostic biomarkers for severe SFTS, which may facilitate patient risk stratification. In addition, we performed stratified analyses by age and sampling time for these four cytokines to examine whether these factors might introduce potential bias into the results. These findings suggest that cytokine profiling may offer adjunctive information for early risk stratification, but should not be used in isolation for clinical decision-making.
