Screening and detection of IgG antibodies against severe fever with thrombocytopenia syndrome virus among blood donors in southwestern part of Japan.

Mammal community composition and season determine the abundance of questing ticks in mountainous forests of central Japan.

Background The Bunyavirales order encompasses hantavirus and severe fever with thrombocytopenia syndrome virus (SFTSV), which could cause hemorrhagic fever with renal syndrome (HFRS) and severe fever with thrombocytopenia syndrome (SFTS), respectively. Both are types of viral hemorrhagic fever (VHF), posing challenges for early differentiation. We focused on identifying predictors for two diseases, assisting clinicians to make diagnosis. Methods We conducted a retrospective analysis of clinical records from patients with SFTS and HFRS patients who were hospitalized at Qingdao No. 6 People’s Hospital and Yantai Qishan Hospital between 2021 and 2023. Independent factors were explored by logistic regression and Lasso regression analysis, following a model was established. The model’s performance was carried out by the receiver operating characteristic curve (ROC) and the area under the curve (AUC), with predictors visualized by nomogram and clinical benefit assessed by decision curve analysis. Results Our study included 129 SFTS patients and 89 HFRS patients. Independent predictors included headache (OR: 0.098, 95% CI: 0.015–0.624, p = 0.014), conjunctival congestion (OR: 0.021, 95% CI: 0.002–0.253, p = 0.002), mucosal hemorrhage (OR: 0.003, 95% CI: 0.000–0.049, p < 0.001), white blood cell count (WBC): 4–10 (OR: 0.019, 95% CI: 0.002–0.186, p = 0.001), WBC > 10 (OR: 0.011, 95% CI: 0.001–0.132, p < 0.001), CD4+ T cells ≥500 (OR: 0.013, 95% CI: 0.001–0.127, p < 0.001). WBC had the strongest predictive power (AUC: 0.916, p < 0.001). The model had optimal predictive ability and clinical net benefit, with an AUC of 0.988. Conclusion Effective predictors were CD4+ T cells, WBC (elevated in HFRS, decreased in SFTS), headache and hemorrhage symptoms.

Severe fever with thrombocytopenia syndrome (SFTS), caused by SFTS virus (SFTSV), is an emerging tick-borne disease in East Asia. SFTS monitoring has been carried out since 2010 in mainland China, but no confirmed human cases or infected vectors had been reported from the northern regions of Hebei Province. We intensified surveillance in this area by collecting serum samples from patients with fever of unknown origin (FUO) and ticks from local habitats. Subsequently, all collected samples were screened for SFTSV by qRT-PCR. SFTSV RNA was detected in two patient sera from Chengde (2.2%). In six, positive ticks were detected among the Haemaphysalis verticalis (8.6%) collected from Zhangjiakou; no positive ticks were detected among the ticks collected from Chengde. Complete viral genomes were recovered from positive tick samples via next-generation sequencing and subjected to a suite of bioinformatic analyses. Two complete genomes from Haemaphysalis verticalis formed a distinct clade with an Inner Mongolia strain across L/M/S (bootstrap = 1.0) and separate from genotypes A–F; pairwise p-distances to genotypes A–F were &gt;0.11 across L/M/S, supporting designation of a distinct genotype. We designate this lineage as genotype G; no credible recombination was detected. Based on the L segment, molecular-clock analyses dated the genotype G lineage to the late 13th century, predating the crown age of genotypes A–F (~18th century) by more than 400 years. We provide the first evidence of SFTSV circulation in northern Hebei and identify a novel, deeply divergent lineage. This finding confirms the co-circulation of distinct viral lineages (G and F) within the province and provides critical new insights into the virus’s diversity and evolutionary history. These results expand the known range and genetic diversity of SFTSV, underscoring the need for enhanced surveillance and ecological investigation in emerging regions. It is necessary to strengthen public health education, improve the early diagnosis and treatment ability of medical workers, and provide a scientific basis for targeted public health interventions.

Abstract Background Severe fever with thrombocytopenia syndrome (SFTS) is a viral hemorrhagic fever caused by the SFTS virus (SFTSV), a tick-borne Phlebovirus. This study investigates the association between viral load and cytokine levels in patients with SFTS. Methods Viral RNA was isolated from plasma collected in EDTA and quantified by real-time reverse transcription-polymerase chain reaction (RT-PCR). Cytokines in the sera of SFTS patients were measured using cytometric bead array (CBA). Results Viral loads ranged from 2.3×10^3 copies/mL to 7.9×10^11 copies/ml. Of the 46 patients, 10 (21.7%) died during treatment. Viral loads were ≥1×10^8 copies/ml in the patients who died. The concentrations of G-CSF, IFN-α, IFN-γ, IL-1β, IL-6, IL-10, MCP-1, and IP-10 were higher in patients with high viral loads. The levels of IFN-α, IFN-γ, IL-6, MCP-1, and IP-10 positively correlated with SFTSV viral load. Conclusion SFTSV RNA load was significantly correlated with the concentration of IFN-α, as well as other cytokines (IFN-γ, IL-6, MIP-1α, and IP-10).

The exploration of age-related clinical characteristics and prognosis of severe fever with thrombocytopenia syndrome (SFTS) has not been extensively addressed in current research. This study aimed to analyze the differences in clinical features and outcomes of SFTS patients across various age groups. Patients were assigned to four groups: those aged ≤ 54 years, those aged 55-64 years, those aged 65-74 years, and those aged ≥ 75 years. Then, their clinical data were compared. A total of 253 patients diagnosed with SFTS were retrospectively included. Compared with patients aged < 65 years, patients aged ≥ 65 years had higher serum levels of laboratory parameters indicating liver, kidney, heart, and coagulation system injury, as well as a higher viral load. Moreover, the serum levels of procalcitonin, SAA, ferritin, IL-6, IL-10, and TNF-α were significantly higher, but the percentages and counts of CD3+ and CD3 + CD4 + lymphocytes were significantly lower in patients aged ≥ 65 years than in patients aged < 65 years. The cumulative survival rate of patients aged ≥ 65 years was also significantly lower than that of patients aged < 65 years. Univariate and multivariate logistic regression analyses identified that age ≥ 65 years was an independent risk factor for the prognosis of patients with SFTS. Age significantly influences the clinical features and prognosis of patients, and age ≥ 65 years is associated with adverse outcomes in patients with SFTS.

Disrupted Microbiome-Metabolome networks underlie gut barrier and immune imbalance in severe fever with thrombocytopenia syndrome.

Virus envelope glycoprotein targeting bispecific T cell engager protects mice from lethal severe fever with thrombocytopenia virus infection.

Profiling of SFTS virus and host protein interactions by affinity purification-mass spectrometry.

Background: The zoonotic infectious disease, severe fever with thrombocytopenia syndrome (SFTS), caused by the SFTS virus (SFTSV), Bandavirus dabieense, was first identified in China in 2009 and reported in the Republic of Korea in 2013. The primary vector is the tick Haemaphysalis (H.) longicornis, which is endemic to the Asia-Pacific region and has a wide range of hosts. While SFTSV has been studied in various wildlife species, no investigation has focused explicitly on bats, which are ecologically significant in the transmission of zoonotic viruses. Materials and Methods: To investigate the relationship between bats and SFTSV, 1,200 ticks were collected from 12 sites in 6 provinces within 1 km of bat habitats using flagging, and 147 bat sera were collected via cardiac puncture after ether anesthesia between November 2021 and September 2022. Total RNA was extracted from the ticks and bat sera, and nested reverse transcription polymerase chain reaction was performed to amplify the S segment of SFTSV. Bat sera were analyzed for IgG antibodies against SFTSV by enzyme-linked immunosorbent assay (ELISA). Results: Within 1 km of bat habitats, 881 H. longicornis, 209 H. flava, 96 Haemaphysalis spp., and 14 Ixodes (I.) nipponensis were identified. SFTSV was detected in 12.3% (147/1,200) of the ticks. Although no SFTSV RNA was detected in bat sera by nested PCR, 3.4% (5/147) were seropositive by ELISA. Conclusion: While molecular evidence of SFTSV infection was not observed in bats, a few serological positives suggest possible past exposure. The detection of SFTSV in ticks collected from bat habitats suggests potential ecological interactions involving bats, ticks, and other wildlife species. These findings highlight the importance of considering both wildlife reservoirs and the indirect role of bats in the geographical spread of SFTSV.

A single-chain mRNA vaccine co-expressing GPC and NP provides complete protection against lethal Dabie bandavirus challenge in mice

Severe fever with thrombocytopenia syndrome (SFTS) is a disease caused by SFTS virus (SFTSV), an RNA virus, and endemic to Asia. The case fatality rate in Japan is estimated to be approximately 27%. Currently, no efficacious drugs are available. Favipiravir (FPV) has the potential to treat SFTS. However, no quantitative studies comparing FPV with conventional treatments have been conducted in the country. We conducted an open-label, interventional study in which patients with SFTS were administered FPV 1800 mg twice on the first day, followed by 800 mg twice daily for nine days. Additionally, we performed a retrospective observational study on patients with SFTS who received the best supportive care (BSC) without FPV treatment by collecting medical data from individuals at the same institutions. Patients aged 20-85 years were recruited, and blood samples were collected on Days 0 (pre-dose), 1, 3, 6, 9, 14, and 27 in the interventional study. Outcomes and laboratory parameters were compared by 1:1 matching using propensity score (PS). Thirty and 78 patients were enrolled in the FPV and the BSC groups, respectively. Twenty-three pairs were identified by PS matching. The risk ratio of fatality for the FPV group compared to the BSC group reduced to 0.500 after matching. Ferritin levels associated with hemophagocytosis severity were significantly different between the FPV and BSC groups on Days 3 to 9 after matching. No concerning serious adverse events were observed in the FPV group.This interventional study has been registered with the Japan Registry of Clinical Trials as jRCT2080223816.

Severe Fever with Thrombocytopenia Syndrome (SFTS) is an emerging tick-borne infectious disease that poses a significant public health threat. SFTS virus (SFTSV) has a broad host range, including humans, cats, and natural reservoir species. Therefore, cultured cell lines derived from different mammalian species are useful for understanding the susceptibility of SFTSV in hosts. In this study, we evaluated pathogenicity and infectivity, focusing on cytopathic effect (CPE) induction and growth kinetics of SFTSV in several mammalian cell lines, including our original tiger-derived TLT, wild deer–derived DFKT and DFLT, and hedgehog-derived HHoVT. Following SFTSV infection, TLT, CRFK (cat), FCWF-4 (cat), and CPK (porcine) cells exhibited CPE, whereas Vero E6 (monkey), A549 (human), BHK-21 (hamster), DFKT, DFLT, and HHoVT cells did not. Infectious viral yields in the supernatants of TLT, CRFK, FCWF-4, Vero E6, and BHK-21 were higher than those of CPK, A549, DFLT, and DFKT. SFTSV infection in hedgehog-derived HHoVT cells was very limited. These observations suggest that features such as viral CPE and virus yield following SFTSV infection depend on cell type. It is noteworthy that TLT formed clear plaques that were easy to count, indicating that TLT cells are useful for the titration of infectious SFTSV by plaque-forming assay. Our results provide useful information and tools for further elucidating the mechanisms of SFTSV infectivity, proliferation, and pathogenicity using in vitro models.

ObjectivesThis study aimed to develop an accurate staging system for SFTS (Severe Fever with Thrombocytopenia Syndrome) based on the dynamic assessment of organ damage. This staging is intended to improve prognostication and guide treatment strategies.MethodsClinical data and laboratory parameters were analyzed from 77 fatal and 398 non-fatal cases of SFTS. Risk factors for mortality were identified using univariate Cox regression analysis. Dynamic changes in laboratory parameters and multi-organ dysfunction were systematically observed.ResultsBy dynamically analyzing clinical symptoms and laboratory parameters over the disease course, combined with assessing the number and severity of multi-organ dysfunction, SFTS progression was categorized into five distinct stages: initial (1–4 days), progressive (5–7 days), MOD (Multiple Organ Dysfunction) (8–10 days), remission (11–14 days), and convalescence (15–20 days). The critical phase, lasting approximately two weeks, accounted for 85.71% of patients succumbed within this two-week period, with 46.75% experiencing mortality during the MOD stage. Moreover, the study findings highlighted the effectiveness of intravenous immunoglobulin, including both its overall and early administration, in improving outcomes for patients with SFTS-associated myocarditis.ConclusionsThe progression of SFTS can be distinctly categorized into five distinct stages. Day 7 represents a critical juncture in disease progression, whereas Day 11 signifies a pivotal moment for clinical recovery. The progression stage is optimal for intervening to prevent further disease advancement. Treatment strategies should be adapted to the evolving patterns and severity of organ dysfunction. Myocarditis remains a significant challenge throughout SFTS progression, and early IVIG administration has been demonstrated to reduce mortality in patients with myocarditis complications significantly.

Severe Fever with Thrombocytopenia Syndrome virus (SFTSV) infection induces hepatitis, myocarditis, and even multi-organ dysfunction with a high mortality rate, while the impact on the pancreas remains unknown. In a retrospective analysis of clinical parameters in a cohort of 290 patients with severe fever with thrombocytopenia syndrome (SFTS), it is observed that pancreatic injury biomarkers in 19.4% (elevated serum amylase ≥3 × upper limit of normal (ULN)) and 25.8% (elevated serum lipase ≥3 × ULN). Notably, 17.6% of patients met the diagnostic criteria for clinically confirmed pancreatitis. Mechanistic studies using human pancreatic organoids and murine models demonstrated that SFTSV directly infects pancreatic tissue, facilitated by viral receptors C-C motif chemokine receptor 2 (CCR2)and lipoprotein receptor-related protein 1 (LRP1), provoking cell death in pancreatic tissue. Transcriptomic profiling revealed that SFTSV infection triggers a robust innate immune response characterized by interferon pathway activation and pro-inflammatory cytokine upregulation. Pathological analysis of infected murine pancreatic tissues showed acinar cell vacuolization, viral inclusions, and immune cell infiltration. Comparative studies with caerulein-induced pancreatitis models identified C3-mediated complement hyperactivation as a key pathological driver. The studies identified that SFTSV exhibits a specific pancreatic tropism, with direct infection leading to cell death and initiating a strong inflammatory immune response, resulting in viral pancreatitis.

Severe fever with thrombocytopenia syndrome (SFTS), an emerging tick-borne infectious disease, is marked by rapid progression and high mortality. Current machine learning (ML)-based prognostic models for SFTS are not only scarce but also lack external validation. This multicenter retrospective cohort study aimed to develop a clinical risk prediction model for SFTS. It involved 1,215 SFTS patients from three Chinese hospitals and utilized multiple machine learning algorithms. ML algorithms were applied for variable selection and model construction. Model performance was evaluated using metrics such as the area under the receiver operating characteristic curve (AUC), accuracy, recall, and F1 score. The logistic regression (LR) algorithm-constructed predictive model achieved the best performance in both training and validation cohorts. Multivariate logistic regression was then used to build nomograms. The clinical utility of the optimal model was assessed via decision curve analysis (DCA) based on net benefit. Five independent risk factors for SFTS-related death were identified: age, consciousness disturbance, activated partial thromboplastin time (APTT), serum creatinine (SCr), and log- transformed viral load (lg viral load). Nomograms based on these factors exhibited high accuracy, with an AUC of 0.881 in the training group and 0.886 in the validation group. In conclusion, ML proves effective for identifying high -risk SFTS patients. ML - based prediction models and nomograms can accurately predict SFTS prognosis, and the five key features serve as valuable early - prognosis indicators deserving clinical attention.

Severe Fever with Thrombocytopenia Syndrome (SFTS) is a zoonotic infectious disease with high mortality, in which coagulation dysfunction triggered by the virus serves as a critical factor in disease progression and patient death. This study comprehensively analyzed coagulation characteristics and the impact of concomitant Disseminated Intravascular Coagulation (DIC) on prognosis in 187 SFTS patients. Significant differences (p < 0.05) in coagulation parameters were observed among SFTS patients with varying disease severity and viral loads. The dynamic changes in coagulation parameters, especially activated partial thromboplastin time(APTT) and d-dimer (DD), differed significantly between the survival group and the death group. Prothrombin time(PT), International Normalized Ratio(INR), APTT, thrombin time(TT), and DD were identified as independent risk factors for death in SFTS patients. Furthermore, APTT ≥ 51.3 s (p = 0.001), TT ≥ 30.5 s (p = 0.023), and DD ≥ 2.39 µg/mL (p = 0.009) were shown to be effective predictors of patient mortality. Additionally, significant differences (p < 0.001) in admission coagulation parameters were found in SFTS patients complicated by DIC, among whom APTT was identified as an independent risk factor for death in this subgroup. Therefore, monitoring coagulation parameters aids in the early identification of high-risk patients, and intensive coagulation management may help improve patient prognosis.

Oral nanoformulation of a host-directed antiviral niclosamide effectively treats severe fever with thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging zoonotic disease caused by the tick-borne SFTS virus (SFTSV), with a case fatality rate of 16.2-32.6% in East Asia. Currently, no approved vaccines or antiviral treatments exist. Monoclonal antibody (mAb) therapy offers rapid immune protection and is a promising strategy against SFTSV. This review outlines advances in SFTSV neutralizing mAb research, covering conventional generation methods (hybridoma, phage display) and innovative approaches such as single B cell sequencing. We also introduce computational tools like artificial intelligence -assisted epitope prediction and in silico mAb design. Furthermore, we discuss the structure-function relationships of mAbs targeting Gn and Gc glycoproteins, their mechanisms (e.g., fusion inhibition, receptor blockade), and key functional attributes including breadth, potency, and cross-reactivity. Challenges such as limited epitope accessibility, immune interference, and antibody-dependent enhancement are highlighted. Finally, we propose a multipronged strategy integrating structure-guided engineering, high-throughput screening, and rigorous preclinical evaluation to accelerate the development of safe and effective SFTSV therapeutics.

Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne viral disease with a mortality rate of 10-30%; however, effective vaccines and therapies for this disease have not yet been developed. Understanding the long-term immune response of recovered individuals is critical for vaccine development and treatment. In this study, we conducted an epidemiological investigation of antibody and memory B cell trends in individuals with SFTS. Peripheral blood mononuclear cells (PBMCs) and plasma were collected from 16 survivors of SFTS and five healthy controls. SFTS virus (SFTSV)-specific humoral immune responses were assessed using enzyme-linked immunosorbent assay (ELISA), biolayer interferometry (BLI), neutralization assays, and flow cytometry. SFTSV Gn-specific IgG was detected in plasma samples from all patients using ELISA and BLI. All patient plasma samples also presented neutralizing activity against SFTSV infection, and the IC₅₀ values were correlated with ELISA OD values (ρ = 0.700, P = 0.003 and BLI signals (ρ = 0.818, P = 0.0002). Neutralizing antibodies and SFTSV Gn-specific memory B cells were detected in samples from patients up to 6.7years post-infection. SFTSV-specific humoral immunity, including neutralizing antibodies and memory B cells, can persist in the majority of recovered patients, including those as late as 6.7years post-infection. This information will be useful for the development of vaccines and antiviral therapies using antibodies against SFTS.