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Objective: To analyze the spatial autocorrelation and spatiotemporal clustering characteristics of severe fever with thrombocytopenia syndrome(SFTS) in Anhui Province from 2011 to 2023., Methods: Data of SFTS in Anhui Province from 2011 to 2023 were collected. Spatial autocorrelation analysis was conducted using GeoDa software, while spatiotemporal scanning was performed using SaTScan 10.0.1 software to identify significant spatiotemporal clusters of SFTS., Results: From 2011 to 2023, 5720 SFTS cases were reported in Anhui Province, with an average annual incidence rate of 0.7131/100,000. The incidence of SFTS in Anhui Province reached its peak mainly from April to May, with a small peak in October. The spatial autocorrelation results showed that from 2011 to 2023, there was a spatial positive correlation(P < 0.05) in the incidence of SFTS in all counties and districts of Anhui Province. Local autocorrelation high-high clustering areas are mainly located in the south of the Huaihe River. The spatiotemporal scanning results show three main clusters of SFTS in recent years: the first cluster located in the lower reaches of the Yangtze River, the eastern region of Anhui Province; the second cluster primarily focused on the region of the Dabie Mountain range, while the third cluster primarily focused on the region of the Huang Mountain range., Conclusions: The incidence of SFTS in Anhui Province in 2011-2023 was spatially clustered., (© 2024. The Author(s).)

Background: Severe fever with thrombocytopenia syndrome (SFTS) is a novel tick-borne infectious disease with a high fatality rate. Although several nomograms based on demographic and laboratory data have been reported to predict the prognosis of SFTS in recent studies, baseline serum glycated albumin (GA)/albumin (ALB) ratio included risk model has not been evaluated for the prediction of clinical outcome., Methods: A total of 214 SFTS patients with integral data admitted to our hospital from May, 2020 to November, 2022 were included in this study. SFTS infection was confirmed by real time fluorescent quantitative PCR (qRT-PCR). The demographic characteristics, clinical and laboratory data were collected with in 24 h of admission and 1 to 2 days before discharge and were analysed retrospectively., Results: Fiffty-seven patients (26.6%) died. Multivariate logistic regression analysis showed that age, aspartate aminotransferase (AST), blood glucose (GLU), GA/ALB ratio, neutrophil counts (NEU) and lymphocyte percentage (LYM%) were the independent risk factors for mortality. A nomogram by these factors was created using RMS package in the R program. Area under the receiver operating characteristic (ROC) curve (AUC) of this nomogram was 0.88 (95% CI: 0.83, 0.93). This model showed the excellent net benefit, as revealed by the decision curve analysis. GA/ALB ratios were also independent risk factors for poor out clinical come in subgroups of patients with hyperglycemia on admission and with diabetes history. Nomograms were constructed by the independent risk factors in the subgroups. AUCs of the nomograms in the subgroups showed high predictive values for adverse prognosis., Conclusions: GA/ALB ratios were independent risk factors for mortality in all SFTS patients and subgroups of with hyperglycemia on admission and diabetes history. The nomograms including GA/ALB ratio had high predictive value for adverse clinical outcome.The nomograms provide a basis for clinical decision-making for the treatment of SFTS patients in different clinical settings., (© 2024. The Author(s).)

Severe fever with thrombocytopenia syndrome (SFTS) is a recently identified infectious ailment triggered by a new strain of bunyavirus. It is distinguished by elevated fatality rates, ranging from 12 % to 30 %. The mechanism underlying the development of severe illness caused by SFTS bunyavirus (SFTSV) is not yet fully understood. To evaluate the role of the TLR2 receptor pathway in regulating Treg function in the progression of SFTS disease and possible mechanisms, sequential serum samples from 29 patients with SFTS (15 mild, 14 severe cases) were examined. Flow cytometry was employed to scrutinize the phenotypic and functional characteristics of TLR2 expression on circulating CD4 T cells, CD8 T cells, and Tregs. In all admitted patients, the evaluation of correlations between the frequencies of the aforementioned cells and SFTS index (SFTSI) was conducted. For SFTS, the levels of TLR2 on CD4 T cells and Tregs were significantly heightened when compared to those in healthy subjects. Additionally, the expression of TLR2 on Tregs exhibited a positive correlation with Ki-67 expression in Tregs and the severity of disease. Additionally, compared with those in uninfected controls, the expression levels of NF-κB in Tregs were significantly increased. Collectively, Tregs may be activated and proliferate through the stimulation of the TLR2/NF-кB pathway in reaction to SFTSV infection., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Background: Epstein-Barr virus (EBV) can be reactivated and proliferated with fatal outcome in immuno-compromised people, but the clinical consequences of EBV infection in patients with severe fever with thrombocytopenia syndrome (SFTS) remain uncertain. In this study, we investigated the infection rate, the influence and the early predictors of EBV infection in SFTS patients., Methods: In this retrospective study, SFTS patients who were treated in the First Affiliated Hospital of Nanjing Medical University from May 2011 to August 2021 were enrolled and divided into infected and non-infected groups. We compared the demographic characteristics, clinical manifestations and signs, laboratory tests and prognosis, and explored the risk factors of EBV infection by receiver operating characteristic (ROC) curve and logistic regression., Results: A total of 120 hospitalized SFTS patients with EBV-DNA testing were enrolled in this study. Patients with EBV infection had statistically significant higher mortality rate (32.0% vs. 11.43%, P = 0.005). Compared with the non-infected group, the EBV-infected group had higher levels of C-reactive protein (CRP), creatine-kinase (CK), fasting blood glucose (FBG), blood urea nitrogen (BUN), D-dimer, and CD56 + cell counts, lower levels of immunoglobulin G (IgG), IgM, complement 3 (C3), and C4. The proportion of patients with age ≥ 60 years and ferritin > 1500.0 ng/ml in the EBV-infected group was significantly higher than that in the non-infected group. The results of ROC analysis showed that the cut-off values of CRP, IgG, C3, C4, and CD56 + cell counts to predict EBV infection were 13.2 mg/l, 12.5 g/l, 1.1 g/l, 0.6 g/l, 0.3 g/l, and 94.0 cells/µl. Multivariable logistic analysis showed that age ≥ 60 years old, CRP > 13.2 mg/l, BUN > 5.4 mmol/l, ferritin > 1500.0 ng/ml, IgG < 12.5 g/l, IgM < 1.1 g/l, C4 < 0.3 g/l, and CD56 + cell counts > 94.0 cells/µl were the independent risk factors of EBV infection in SFTS patients., Conclusions: SFTS combined with EBV infection is associated with high morbidity and mortality. It is necessary to strengthen screening for EBV infection and its early predictive markers after admission in SFTS patients., (© 2024. The Author(s).)

Introduction: Severe fever with thrombocytopenia syndrome (SFTS) is prevalent in East Asia. However, the use of glucocorticoids (GCs) in the treatment of SFTS remains controversial., Methods: In this retrospective cohort study, we collected the data from patients with SFTS at Wuhan Union Hospital to evaluate the effect of GC therapy. Mortality and secondary infections were compared as outcomes. After searching public databases, we also included articles that examined GC use in patients with SFTS for meta-analysis., Results: Patients treated with GC had higher fatality rates (21.1% vs. 11.9%, respectively; P =0.006) and a longer length of stay (10.6 ± 5.1 vs. 9.5 ± 4.2, respectively; P =0.033). In cohorts adjusted using propensity score matching and inverse probability of treatment weighting, no significant differences in fatality rates and length of stay were observed. A meta-analysis of 4243 SFTS patient revealed that those treated with GCs had significantly higher mortality (OR=3.46, 95% CI =2.12-5.64, P <0.00001) and secondary infection rate (OR=1.97, 95% CI=1.45-2.67, P <0.0001)., Discussion: GC should be used cautiously when treating SFTS. No significant differences were identified in terms of mortality and secondary infection rates between patients with SFTS treated with or without GC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Wang, Zhou and Guo.)

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that was first identified in mainland China in 2009 and has been reported in Zhejiang Province, China, since 2011. However, few studies have focused on the association between ticks, host animals, and SFTS., Objective: In this study, we analyzed the influence of meteorological and environmental factors as well as the influence of ticks and host animals on SFTS. This can serve as a foundational basis for the development of strategic policies aimed at the prevention and control of SFTS., Methods: Data on SFTS incidence, tick density, cattle density, and meteorological and environmental factors were collected and analyzed using a maximum entropy-based model., Results: As of December 2019, 463 laboratory-confirmed SFTS cases were reported in Zhejiang Province. We found that the density of ticks, precipitation in the wettest month, average temperature, elevation, and the normalized difference vegetation index were significantly associated with SFTS spatial distribution. The niche model fitted accurately with good performance in predicting the potential risk areas of SFTS (the average test area under the receiver operating characteristic curve for the replicate runs was 0.803 and the SD was 0.013). The risk of SFTS occurrence increased with an increase in tick density, and the response curve indicated that the risk was greater than 0.5 when tick density exceeded 1.4. The risk of SFTS occurrence decreased with increased precipitation in the wettest month, and the risk was less than 0.5 when precipitation exceeded 224.4 mm. The relationship between elevation and SFTS occurrence showed a reverse V shape, and the risk peaked at approximately 400 m., Conclusions: Tick density, precipitation, and elevation were dominant influencing factors for SFTS, and comprehensive intervention measures should be adjusted according to these factors to reduce SFTS incidence in Zhejiang Province., (© Mingyong Tao, Ying Liu, Feng Ling, Jiangping Ren, Rong Zhang, Xuguang Shi, Song Guo, Jianmin Jiang, Jimin Sun. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org).)

Hemorrhagic fever with renal syndrome (HFRS) and severe fever with thrombocytopenia syndrome (SFTS) are both endemic in rural areas and some characteristics are similar between HFRS and SFTS, which usually lead to misdiagnosis. In this study, we summarized and compared some characteristics of HFRS and SFTS which will provide scientific information for differential diagnosis. From 2011 to 2022, a total of 4336 HFRS cases and 737 SFTS cases were reported in Zhejiang Province. Compared to SFTS, there was a higher proportion of males among HFRS cases (72.46% [3142/4336] vs. 50.88% [375/737], p = 0.000). The median age of all 4336 HFRS cases was 49 (39, 59), while the median age of SFTS cases was 66 (57, 74). In addition, the involved counties of HFRS were more than SFTS, but the number of counties affected by SFTS increased from 2011 to 2022. The majority of SFTS cases occurred in summer (from May to July), but besides summer, HFRS cases also showed a peak in winter. Finally, our results showed that the case fatality rate of SFTS was significantly higher than that of HFRS. Although there were some similarities between HFRS and SFTS, our study found several differences between them, such as gender distribution, age distribution, and seasonal distribution, which will provide scientific information for differential diagnosis of HFRS and SFTS. Further studies should be carried out to explore the mechanism of these differences., (© 2024 Wiley Periodicals LLC.)

Background: Since its discovery, severe fever with thrombocytopenia syndrome (SFTS) has been characterized by rapid progression and poor prognosis, and no specific treatment is available. The aim of this study was to investigate the early warning indicators of mortality in SFTS patients., Methods: This is a retrospective cross-sectional study. The study subjects were patients who were admitted to the hospital with a confirmed diagnosis of SFTS from January 2023 to October 2023, and their clinical symptoms and signs at the time of admission, as well as the laboratory indexes of the first blood collection after admission were collected, grouped according to the prognosis, and statistically analyzed., Results: A total of 141 patients were collected, of which 27 patients died and 114 patients were in the survival group. Through statistical analysis, patients with combined hemorrhagic manifestations, disturbance of consciousness, lymphopenia, elevated lipase, and prolonged thrombin time on admission were independent risk factors for patients' death. By plotting the working characteristic curve of the subjects, as well as calculating the area under the curve, the results showed that the AUC of lymphopenia count was 0.670, 95% CI (0.563-0.776), P = 0.006; the AUC of elevated serum lipase index was 0.789, 95% CI (0.699-0.878), p < 0.001; the AUC of prolonged thrombin time was 0.749, 95% CI (0.645-0.854), p < 0.001., Conclusion: Patients with hemorrhagic manifestations, disturbance of consciousness, lymphocyte reduction, elevated serum lipase, and prolonged thrombin time on admission are more worthy of the clinician's attention, and require early and effective interventions to avoid further disease progression., (© 2024. The Author(s).)

Background: Severe Fever with Thrombocytopenia Syndrome (SFTS) is a tick-borne disease caused by the SFTS virus (SFTSV) which has the potential to become a pandemic and is currently a major public health concern., Case Presentation: We present the case of a 74-year-old female from an urban area of Chongqing, with leukocytopenia, thrombocytopenia, organ function, inflammatory, blood coagulation, and immune abnormalities. SFTSV infection was confirmed through molecular detection and metagenomic next-generation sequencing (mNGS) analysis, indicating a diagnosis of SFTS due to the patient's history of tick bites. The patient received symptomatic and supportive therapy, including antibiotics, antiviral treatment, and antifungal therapy, and finally discharged from the hospital on day 18., Conclusions: This study highlights the need for increased awareness, early diagnosis, and prompt treatment for tick-borne SFTS. It also provides a comprehensive understanding of the disease's characteristics, pathogenesis, detection methods, and available treatments., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease known for its high mortality rate and its correlation with Cytokine Storms (CS). Timely detection of CS is crucial for improving the prognosis of the disease. The objective of this investigation was to develop a model for identifying cytokine storms in the acute phase of SFTS., Methods: A total of 245 patients diagnosed with SFTS were included in this study between January 2020 and July 2022. Among them, 184 patients were part of the training set, while 61 patients were part of the validation set. Variables identified by LASSO were subsequently included in a multivariate logistic regression analysis to determine independent predictors. Subsequently, a nomogram was then developed to predict the likelihood of CS in SFTS patients. The predictive efficacy and clinical applicability of the nomogram model were further assessed through ROC analysis and the DCA curve., Results: Following LASSO analysis, a total of 11 indicators were included in multivariate logistic regression analysis. The findings indicated that PLT (OR 0.865, P < 0.001), LDH (OR 1.002, P < 0.001), Na + (OR 1.155, P = 0.005), and ALT (OR 1.019, P < 0.001) serve as independently predictors of CS in the acute phase of SFTS. Furthermore, a nomogram named the PLNA was constructed by integrating these four factors. The PLNA model exhibited favorable predictive accuracy with an AUC of 0.958. Moreover, the PLNA model exhibited excellent clinical applicability in both the training and validation sets, as evidenced by the DCA curve., Conclusions: The PLNA model, constructed using clinical indicators, can predict the probability of cytokine storm in the acute phase of SFTS patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Severe fever with thrombocytopenia syndrome (SFTS) virus and hantavirus are categorized under the Bunyavirales order. The severe disease progression in both SFTS and hemorrhagic fever with renal syndrome (HFRS) is associated with cytokine storms. This study aimed to explore the differences in cytokine profiles and immune responses between the two diseases. A cross-sectional, single-center study involved 100 participants, comprising 46 SFTS patients, 48 HFRS patients, and 6 healthy controls. The study employed the Luminex cytokine detection platform to measure 48 cytokines. The differences in cytokine profiles and immune characteristics between the two diseases were further analyzed using multiple linear regression, principal component analysis, and random forest method. Among the 48 cytokines tested, 30 showed elevated levels in SFTS and/or HFRS compared to the healthy control group. Furthermore, there were 19 cytokines that exhibited significant differences between SFTS and HFRS. Random forest analysis suggested that TRAIL and CTACK were predictive of SFTS, while IL2Ralpha, MIG, IL-8, IFNalpha2, HGF, SCF, MCP-3, and PDGFBB were more common with HFRS. It was further verified by the receiver operating characteristic with area under the curve >0.8 and P -values <0.05, except for TRAIL. Significant differences were observed in the cytokine profiles of SFTS and HFRS, with TRAIL, IL2Ralpha, MIG, and IL-8 being the top 4 cytokines that most clearly distinguished the two diseases., Importance: SFTS and HFRS differ in terms of cytokine immune characteristics. TRAIL, IL-2Ralpha, MIG, and IL-8 were the top 4 that differed markedly between SFTS and HFRS., Competing Interests: The authors declare no conflict of interest.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging epidemic infectious disease with high mortality rate. This study aimed to investigate the association of red blood cell distribution width (RDW) and mortality risk in hospitalized SFTS patients., Methods: Clinical data of SFTS patients was retrospectively collected from three hospitals between October 2010 and August 2022. Cox proportional hazards model was used to identity the risk factors for fatal outcome. The predictive value of RDW for fatal outcome was evaluated by the receiver operating characteristic (ROC) analysis and Kaplan-Meier methods., Results: Of 292 patients, the median age was 61.5 years. Non-survivors showed higher RDW value than survivors (13.6% vs.13.0%, P < 0.001). The mortality rate was 44.8% in patients with elevated RDW compared to 18.4% of patients with normal RDW, with a relative risk (RR) of 2.439. Elevated RDW was an independent risk factor of mortality (hazards ratio: 1.167, P = 0.019). Patients with elevated RDW had a higher cumulative mortality than patients with normal RDW. The area under the ROC curve (AUC) of RDW for the prediction of mortality was 0.690 (P < 0.001)., Conclusion: Elevated RDW was associated with higher mortality risk for patients hospitalized for SFTS. RDW may be helpful for risk stratification in SFTS patients., Competing Interests: All authors report no conflicts of interest in this work., (© 2024 Zhang et al.)

What Is Already Known About This Topic?: Brucellosis and severe fever with thrombocytopenia syndrome (SFTS) are neglected zoonoses, attributable respectively to Brucella and the SFTS virus (SFTSV). While the incidence of these diseases has been rising, instances of co-infection remain uncommon., What Is Added by This Report?: This represents the first documented case of a rare coinfection involving Brucella and SFTSV. We carried out an epidemiological analysis of patients diagnosed with brucellosis and those with SFTS at Yidu Central Hospital of Weifang. Our findings demonstrate a temporal and spatial overlap among the affected individuals., What Are the Implications for Public Health Practice?: Our findings suggest that co-infections arising from the spatiotemporal overlap of Brucella and SFTSV are plausible, necessitating heightened awareness and enhanced diagnostic measures., Competing Interests: No conflicts of interest., (Copyright and License information: Editorial Office of CCDCW, Chinese Center for Disease Control and Prevention 2024.)

Background: Since the initial identification of the Severe Fever with Thrombocytopenia Syndrome (SFTS) in ticks in rural areas of China in 2009, the virus has been increasingly isolated from a diverse array of hosts globally, exhibiting a rising trend in incidence. This study aims to conduct a systematic analysis of the temporal and spatial distribution of SFTS cases, alongside an examination of the infection rates across various hosts, with the objective of addressing public concerns regarding the spread and impact of the disease., Methods: In this systematic review and meta-analysis, an exhaustive search was conducted across multiple databases, including PubMed, Web of Science, Embase, and Medline, CNKI, WanFang, and CQVIP. The literature search was confined to publications released between January 1, 2009, and May 29, 2023. The study focused on collating data pertaining to animal infections under natural conditions and human infection cases reported. Additionally, species names were unified using the National Center for Biotechnology Information (NCBI) database. The notification rate, notification death rate, case fatality rate, and infection rates (or MIR) were assessed for each study with available data. The proportions were pooled using a generalized linear mixed-effects model (GLMM). Meta-regressions were conducted for subgroup analysis. This research has been duly registered with PROSPERO, bearing the registration number CRD42023431010., Findings: We identified 5492 studies from database searches and assessed 238 full-text studies for eligibility, of which 234 studies were included in the meta-analysis. For human infection data, the overall pooled notification rate was 18.93 (95% CI 17.02-21.05) per ten million people, the overall pooled notification deaths rate was 3.49 (95% CI 2.97-4.10) per ten million people, and the overall pooled case fatality rate was 7.80% (95% CI 7.01%-8.69%). There was an increasing trend in notification rate and deaths rate, while the case fatality rate showed a significant decrease globally. Regarding animal infection data, among 94 species tested, 48 species were found to carry positive nucleic acid or antibodies. Out of these, 14 species were classified under Arthropoda , while 34 species fell under Chordata , comprising 27 Mammalia and 7 Aves ., Interpretation: This systematic review and meta-analysis present the latest global report on SFTS. In terms of human infections, notification rates and notification deaths rates are on the rise, while the case fatality rate has significantly decreased. More SFTSV animal hosts have been discovered than before, particularly among birds, indicating a potentially broader transmission range for SFTSV. These findings provide crucial insights for the prevention and control of SFTS on a global scale., Funding: None., Competing Interests: All authors declare no competing interests., (© 2024 The Author(s).)

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease with an increasing annual incidence rate. In this case report, we presented two patients infected with the SFTS virus, suggesting a potential direct transmission route from camels to humans through blood contact. Both patients developed symptoms after engaging in the slaughtering of one sick camel, while their family members living in the same environment or co-diners remained unaffected. Subsequent detection revealed a high viral load of SFTS virus, reaching 10 10 viral RNA copies/ml, in the sample obtained from the sick camel. Metagenomic sequencing did not identify any other pathogens. The SFTS virus was successfully isolated from both patient and camel samples. The complete nucleotide sequences obtained from the infected patients demonstrated a remarkable 100% similarity to those found in the camel, and genetic evolution analysis classified the virus as genotype A. Additionally, partial sequences of the SFTS virus were identified in ticks captured from the camel rearing environment, however, these sequences showed only 95.9% similarity to those found in camel and humans. Furthermore, immunoglobulin M and immunoglobulin G antibodies were detected in serum samples collected from the patient. Our findings provide evidence that camel may serve as a competent reservoir for transmitting the SFTS virus to humans. Further in vitro investigations into SFTS virus infections in large animals are warranted to understand their role in viral maintenance and transmission.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an infectious disease that presents a formidable challenge due to the absence of established therapeutic strategies that are explicitly tailored to its management. This study aimed to assess the impact of routine antimicrobial therapy on patients diagnosed with SFTS in Japan. We conducted a comprehensive retrospective cohort analysis using extensive data from a national inpatient database., Methods: This study scrutinized data from adult patients with SFTS and categorized them based on whether they received antimicrobial treatment within the initial 2 days of hospital admission. A meticulous evaluation was carried out on a range of outcomes, such as in-hospital mortality rates, overall costs associated with hospitalization, and length of hospital stay. Overlap weighting was applied along with multivariate regression models to enhance the reliability of the findings through confounder adjustment. The outcomes showed no significant improvement in the prognosis of patients with SFTS who received routine antimicrobial therapy. The use of antimicrobials did not yield statistically significant improvements in in-hospital mortality rates or other secondary outcomes, suggesting that such therapeutic interventions may not be necessary during the early stages of hospital admission., Conclusion: In our study, administration of antimicrobials within 2 days of admission for SFTS did not affect prognosis. The standard use of antimicrobial treatments may be an issue that should be reconsidered., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: Myocardial injury is common in severe fever with thrombocytopenia syndrome (SFTS) patients. Currently, research on the prognostic value of cardiac troponin I (cTnI) for predicting the mortality of SFTS patients, especially death within 7 days is limited., Methods: Between May 2011 and October 2022, clinical and laboratory data on admission of consecutive SFTS cases were collected from six medical centres in China. The clinical endpoint was in-hospital all-cause death within seven days. Risk factors of myocardial injury and death were analysed using multivariable regression models. Prognostic models were established using Cox regression and performance of indicators was evaluated in terms of calibration, discrimination., Results: A total of 1379 laboratory-confirmed patients were enrolled, in which 686 subjects were included for analysis. The median age was 66 years, with 48.1% of male. Eighty-seven patients died within seven days and 396 patients diagnosed with myocardial injury during hospitalization. Non-survivors had significant higher levels of cardiac indices than survivors, including cTnI, aspartic transaminase (AST) and lactate dehydrogenase (LDH). Elevated levels of cTnI (HR = 1.058, 95% CI:1.032-1.085), AST (HR = 1.191, 95% CI:1.150-1.234) and LDH (HR = 1.019, 95% CI:1.009-1.029) predicted risk of early in-hospital mortality. cTnI model performed best, with area under curve of 0.850 (0.774-0.926) and concordance index of 0.842, respectively. Statistical differences were found between high and low levels of cTnI for mortality ( P <0.001) using 0.35 ng/mL as the optimal cut-off., Conclusion: The risk of early in-hospital death can be predicted by cTnI. Clinical doctors should remind vigilant concerning the elevation of cardiac enzyme as soon as possible., Competing Interests: The authors declare no conflicts of interest in this work., (© 2024 Li et al.)

Background: The primary aim of this study is to investigate the correlation between serum levels of fibrinogen-to-prealbumin ratio (FPR) and C-reactive protein-to-prealbumin ratio (CPR) and prognostic outcomes among patients with severe fever with thrombocytopenia syndrome (SFTS). SFTS, characterized by elevated mortality rates, represents a substantial public health challenge as an emerging infectious disease., Methods: The study included 159 patients with SFTS. Clinical and laboratory data were compared between the survival and death groups. Univariate and multivariate logistic regression analysis were utilized to identify independent risk factors for mortality. The predictive efficacy of FPR and CPR was evaluated using receiver operating characteristic (ROC) curve. Survival analysis was conducted using the Kaplan-Meier curve and the log-rank test was employed for comparison., Results: The death group exhibited significantly elevated levels of FPR and CPR compared to the survival group ( P < 0.05). Multivariate logistic regression analysis confirmed that both FPR and CPR independently correlated with a poorer prognosis among patients with SFTS. The ROC curve analysis indicated that FPR and CPR had superior predictive capabilities compared to C-reactive protein and fibrinogen. Kaplan-Meier survival analysis demonstrated that patients with SFTS who have FPR > 0.045 (log-rank test; χ2 = 17.370, P < 0.001) or CPR > 0.05 (log-rank test; χ2 = 19.442, P < 0.001) experienced significantly lower survival rates within a 30-day follow-up period., Conclusion: Elevated levels of FPR and CPR serve as distinct risk factors for mortality among patients with SFTS, indicating their potential to predict an unfavorable prognosis in these patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Liu, Qiao and He.)

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by severe fever with thrombocytopenia syndrome virus (SFTSV). Previous studies have indicated that SFTS patients have a high mortality rate, which may be related to cytokine storm and immune dysfunction. In our study, we analyzed differences in cytokines and lymphocyte subsets between severe and non-severe SFTS patients, with the aim of identifying predictors of severity., Methods: We retrospectively analyzed demographic characteristics, clinical data, cytokine profiles, and lymphocyte subsets from 96 laboratory confirmed SFTS patients between April 2021 and August 2023., Results: A total of 96 SFTS patients were enrolled, with a mean age of 65.05 (± 7.92) years old. According to our grouping criteria, 35 (36.5%) of these patients were classified as severe group, while 61 (63.5%) were classified as non-severe group. Univariate analysis revealed that age, interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), interferon-α (IFN-α), CD4 + T cell, and CD8 + T cell counts were risk predictors for the severity of SFTS. Further multivariable logistic regression analysis confirmed age, IL-6 levels, and CD4 + T cell counts as independent predictors of SFTS severity., Conclusions: Severe SFTS patients may experience cytokine storms and immune dysfunction. Aging, elevated levels of IL-6, and decreased CD4 + T cell count may serve as independent predictors for the severity of SFTS., (© 2024. The Author(s).)

Background: Severe fever with thrombocytopenia syndrome (SFTS) is a zoonotic infectious disease caused by the severe fever with thrombocytopenia syndrome virus (SFTSV). Endemic in East Asia, SFTS is characterized by an exceptionally high mortality rate. Presently, there is no established treatment for SFTS, particularly for patients in critical condition. In this study, we collected and analyzed laboratory and clinical data from 92 critically ill patients with SFTS treated at Weihai Municipal Hospital between 2019 and 2022. We hope that our study will provide some hints for the treatment of critically ill patients with SFTS., Methods: A total of 92 critically ill patients with SFTS were included in this study. Of these patients, 45 received treatment with therapeutic plasma exchange (TPE) and ribavirin (referred to as the TPE group), while the remaining patients received only ribavirin (referred to as the non-TPE group). Clinical and laboratory parameters were analyzed retrospectively., Results: The results showed significant improvements in multiple laboratory parameters following treatment with TPE and ribavirin, including white blood cell and neutrophil count, lactate dehydrogenase, creatine kinase isoenzyme-MB, prothrombin time, activated partial thromboplastin time, D-Dimer, serum sodium and copies of virus genomes. The combination of TPE with ribavirin demonstrated a significant reduction in mortality rates, with a mortality rate of 20.0% in the TPE group compared to 40.4% in the non-TPE group (P = 0.033)., Conclusions: Our findings suggest that critically ill patients with SFTS who received TPE and ribavirin experienced improvements in both clinical and laboratory parameters. These results indicate that TPE combined with ribavirin may represent a promising novel therapeutic approach for managing critically ill patients with SFTS. However, comparative studies of large sample size or randomized clinical trials are warranted to confirm the effectiveness of this combination therapy in the treatment of severe SFTS cases., (© 2024 Wiley Periodicals LLC.)

Introduction: Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infectious disease caused by the SFTS virus (SFTSV). The Miyazaki Prefecture has the highest number of SFTS cases in Japan and requires countermeasures for prevention. In this study, we aimed to conduct an epidemiological survey in Miyazaki Prefecture to determine the exposure conditions of SFTSV by measuring the seroprevalence among residents of Miyazaki and to evaluate the factors that influence the endemicity of SFTS., Methods: The survey was conducted between June 2014 and April 2019 in all 26 municipalities in Miyazaki Prefecture. SFTSV antibodies were detected using an enzyme-linked immunosorbent assay in the blood samples of 6013 residents (3184 men and 2829 women). A questionnaire-based survey of the living environment was also conducted., Results: Multiple logistic regression analysis revealed that age and occupation were significant factors related to the proportion of participants with an optical density (OD) value > 0.2 and a seroprevalence of 0.9 % (54/6013). Seven seropositive individuals (0.1 %) with an OD value of >0.4 were identified (three men and four women, aged 54-69 years), and all were asymptomatic. One participant had a higher OD than the positive control., Conclusion: Although SFTS is endemic in Miyazaki Prefecture, Japan, its seroprevalence is relatively low. Since some risk areas in Miyazaki prefecture have been identified, it is important to enhance awareness of SFTS in residences and reduce contact with ticks, especially in high-risk areas., Competing Interests: Declarations of competing interest None of declare., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease. Previous studies have primarily focused on the epidemiological and clinical characteristics of patients with SFTS, whereas pancreatic injury has received little attention. This study investigated the effects of pancreatic injury on the prognosis of patients with SFTS. A total of 156 patients diagnosed with SFTS between April 2016 and April 2022 were included in the analysis. Multivariate logistic regression analysis showed that pancreatic injury (odds ratio [OR] = 3.754, 95% confidence interval [CI]: 1.361-79.036, P = 0.024) and neurological symptoms (OR = 18.648, 95% CI: 4.921-70.668, P < 0.001) were independent risk factors for mortality. The receiver operating characteristic curve indicated that serum pancreatic enzymes were predictive of progression to death in patients with SFTS. The area under the curve (AUC) for amylase was 0.711, with an optimal cutoff value of 95.5 U/L, sensitivity of 96.4%, and specificity of 35.9%. Lipase had an AUC of 0.754, an optimal cutoff value of 354.75 U/L, sensitivity of 75%, and specificity of 67.2%. Thus, pancreatic injury was associated with a poor prognosis of SFTS and can be used as an important reference for SFTS determination and prognostic assessment.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high lethality. This study aimed to determine whether prolonged activated partial thromboplastin time (APTT) predicted SFTS mortality., Methods: SFTS patients were enrolled from 6 hospitals in the north China. Subjects were divided into training cohort and 5 externally validation cohorts. The least absolute shrinkage and selection operator Cox regression model was performed to screen potential prognostic factors. Risk factors were analyzed using multivariable regression models. Prognostic models were established by Cox regression and random survival forest (RSF) methods, and evaluated regarding discrimination, validity and clinical benefit. Time-dependent receiver operating characteristic (ROC) curve was used to evaluate the predictive effectiveness of variables., Results: 1332 SFTS cases were included, in which 211 patients died. Six potential prognostic factors were screened, and pulse, breath, APTT and aspartic transaminase (AST) were independently associated with mortality in both training cohort (Yantai, N = 791) and external validation cohort (N = 541). APTT was steadily correlated with the fatality (HR: 1.039-1.144; all P  < 0.01) in each five sub-validation cohorts (Dandong, Dalian, Tai'an, Qingdao and Beijing). RSF model with variables of APTT, AST, pulse and breath had considerable prognostic effectiveness, which APTT showed the highest prognostic ability with the area under the curve of 0.848 and 0.787 for 7-day and 14-day survival, respectively. Survival differences were found between high and low levels of APTT for mortality using 50s as the optimal cut-off., Conclusions: SFTS patients have prolonged APTT, which is an independent risk factor for fatality. APTT≥50s was recommended as a biomarker to remind physicians to monitor and treat patients more aggressively to improve clinical prognosis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease, and its morbidity and mortality are increasing. At present, there is no specific therapy available. An exacerbated IFN-I response and cytokine storm are related to the mortality of patients with SFTS. Ruxolitinib is a Janus kinase (JAK) 1/2 inhibitor that can block proinflammatory cytokines and inhibit the type I IFN pathway. We aimed to explore the use of ruxolitinib plus standard of care for severe SFTS., Methods: We conducted a prospective, single-arm study of severe SFTS. We recruited participants aged 18 years or older who were admitted to the hospital with laboratory-confirmed severe SFTS and whose clinical score exceeded 8 points within 6 days of symptom onset. Participants received oral ruxolitinib (10 mg twice a day) for up to 10 days. The primary endpoint was 28-day overall survival. The secondary endpoints included the proportion of participants who needed intensive care unit (ICU) admission, total cost, changes in neurologic symptoms and clinical laboratory parameters, and adverse events (AEs) within 28 days. A historical control group (HC group, n = 26) who met the upper criteria for inclusion and hospitalized from April 1, 2021, to September 16, 2022, was selected and 1:1 matched for baseline characteristics by propensity score matching., Results: Between Sep 16, 2022, and Sep 16, 2023, 26 participants were recruited into the ruxolitinib treatment group (RUX group). The 28-day overall mortality was 7.7% in the RUX group and 46.2% in the HC group (P = 0.0017). There was a significantly lower proportion of ICU admissions (15.4% vs 65.4%, p < 0.001) and total hospitalization cost in the RUX group. Substantial improvements in neurologic symptoms, platelet counts, hyperferritinemia, and an absolute decrease in the serum SFTS viral load were observed in all surviving participants. Treatment-related adverse events were developed in 6 patients (23.2%) and worsened in 8 patients (30.8%), and no treatment-related serious adverse events were reported., Conclusions: Our findings indicate that ruxolitinib has the potential to increase the likelihood of survival as well as reduce the proportion of ICU hospitalization and being tolerated in severe SFTS. Further trials are needed., Trail Registration: ChiCTR2200063759, September 16, 2022., (© 2024. The Author(s).)

Introduction: Severe fever with thrombocytopenia syndrome (SFTS) is characterized by a high mortality rate and is associated with immune dysregulation. Cytokine storms may play an important role in adverse disease regression, this study aimed to assess the validity of MCP-3 in predicting adverse outcomes in SFTS patients and to investigate the longitudinal cytokine profile in SFTS patients., Methods: The prospective study was conducted at Yantai Qishan Hospital from May to November 2022. We collected clinical data and serial blood samples during hospitalization, patients with SFTS were divided into survival and non-survival groups based on the clinical prognosis., Results: The levels of serum 48 cytokines were measured using Luminex assays. Compared to healthy controls, SFTS patients exhibited higher levels of most cytokines. The non-survival group had significantly higher levels of 32 cytokines compared to the survival group. Among these cytokines, MCP-3 was ranked as the most significant variable by the random forest (RF) model in predicting the poor prognosis of SFTS patients. Additionally, we validated the predictive effects of MCP-3 through receiver operating characteristic (ROC) curve analysis with an AUC of 0.882 (95% CI, 0.787-0.978, P < 0.001), and the clinical applicability of MCP-3 was assessed favorably based on decision curve analysis (DCA). The Spearman correlation analysis indicated that the level of MCP-3 was positively correlated with ALT, AST, LDH, α-HBDH, APTT, D-dimer, and viral load ( P <0.01)., Discussion: For the first time, our study identified and validated that MCP-3 could serve as a meaningful biomarker for predicting the fatal outcome of SFTS patients. The longitudinal cytokine profile analyzed that abnormally increased cytokines were associated with the poor prognosis of SFTS patients. Our study provides new insights into exploring the pathogenesis of cytokines with organ damage and leading to adverse effects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Zhao, Yu, Zhang, Xue, Jiang, Ge, Xu, Zhang, Lin and Chen.)

A 75-year-old Japanese woman was admitted to our hospital and diagnosed with hemophagocytic syndrome secondary to severe fever with thrombocytopenia syndrome (SFTS). The patient recovered after steroid treatment and was discharged from the hospital. Two months after the onset of SFTS, the patient revisited our hospital with a fever and palpable purpura on the extremities and trunk. A histopathological examination of a punch skin biopsy specimen revealed leukocytoclastic vasculitis. Symptomatic treatment resolved the fever, and palpable purpura disappeared 14 days later. No other clinical symptoms or abnormal immunological findings contributed to the leukocytoclastic vasculitis. This is the first report to describe leukocytoclastic vasculitis secondary to SFTS, highlighting a potential association between the two conditions.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is a natural focal disease transmitted mainly by tick bites, and the causative agent is SFTS virus (SFTSV). SFTS can rapidly progress to severe disease, with multiple-organ failure (MOF) manifestations such as shock, respiratory failure, disseminated intravascular coagulation (DIC) and death, but cases of SFTS patients with central nervous system (CNS) symptoms onset and marked persistent involuntary shaking of the perioral area and limbs have rarely been reported., Case Presentation: A 69-year-old woman with fever and persistent involuntary shaking of the perioral area and limbs was diagnosed with SFTS with CNS symptom onset after metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) and peripheral blood identified SFTSV. The patient developed a cytokine storm and MOF during the course of the disease, and after aggressive antiviral, glucocorticoid, and gamma globulin treatments, her clinical symptoms improved, her laboratory indices returned to normal, and she had a good prognosis., Conclusion: This case gives us great insight that when patients with CNS symptoms similar to those of viral encephalitis combined with thrombocytopenia and leukopenia are encountered in the clinic, it is necessary to consider the possibility of SFTS involving the CNS. Testing for SFTSV nucleic acid in CSF and blood (mNGS or polymerase chain reaction (PCR)) should be carried out, especially in critically ill patients, and treatment should be given accordingly., (© 2024. The Author(s).)

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne viral disease caused by the SFTS virus (Dabie bandavirus), which has become a substantial risk to public health. No specific treatment is available now, that calls for an effective vaccine. Given this, we aimed to develop a multi-epitope DNA vaccine through the help of bioinformatics. The final DNA vaccine was inserted into a special plasmid vector pVAX1, consisting of CD8 + T cell epitopes, CD4 + T cell epitopes and B cell epitopes (six epitopes each) screened from four genome-encoded proteins--nuclear protein (NP), glycoprotein (GP), RNA-dependent RNA polymerase (RdRp), as well as nonstructural protein (NSs). To ascertain if the predicted structure would be stable and successful in preventing infection, an immunological simulation was run on it. In conclusion, we designed a multi-epitope DNA vaccine that is expected to be effective against Dabie bandavirus, but in vivo trials are needed to verify this claim., (© 2024. The Author(s).)

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with a high mortality rate. Differentiating between SFTS and hemorrhagic fever with renal syndrome (HFRS) is difficult and inefficient. Retrospective analysis of the medical records of individuals with SFTS and HFRS was performed. Clinical and laboratory data were compared, and a diagnostic model was developed based on multivariate logistic regression analyzes. Receiver operating characteristic curve analysis was used to evaluate the diagnostic model. Among the 189 patients, 113 with SFTS and 76 with HFRS were enrolled. Univariate analysis revealed that more than 20 variables were significantly associated with SFTS. Multivariate logistic regression analysis revealed that gender, especially female gender (odds ratio [OR]: 4.299; 95% confidence interval [CI]: 1.163-15.887; p = 0.029), age ≥65 years (OR: 16.386; 95% CI: 3.043-88.245; p = 0.001), neurological symptoms (OR: 12.312; 95% CI: 1.638-92.530; p = 0.015), leukopenia (<4.0 × 10 9 /L) (OR: 17.355; 95% CI: 3.920-76.839; p < 0.001), and normal Cr (OR: 97.678; 95% CI: 15.483-616.226; p < 0.001) were significantly associated with SFTS but not with HFRS. The area under the curve of the differential diagnostic model was 0.960 (95% CI: 0.936-0.984), which was significantly better than that of each single factor. In addition, the model exhibited very excellent sensitivity and specificity (92.9% and 85.5%, respectively). In cases where HFRS and SFTS are endemic, a diagnostic model based on five parameters, such as gender, age ≥65 years, neurological symptoms, leukopenia and normal Cr, will facilitate the differential diagnosis of SFTS and HFRS in medical institutions, especially in primary care settings., (© 2024 Wiley Periodicals LLC.)

Background: This study aimed to analyze the correlation between the cycle threshold (Ct) values of severe fever with thrombocytopenia syndrome (SFTS) virus small (S) and middle (M) segments and the SFTS viral load, aiming to estimate the initial viral load and predict prognosis in the early clinical course., Method: A retrospective study was conducted with confirmed SFTS patients at Jeju National University Hospital (2016-2022). Patients were categorized into non-fatal and fatal groups., Results: This study included 49 patients with confirmed SFTS (non-fatal group, n = 42; fatal group, n = 7). A significant negative correlation (-0.783) was observed between the log SFTS viral load and Ct values ( p < 0.001). This negative correlation was notably stronger in the fatal group (correlation coefficient -0.940) than in the non-fatal group (correlation coefficient -0.345)., Conclusion: In this study, we established a correlation between SFTS viral load and Ct values for estimating the initial viral load and early predicting prognosis. These results are expected to offer valuable insights for SFTS patient treatment and prognosis prediction.

Introduction: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus infection with a high lethality rate. The purpose of this study was to investigate the changes in coagulation parameters in patients with SFTS, aiming to provide clinical evidence for early diagnosis, treatment, and disease analysis., Methods: A total of 40 patients with SFTS attended from April 1, 2020 to May 21, 2022 in Nanjing Drum Tower Hospital were selected and grouped according to the duration of the disease, mild and severe disease, cure and death, with 50 healthy physical examiners as controls, and the risk of severe and death disease was predicted using ROC curves., Results: Comparison between the healthy, mild and severe groups revealed that PT, INR, APTT, TT, D-D and vWF levels were higher than those in the healthy control group, and FII, FIX, FX, FXI, FXII, PC and PS levels were lower than those in the healthy control group, the differences were statistically significant ( p < 0.05). Comparing the results of SFTS patients with different course times, the results of Fib, FV, FVII, FVIII, FIX, FX, FXI were statistically significant ( p < 0.05). Among the survived and deceased patients, the PT, INR, DD and PS results of the deceased patients were higher than those of the survived patients, and the FVIII, FIX, FXI, FXII and PC were lower than those of the survived patients. The area under the ROC curve showed that D-D had higher predictive ability for the risk of severe disease (AUROC 0.93, sensitivity and specificity at a Cut-off value of 1.50 mg/L were 90.0 and 86.5%, respectively) and the risk of death occurring (AUROC 0.84, sensitivity and specificity at a Cut-off value of 3.39 mg/L were 87.5 and 80.0%, respectively)., Discussion: The monitoring of the coagulation parameters in patients with SFTS is great significance for identifying the severity and death of the patient's condition, and it is of great clinical value to provide early attention, timely intervention and maximum reduction of the mortality rate for patients at risk of severe disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xia, Jia, Chen, Wang and Xu.)

To explore the association and impact between viral myocarditis and mortality in patients with severe fever with thrombocytopenia syndrome. A dynamic analysis was conducted between fatal group and nonfatal group regarding the daily epidemiology data, clinical symptoms, and electrocardiogram (ECG), echocardiogram, and laboratory findings. Outcomes of patients with and without viral myocarditis were compared. The association between viral myocarditis and mortality was analyzed. Among 183 severe fever with thrombocytopenia syndrome patients, 32 were in the fatal group and 151 in the nonfatal group; there were 26 (81.25%) with viral myocarditis in the fatal group, 66 (43.70%) with viral myocarditis in the nonfatal group (p < 0.001), 79.35% of patients had abnormal ECG results. The abnormal rate of ECG in the fatal group was 100%, and in the nonfatal group was 74.83%. Univariate analysis found that the number of risk factors gradually increased on Day 7 of the disease course and reached the peak on Day 10. Combined with the dynamic analysis of the disease course, alanine aminotransferase, aspartate aminotransferase, creatine kinase, creatine kinase fraction, lactate dehydrogenase, hydroxybutyrate dehydrogenase, neutrophil count, serum creatinine, Na, Ca, carbon dioxide combining power, amylase, lipase, activated partial thromboplastin time and thrombin time had statistically significant impact on prognosis. The incidence of fever with thrombocytopenia syndrome combined with viral myocarditis is high, especially in the fatal group of patients. Viral myocarditis is closely related to prognosis and is an early risk factor. The time point for changes in myocarditis is Day 7 of the course of the disease., (© 2024 Wiley Periodicals LLC.)

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus with high pathogenicity. There has been a gradual increase in the number of reported cases in recent years, with high morbidity and mortality rates. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway plays an important role in the innate immune defense activated by viral infection; however, the role of the cGAS-STING signaling pathway during SFTSV infection is still unclear. In this study, we investigated the relationship between SFTSV infection and cGAS-STING signaling. We found that SFTSV infection caused the release of mitochondrial DNA into the cytoplasm and inhibits downstream innate immune signaling pathways by activating the cytoplasmic DNA receptor cGAS. We found that the SFTSV envelope glycoprotein Gn was a potent inhibitor of the cGAS-STING pathway and blocked the nuclear accumulation of interferon regulatory factor 3 and p65 to inhibit downstream innate immune signaling. Gn of SFTSV interacted with STING to inhibit STING dimerization and inhibited K27-ubiquitin modification of STING to disrupt the assembly of the STING-TANK-binding kinase 1 complex and downstream signaling. In addition, Gn was found to be involved in inducing STING degradation, further inhibiting the downstream immune response. In conclusion, this study identified the important role of the glycoprotein Gn in the antiviral innate immune response and revealed a novel mechanism of immune escape for SFTSV. Moreover, this study increases the understanding of the pathogenic mechanism of SFTSV and provides new insights for further treatment of SFTS., Importance: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a newly discovered virus associated with severe hemorrhagic fever in humans. However, the role of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway during SFTSV infection is still unclear. We found that SFTSV infection inhibits downstream innate immune signaling pathways by activating the cytoplasmic DNA receptor cGAS. In addition, SFTSV Gn blocked the nuclear accumulation of interferon regulatory factor 3 and p65 to inhibit downstream innate immune signaling. Moreover, we determined that Gn of SFTSV inhibited K27-ubiquitin modification of STING to disrupt the assembly of the STING-TANK-binding kinase 1 complex and downstream signaling. We found that the SFTSV envelope glycoprotein Gn is a potent inhibitor of the cGAS-STING pathway. In conclusion, this study highlights the crucial function of the glycoprotein Gn in the antiviral innate immune response and reveals a new method of immune escape of SFTSV., Competing Interests: The authors declare no conflict of interest.

Background: Ticks serve as vectors for a diverse array of pathogens, including viruses responsible for both human and livestock diseases. Symbiotic bacteria hold significant potential for controlling tick-borne disease. However, the alteration of tick gut bacterial community in response to pathogen infection has not been analyzed for any tick-borne viruses. Here, the impact of severe fever with thrombocytopenia syndrome virus (SFTSV) infection on bacterial diversity in the gut of Haemaphysalis longicornis is investigated., Methods: Unfed tick females were artificially infected with SFTSV. The gut samples were collected and the genomic DNA was extracted. We then investigated alterations in gut bacterial composition in response to SFTSV infection through 16S rRNA gene sequencing., Results: The study found that a reduction in the number of operational taxonomic units (OTUs) in the tick gut following SFTSV infection. However, there were no significant changes in alpha diversity indices upon infection. Four genera, including Corynebacterium, Arthrobacter, Sphingomonas, and Escherichia, were identified as biomarkers for the tick gut without SFTSV infection. Notably, the predicted correlation network indicated that the biomarkers Sphingomonas and Escherichia exhibited positive correlations within the same subcommunity, which was altered upon viral infection., Conclusions: These findings revealed that the change in tick gut bacterial composition upon SFTSV infection and could facilitate the discovery new target for tick-borne viral disease control., (© 2024. The Author(s).)

Severe fever with thrombocytopenia syndrome (SFTS), a tick-borne zoonotic disease, is caused by infection with SFTS virus (SFTSV). A previous study reported that human-to-human direct transmission of SFTSV can occur. However, potential animal-to-animal transmission of SFTSV without ticks has not been fully clarified. Thus, the objective of this study was to investigate potential mice-to-mice transmission of SFTSV by co-housing three groups of mice [i.e., wild-type mice (WT), mice injected with an anti-type I interferon-α receptor-blocking antibody (IFNAR Ab), and mice with knockout of type I interferon-α receptor (IFNAR KO)] as spreaders or recipients with different immune competence. As a result, co-housed IFNAR Ab and IFNAR KO mice showed body weight loss with SFTS viral antigens detected in their sera, extracorporeal secretions, and various organs. Based on histopathology, white pulp atrophy in the spleen was observed in all co-housed mice except WT mice. These results obviously show that IFNAR Ab and IFNAR KO mice, as spreaders, exhibited higher transmissibility to co-housed mice than WT mice. Moreover, IFNAR KO mice, as recipients, were more susceptible to SFTSV infection than WT mice. These findings suggest that type I interferon signaling is a pivotal factor in mice intraspecies transmissibility of SFTSV in the absence of vectors such as ticks.

Solitary fibrous tumor (SFT) is a relatively rare mesenchymal fibroblastic tumor occurring most commonly in adults with no gender predilection. Although the pathological diagnosis of SFT is usually straightforward, some difficulties may occasionally arise mainly due to the wide morphological spectrum exhibited by this tumor. In the present paper we aimed to evaluate the unusual clinicopathological features in a series of 31 SFTs arising from parenchymal organs, superficial soft tissues and deep soft tissues. Our results emphasize that SFTs may occur anywhere, including unusual sites such as periosteum of the thoracic spine, mesorectal tissue, hepatic hilum, paravescial space, kidney and breast. Moreover, a wide morphological spectrum was observed in tumors included in our series. The most striking morphological features observed included: extensive lipomatous component, myxoid stromal changes, epithelioid cell component, metaplastic mature bone, neurofibroma-like, myxofibrosarcoma-like and pseudoalveolar-like areas. Additionally, multinucleated giant cells and sarcomatous dedifferentiation were also identified. Our paper emphasizes that SFT may occur in unusual anatomical locations and exhibits a wide morphological spectrum. Pathologists must be aware of these features to avoid confusion with other benign and malignant neoplasms that may show overlapping morphological features., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024. Published by Elsevier GmbH.)

Background: Major trauma is a leading cause of unexpected death globally, with increasing age-adjusted death rates for unintentional injuries. Field triage schemes (FTSs) assist emergency medical technicians in identifying appropriate medical care facilities for patients. While full FTSs may improve sensitivity, step-by-step field triage is time-consuming. A simplified FTS (sFTS) that uses only physiological and anatomical criteria may offer a more rapid decision-making process. However, evidence for this approach is limited, and its performance in identifying all age groups requiring trauma center resources in Asia remains unclear., Methods: We conducted a multinational retrospective cohort study involving adult trauma patients admitted to emergency departments in the included countries from 2016 to 2020. Prehospital and hospital data were reviewed from the Pan-Asia Trauma Outcomes Study database. Patients aged ≥18 years transported by emergency medical services were included. Patients lacking data regarding age, sex, physiological criteria, or injury severity scores were excluded. We examined the performance of sFTS in all age groups and fine-tuned physiological criteria to improve sFTS performance in identifying high-risk trauma patients in different age groups., Results: The sensitivity and specificity of the physiological and anatomical criteria for identifying major trauma (injury severity score ≥ 16) were 80.6% and 58.8%, respectively. The modified sFTS showed increased sensitivity and decreased specificity, with more pronounced changes in the young age group. Adding the shock index further increased sensitivity in both age groups., Conclusions: sFTS using only physiological and anatomical criteria is suboptimal for Asian adult patients with trauma of all age groups. Adjusting the physiological criteria and adding a shock index as a triage tool can improve the sensitivity of severely injured patients, particularly in young age groups. A swift field triage process can maintain acceptable sensitivity and specificity in severely injured patients., Competing Interests: Declaration of Competing Interest This study received no financial support and there are no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

We herein report a case of severe fever with thrombocytopenia syndrome (SFTS) with Pasteurella multilocida bacteremia in a 65-year-old man with alcoholic cirrhosis who was admitted to our hospital with anorexia and severe fatigue. Laboratory tests revealed pancytopenia and liver and kidney dysfunction. After admission, he developed impaired consciousness, mucosal hemorrhaging, and septic shock. SFTS virus was detected on polymerase chain reaction testing of blood and throat swabs, and Pasteurella multocida was detected on blood culture. Despite being treated with invasive mechanical ventilation, vasopressors, and antibiotics, the patient's condition progressively deteriorated, and he died four days after admission.

Severe fever with thrombocytopenia syndrome (SFTS) is a life-threatening disease caused by a novel bunyavirus (SFTSV), mainly transmitted by ticks. With no effective therapies or vaccines available, understanding the disease's mechanisms is crucial. Recent studies found increased expression of programmed cell death-1 (PD-1) on dysfunctional T cells in SFTS patients. However, the role of the PD-1/programmed cell death-ligand 1 (PD-L1) pathway in SFTS progression remains unclear. We investigated PD-1 blockade as a potential therapeutic strategy against SFTSV replication. Our study analyzed clinical samples and performed in vitro experiments, revealing elevated PD-1/PD-L1 expression in various immune cells following SFTSV infection. An anti-PD-1 nanobody, NbP45, effectively inhibited SFTSV infection in peripheral blood mononuclear cells (PBMCs), potentially achieved through the mitigation of apoptosis and the augmentation of T lymphocyte proliferation. Intriguingly, subcutaneous administration of NbP45 showed superior efficacy compared to a licensed anti-PD-1 antibody in an SFTSV-infected humanized mouse model. These findings highlight the involvement of the PD-1/PD-L1 pathway during acute SFTSV infection and suggest its potential as a host target for immunotherapy interventions against SFTSV infection., (© 2024. The Author(s).)

Objective: This study aimed to investigate the clinical characteristics of severe fever with thrombocytopenia syndrome complicated by viral myocarditis (SFTS-VM) and analyze relevant influencing factors., Methods: Retrospective analysis was conducted on clinical data from 79 SFTS-VM patients, categorized into common (SFTS-CVM, n = 40) and severe groups (SFTS-SVM, n = 39). Clinical manifestations, laboratory results, cardiac ultrasonography, and electrocardiogram features were analyzed. Univariate and multivariate analyses identified significant indicators, which were further assessed using ROC curves to predict SFTS-SVM., Results: SFTS-SVM group exhibited higher rates of hypotension, shock, abdominal pain, cough with sputum, and consciousness disorders compared to SFTS-CVM group. Laboratory findings showed elevated platelet count, ALT, AST, amylase, lipase, LDH, D-dimer, procalcitonin, TNI, and NT-proBNP in SFTS-SVM. Abnormal electrocardiograms, especially atrial fibrillation, were more prevalent in SFTS-SVM (P < 0.05). Multivariate analysis identified elevated LDH upon admission (OR = 1.004, 95% CI: 1-1.008, P = 0.050), elevated NT-proBNP (OR = 1.005, 95% CI: 1.001-1.008, P = 0.007), and consciousness disorders (OR = 112.852, 95% CI: 3.676 ~ 3464.292, P = 0.007) as independent risk factors for SFTS-SVM. LDH and NT-proBNP had AUCs of 0.728 and 0.744, respectively, in predicting SFTS-SVM. Critical values of LDH (> 978.5U/L) and NT-proBNP (> 857.5pg/ml)) indicated increased likelihood of SFTS progression into SVM., Conclusion: Elevated LDH, NT-proBNP, and consciousness disorders independently correlate with SFTS-SVM. LDH and NT-proBNP can aid in early identification of SFTS-SVM development when above specified thresholds., (© 2024. The Author(s).)

Severe fever with thrombocytopenia syndrome (SFTS) is a hemorrhagic fever caused by SFTS virus (SFTSV), which is primarily found in East Asian countries. Despite its high mortality rate and increasing incidence, no vaccines or therapeutics have yet been approved for use against SFTS. Antibody drugs have shown promise in treating lethal infectious diseases that currently have no established treatments. In the case of SFTS, however, only a limited amount of research has been done on SFTSV-neutralizing antibodies targeting the transmembrane proteins Gn and Gc, which play critical roles in viral infection. This study focuses on the production and characterization of antibodies targeting the SFTSV Gc protein. Monoclonal antibodies against Gc were generated through immunization of mice, and their antiviral activity was evaluated. Three out of four anti-Gc antibody clones from this study demonstrated dose-dependent SFTSV neutralization activity, two of which exhibited a synergistic effect on the neutralization activity of the anti-Gn antibody clone Mab4-5. Further studies are necessary to identify key sites on the SFTSV glycoprotein and to develop novel agents as well as antibodies with diverse mechanisms of action against SFTSV., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background and Objectives: Meningeal solitary fibrous tumors (SFTs) comprise 0.4% of primary central nervous system neoplasms and carry metastatic potential. Disease course and optimal management are largely unknown, and there is currently no literature rigorously describing neurological outcomes in surgically managed SFTs. We present one of the largest craniospinal SFT series, analyze patient outcomes, and extensively review the associated literature., Methods: All surgically managed SFTs at our institution between January 2005 and March 2023 were retrospectively reviewed. Patient demographics, tumor and radiographic features, treatment, and clinical outcomes were collected. Neurological function was quantified using Frankel grade and Neurologic Assessment in Neuro-Oncology scores. Descriptive statistics, multivariate analysis, log-rank test, and Kaplan-Meier survival analysis were performed., Results: Twenty-one patients satisfied inclusion criteria. Tumor locations included 15 supratentorial, three infratentorial, and three spinal. All patients underwent surgical resection, and 16 (76.2%) underwent radiation. Six (28.6%) patients had tumor recurrence, and three (14.3%) developed metastasis. Younger age and higher postoperative Frankel grade were significantly associated with increased overall survival (OS) ( P = .011, P = .002, respectively). All patients symptomatically improved or stabilized after surgery, and Neurologic Assessment in Neuro-Oncology score ( P = .001) and functional status significantly improved postoperatively (Karnofsky Performance Status: 65.2 ± 25.2 vs 91.4 ± 13.5, P = .001). Sex, adjuvant radiation, and extent of resection were not significantly associated with OS., Conclusion: SFT of the central nervous system is a rare entity with a variable clinical course. Surgical resection was associated with improved postoperative functional and neurological status. Higher postoperative neurological function was significantly associated with OS. Further studies are warranted to validate a standardized treatment algorithm and investigate the efficacy of adjuvant radiation in SFT., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Solitary fibrous tumors (SFTs) are known for their heterogeneous morphology, characterized by a variety of cell shapes and different growth patterns. They can also arise in various anatomical locations, most commonly in extremities and deep soft tissues. Despite this diversity in morphology and location, all SFTs share a common molecular signature involving the NAB2::STAT6 gene fusion. Due to their unpredictable clinical behavior, establishing prognostic factors is crucial. This study aims to evaluate an orbital risk stratification system (RSS) proposed by Huang et al. for use in extraorbital SFTs using a database of 97 cases. The Huang model takes into consideration tumor size, mitotic figures, Ki-67 index, and dominant constituent cell (DCC) as key variables. Survival analysis confirmed the model's predictive value, with higher-risk scores being associated with poorer outcomes. However, in contrast to the orbital SFTs studied by Huang et al., our study did not find a correlation between tumor size and recurrence in extraorbital cases. While the Huang model performs slightly better than other RSS, it falls short on achieving statistical significance in distinguishing recurrence risk groups in extraorbital locations. In conclusion, this study validates the Huang RSS for use in extraorbital SFTs and underscores the importance of considering DCC, mitotic count, and Ki-67 together. However, we found that including tumor size in this model did not improve prognostic significance in extraorbital SFTs. Despite the benefits of this additional RSS, vigilant monitoring remains essential, even in cases classified as low-risk due to the inherent unpredictability of SFT clinical outcomes., Competing Interests: Declaration of Competing Interest All authors declare that he/she has no conflict of interest in relation to this study., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: This study aimed to identify a novel inflammatory index and construct a nomogram for predicting in-hospital mortality due to severe fever with thrombocytopenia syndrome (SFTS)., Methods: This cohort included 610 patients with SFTS hospitalized in Wuhan Union Hospital between March 2017 and November 2022. The ratio of C-reactive protein (CRP) to the prognostic nutritional index (PNI) was calculated and used to reflect patients' inflammatory status. Propensity score matching (PSM) was utilized to balance confounding factors between the low- and high-CRP/PNI groups. SFTS individuals from Jinyinhu Hospital were used as the validation cohort., Results: Patients with SFTS and high CRP/PNI were significantly correlated with a higher percentage of severe and critical SFTS types and higher in-hospital mortality rates than those with low CRP/PNI. CRP/PNI was the potent risk indicator for in-hospital mortality in individuals with SFTS. The CRP/PNI nomogram showed a good predictive value for in-hospital mortality in patients with SFTS. After PSM, the predictive performance of CRP/PNI for 28-day mortality was excellent. Finally, the CRP/PNI could still assess patients with SFTS at different risks based on SFTS data from another medical center., Conclusion: The CPR/PNI ratio exhibited a strong positive correlation with the SFTS disease type and could predict in-hospital mortality in the early stages of SFTS. The CPR/PNI ratio could substantially help clinicians facilitate the early identification of patients with high-risk SFTS and the timely initiation of intensive therapy., (© 2024 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging zoonosis with a high fatality rate in China. Previous studies have reported that dysregulated inflammatory response is associated with disease pathogenesis and mortality in patients with SFTS. This investigation aimed to evaluate the prevalence and characteristics of systemic inflammatory response syndrome (SIRS), and its impact on prognosis., Methods: Data on demographic characteristics, comorbid conditions, clinical manifestations, laboratory parameters, and survival time of patients with SFTS were collected. Patients were divided into the non-SIRS and SIRS groups according to the presence of SIRS, then their clinical data were compared., Results: A total of 290 patients diagnosed with SFTS were retrospectively enrolled, including 126(43.4%) patients with SIRS. Patients in the non-survivor group had more prevalence of SIRS than patients in the survivor group (P < 0.001), and SIRS (adjusted OR 2.885, 95% CI 1.226-6.786; P = 0.005) was shown as an independent risk factor for prognosis of patients with SFTS. Compared with patients without SIRS, patients with SIRS had lower WBC and neutrophils counts, and fibrinogen levels, but higher AST, LDH, amylase, lipase, CK, CK-MB, troponin I, APTT, thrombin time, D-dimer, CRP, IL-6, SAA levels, and viral load. The cumulative survival rate of patients with SIRS was significantly lower than that of patients without SIRS. Patients with SIRS also showed a higher incidence of bacterial or fungal infections than patients without SIRS., Conclusions: SIRS is highly frequent in patients with SFTS, and it is associated with high mortality., (© 2024. The Author(s).)

Background: Severe fever with thrombocytopenia syndrome (SFTS), a lethal tick-borne hemorrhagic fever, prompted our investigation into prognostic predictors and potential drug targets using plasma Olink Proteomics., Methods: Employing the Olink assay, we analyzed 184 plasma proteins in 30 survivors and 8 non-survivors of SFTS. Validation was performed in a cohort of 154 SFTS patients using enzyme-linked immunosorbent assay. We utilized the Drug Gene Interaction database to identify protein-drug interactions., Results: Non-survivors exhibited 110 differentially expressed proteins (DEPs) compared to survivors, with functional enrichment in the cell chemotaxis-related pathway. Thirteen DEPs, including C-C motif chemokine 20 (CCL20), calcitonin gene-related peptide alpha and Pleiotrophin, were associated with multiple organ dysfunction syndrome. CCL20 emerged as the top predictor of death, demonstrating an area under the curve of 1 (P = .0004) and 0.9033 (P < .0001) in the discovery and validation cohort, respectively. Patients with CCL20 levels exceeding 45.74 pg/mL exhibited a fatality rate of 45.65%, while no deaths occurred in those with lower CCL20 levels. Furthermore, we identified 202 FDA-approved drugs targeting 37 death-related plasma proteins., Conclusions: Distinct plasma proteomic profiles characterize SFTS patients with different outcomes, with CCL20 emerging as a novel, sensitive, accurate, and specific biomarker for predicting SFTS prognosis., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by the SFTS virus (SFTSV). Predicting the incidence of this disease in advance is crucial for policymakers to develop prevention and control strategies. In this study, we utilized historical incidence data of SFTS (2013-2020) in Shandong Province, China to establish three univariate prediction models based on two time-series forecasting algorithms Autoregressive Integrated Moving Average (ARIMA) and Prophet, as well as a special type of recurrent neural network Long Short-Term Memory (LSTM) algorithm. We then evaluated and compared the performance of these models. All three models demonstrated good predictive capabilities for SFTS cases, with the predicted results closely aligning with the actual cases. Among the models, the LSTM model exhibited the best fitting and prediction performance. It achieved the lowest values for mean absolute error (MAE), mean square error (MSE), and root mean square error (RMSE). The number of SFTS cases in the subsequent 5 years in this area were also generated using this model. The LSTM model, being simple and practical, provides valuable information and data for assessing the potential risk of SFTS in advance. This information is crucial for the development of early warning systems and the formulation of effective prevention and control measures for SFTS., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

SFTSV is an emerging tick-borne virus causing hemorrhagic fever with a case fatality rate (CFR) that can reach up to 27%. With endemic infection in East Asia and the recent spread of the vector tick to more than 20 states in the United States, the SFTSV outbreak is a globally growing public health concern. However, there is currently no targeted antiviral therapy or licensed vaccine against SFTSV. Considering the age-dependent SFTS pathogenesis and disease outcome, a sophisticated vaccine development approach is required to safeguard the elderly population from lethal SFTSV infection. Given the recent emergence of SFTSV, the establishment of animal models to study immunogenicity and protection from SFTS symptoms has only occurred recently. The latest research efforts have applied diverse vaccine development approaches-including live-attenuated vaccine, DNA vaccine, whole inactivated virus vaccine, viral vector vaccine, protein subunit vaccine, and mRNA vaccine-in the quest to develop a safe and effective vaccine against SFTSV. This review aims to outline the current progress in SFTSV vaccine development and suggest future directions to enhance the safety and efficacy of these vaccines, ensuring their suitability for clinical application.