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Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease with a high case fatality rate. Key gaps remained as to the assessment of the clinical picture in fatal cases.A retrospective study was performed on 496 patients with fatal SFTS. The dynamic pattern of clinical manifestations and laboratory indicators were delineated.The mean age of the fatal cases was 69.0 years (standard deviation: 9.3), and 52.8% were male. The median clinical course from disease onset to death was 11 (interquartile range: 10-13) days. A total of 11 laboratory indicators (neutrophil %, platelet, aspartate aminotransferase, aspartate aminotransferase/alanine transaminase, lactate dehydrogenase, creatine kinase, cystatin C, D-dimer, activated partial thromboplastin time, thrombin time, glucose) persistently deviated from normality across hospitalization. The critical time points when the rapid worsening of the indicators was at 6-9 days after disease onset. Alanine transaminase, AST, lactate dehydrogenase, total bile acid, gamma-glutamyl transpeptidase, and glucose were all elevated to a more pronounced level in fatal cases of those aged ≤70 years.The fatal outcome was developed in rather a short course after the disease onset of SFTS. High vigilance should be put on the key time points when the severe worsening and severe complications occur.

To evaluate the effect and safety of corticosteroid (CS) treatment in patients with severe fever with thrombocytopenia syndrome (SFTS).Patients with and without CS were retrospectively compared by Cox regression and 1:1 propensity score matching analysis to evaluate the effects of CS on mortality and secondary infections in patients with SFTS.A total of 467 patients with SFTS were enrolled in the cohort study, there were 52 fatal cases and 415 nonfatal cases, the overall fatality rate was 11.1%. The mortality was observed in 36/144 (25%) and 16/323 (5%) patients in the CS-treated and non-CS-treated groups, respectively (P0.001). Multi variate Cox regression analysis showed that the difference was not statistically significant for CS treatment in fatality (P0.05, aHR 0.767, 95% CI 0.360-1.634). Difference in survival time between the CS-treated and non-CS-treated groups after propensity score matching had no statistical significance (Log-rank test P = 0.390), whereas there was a significant difference in secondary infections between the CS-treated and non-CS-treated groups (P = 0.007).Although the CS treatment had no impact on fatality in patients with SFTS, it increased the risk of secondary infections. Administration of CS in patients with SFTS should be carefully considered and evaluated the balance between therapeutic efficacy and adverse effects.

Selenium deficiency can be associated with increased susceptibility to some viral infections and even more severe diseases. In this study, we aimed to examine whether this association applies to severe fever with thrombocytopenia syndrome (SFTS).An observational study was conducted based on the data of 13,305 human SFTS cases reported in mainland China from 2010 to 2020. The associations among incidence, case fatality rate of SFTS, and crop selenium concentration at the county level were explored. The selenium level in a cohort of patients with SFTS was tested, and its relationship with clinical outcomes was evaluated.The association between selenium-deficient crops and the incidence rate of SFTS was confirmed by multivariate Poisson analysis, with an estimated incidence rate ratio (IRR, 95% confidence interval [CI]) of 4.549 (4.215-4.916) for moderate selenium-deficient counties and 16.002 (14.706-17.431) for severe selenium-deficient counties. In addition, a higher mortality rate was also observed in severe selenium-deficient counties with an IRR of 1.409 (95% CI: 1.061-1.909). A clinical study on 120 patients with SFTS showed an association between serum selenium deficiency and severe SFTS (odds ratio, OR: 2.94; 95% CI: 1.00-8.67) or fatal SFTS (OR: 7.55; 95% CI: 1.14-50.16).Selenium deficiency is associated with increased susceptibility to SFTS and poor clinical outcomes.

Nucleic acid molecular diagnostic technology plays an important role in the detection of severe fever with thrombocytopenia syndrome (SFTS). However, no relevant reports have been published on the accuracy of reverse-transcription polymerase chain reaction (RT-PCR) and reverse-transcription loop-mediated isothermal amplification (RT-LAMP) in the diagnosis of SFTS. Thus, we conducted a meta-analysis and systematic review to evaluate the accuracy of the two methods. On June 19, 2022, we comprehensively searched the PubMed, Embase, Cochrane Library, Web of Science, Scoups, Ovid, Proquest, China National Knowledge Infrastructure Database, Wan Fang Data, Traditional Chinese Medicine Database (Sinomed), VIP Database, and Reading Showing Database for articles on nucleic acid diagnostic techniques, such as RT-PCR and RT-LAMP, used to diagnose SFTS. Statistical analysis was performed using STATA 14.0 and Meta-Disc 1.4. Sixteen articles involving 2942 clinical blood samples were included in the analysis. RT-PCR and RT-LAMP were used as index tests, whereas RT-PCR or other detection methods were used as reference standards. The pooled values for the sensitivity, specificity, positive and negative likelihood ratios of the RT-PCR test were 0.97 (95% confidence interval [CI]: 0.92-0.99), 1.00 (95% CI: 0.98-1.00), 483.87 (95% CI: 58.04-4033.76), and 0.03 (95% CI:0.01-0.08), respectively. Those for the RT-LAMP test were 0.95 (95% CI: 0.91-0.97), 0.99 (95% CI: 0.93-1.00), 111.18 (95% CI: 13.96-885.27), and 0.05 (95% CI: 0.03-0.09), respectively. Both RT-PCR and RT-LAMP have high diagnostic value in SFTS and can be applied in different scenarios for laboratory confirmation or on-site screening.

Severe fever with thrombocytopenia syndrome (SFTS) is a zoonotic disease with a high mortality rate for humans and cats. The clinical course and prognosis of SFTS in dogs remains unclear. In the present study, we investigated the clinical and epidemiological characteristics of SFTS virus (SFTSV) infection in dogs. All evaluated dogs exhibited an acute course and symptoms including fever (57.1%), anorexia (57.1%), depression (42.9%), and vomiting (35.7%). Thrombocytopenia was present in 45.5% of dogs, while jaundice was not observed. C-reactive protein, alanine transaminase, and alkaline phosphatase were elevated in some cases. Viral clearance occurred within 6 to 26 days. Phylogenetic analysis revealed that the SFTSV sequences were consistent with viruses circulating in the Republic of Korea. As dogs often live in close contact with humans, awareness of the clinical and epidemiological features of SFTS in dogs is crucial. Further large-scale studies are necessary to investigate SFTSV infection in dogs.

Solitary fibrous tumors (SFTs) are rare mesenchymal neoplasms that are usually localized in the mesothelium of soft tissues. Although SFTs of pleural origin are common, SFTs arising in the small intestine are extremely rare, and there are few reports of laparoscopic resection of these tumors. A 74-year-old woman presented to her local physician with intermittent pain in the lower abdomen. Computed tomography showed a 25 mm mass in the ileum with extramural protrusion and small intestine capsule endoscopy showed a submucosal tumor-like elevation covered by normal mucosa. The diagnosis was ileal tumor, which was removed by laparoscopic partial resection of the small intestine. Macroscopically, the tumor was found to be a substantial mass within subplasmalemmal fatty tissue that had no continuity with the muscular layer. Histological analysis showed proliferation of homogeneous spindle-shaped cells against a background of fibrous stroma. Immunostaining was positive for STAT6 and negative for KIT, Dog1, and S100, and SFT was diagnosed. The tumor was low risk according to Demicco's risk classification. In conclusion, a less invasive laparoscopic procedure is preferable if the tumor can be resected completely without applying excessive external force that results in seeding of tumor cells in the abdominal cavity.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever with high mortality. Severe cases progressed rapidly, with deaths occurring within 2 weeks. Therefore, constructing a model to predict disease progression among hospitalized patients plays an important role in clinical practice. The development cohort included 121 patients with SFTS, 25 with severe SFTS, and 96 with mild SFTS. Two of the 64 variables were independent risk factors, including neurological symptoms (odds ratio [OR], 12.915; 95% confidence interval [CI], 3.342-49.916; P0.001) and aspartate aminotransferase/alanine aminotransferase levels (OR, 1.891; 95% CI, 1.272-2.813; P = 0.002). The model's area under the curve (AUC) was 0.882 (95% CI: 0.808-0.956). The mean AUC value obtained from the internal validation was 0.883 (95% CI: 0.809-0.957). The AUC in the external validation cohort was 0.873 (95% CI: 0.775-0.972). This model can be used to identify severely ill patients as early as possible with high predictive value, stability, and repeatability. This model can help clinicians with their treatment plans.

Severe fever with thrombocytopenia syndrome (SFTS) caused by Dabie bandavirus (formerly SFTS virus, SFTSV), which belongs to the Bandavirus genus (formerly Phlebovirus genus) of the Phenuiviridae family (formerly Bunyaviridae family), is a tick-borne novel bunyavirus infection with high rates of mortality. SFTSV infection was diagnosed virologically in a 4-year-old dog with symptoms of lethargy and anorexia in western Japan in June 2017. The dog's owner, a man in his 40s, had taken care of the sick dog and became sick 10 days after disease onset in the dog, showing symptoms, such as fever, arthralgia, headache, nausea, and vomiting. Total blood cell counts revealed leukocytopenia and thrombocytopenia. He was treated as an outpatient. He had no scars suggesting that he had not been bitten by ticks. He was diagnosed as having SFTS via the detection of IgM and neutralizing antibodies to SFTSV. The patient was directly infected with SFTSV from the SFTSV-infected dog. In conclusion, humans can be at a risk of SFTSV infection through direct contact with sick dogs infected with SFTSV.

C-reactive protein-to-albumin ratio (CAR) can be used to assess the prognosis of various diseases. This study aimed to evaluate the relationship between CAR on the prognosis of patients with severe fever with thrombocytopenia syndrome (SFTS). This study included 155 SFTS patients from the Public Health Clinical Center of Dalian from January to December 2021. They were divided into survival and deceased groups based on the clinical prognosis. The independent risk factors for poor prognosis of SFTS patients at an early stage were determined by Cox regression. The efficacy of CAR prediction was assessed by the receiver operating characteristic (ROC) curve. A total of 155 patients were included in this study, with an average age of 61.98± 11.70 years, including 77 males and 65 females. The mortality rate of the patients enrolled in this study was 14.19%. Multivariate Cox regression indicated that CAR (hazard ratio = 2.585, 95% confidence interval [CI] 1.405-4.753, p = 0.002) could be an independent predictor for prognosis in SFTS patients at an early stage. CAR had an AUC of 0.781 (95% CI, 0.665-0.898, p = 0.000), a cutoff value of 0.57, a sensitivity of 0.77, and a specificity of 0.80, with better predictive efficacy, compared to neutrophil-to-lymphocyte ratio (NLR). High levels of CAR are associated with poor prognosis in SFTS patients, and CAR can be used as an independent predictor for SFTS patients.

Infection with severe fever with thrombocytopenia syndrome (SFTS) virus, which can cause hemorrhagic febrile illness, is often transmitted by ticks. We identified 3 patients with SFTS in or near Bangkok, Thailand. Our results underscore a need for heightened awareness by clinicians of possible SFTS virus, even in urban centers.

A 67-year-old man, hospitalized with fever and pancytopenia, experienced cardiogenic shock on the 3rd day of hospitalization. He complained of chest pain and exhibited cardiac dysfunction, upregulated serum troponin levels, and an ST elevation on electrocardiogram. Severe fever with thrombocytopenia syndrome (SFTS) was suspected based on the symptom course after a tick bite and was definitively diagnosed using the serum polymerase chain reaction (PCR) test. An endomyocardial biopsy performed in the convalescent phase revealed a sign of myocardial inflammation with increases in CD3- and CD68-positive cells. We herein report the first case of acute myocarditis complicated with SFTS.

Severe fever with thrombocytopenia syndrome (SFTS), a novel infectious disease caused by a novel bunyavirus and with a high case fatality rate (CFR), was reported by Chinese scientists in 2011. The causative virus, Dabie bandavirus also known as the SFTS virus (SFTSV), belongs to the genus Bandavirus (formerly named Phlebovirus) of the family Phenuiviridae (formerly named Bunyaviridae). SFTS was also reported to be endemic in South Korea and Japan in 2013. SFTSV circulates between some species of ticks and animals in nature. Humans are infected with SFTSV through bites from ticks such as Haemaphysalis longicornis and Amblyomma testidinarium. Domesticated animals, such as cats and dogs, are also infected with SFTSV and shown SFTS-like symptoms with a high CFR, likely having been infected through tick bites in the living environment. Furthermore, there have been cases of patients with SFTS who were infected with SFTSV through close contact with sick cats or dogs. The CFR in patients with SFTS is approximately 30% in Japan. There is always a risk of SFTSV infection in human populations living in endemic areas. Therefore, the development of specific therapies and vaccines is urgently needed to reduce the number of fatal SFTS cases.

Severe fever with thrombocytopenia syndrome (SFTS) caused by Dabie bandavirus (SFTSV) is a serious public health concern in endemic areas, particularly in Asian and Southeast Asian countries. SFTSV is transmitted by direct contact with body fluids from infected humans and animals. Therefore, environmental hygiene in hospitals and veterinary clinics in SFTSV-endemic areas is highly important. This study assessed the effects of continuous and intermittent irradiation with deep-ultraviolet light-emitting diode (DUV-LED) on SFTSV. Evaluation was performed by conducting plaque assay in which SFTSV irradiated with deep-ultraviolet (DUV; 280 ± 5 nm) was inoculated onto Vero cells. The results showed that continuous and intermittent irradiation for 5 s, resulting in 18.75 mJ/cm

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a newly emerging tick-borne virus with a case fatality rate between 12% and 50%. Currently, effective vaccines or antiviral drugs are not available, and a diagnostic method for detecting SFTSV is urgently needed. The monoclonal (MAb) and polyclonal antibodies (PAb) against SFTSV were prepared by immunizing animals with SFTSV nucleocapsid protein (NP), and using both monoclonal and polyclonal antibodies as capture antibodies against NP, we developed two different double-antibody sandwich enzyme-linked immunosorbent assays (DAS-ELISAs) for detecting the NP of SFTSV. Both methods were applicable for the diagnosis of SFTSV-infected patients, as confirmed by quantitative polymerase chain reaction. Furthermore, the sensitivity and specificity of two assays for diagnosing SFTS were both 100%, and had no reaction to recombinant Dabieshan NP or recombinant Dengue virus NS1 subtype 1 and 2 proteins. In addition, two standard curves were established for quantitative detection of the NP, and the monoclonal antibody-based ELISA (MAb-based ELISA) test had a lower limit of detection than the polyclonal-based ELISA (PAb-based ELISA) test. Therefore, the MAb-based ELISA could be employed for detecting SFTSV in a convenient and effective way.

Since the Dabie bandavirus (DBV; former SFTS virus, SFTSV) was identified, the epidemics of severe fever with thrombocytopenic syndrome (SFTS) caused by this virus have occurred in several countries in East Asia. The rapid increase in incidence indicates that this infectious agent has a pandemic potential and poses an imminent global public health threat.The analysis of molecular evolution of SFTS agent that includes its variants isolated in China, Japan and South Korea was performed in this review. The evolution rate of DBV and the estimated dates of existence of the common ancestor were ascertained, and the possibility of reassortation was demonstrated.The evolutionary rates of DBV genome segments were estimated to be 2.28 × 10-4 nucleotides/site/year for S-segment, 2.42 × 10-4 for M-segment, and 1.19 × 10-4 for L-segment. The positions of positive selection were detected in the viral genome.Phylogenetic analyses showed that virus may be divided into two clades, containing six different genotypes. The structures of phylogenetic trees for S-, M- and L-segments showed that all genotypes originate from the common ancestor.Data of sequence analysis suggest that DBV use several mechanisms to maintain the high level of its genetic diversity. Understanding the phylogenetic factors that determine the virus transmission is important for assessing the epidemiological characteristics of the disease and predicting its possible outbreaks.

Background To understand the clinical characteristics of and explore the risk factors for mortality in patients with severe fever with thrombocytopenia syndrome (SFTS). Methods Data from SFTS patients diagnosed by laboratory examination at Chaohu Hospital affiliated with Anhui Medical University from June 2017 to January 2021 were retrospectively analysed. According to the clinical results, all confirmed patients were divided into the surviving group (80 patients) and non-surviving group (20 patients). The two groups were compared in terms of general characteristics, clinical symptoms and signs, laboratory indicators and other aspects. The independent risk factors for mortality in SFTS patients were analysed by multivariate binary logistic regression. Results Univariate analysis showed a significant difference in age and the incidence of consciousness disturbance, respiratory failure, haemorrhagic manifestations, renal dysfunction, shock, aspartate aminotransferase (AST) ≥400 U/L, creatine kinase (CK)≥1000 U/L, creatine kinase isoenzymes (CK-MB) ≥100 U/L, lactate dehydrogenase (LDH) ≥1000 U/L, serum creatinine ≥100 mmol/L, blood urea nitrogen ≥7.5 mmol/L and C-reactive protein ≥8 mg/L between the two groups (P Conclusions Consciousness disorder, haemorrhagic manifestations, renal dysfunction, AST ≥ 400 U/L, and LDH ≥ 1000 U/L are independent risk factors for mortality in SFTS patients and merit close attention in clinical treatment to avoid fatal consequences.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging negatively stranded enveloped RNA bunyavirus that causes SFTS with a high case fatality rate of up to 30%. Macroautophagy/autophagy is an evolutionarily conserved process involved in the maintenance of host homeostasis, which exhibits anti-viral or pro-viral responses in reaction to different viral challenges. However, the interaction between the bunyavirus SFTSV and the autophagic process is still largely unclear. By establishing various autophagy-deficient cell lines, we found that SFTSV triggered RB1CC1/FIP200-BECN1-ATG5-dependent classical autophagy flux. SFTSV nucleoprotein induced BECN1-dependent autophagy by disrupting the BECN1-BCL2 association. Importantly, SFTSV utilized autophagy for the viral life cycle, which not only assembled in autophagosomes derived from the ERGIC and Golgi complex, but also utilized autophagic vesicles for exocytosis. Taken together, our results suggest a novel virus-autophagy interaction model in which bunyavirus SFTSV induces classical autophagy flux for viral assembly and egress processes, suggesting that autophagy inhibition may be a novel therapy for treating or releasing SFTS.

Severe fever with thrombocytopenia syndrome (SFTS), caused by SFTS virus (SFTSV) is an emerging tick-borne infectious disease. Few studies have assessed the clinical usefulness of nested reverse-transcription polymerase chain reaction (RT-PCR) for diagnosing SFTS. We performed conventional RT-PCR targeting the M segment, nested RT-PCR targeting M and S segments, and real-time RT-PCR targeting the S segment of SFTSV for four patients with suspected SFTS. Although conventional RT-PCR results for the first two patients were negative at admission, nested RT-PCR using the S or M targets was positive for the same samples. Likewise, in the other two patients, initial samples were confirmed positive in all three tests, but follow-up testing demonstrated negative conventional RT-PCR and positive nested RT-PCR results. Thus, delayed testing using conventional RT-PCR or real-time RT-PCR in symptomatic patients with SFTS may result in missed diagnoses, and compared with these methods, nested RT-PCR may increase the window for obtaining positive SFTSV PCR results. Meanwhile, the indirect immunofluorescence assay showed seroconversion to SFTSV antibodies in all four patients. Nested RT-PCR for SFTSV M and S segments could help diagnose SFTS in patients testing negative by conventional RT-PCR.

Solitary fibrous tumors (SFT) are uncommon mesenchymal neoplasms which can arise in any anatomical location. Pleural SFTs have been most frequently documented; however, breast SFT is an exceedingly rare entity and seldom present in male breast, with only 8 previously reported cases. Recently, STAT6 immunostaining was considered to be a definitive marker of SFT, however, no case of the male breast SFT showing STAT6 positivity preoperatively has been reported.We describe a case of breast SFT in a 73-year-old male patient with a 12-month history of a palpable breast mass. The only associated clinical symptom was bilateral gynecomastia. An ultrasound scan examination revealed an oval, well-circumscribed and hypoechoic mass with hypervascularity. A core-needle biopsy was performed, and microscopic examination with immunohistochemistry confirmed the diagnosis of SFT. He underwent a complete surgical resection with clear margins, and there were no signs of high cellularity, remarkable mitotic activity, pleomorphism, hemorrhage or necrosis.A perioperative immunohistochemical evaluation for diffuse and intense nuclear expression of STAT6 was helpful to distinguish SFT from myofibroblastoma. We, herein, describe the first case of SFT in a male breast, confirmed by STAT6 immunostaining positivity. We also conducted a literature review of all previous cases of breast SFTs.

To analyze the epidemiological distribution, clinical characteristics, and prognostic risk factors of patients having severe fever with thrombocytopenia syndrome (SFTS).We enrolled 790 patients with SFTS divided into the ordinary group and the severe group, analyzed the clinical characteristics, and screened the risk factors of severious patients by univariate logistic regression analysis.Most of the 790 patients (SFTS) are farmers (84.56%). The proportion of patients with fieldwork history was 72.41%, of which 21.27% had a clear history of a tick bite and 98.61% were sporadic cases. The annual peak season is from April to November. 16.33% patients were not accompanied by fever. The incidence of severe thrombocytopenia was 47.59%. They were statistically significant between the 2 groups in indicators such as age, hypertension, coronary heart disease, diabetes mellitus, bunyavirus nucleic acid load and mean platelet count (P .05). Multivariate non conditional Logistic regression analysis showed that the risk factors of the mild patients deteriorating severe disease were age (OR = 1.985, P ≤ .003), diabetes mellitus (OR = 1.702, P ≤ .001), coronary heart disease (OR = 1.381, P ≤ .003), platelet count (OR = 2.592, P ≤ .001), viral nucleic acid loading (OR = 3.908, P ≤ .001).The incidence population and seasonal distribution characteristics of patients with SFTS are obvious. The risk factors for poor prognosis of severe patients are old age, multiple basic medical histories, high viral load, a serious decrease of mean platelet count, and delay of treatment time.

BackgroundSevere fever with thrombocytopenia syndrome (SFTS) is a novel infectious disease with no specific therapeutics and vaccines. We hypothesize that health education in vulnerable people would ameliorate their knowledge, attitudes and practices (KAP) regarding SFTS and reduce its prevalence.MethodsA four-stage cluster cross-section study in sixteen community units was performed. Sixteen groups were allocated to the intervention or control groups. A 6 months education program was administrated. The primary outcome was KAP scores 6 months after intervention. Predictors of KAP score changes were also analyzed.ResultsEight hundred and fifteen valid questionnaires pre-intervention and 767 ones post-intervention were retreated. No significant differences were found in demographic characteristics and KAP scores before intervention. A significant improvement in KAP score (16.8 ± 4.7 vs. 22.0 ± 4.2, p < 0.001) in the intervention group was observed compare with the controls. Educational level and intervention program were the common predictors of KAP score changes.ConclusionsEducation improved KAP scores in SFTS vulnerable people which may contribute to the control of the disease.

To investigate the seroprevalence of severe fever with thrombocytopenia syndrome (SFTS) among wild and companion animals on Tsushima Island, Japan, SFTS virus (SFTSV)-specific ELISA and virus-neutralizing tests were conducted on 50 wild boars, 71 Sika deer, 84 dogs, 323 domestic cats, and 6 Tsushima leopard cats. In total, 1 wild boar (1.8%), 2 dogs (2.4%), 7 domestic cats (2.2%), and 1 Tsushima leopard cat (16.7%) were positive for anti-SFTSV antibodies. Among the 11 positive animals, 10 were collected after 2019, and all were found on the southern part of the island. SFTSV, thus far, seems to be circulating within a limited area of Tsushima Island. To protect humans and animals, including endangered Tsushima leopard cats, from SFTSV infection, countermeasures are needed to prevent the spread of SFTSV on Tsushima Island.

Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne viral hemorrhagic fever caused by the SFTS virus (SFTSV). Approximately 80 patients are infected annually, mainly in western Japan, and the case fatality rate is20%. The clinical presentation of SFTS typically includes fever, thrombocytopenia, leukocytopenia, and gastrointestinal symptoms. Localized lymphadenopathy, coagulopathy associated with prolonged activated partial thromboplastin time, muscular symptoms, and neurological abnormalities referred to as SFTS encephalopathy are often observed. Besides tick-borne spread, SFTSV infection is increasingly being transmitted via SFTS-infected cats. Clinicians should remain mindful of this emerging viral infection.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease worldwide. It can be transmitted from person to person, and the fatality rate is very high. During this study, three SFTS clusters including 12 associated cases were identified in three counties in Zhejiang Province from 2018 to 2020. The median age of the three index patients was 70 years, and that of secondary case patients was 59 years. Of note, the mortality rate of the index patients was 100%. The mortality rate of secondary case patients was 11%. The total secondary attack rate (SAR) was 30% (9/30). The SARs of cluster A, cluster B, and cluster C were 38% (3/8), 21% (3/14), and 38% (3/8), respectively. Additionally, the interval from onset to diagnosis was 4 days. The intervals from disease onset to confirmation of the index cases and secondary cases were 7 days and 4 days, respectively. All secondary case patients had a history of close contact with blood or body fluids of the index patients. These results indicate that SFTS patients should not be discharged until recovery. When SFTS patients die, the corpses should be transferred directly from the hospital to the crematorium for cremation by persons wearing proper protective equipment to prevent virus transmission.

Objective To identify the correlation between the level of at-admission fasting blood glucose (FBG) with poor outcomes in hospitalized patients suffering from severe fever with thrombocytopenia syndrome (SFTS). Methods Between April 1 and December 1, 2020, the list of hospitalized patients affected with SFTS infection was provided by the Infectious Disease Department at First Affiliated Hospital of Anhui Medical University, followed by the collection of information I.e., gender, age, diabetic history and the level of FBG on admission. Results In this study, a total of 77 patients were included and were categorized into three groups (r = − 0.28, P = 0.01), however, a linear positive correlation was observed between AST, IL10, D-Dimer, and FDP levels and FBG (P-value P P P = 0.96). With the prolongation of time, the changes of FBG were different between survivor group and non-survivor group. The FBG in survival group shown a downward trend; The non-survivor group shown an upward trend. Conclusions Elevated level of FBG has been correlated with hypercoagulability, inflammation, and lower PLT in SFTS patients. The measurement of FBG level can help in evaluating the inflammatory process, hypercoagulability, and prognosis of patients suffering from SFTS. FBG can predict the prognosis of SFTS. It is necessary to pay attention to the role of FBG in the process of treatment in patients with SFTS.

We designed a highly sensitive reverse transcription nested polymerase chain reaction targeting the M-segment (NPCR-M) of severe fever with thrombocytopenia syndrome (SFTS) virus. NPCR-M was performed in parallel with three other referenced PCR assays QPCR-S, PCR-M, and NPCR-S to assess their clinical usefulness as routine diagnostic techniques for SFTS. In this multi-centered prospective study, 122 blood samples from 38 laboratory-confirmed SFTS patients and 85 control samples were used. The results demonstrated that QPCR-S and NPCR-S had better sensitivity rate up to 21 days after symptom onset however, the PCR-M showed poor sensitivity after 7 days of symptom onset. Our designed NPCR-M had a higher detection rate up to 40 days from symptom onset and revealed the persistence of SFTSV RNA in the early convalescent phase. No false-positive results were seen for the control samples. Additionally, NPCR-M showed positive results for a sample that initially showed negative results from other PCRs and for many other samples collected in the convalescent phase of SFTS. Our designed nested PCR is suitable for SFTSV detection in patients’ blood collected in the acute and early convalescent phase of SFTS, and shows better sensitivity and high specificity even up to 40 days after symptom onset.

Severe fever with thrombocytopenia syndrome (SFTS) is an acute infectious disease caused by novel bunyavirus (SFTSV), with a mortality rate of 6.3% ~ 30%. To date, there is no specific treatment for SFTS. Previously, we demonstrated that SFTSV surface glycoprotein (Glycoprotein N, Gn) was a potential target for the development of SFTS vaccine or therapeutic antibodies, and anti-Gn neutralizing antibodies played a protective role in SFTS infection. Compared with traditional antibodies, nanobodies from camelids have various advantages, including small molecular weight, high affinity, low immunogenicity, convenient production by gene engineering, etc. In this study, we combined next-generation sequencing (NGS) with proteomics technology based on affinity purification-mass spectrometry (AP-MS) and bioinformatics analysis to high-throughput screen monoclonal anti-Gn nanobodies from camel immunized with Gn protein. We identified 19 anti-Gn monoclonal nanobody sequences, of which six sequences were selected for recombinant protein expression and purification. Among these six anti-Gn nanobodies, nanobody 57,493 was validated to be highly specific for Gn. The innovative high-throughput technical route developed in this study could also be expanded to the production of nanobodies specific for other viruses like SARS-CoV-2.

BACKGROUND Solitary fibrous tumors (SFT), rare soft-tissue neoplasms, are usually found in the thoracic cavity, and a uterine origin is extremely rare. SFTs with insulin-like growth factor-II (IGF-II) production induce non-islet cell tumor-induced hypoglycemia (NICTH), referred to as Doege-Potter syndrome. CASE REPORT A 70-year-old woman presented with urinary retention, and imaging revealed a huge mass occupying almost the entire pelvic space. She had a history of hysterectomy for leiomyoma of the uterus 7 years earlier. In her present course, she developed hypoglycemia, and NICTH was suspected. Her previous uterine specimen was reexamined, and immunohistochemistry (IHC) revealed the specimen to be CD34-positive and alpha-smooth muscle actin-negative, indicating that the uterine specimen was not leiomyoma but SFT. Therefore, the present pelvic tumor was considered to be a recurrence of SFT with NICTH, namely Doege-Potter syndrome. Surgical resection was performed, and the pathological examination showed the same histologic features as the previous uterine specimen, while IHC revealed the present specimen to be positive for CD34, signal transducers and activator of transcription 6, and IGF-II, consistent with the diagnosis of recurrent SFT with IGF-II production. The patient's hypoglycemia improved after tumor resection. To confirm the IGF-II secretion from the SFT, we conducted immunoblotting of the patient's perioperative serum, with results showing that the strong band of IGF-II in the preoperative serum disappeared after surgery. CONCLUSIONS Because SFTs, especially those with Doege-Potter syndrome, often recur, sometimes with a very long interval, long-term cautious surveillance is required, even after complete tumor resection.

Background The transmission and fatal risk of severe fever with thrombocytopenia syndrome (SFTS), an emerging infectious disease first discovered in China in 2009, still needed further quantification. This research aimed to analyze the SFTS clusters and assess the transmission and mortality risk for SFTS. Methods Both epidemiological investigation and case reports regarding SFTS clusters in China during 2011–2021 were obtained from the Public Health Emergency Information Management System of the Chinese Center for Disease Control and Prevention Information System. The transmission risk was evaluated by using the secondary attack rate (SAR) and relative risk (RR). Mortality risk factors were analyzed using a logistic regression model. Results There were 35 SFTS clusters during 2011–2021 involving 118 patients with a fatality rate of 22.0%. The number of clusters annually increased seasonally from April to September. The clusters mainly occurred in Anhui (16 clusters) and Shandong provinces (8 clusters). The SAR through contact with blood or bloody fluids was much higher than that through contact with non-bloody fluids (50.6% vs 3.0%; χ2 = 210.97, P RR of 16.61 [95% confidence interval (CI): 10.23–26.97]. There was a statistically significant difference in the SAR between exposure to the blood of a deceased person during burial preparation and exposure to the living patients’ blood (66.7% vs 34.5%; χ2 = 6.40, P RR of 1.93 (95% CI: 1.11–3.37). The mortality risk factors were a long interval from onset to diagnosis [odds ratio (OR) = 1.385), 95% CI: 1.083–1.772, P = 0.009) and advanced age (OR: 1.095, 95% CI: 1.031–1.163, P = 0.01). Conclusions The SFTS clusters showed a high mortality rate and resulted in a high SAR. Contact with a bleeding corpse was associated with a higher infection risk, compared with contacting the blood from living patients. It is important to promote early detection and appropriate case management of patients with SFTS, as well as improved handling of their corpses, to prevent further transmission and mortality. Graphical abstract

Severe fever with thrombocytopenia syndrome (SFTS) and Japanese spotted fever (JSF; a spotted fever group rickettsiosis) are tick-borne zoonoses that are becoming a significant public health threat in Japan and East Asia. Strategies for treatment and infection control differ between the two; therefore, initial differential diagnosis is important. We aimed to compare the clinical characteristics of SFTS and JSF based on symptomology, physical examination, laboratory data, and radiography findings at admission. This retrospective study included patients with SFTS and JSF treated at five hospitals in Nagasaki Prefecture, western Japan, between 2013 and 2020. Data from 23 patients with SFTS and 38 patients with JSF were examined for differentiating factors and were divided by 7:3 into a training cohort and a validation cohort. Decision tree analysis revealed leukopenia (white blood cell [WBC] < 4000/µL) and altered mental status as the best differentiating factors (AUC 1.000) with 100% sensitivity and 100% specificity. Using only physical examination factors, absence of skin rash and altered mental status resulted in the best differentiating factors with AUC 0.871, 71.4% sensitivity, and 90.0% specificity. When treating patients with suspected tick-borne infection, WBC < 4000/µL, absence of skin rash, and altered mental status are very useful to differentiate SFTS from JSF., Viruses, 14(8), art. no. 1807; 2022

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease with a high case fatality rate. Few studies have been performed on bacterial or fungal coinfections or the effect of antibiotic therapy. A retrospective, observational study was performed to assess the prevalence of bacterial and fungal coinfections in patients hospitalized for SFTSV infection. The most commonly involved microorganisms and the effect of antimicrobial therapy were determined by the site and source of infection. A total of 1201 patients hospitalized with SFTSV infection were included; 359 (29.9%) had microbiologically confirmed infections, comprised of 292 with community-acquired infections (CAIs) and 67 with healthcare-associated infections (HAIs). Death was independently associated with HAIs, with a more significant effect than that observed for CAIs. For bacterial infections, only those acquired in hospitals were associated with fatal outcomes, while fungal infection, whether acquired in hospital or community, was related to an increased risk of fatal outcomes. The infections in the respiratory tract and bloodstream were associated with a higher risk of death than that in the urinary tract. Both antibiotic and antifungal treatments were associated with improved survival for CAIs, while for HAIs, only antibiotic therapy was related to improved survival, and no effect from antifungal therapy was observed. Early administration of glucocorticoids was associated with an increased risk of HAIs. The study provided novel clinical and epidemiological data and revealed risk factors, such as bacterial coinfections, fungal coinfections, infection sources, and treatment strategies associated with SFTS deaths/survival. This report might be helpful in curing SFTS and reducing fatal SFTS.

Background Severe fever with thrombocytopenia syndrome (SFTS), one kind of tick-borne acute infectious disease, is caused by a novel bunyavirus. The relationship between meteorological factors and infectious diseases is a hot topic of current research. Liaoning Province has reported a high incidence of SFTS in recent years. However, the epidemiological characteristics of SFTS and its relationship with meteorological factors in the province remain largely unexplored. Methods Data on reported SFTS cases were collected from 2011 to 2019. Epidemiological characteristics of SFTS were analyzed. Spearman’s correlation test and generalized linear models (GLM) were used to identify the relationship between meteorological factors and the number of SFTS cases. Results From 2011 to 2019, the incidence showed an overall upward trend in Liaoning Province, with the highest incidence in 2019 (0.35/100,000). The incidence was slightly higher in males (55.9%, 438/783), and there were more SFTS patients in the 60–69 age group (31.29%, 245/783). Dalian City and Dandong City had the largest number of cases of SFTS (87.99%, 689/783). The median duration from the date of illness onset to the date of diagnosis was 8 days [interquartile range (IQR): 4–13 days]. Spearman correlation analysis and GLM showed that the number of SFTS cases was positively correlated with monthly average rainfall (rs = 0.750, P β = 0.285, P rs = 0.683, P β = 0.096, P rs = 0.822, P β = 0.154, P rs = 0.810, P β = 0.134, P rs = −0.728, P β = −0.145, P rs = −0.272, P β = −1.048, P Conclusion The annual incidence of SFTS increased year on year in Liaoning Province. Incidence of SFTS was affected by several meteorological factors, including monthly average air pressure, monthly average temperature, and monthly average wind speed. Graphical Abstract

The purpose of this study is to assess the incidence and management of co-infections in hospitalized severe fever with thrombocytopenia syndrome bunyavirus (SFTSV) patients. We retrospectively evaluated the microbiological database records of the SFTS patients in the first affiliated hospital of Anhui Medical University from January 1, 2018, to December 1, 2021. According to the obtained results, co-infections including pulmonary infection, bloodstream infection, biliary tract infection, urinary tract infection, and abdominal infection were observed in SFTS patients. The incidence rate of fungal infections was found to be high in SFTS patients. Furthermore, we suggest that old age people should be evaluated for the risk of fungal infection. In comparison to the non-infection group, patients in the co-infection group were more likely to get mechanical ventilation, antibacterial treatment, antifungal treatment, and blood product therapy (p 0.001), with a significantly longer length of stay (p 0.05). In SFTS patients, the most prevalent strains were Aspergillus fumigatus, Aspergillus flavus, Candida, Klebsiella pneumonia, and Escherichia coli. In this investigation, 66.2% (106/160) of patients were given antibiotics, most often Piperacillin/tazobactam or minocycline. 15.6% (25/160) of patients were treated with antifungal drugs: 13.1% (21/160) with voriconazole. Patients with SFTS Associated Pulmonary Aspergillosis (SAPA) received active antifungal treatment, but the mortality rate was still 23.5% (8/34). Only 6 of the 11 patients with SFTS Associated Candidiasis were treated with antifungal drugs with no mortality. Due to the high frequency of fungal pulmonary infection in SFTS patients, more standardized fungal detection program should be strengthened.

Severe fever with thrombocytopenia syndrome (SFTS), which is caused by SFTS virus (SFTSV), poses a serious threat to global public health, with high fatalities and an increasing prevalence. As effective therapies and prevention strategies are limited, there is an urgent need to elucidate the pathogenesis of SFTS. SFTSV has evolved several mechanisms to escape from host immunity. In this review, we summarize the mechanisms through which SFTSV escapes host immune responses, including the inhibition of innate immunity and evasion of adaptive immunity. Understanding the pathogenesis of SFTS will aid in the development of new strategies for the treatment of this disease.

Background Hemangiopericytomas (HPCs) are uncommon soft tissue tumors. HPCs that grow in the cranial base are rare. Therefore, skull-base surgeons tend to overlook this disease. This study aimed to increase the awareness of HPCs by summarizing case data from our institution and related publications. We also aimed to contribute to the number of reported cases for future systematic reviews of HPCs. Methods This study included all patients who underwent surgery for HPC/solitary fibrous tumor (SFT) between August 2015 and August 2019. All surgeries were performed at Xiangya Hospital Central South University. We analyzed clinical characteristics, surgical highlights, treatment modalities, and outcomes. Results We included six patients, aged 32–64 years. Lesions were located in the parapharyngeal space in three patients, pterygopalatine fossa in two, and saddle area in one. All patients underwent nasal endoscopic endonasal surgery. In five patients, tumors involved the internal carotid artery (ICA). The exposure and protection of the ICA during surgery are challenging but critical to complete tumor removal. The 3-year overall survival(OS) rate was 66.7%. Conclusions HPC/SFTs are rare tumors of the cranial base that are prone to recurrence. Cranial base HPC/SFTs are often closely associated with the ICA. To our knowledge, this case series reports the largest number of cases of HPCs associated with the ICA. We believe that there is a strong relationship between patient prognosis and whether the tumor encircles the ICA and whether the tumor is completely resected. To confirm this suggestion, more cases are needed for further analysis.

Background Due to recent emergence, severe fever with thrombocytopenia syndrome (SFTS) is becoming one of the major public health problems in Shandong Province, China. The numbers of reported SFTS cases in general and the area with reported SFTS cases are both continuously increasing in recent years. However, spatiotemporal patterns and clusters of SFTS in Shandong Province have not been investigated yet. Methods The surveillance data of SFTS in Shandong Province, China, during 2014–2018 were extracted from China Information System for Disease Control and Prevention (CISDCP). Geoda software was used to explore spatial autocorrelation analysis, and Satscan software was used to identify spatio-temporal clustering of cases. The results were presented in ArcMap. Results The annual average incidence was 0.567/100,000 in Shandong Province during 2014–2018. Results showed that the distribution of SFTS was not random but clustered in space and time. A most likely cluster including 15 counties was observed in the northeastern region of Shandong Province from January 1, 2015 to December 31, 2015 (Relative risk = 5.13, Log likelihood ratio = 361.266, P Conclusions The number of SFTS cases in Shandong Province increased overall. Geographic information system analysis coupled with spatial analysis illustrated regions with SFTS clusters. Our results provide a sound evidence base for future prevention and control programs of SFTS such as allocation of the health resources, surveillance in high-risk regions, health education, improvement of diagnosis and so on.

An emerging infectious disease first identified in central China in 2009, severe fever with thrombocytopenia syndrome (SFTS) was found to be caused by a novel phlebovirus. Since SFTSV was first identified, epidemics have occurred in several East Asian countries. With the escalating incidence of SFTS and the rapid, worldwide spread of SFTSV vector, it is clear this virus has pandemic potential and presents an impending global public health threat. In this review, we concisely summarize the latest findings regarding SFTSV, including vector and virus transmission, genotype diversity and epidemiology, probable pathogenic mechanism, and clinical presentation of human SFTS. Ticks most likely transmit SFTSV to animals including humans; however, human-to-human transmission has been reported. The majority of arbovirus transmission cycle includes vertebrate hosts, and potential reservoirs include a variety of both domestic and wild animals. Reports of the seroprevalence of SFTSV in both wild and domestic animals raises the probability that domestic animals act as amplifying hosts for the virus. Major clinical manifestation of human SFTS infection is high fever, thrombocytopenia, leukocytopenia, gastrointestinal symptoms, and a high case-fatality rate. Several animal models were developed to further understand the pathogenesis of the virus and aid in the discovery of therapeutics and preventive measures., Virology: An emerging tick-borne disease Severe fever with thrombocytopenia syndrome (SFTS), a tick-borne infectious disease caused by a novel phlebovirus, is a growing global health concern. The main symptoms are high fever, low platelet and white blood cell levels, and gastrointestinal problems. The disease was first identified in China in 2009, and several SFTS epidemics have occurred in East Asia, with mortality rates of between 6 and 27 per cent. Researchers in South Korea led by Young Ki Choi at Chungbuk National University, Cheongju, review the latest research into SFTS virus and disease, including transmission, genetic diversity, epidemiology, pathology and clinical features, and pandemic potential. Animal models are helping researchers understand the virus and disease and develop treatments and vaccines.

Knowledge of the clinical progress of severe fever with thrombocytopenia syndrome (SFTS) and the associated predictors of mortality is important for providing appropriate treatment in severe cases. A multihospital retrospective study was conducted in three SFTS-endemic cities, in 2018. Of the 208 SFTS-confirmed cases, there were 189 survivors and 19 deaths. The median age was 64 years; 104 (50.0%) patients were men, and 188 (90.4%) were farmers. Furthermore, 203 (97.6%) patients reported fever and 70 (33.7%) reported fatigue. Most fatal cases had complications including multiple-organ failure, central nervous syndrome (CNS) abnormalities, and disseminated intravascular coagulation. During the fever phase, alanine transaminase, aspartate aminotransferase (AST), blood urea nitrogen (BUN), creatinine, D-dimer, glucose, hydroxybutyrate dehydrogenase, lactate dehydrogenase (LDH), procalcitonin, prothrombin time, and uric acid levels were higher in fatal than in nonfatal cases (P < 0.05). Creatine kinase (CK), CK-MB (CKMB), AST, and LDH levels were significantly lower in nonfatal than in fatal cases (P < 0.05). Central nervous syndrome abnormalities (odds ratio [OR] = 20.9, 95% CI: 4.3, 100), body temperature ≥ 38.5°C (OR = 23.2, 95% CI: 3.4, 158), BUN levels ≥ 6.4 mmol/L (OR = 9.9, 95% CI: 2.2, 44), CKMB levels ≥ 100 U/L (OR = 33.2, 95% CI: 5.8, 192), and LDH levels ≥ 1,000 U/L (OR = 8.3, 95% CI: 1.9, 37) were predictors of mortality. Our findings reveal that the presence of specific complications and laboratory parameters may serve as predictors of mortality and aid in early identification of severe SFTS cases in clinical practice.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tickborne infectious disease caused by SFTS virus (SFTSV). We report 7 cases of spontaneous fatal SFTS in felines. Necropsies revealed characteristic lesions, including necrotizing lymphadenitis in 5 cases and necrotizing splenitis and SFTSV-positive blastic lymphocytes in all cases. We detected hemorrhagic lesions in the gastrointestinal tract in 6 cases and lungs in 3 cases, suggesting a more severe clinical course of SFTS in felids than in humans. We noted necrotic or ulcerative foci in the gastrointestinal tract in 3 cases, the lung in 2 cases, and the liver in 4 cases. We clarified that blastic lymphocytes are predominant targets of SFTSV and involved in induction of necrotic foci. We also found that thymic epithelial cells were additional targets of SFTSV. These results provide insights for diagnosing feline SFTS during pathological examination and demonstrate the similarity of feline and human SFTS cases.

To analyze the changes of coagulation function in severe fever with thrombocytopenia syndrome (SFTS) and its relationship with thrombocytopenia, and to explore its value as an early predictor of the severity of SFTS. The clinical data of 428 SFTS patients (70 deaths and 358 survivors) admitted to the Department of Infectious Disease at Wuhan Union Hospital from January 2014 to July 2020 were retrospectively analyzed. The differences of coagulation parameters and disseminated intravascular coagulation (DIC) scores between the two groups were compared. The results showed that abnormal coagulation function was commonly presented in SFTS patients. Bleeding was more frequent in mortality group (41.4% vs. 26.5%). The D-dimer levels in mortality patients were significantly higher above normal range. Activated partial thrombin time (APTT) and thrombin time (TT) were significantly prolonged. The levels of prothrombin time (PT), TT, APTT, international standardized ratio (INR) and D-dimer between mortality group and survival group started to separate from day 5-6. The difference of fibrinogen (FIB) level developed on day 7-8, while platelet counts between the two groups were significant different from day 9-10. The mortality rate increased according to the increase of baseline DIC score. When DIC score reached 6, the mortality rate surged to 66.67%. Excessive platelet consumption is mediated by significant coagulation abnormalities during disease course, and coagulation parameters are more sensitive than platelet count as an early predictor of severe SFTS.分析发热伴血小板减少综合征（severe fever with thrombocytopenia syndrome，SFTS）患者凝血功能的临床变化特点及其与血小板减少的关系，探索其作为早期预测SFTS患者重症化趋势的价值。分析2014年1月至2020年7月华中科技大学同济医学院附属协和医院感染科收治的428例SFTS患者（其中死亡组70例，存活组358例）的临床资料，统计分析两组患者凝血相关指标以及弥散性血管内凝血（DIC）评分的差异。结果显示，SFTS患者凝血功能异常常见，死亡组较存活组更易出现出血症状（出血发生率41.4%比26.5%）；死亡组D-二聚体水平显著高于正常水平，活化部分凝血酶时间（APTT）、凝血酶时间（TT）均显著延长。死亡组与存活组患者凝血酶原时间（PT）、TT、APTT、国际标准化比值（INR）、D-二聚体在第5~6天开始出现统计学差异；纤维蛋白原（FIB）水平在第7~8天开始出现统计学差异，均早于血小板计数水平在两组患者中出现差异的时间（第9~10天）。SFTS病死率随基线DIC评分升高而升高，当DIC评分达到6时，病死率达到66.67%。疾病过程中显著的凝血异常介导血小板消耗过多，凝血相关指标较血小板计数对早期识别SFTS重症化更有帮助。.

Severe fever with thrombocytopenia syndrome (SFTS) virus has caused a large number of human infections since discovered in 2009. This study elucidated epidemiological features and fatal risk factors of SFTS cases accumulated up to ten years in Taizhou, a coastal prefecture of Zhejiang Province in Eastern China. A total of 188 hospitalised SFTS cases (including 40 deaths) reported to Taizhou Center for Disease Control and Prevention (CDC) during 2011–2020 were enrolled in the study. In the past decade, the annual incidence of SFTS increased over the years (P < 0.001) along with an expanding epidemic area, and the case fatality of hospitalised cases has remained high (21.3%). Although most cases occurred in hilly areas, a coastal island had the highest incidence and case fatality. The majority of cases were over the age of 60 years (72.3%), and both incidence and case fatality of SFTS increased with age. Multivariate logistic regression analysis showed that age (OR 7.47, 95% CI 1.32–42.33; P = 0.023), and haemorrhagic manifestations including petechiae (OR 7.76, 95% CI 1.17–51.50; P = 0.034), gingival haemorrhage (OR 5.38, 95% CI 1.25–23.15; P = 0.024) and melena (OR 5.75, 95% CI 1.18–28.07; P = 0.031) were significantly associated with the death of SFTS cases. Five family clusters identified were farmers, among four of which the index patients were female with a history of hypertension. Based on the study, age is a critical risk factor for incidence and case fatality of SFTS. With an increased annual incidence over the last ten years, SFTS remains a public health threat that should not be ignored. Further study is needed to look at the natural foci in the coastal islands.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging arboviral infectious disease with a high rate of lethality in susceptible humans and caused by severe fever with thrombocytopenia syndrome bunyavirus (SFTSV). Currently, neither vaccine nor specific antiviral drugs are available. In recent years, given the fact that both the number of SFTS cases and epidemic regions are increasing year by year, SFTS has become a public health problem. SFTSV can be internalized into host cells through the interaction between SFTSV glycoproteins and cell receptors and can activate the host immune system to trigger antiviral immune response. However, SFTSV has evolved multiple strategies to manipulate host factors to create an optimal environment for itself. Not to be discounted, host genetic factors may be operative also in the never-ending winning or losing wars. Therefore, the identifications of SFTSV, host immune and genetic factors, and their interactions are critical for understanding the pathogenic mechanisms of SFTSV infection. This review summarizes the updated pathogenesis of SFTS with regard to virus, host immune response, and host genetic factors to provide some novel perspectives of the prevention, treatment, as well as drug and vaccine developments.

Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne febrile disease caused by SFTS virus (SFTSV), or Dabie bandavirus, in the Phenuiviridae family. Clinically neurological disorders in SFTS have been commonly reported, but their neuropathogenesis has rarely been studied. Microglia are a type of neuroglia accounting for 10 to 12% of all cells in the brain. As resident immune cells, microglial cells are the first line of immune defense present in the central nervous system (CNS). Here, we report that SFTSV was able to infect microglial cells and stimulate interleukin 1β (IL-1β) secretion in the brains of infected neonatal BALB/c mice. We characterized the cell death induced in infected human microglial HMC3 cells, also susceptible to SFTSV, and found that the NOD-like receptor protein 3 (NLRP3) inflammasome was activated, leading to secretion of IL-1β and pyroptosis. Knockdown of NLRP3 or inhibition of the NLRP3 inflammasome activation suppressed the viral replication, suggesting that the activation of the NLRP3 inflammasome may support SFTSV replication in microglial cells. Viral nonstructural protein NSs, a known modulator of immune responses, interacted and colocalized with NLRP3 for the inflammasome activation. It appeared that the N-terminal fragment, amino acids 1 to 66, of NSs was critical to promote the assembly of the inflammasome complex by interacting with NLRP3 for its activation in microglial cells. Our findings provide evidence that SFTSV may cause neurological disorders through infecting microglia and activating the inflammasome through its nonstructural protein NSs for neural cell death and inflammation. This study may have revealed a novel mechanism of SFTSV NSs in dysregulating host response. IMPORTANCE Encephalitis or encephalopathy during severe fever with thrombocytopenia syndrome (SFTS) is considered a critical risk factor leading to high mortality, but there have been no studies to date on the pathogenesis of encephalitis or encephalopathy caused by SFTS virus. Here, we report that SFTSV infection can active the NLRP3 inflammasome and induce IL-1β secretion in the brains of infected newborn mice. In infected human HMC3 microglia, SFTSV activated the NLRP3 inflammasome via the viral nonstructural protein NSs through interaction with its N-terminal fragment. Notably, our findings suggest that the activation of the NLRP3 inflammasome may promote SFTSV replication in infected microglial cells. This study may reveal a novel mechanism by SFTSV to dysregulate host responses through its nonstructural protein, which could help us understand viral neuropathogenesis in SFTS patients.

The threat of severe fever with thrombocytopenia syndrome (SFTS) to public health has been increasing due to the rapid spread of the ticks that carry the causative viral agent. The SFTS virus (SFTSV) was first identified in China and subsequently detected in neighboring countries, including South Korea, Japan, and Vietnam. In addition to the tick-mediated infection, human-to-human transmission has been recently reported with a high mortality rate; however, differential study of the pathogen has been limited by the route of infection. In this study, we investigated the pathogenic potential of SFTSV based on the infection route in aged ferrets, which show clinical signs similar to that of human infections. Ferrets inoculated with SFTSV via the intramuscular and subcutaneous routes show clinical signs comparable to those of severe human infections, with a mortality rate of 100%. Contrastingly, intravascularly infected ferrets exhibit a comparatively lower mortality rate of 25%, although their early clinical signs are similar to those observed following infection via the other routes. These results indicate that the infection route could influence the onset of SFTS symptoms and the pathogenicity of SFTSV. Thus, infection route should be considered in future studies on the pathogenesis of SFTSV infection.

Severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging tick-borne bunyavirus, causes mild-to-moderate infection to critical illness or even death in human patients. The effect of virus variations on virulence and related clinical significance is unclear. We prospectively recruited SFTSV-infected patients in a hotspot region of SFTS endemic in China from 2011 to 2020, sequenced whole genome of SFTSV, and assessed the association of virus genomic variants with clinical data, viremia, and inflammatory response. We identified seven viral clades (I-VII) based on phylogenetic characterization of 805 SFTSV genome sequences. A significantly increased case fatality rate (32.9%) was revealed in one unique clade (IV) that possesses a specific co-mutation pattern, compared to other three common clades (I, 16.7%; II, 13.8%; and III, 11.8%). The phenotype-genotype association (hazard ratios ranged 1.327-2.916) was confirmed by multivariate regression adjusting age, sex, and hospitalization delay. We revealed a pronounced inflammation response featured by more production of CXCL9, IL-10, IL-6, IP-10, M-CSF, and IL-1β, in clade IV, which was also related to severe complications. We observed enhanced cytokine expression from clade IV inoculated PBMCs and infected mice. Moreover, the neutralization activity of convalescent serum from patients infected with one specified clade was remarkably reduced to other viral clades. Together, our findings revealed a significant association between one specific viral clade and SFTS fatality, highlighting the need for molecular surveillance for highly lethal strains in endemic regions and unravelled the importance of evaluating cross-clade effect in development of vaccines and therapeutics.

Objectives We investigated the infectious causes and management of Japanese spotted fever (JSF) and severe fever thrombocytopenia syndrome (SFTS), which are usually tick-borne infections, at a public health center in Ehime prefecture.Methods The doctor diagnosing JSF and SFTS at the public health center reported the infectious cases using the questionnaire based on the Ehime Epidemiological Surveillance of Infectious Diseases Program.Results There were 91 cases of JSF reported from August 2003, accounting for 56.5% of the whole Ehime prefecture. Since 67.0% of the JSF patients resided near the mountains with citrus cultivations, there were high chances of contact with ticks during farm work or their daily routine even if they did not visit the mountain areas. The distribution of the occupations of the JSF patients was as follows: citrus cultivator, 31.9%; farmer, 14.3%; and retired, 26.4%. The incidence of various clinical symptoms in the JSF patients was as follows: fever and systemic erythema, 100%; tick bite, 73.6%; liver dysfunction, 69.2%; disseminated intravascular coagulation (DIC), 14.3%; and neurological symptoms, 11.0%. The mortality rate was 1.1%. The incidence of DIC, which was considered a severe condition, was significantly low in patients with confirmed tick bites. There were 14 cases of SFTS reported from December 2013, accounting for 42.4% of the whole Ehime prefecture. Notably, 85.7% of the SFTS patients resided in the mountains. Moreover, 85.7% of the SFTS patients were retired. The incidence of various clinical symptoms in the SFTS patients was as follows: fever and marked leucopenia and thrombocytopenia, 100%; tick bite, 57.1%; diarrhea, 71.4%; neurological symptoms, 57.1%; and bleeding tendency, 42.9%. The mortality rate was 35.7%, and the average number of days from onset to death was 11.2 days.Conclusion Since this region is one of the leading citrus producing areas in Ehime prefecture, JSF is considered an occupational disease. It is frequently caused by tick bites while working in the mountain areas of citrus cultivations. Hence, citrus growers should be cautious of tick-borne infections. Recently, the number of JSF cases has been gradually decreasing due to awareness and education of the inhabitants. Currently, SFTS is considered a category IV infection disease, but it can rapidly lead to death after the onset of hemophagocytic syndrome. Therefore, doctors should immediately transfer the patients diagnosed with SFTS to a hospital with an intensive care unit.

Solitary fibrous tumors (SFT) are rare mesenchymal neoplasms with a potential to metastasize in 10-30% of cases. Several risk models have been designed to predict tumor behavior at the pleura and extrapleural sites. Intrabdominal SFTs primarily involving the gastrointestinal tract (SFTGI) and liver (SFTL) are rare. We analyzed a series of SFTGI and SFTL to describe the clinicopathologic features and evaluate prognostic factors. The cohort included 33 males and 25 females, with a median age of 58.5 years and a mean tumor size of 15.6 cm. Patients with SFTL were predominantly older females compared to patients with SFTGI. By univariate analysis, high mitotic count ( 4/10 HPF), tumor size, tumor necrosis, and nuclear pleomorphism were associated with both disease-specific survival (DSS) and metastasis-free survival (MFS) (p 0.05). Tumor location (SFTL vs. SFTGI) also predicted MFS (p = 0.026). Only very high mitotic count ( 9/10 HPF) predicted local recurrence-free survival (LFS, p = 0.001). Further analysis showed that all adverse histologic parameters (necrosis, hypercellularity, pleomorphism) correlated with high mitotic grade ( 4/10 HPF) (p 0.05). On multivariate analysis, only mitosis predicted DSS (p = 0.023), MFS (p = 0.01), and LFS (p = 0.017). Validation of the 3 risk models (mDemicco, Salas, Pasquali) showed variable associations with DSS, MFS, and LFS, while a simplied 3-tiered risk model based on mitosis (0-4, 5-9, 9/10 HPF) performed well in predicting all risks. Our results suggest that prognostication of SFTs is mainly associated with mitotic activity, supporting the use of mitosis ( 4 and/or 9/10 HPF) for tumor grading and risk stratification at specific locations.

Severe fever with thrombocytopenia syndrome (SFTS), caused by novel bunyavirus (SFTSV), is a hemorrhagic fever with a high mortality rate of over 10%. We have previously shown that granulocytic myeloid-derived suppressor cell (gMDSC) might affect arginine metabolism, which was associated with decreased platelet count and T lymphocyte dysfunction in this disease. The study was designed to investigate the expression of the gMDSCs subsets in SFTS patients, and to evaluate its association with disease severity. A prospective study was performed on 166 confirmed SFTSV infected patients. Sequential blood samples were collected during hospitalization and after recovery. SFTSV RNA was quantified by real-time RT-PCR. The gMDSCs and NK cells were determined by flow cytometry analysis, which were associated with disease severity. Elevation of the activated gMDSC was observed in SFTS patients at the acute phase, with a significantly higher level of gMDSC attained in 79 severe and 29 fatal SFTS patients than in the mild patients. The NK cells were depleted at the early infection and not restored to normal level until 4 months after the disease. The expansion of gMDSC was accompanied by the elevated expressions of CD3-ζ of NK and Arginase-1, in contrast with the decreased reactive oxygen species (ROS) in gMDSC. The levels of NK, CD3-ζ of NK, viral load, and platelet count were significantly associated with the level of gMDSC. Expansion of gMDSC was demonstrated in SFTS, which was associated with severe disease and suppressed antiviral NK cell via other mechanisms than Arginase-1 or ROS.

To better understand the progression of severe fever with thrombocytopenia syndrome (SFTS), identify early predictors of mortality, and improve the cure rate, the present study aimed to analyze the demographic feature, clinical characteristics, and laboratory parameters of patients with SFTS and to explore the risk factors associated with fatal outcome. We retrospectively analyzed demographic feature, clinical characteristics, and laboratory parameters of 216 laboratory-confirmed SFTS patients in Shandong province between January 2015 and December 2019. Univariate analysis was used to assess the relevance between these factors and fatal outcome. Factors with P 0.05 in univariate analysis were further analyzed using multivariable logistic regression analysis to identify the independent risk factors for mortality of SFTS. Age, five complications (including CNS symptoms, pulmonary infection, heart failure, arrhythmia, and bleeding events), and ten abnormal laboratory parameters (including serum viral load, blood platelet, ALT, AST, LDH, CK, CK-MB, Cr, serum Ca