The differences in cytokine signatures between severe fever with thrombocytopenia syndrome (SFTS) and hemorrhagic fever with renal syndrome (HFRS).

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.

A full-length glycoprotein mRNA vaccine confers complete protection against severe fever with thrombocytopenia syndrome virus, with broad-spectrum protective effects against bandaviruses.

Highly pathogenic viruses from family Phenuiviridae, which are mainly transmitted by arthropods, have intermittently sparked epidemics worldwide. In particular, tick-borne bandaviruses, such as severe fever with thrombocytopenia syndrome virus (SFTSV), continue to spread in mountainous areas, resulting in an average mortality rate as high as 10.5%, highlighting the urgency and importance of vaccine development. Here, an mRNA vaccine developed based on the full-length SFTSV glycoprotein, containing both the receptor-binding domain and the fusion domain, was shown to confer complete protection against SFTSV at a very low dose by triggering a type 1 helper T cell-biased cellular immune response in rodents. Moreover, the vaccine candidate elicited long-term immunity and protection against SFTSV for at least 5 months. Notably, it provided complete cross-protection against other bandaviruses, such as the Heartland virus and Guertu virus, in lethal challenge models. Further research revealed that the conserved epitopes among bandaviruses within the full-length SFTSV glycoprotein may facilitate broad-spectrum protection mediated by the cellular immune response. Collectively, these findings demonstrate that the full-length SFTSV glycoprotein mRNA vaccine is a promising vaccine candidate for SFTSV and other bandaviruses, and provide guidance for the development of broad-spectrum vaccines from conserved antigens and epitopes. IMPORTANCE: Tick-borne bandaviruses, such as SFTSV and Heartland virus, sporadically trigger outbreaks in addition to influenza viruses and coronaviruses, yet there are no specific vaccines or therapeutics against them. mRNA vaccine technology has advantages in terms of enabling in situ expression and triggering cellular immunity, thus offering new solutions for vaccine development against intractable viruses, such as bandaviruses. In this study, we developed a novel vaccine candidate for SFTSV by employing mRNA vaccination technology and using a full-length glycoprotein as an antigen target. This candidate vaccine confers complete and durable protection against SFTSV at a notably low dose while also providing cross-protection against Heartland virus and Guertu virus. This study highlights the prospective value of full-length SFTSV-glycoprotein-based mRNA vaccines and suggests a potential strategy for broad-spectrum bandavirus vaccines.

Interaction between the SFTSV envelope glycoprotein Gn and STING inhibits the formation of the STING-TBK1 complex and suppresses the NF-κB signaling pathway.

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.

Identification of CCL20 as a prognostic predictor for severe fever with thrombocytopenia syndrome based on plasma proteomics.

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.

Outbreak of Natural Severe Fever with Thrombocytopenia Syndrome Virus Infection in Farmed Minks, China.

We isolated severe fever with thrombocytopenia syndrome virus (SFTSV) from farmed minks in China, providing evidence of natural SFTSV infection in farmed minks. Our findings support the potential role of farmed minks in maintaining SFTSV and are helpful for the development of public health interventions to reduce human infection.

Prolonged coagulation times in severe fever with thrombocytopenia syndrome virus infection, the indicators of heparin-like effect and increased haemorrhagic risk.

Prolonged coagulation times, such as activated partial thromboplastin time (APTT) and thrombin time (TT), are common in patients infected with severe fever with thrombocytopenia syndrome virus (SFTSV) and have been confirmed to be related to patient's poor outcome by previous studies. To find out the reason for prolonged coagulation time in patients with SFTSV infection, and whether it predicts haemorrhagic risk or not. Seventy-eight consecutive patients with confirmed SFTSV infection were enrolled in this prospective, single-centre, observational study. Several global and specific coagulation parameters of these patients on admission were detected, and the haemorrhagic events during hospitalization and their outcomes were recorded. Most of the enrolled patients had prolonged APTT (82.1%) and TT (80.8%), normal prothrombin time (83.3%) and intrinsic coagulation factors above haemostatic levels (97.4%). The heparin-like effect was confirmed by a protamine neutralization test and anti-Xa activity detection in most patients. Interestingly, the APTT and TT results were significantly positively correlated with the levels of endothelial markers and viral load, respectively. The APTT was independently associated with the haemorrhage of patients. The prolonged APTT and TT of SFTS patients may mainly be attributed to endogenous heparinoids and are associated with increased haemorrhagic risk.

Ruxolitinib plus standard of care in severe hospitalized adults with severe fever with thrombocytopenia syndrome (SFTS): an exploratory, single-arm trial.

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.

Identification of tanshinone I as cap-dependent endonuclease inhibitor with broad-spectrum antiviral effect.

IMPORTANCE: The spread of avian-borne, tick-borne, and rodent-borne pathogens has the potential to pose a serious threat to human health, and candidate vaccines as well as therapeutics for these pathogens are urgently needed. Tanshinones, especially tanshinone I, were identified as a cap-dependent endonuclease inhibitor with broad-spectrum antiviral effects on negative-stranded, segmented RNA viruses including bandavirus, orthomyxovirus, and arenavirus from natural products, implying an important resource of candidate antivirals from the traditional Chinese medicines. This study supplies novel candidate antivirals for the negative-stranded, segmented RNA virus and highlights the endonuclease involved in the cap-snatching process as a reliable broad-spectrum antiviral target.

Activation of neurotoxic A1-reactive astrocytes by SFTS virus infection accelerates fatal brain damage in IFNAR1-/- mice.

Severe fever with thrombocytopenia syndrome (SFTS) has a high mortality rate compared to other infectious diseases. SFTS is particularly associated with a high risk of mortality in immunocompromised individuals, while most patients who die of SFTS exhibit symptoms of severe encephalitis before death. However, the region of brain damage and mechanisms by which the SFTS virus (SFTSV) causes encephalitis remains unknown. Here, we revealed that SFTSV infects the brainstem and spinal cord, which are regions of the brain associated with respiratory function, and motor nerves in IFNAR1-/- mice. Further, we show that A1-reactive astrocytes are activated, causing nerve cell death, in infected mice. Primary astrocytes of SFTSV-infected IFNAR1-/- mice also induced neuronal cell death through the activation of A1-reactive astrocytes. Herein, we showed that SFTSV induces fatal neuroinflammation in the brain regions important for respiratory function and motor nerve, which may underlie mortality in SFTS patients. This study provides new insights for the treatment of SFTS, for which there is currently no therapeutic approach.

Prevalence and impact of viral myocarditis in patients with severe fever with thrombocytopenia syndrome.

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.

Construction of an early differentiation diagnosis model for patients with severe fever with thrombocytopenia syndrome and hemorrhagic fever with renal syndrome.

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 × 109/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.

Comparison of epidemiological characteristics between hemorrhagic fever with renal syndrome patients and severe fever with thrombocytopenia syndrome patients.

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.

Metabolic alterations in urine among the patients with severe fever with thrombocytopenia syndrome.

BACKGROUND: The pathogenesis of severe fever with thrombocytopenia syndrome (SFTS) remained unclear. We aimed to profile the metabolic alterations in urine of SFTS patients and provide new evidence for its pathogenesis. METHODS: A case-control study was conducted in the 154th hospital in China. Totally 88 cases and 22 controls aged ≥ 18 years were enrolled. The cases were selected from laboratory-confirmed SFTS patients. The controls were selected among SFTSV-negative population. Those with diabetes, cancer, hepatitis and other sexually transmitted diseases were excluded in both groups. Fatal cases and survival cases were 1:1 matched. Inter-group differential metabolites and pathways were obtained, and the inter-group discrimination ability was evaluated. RESULTS: Tryptophan metabolism and phenylalanine metabolism were the top one important metabolism pathway in differentiating the control and case groups, and the survival and fatal groups, respectively. The significant increase of differential metabolites in tryptophan metabolism, including 5-hydroxyindoleacetate (5-HIAA), L-kynurenine (KYN), 5-hydroxy-L-tryptophan (5-HTP), 3-hydroxyanthranilic acid (3-HAA), and the increase of phenylpyruvic acid and decrease of hippuric acid in phenylalanine metabolism indicated the potential metabolic alterations in SFTSV infection. The increase of 5-HIAA, KYN, 5-HTP, phenylpyruvic acid and hippuric acid were involved in the fatal progress of SFTS patients. CONCLUSIONS: Tryptophan metabolism and phenylalanine metabolism might be involved in the pathogenesis of SFTSV infection. These findings provided new evidence for the pathogenesis and treatment of SFTS.

Cytokines and lymphocyte subsets are associated with disease severity of severe fever with thrombocytopenia syndrome.

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.

Direct transmission of severe fever with thrombocytopenia syndrome virus from farm-raised fur animals to workers in Weihai, China.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease. SFTS virus (SFTSV) is transmitted by tick bites and contact with the blood or body fluids of SFTS patients. Animal-to-human transmission of SFTS has been reported in Japan, but not in China. In this study, the possible transmission route of two patients who fed and cared for farm-raised fur animals in a mink farm was explored. METHOD: An epidemiological investigation and a genetic analysis of patients, animals and working environment were carried out. RESULTS: It was found that two patients had not been bitten by ticks and had no contact with patients infected with SFTS virus, but both of them had skinned the dying animals. 54.55% (12/22) of the farm workers were positive for SFTS virus antibody. By analyzing the large, medium and small segments sequences, the viral sequences from the two patients, animals and environments showed 99.9% homology. CONCLUSION: It is suspected that the two patients may be directly infected by farm-raised animals, and that the virus may have been transmitted by aerosols when skinning dying animals. Transmission by direct blood contacts or animal bites cannot be ignored.

Early predictors of Epstein-Barr virus infection in patients with severe fever with thrombocytopenia syndrome.

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.

Severe fever with thrombocytopenia syndrome with central nervous system symptom onset: a case report and literature review.

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.

Analysis of early warning indicators of death in patients with severe fever with thrombocytopenia syndrome.

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.

A nomogram including admission serum glycated albumin/albumin ratio to predict mortality in patients with severe fever with thrombocytopenia syndrome.

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.

Computer-aided designing of a novel multi­epitope DNA vaccine against severe fever with thrombocytopenia syndrome virus.

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.