Difference in hematocrit and plasma albumin levels as an early biomarker of severity and prognosis in patients with severe fever and thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is a widespread infectious disease with high mortality. Hence, identifying valuable biomarkers for detecting the early changes in SFTS is crucial. In this study, we investigated the relationship between the difference in hematocrit (HCT) and serum albumin (ALB) levels (HCT-ALB) and the prognosis of patients with SFTS virus infection. After excluding the patients who did not meet the SFTS diagnostic criteria, those with SFTS from the First Affiliated Hospital of Wannan Medical College were divided into a fatal and Nonfatal group based on their disease prognosis. A dynamic analysis of the daily laboratory data was conducted for 14 days following SFTS onset. A receiver operating characteristic (ROC) curve was used to evaluate the predictive value of HCT-ALB. Another sample of patients with SFTS admitted to the First Affiliated Hospital of Nanjing Medical University was utilized to verify the study conclusions. A total of 158 patients with SFTS were included. Among them, 126 patients were categorized in the Nonfatal group and 32 in the fatal group, leading to a mortality rate of 20.25% (32/158). Univariate analysis of the laboratory test findings and ROC curve analysis showed that alanine aminotransferase (ALT), aspartate aminotransferase (AST), HCT-ALB, and lactate dehydrogenase (LDH) had a relatively better ability to discriminate the disease condition of the patients with SFTS. Moreover, HCT-ALB served as a predictor of SFTS prognosis. Additionally, an area under the ROC curve (AUC) of 0.777 and a critical HCT-ALB value of 4.75 on day 7 were associated with a sensitivity of 83.3% and a specificity of 73.9%. On day 8 (AUC = 0.882), the critical value of HCT-ALB was 9.25, while the sensitivity was 100% and specificity was 76.5%. Further verification based on the data of 91 patients with SFTS admitted to the First Affiliated Hospital of Nanjing Medical University demonstrated a mortality rate of 51% (24/47) among those with HCT-ALB values >4.75 on day 7 of the disease course, highlighting the potential of the HCT-ALB value of >4.75 for predicting SFTS prognosis. High HCT-ALB values are closely related to the mortality of patients with SFTS. HCT-ALB is a sensitive and independent predictor of early disease in patients with SFTS.

Construction and validation of a dynamic nomogram using Lasso-logistic regression for predicting the severity of severe fever with thrombocytopenia syndrome patients at admission.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is a highly fatal infectious disease caused by the SFTS virus (SFTSV), posing a significant public health threat. This study aimed to construct a dynamic model for the early identification of SFTS patients at high risk of disease progression. METHODS: All eligible patients enrolled between April 2014 and July 2023 were divided into training and validation sets. Thirty-four clinical variables in the training set underwent analysis using least absolute shrinkage and selection operator (LASSO) logistic regression. Selected variables were then input into the multivariate logistic regression model to construct a dynamic nomogram. The model's performance was assessed using the area under the receiver operating characteristic curve (AUC-ROC), concordance index (C-index), calibration curve, and decision curve analysis (DCA) in both training and validation sets. Kaplan-Meier survival analysis was utilized to evaluate prognostic performance. RESULTS: 299 SFTS patients entered the final investigation, with 208 patients in the training set and 90 patients in the validation set. LASSO and the multivariate logistic regression identified six significant prediction factors: age (OR, 1.060; 95% CI, 1.017-1.109; P = 0.007), CREA (OR, 1.017; 95% CI, 1.003-1.031; P = 0.019), PT (OR, 1.765; 95% CI, 1.175-2.752; P = 0.008), D-dimer (OR, 1.039; 95% CI, 1.005-1.078; P = 0.032), nervous system symptoms (OR, 8.244; 95% CI, 3.035-26.858; P < 0.001) and hemorrhage symptoms (OR, 3.414; 95% CI, 1.096-10.974; P = 0.035). The AUC-ROC, C-index, calibration plots, and DCA demonstrated the robust performance of the nomogram in predicting severity at admission, and Kaplan-Meier survival analysis indicated its utility in predicting 28-day mortality among SFTS patients. The dynamic nomogram is accessible at https://sfts.shinyapps.io/SFTS_severity_nomogram/ . CONCLUSION: This study provided a practical and readily applicable tool for the early identification of high-risk SFTS patients, enabling the timely initiation of intensified treatments and protocol adjustments to mitigate disease progression.

Procalcitonin levels in severe fever with thrombocytopenia syndrome patients: a retrospective investigation in Anhui, China.

INTRODUCTION: This work aim to evaluate the association of procalcitonin (PCT) levels with disease severity and prognosis in severe fever with thrombocytopenia syndrome (SFTS) patients. METHODOLOGY: The medical records of 158 confirmed SFTS patients at two hospitals were reviewed. The patients were divided into survival group and nonsurvival group according to outcomes. Additionally, to assess mortality rates at different PCT levels, patients were divided into two groups, PCT < 0.25 ng/mL and PCT ≥ 0.25 ng/mL. RESULTS: Among the 158 confirmed SFTS patients, 26 died; the case fatality rate was 16.46%. PCT data were available for 132 of these patients; 66 were in the PCT < 0.25 ng/mL group, and 66 were in the PCT ≥ 0.25 ng/mL group. The SFTS patients had abnormal results on routine blood tests, indicating varying degrees of thrombocytopenia and leukopenia, and most patients presented with multiple organ dysfunction. The PCT level of the nonsurvival group was significantly higher than that of the survival group (p < 0.01). Additionally, the mortality of the PCT ≥ 0.25 ng/mL group was significantly higher than that of the PCT < 0.25 ng/mL group (p < 0.01); mortality increased sharply ( ≥ 25%) when the PCT level exceeded 0.1 ng/mL. CONCLUSIONS: PCT levels in SFTS patients are closely related to the severity and prognosis of their illness. The serum PCT level is a promising predictor of mortality and severity in SFTS patients when considered in combination with clinical data and other laboratory tests.

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.

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.

Japanese spotted fever in an area endemic to SFTS virus: Case report and review of the literature.

RATIONALE: The geographic spread of Japanese spotted fever (JSF) in China is gradually expanding, particularly in regions where severe fever with thrombocytopenia syndrome (SFTS) is highly prevalent, with both diseases sharing similarities in epidemiology and clinical presentation. The microbiological diagnosis of JSF is challenging, compounded by low awareness among healthcare professionals in newly affected areas. Moreover, primary healthcare facilities without polymerase chain reaction (PCR) testing capabilities for SFTS often misdiagnose JSF as SFTS. PATIENT CONCERNS: All 3 patients had a history of working in the fields, with cold like symptoms in the early fever stages, but the fever did not improve after a few days. The accompanying symptoms were also very different. Physical examination revealed enlarged lymph nodes, different forms of rash, with or without eschar. Laboratory tests showed thrombocytopenia, eosinophilia, elevated lactate dehydrogenase, and transaminase, with 1 patient experiencing renal damage. It is worth noting that these 3 patients reside in an area where SFTS is endemic, and there have been no prior reports of JSF. They exhibited clinical symptoms and laboratory test results closely resembling those of SFTS. Therefore, they were initially misdiagnosed with SFTS in their local hospitals. DIAGNOSES: The 3 patients who arrived at our hospital 7 days after symptom onset and were subsequently diagnosed with JSF by metagenomic next-generation sequencing (mNGS). INTERVENTIONS: Doxycycline treatment for 1 week. OUTCOMES: The patients' symptoms quickly improved with no side effects, and the results of laboratory tests went back to normal. LESSONS: By comparing the clinical characteristics of JSF patients and SFTS patients comprehensively, we found that APTT and procalcitonin levels may be valuable in assisting in the identification of SFTS and JSF. In all areas where tick-borne diseases are endemic, include SFTS-epidemic areas, we recommend using the Weil-Felix test to screen for potential rickettsiosis in patients presenting with fever and thrombocytopenia with or without rash in primary healthcare settings, as well as simultaneous testing for the SFTS virus and spotted fever group rickettsioses sequence. Additionally, mNGS sequencing should be used to confirm the diagnosis and provide information for epidemiological investigations in patients who are suspected of having spotted fever group rickettsiosis.

Development of an all-in-one real-time PCR assay for simultaneous detection of spotted fever group rickettsiae, severe fever with thrombocytopenia syndrome virus and hantaan virus prevalent in central China.

Central China has been reported to be one of the most important endemic areas of zoonotic infection by spotted fever group rickettsiae (SFGR), severe fever with thrombocytopenia syndrome virus (SFTSV) and hantaan virus (HTNV). Due to similar clinical symptoms, it is challenging to make a definite diagnosis rapidly and accurately in the absence of microbiological tests. In the present study, an all-in-one real-time PCR assay was developed for the simultaneous detection of nucleic acids from SFGR, SFTSV and HTNV. Three linear standard curves for determining SFGR-ompA, SFTSV-L and HTNV-L were obtained within the range of 101-106 copies/µL, with the PCR amplification efficiencies ranging from 93.46% to 96.88% and the regression coefficients R2 of >0.99. The detection limit was 1.108 copies/µL for SFGR-ompA, 1.075 copies/µL for SFTSV-L and 1.006 copies/µL for HTNV-L, respectively. Both the within-run and within-laboratory coefficients of variation on the cycle threshold (Ct) values were within the range of 0.53%-2.15%. It was also found there was no statistical difference in the Ct values between single template and multiple templates (PSFGR-ompA = 0.186, PSFTSV-L = 0.612, PHTNV-L = 0.298). The sensitivity, specificity, positive and negative predictive value were all 100% for determining SFGR-ompA and SFTSV-L, 97%, 100%, 100% and 99.6% for HTNV-L, respectively. Therefore, the all-in-one real-time PCR assay appears to be a reliable, sensitive, rapid, high-throughput and low cost-effective method to diagnose the zoonotic infection by SFGR, SFTSV and HTNV.

Blood urea nitrogen to albumin ratio is a novel predictor of fatal outcome for patients with severe fever with thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is associated with a high death rate and lacks a targeted therapy plan. The ratio of blood urea nitrogen to albumin, known as BAR, is a valuable method for assessing the outlook of various infectious diseases. The objective of this research was to evaluate the effectiveness of BAR in forecasting the outcome of individuals with SFTS. Four hundred and thirty-seven patients with SFTS from two clinical centers were included in this study according to inclusion and exclusion criteria. Clinical characteristics and test parameters of SFTS patients were analyzed between survival and fatal groups. Least absolute shrinkage and selection operator (LASSO) regression and Cox regression suggested that BAR might serve as a standalone prognostic indicator for patients with SFTS in the initial phase (hazard ratio = 18.669, 95% confidence interval [CI]: 8.558-40.725, p < 0.001). And BAR had a better predictive effectiveness in clinical outcomes in patients with SFTS with an AUC of 0.832 (95% CI: 0.788-0.876, p < 0.001), a cutoff value of 0.19, a sensitivity of 0.812, and a specificity of 0.726 compared to C-reactive protein, procalcitonin, and platelet to lymphocyte ratio via receiver operating characteristic curve. KM (Kaplan Meier) curves demonstrated that high level of BAR was associated with poor survival condition in patients with SFTS. Furthermore, the high level of BAR was associated with long hospital stays and test paraments of kidney, liver, and coagulation function in survival patients. So, BAR could be used as a promising early warning biomarker of adverse outcomes in patients with SFTS.

Clinical Factors Associated with SFTS Diagnosis and Severity in Cats.

Severe fever with thrombocytopenia syndrome (SFTS) is a potentially fatal tick-borne zoonosis caused by SFTS virus (SFTSV). In addition to tick bites, animal-to-human transmission of SFTSV has been reported, but little is known about feline SFTSV infection. In this study, we analyzed data on 187 cats with suspected SFTS to identify biomarkers for SFTS diagnosis and clinical outcome. Body weight, red and white blood cell and platelet counts, and serum aspartate aminotransferase and total bilirubin levels were useful for SFTS diagnosis, whereas alanine aminotransferase, aspartate aminotransferase and serum SFTSV RNA levels were associated with clinical outcome. We developed a scoring model to predict SFTSV infection. In addition, we performed a phylogenetic analysis to reveal the relationship between disease severity and viral strain. This study provides comprehensive information on feline SFTS and could contribute to the protection of cat owners, community members, and veterinarians from the risk of cat-transmitted SFTSV infection.

Development and validation of the PLNA score to predict cytokine storm in acute-phase SFTS patients: A single-center cohort study.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease known for its high mortality rate and its correlation with Cytokine Storms (CS). Timely detection of CS is crucial for improving the prognosis of the disease. The objective of this investigation was to develop a model for identifying cytokine storms in the acute phase of SFTS. METHODS: A total of 245 patients diagnosed with SFTS were included in this study between January 2020 and July 2022. Among them, 184 patients were part of the training set, while 61 patients were part of the validation set. Variables identified by LASSO were subsequently included in a multivariate logistic regression analysis to determine independent predictors. Subsequently, a nomogram was then developed to predict the likelihood of CS in SFTS patients. The predictive efficacy and clinical applicability of the nomogram model were further assessed through ROC analysis and the DCA curve. RESULTS: Following LASSO analysis, a total of 11 indicators were included in multivariate logistic regression analysis. The findings indicated that PLT (OR 0.865, P < 0.001), LDH (OR 1.002, P < 0.001), Na+ (OR 1.155, P = 0.005), and ALT (OR 1.019, P < 0.001) serve as independently predictors of CS in the acute phase of SFTS. Furthermore, a nomogram named the PLNA was constructed by integrating these four factors. The PLNA model exhibited favorable predictive accuracy with an AUC of 0.958. Moreover, the PLNA model exhibited excellent clinical applicability in both the training and validation sets, as evidenced by the DCA curve. CONCLUSIONS: The PLNA model, constructed using clinical indicators, can predict the probability of cytokine storm in the acute phase of SFTS patients.

Seroprevalence study in humans and molecular detection in Rhipicephalus sanguineus ticks of severe fever with thrombocytopenia syndrome virus in Thailand.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne virus with a mortality rate of up to 30%. First identified in China in 2009, it was later reported in other Asian countries, including Thailand in 2020. SFTSV has been detected in several tick species, including Rhipicephalus sanguineus, known for infesting dogs. We conducted a seroprevalence study of SFTSV in Bangkok and Nong Khai, Thailand, by analyzing 1162 human samples collected between 2019 and 2023. The testing method relied on IgG detection using ELISA and confirmed though a virus seroneutralization test. The results indicated that out of the participants, 12 (1.1%) tested positive for anti-SFTSV IgG antibodies; however, none exhibited positive results in the seroneutralization assay. Additionally, molecular detection of SFTSV, Crimean-Congo hemorrhagic fever (CCHF), Coxiella spp., Bartonella spp., and Rickettsia spp. was performed on 433 Rh. sanguineus ticks collected from 49 dogs in 2023 in Chachoengsao Province, Thailand. No evidence of these pathogens was found in ticks. These findings highlight the importance of exploring viral cross-reactivity. Furthermore, it is important to conduct additional studies to isolate SFTSV from animals and ticks in order to identify the potential transmission routes contributing to human and animal infections in Thailand.

Rapid Detection of Severe Fever with Thrombocytopenia Syndrome Virus in the Acute Phase of Infection by Direct Real-Time Reverse Transcription without RNA Extraction.

No specific treatment has been developed for severe fever with thrombocytopenia syndrome (SFTS). However, the prognosis can improve with early plasma exchange. Therefore, rapid and accurate detection of SFTS virus is important for diagnosis and prognosis. Direct real-time reverse transcription polymerase chain reaction (RT-PCR) testing is easier and more time-efficient than conventional real-time RT-PCR. Our study compared direct real-time RT-PCR efficiency without the RNA extraction and purification of conventional real-time RT-PCR. Samples were collected from 18 patients with SFTS and five without SFTS. A strong correlation (r = 0.774, 95% CI: 0.652-0.857, P <0.01) was found between conventional and direct real-time RT-PCR assays. Direct real-time RT-PCR showed 84.4% sensitivity and 92.0% specificity for viral detection. Direct real-time RT-PCR is an effective diagnostic tool for patients with acute phase SFTS, but further optimization is required for viral detection.

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.

Blood Urea Nitrogen-to-Serum Albumin Ratio Predicts Fatal Outcomes in Severe Fever with Thrombocytopenia Syndrome Patients.

There are no effective therapies for severe fever with thrombocytopenia syndrome (SFTS), and existing predictors of mortality are still controversial. This retrospective study aimed to identify reliable early-stage indicators for predicting fatal outcomes in 217 patients hospitalized with an SFTS diagnosis between March 2021 and November 2023; 157 of the patients survived, and 60 died. Demographics, clinical characteristics, and laboratory parameters were reassessed in both groups. The mean age of participants was 64.0 (interquartile range: 54.5-71.0) years, and 42.4% (92/217) were males. Based on a multivariate Cox regression analysis, the blood urea nitrogen-to-serum albumin ratio (BAR) (hazard ratio [HR]:4.751; 95% CI: 2.208-10.226; P <0.001), procalcitonin level (HR: 1.946; 95% CI: 1.080-3.507; P = 0.027), and central nervous system symptoms (HR: 3.257; 95% CI, 1.628-6.513; P = 0.001) were independent risk factors for mortality in SFTS patients. According to a receiver operating characteristic curve analysis, a BAR with an area under the curve of 0.913 (95% CI: 0.873-0.953; P <0.001), a sensitivity of 76.7%, and a specificity of 90.4% showed better predictive performance for fatal outcomes than other classical indicators reported. The Kaplan-Meier survival curve confirmed that an increased BAR was linked with an unfavorable prognosis in SFTS patients (P <0.001 by log-rank test). In conclusion, the results indicate that high BAR levels are markedly related to substandard outcomes and are a reliable and readily accessible predictor of fatal outcomes in SFTS patients.

MCP-3 as a prognostic biomarker for severe fever with thrombocytopenia syndrome: a longitudinal cytokine profile study.

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

Correlation between the Cycle Threshold Values in Detection of Severe Fever with Thrombocytopenia Syndrome Virus Using PowerChekTM SFTSV Real-Time PCR Kit and Viral Load: Prognostic Implications.

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

The first diagnosis of Severe Fever with Thrombocytopenia Syndrome caused by tick-borne Severe Fever with Thrombocytopenia Syndrome virus in Chongqing, China: A case report and literature review.

BACKGROUND: Severe Fever with Thrombocytopenia Syndrome (SFTS) is a tick-borne disease caused by the SFTS virus (SFTSV) which has the potential to become a pandemic and is currently a major public health concern. CASE PRESENTATION: We present the case of a 74-year-old female from an urban area of Chongqing, with leukocytopenia, thrombocytopenia, organ function, inflammatory, blood coagulation, and immune abnormalities. SFTSV infection was confirmed through molecular detection and metagenomic next-generation sequencing (mNGS) analysis, indicating a diagnosis of SFTS due to the patient's history of tick bites. The patient received symptomatic and supportive therapy, including antibiotics, antiviral treatment, and antifungal therapy, and finally discharged from the hospital on day 18. CONCLUSIONS: This study highlights the need for increased awareness, early diagnosis, and prompt treatment for tick-borne SFTS. It also provides a comprehensive understanding of the disease's characteristics, pathogenesis, detection methods, and available treatments.

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.

Gn protein expressed in plants for diagnosis of severe fever with thrombocytopenia syndrome virus.

Severe fever with thrombocytopenia syndrome virus (SFTSV) causes the highly fatal disease in humans. To facilitate diagnosis, the native form of subunit glycoprotein (Gn), a prime target for potential vaccines and therapies, was produced in Nicotiana benthamiana using a Bamboo mosaic virus-based vector system. By fusion with secretory signal tags, SSExt, derived from the extension protein, and the (SP)10 motif, the yield of the recombinant Gn (rGn) was remarkably increased to approximately 7 mg/kg infiltrated leaves. Ultimately, an rGn-based ELISA was successfully established for the detection of SFTSV-specific antibodies in serum samples from naturally infected monkeys. As validated with the reference method, the specificity and sensitivity of rGn-ELISA were 94% and 96%, respectively. In conclusion, utilizing well-suited fusion tags facilitates rGn production and purification in substantial quantities while preserving its antigenic properties. The rGn-ELISA, characterized by its commendable sensitivity and specificity could serve as a viable alternative diagnostic method for assessing SFTSV seroprevalence. KEY POINTS: • SFTSV Gn, fused with secretory signal tags, was expressed by the BaMV-based vector. • The plant fusion tags increased expression levels and eased the purification of rGn. • The rGn-ELISA was established and validated; its specificity and sensitivity > 94%.