Clinical and etiological characteristics of severe hemorrhagic fever caused by coinfection of hantaan orthohantavirus and severe fever with thrombocytopenia syndrome virus.

Severe fever with thrombocytopenia syndrome (SFTS) and hemorrhagic fever with renal syndrome (HFRS) usually have different infection routes, and coinfection is relatively rare. This study examines the clinical and etiological characteristics of coinfection by these two pathogens to provide important references for clinical diagnosis and treatment. Blood samples from 22 clinically diagnosed patients with HFRS were collected for molecular detection of HFRS and common tick and mouse borne diseases. Inoculate the blood of six severe and critically patients into cells to isolate and proliferate potential viruses, and retest the cell culture to determine the pathogen. In addition, complete data were collected from these 22 HFRS and concurrent SFTS patients, and white blood cells (WBCs), platelet (PLT), blood urea nitrogen (BUN), creatinine (Cr) and other data were compared and analyzed. A total of 31 febrile patients, including 22 HFRS patients and 9 SFTS patients, were collected from September 2021 to October 2022. Among these HFRS patients, 11 were severe or critical. Severe and critical HFRS patients were characterized by rodent exposure history, pharyngeal and conjunctival hyperemia, abnormal WBC and PLT counts, and elevated BUN and Cr values. Virus isolation and molecular detection on blood samples from 6 patients showed that three of the six severe patients were positive for hantaan virus (HTNV), and two of the three HTNV positives were also positive for SFTS bunyavirus (SFTSV). The two coinfected patients exhibited different clinical and laboratory characteristics compared to those infected by either virus alone. Coinfection of HTNV and SFTSV leads to severe and complex hemorrhagic fever. Laboratory characteristics, such as the indicators of WBC, PLT, BUN, and Cr, may differ between HFRS and SFTS. These findings have implications and provide references for the diagnosis and treatment of coinfected cases.

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.

Establishment and validation of a clinical risk scoring model to predict fatal risk in SFTS hospitalized patients.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infection with a high case fatality rate. Significant gaps remain in studies analyzing the clinical characteristics of fatal cases. METHODS: From January 2017 to June 2023, 427 SFTS cases were included in this study. A total of 67 variables about their demographic, clinical, and laboratory data were collected. Univariate logistic regression and the least absolute shrinkage and selection operator (LASSO) method was used to screen predictors from the cohort. Multivariate logistic regression was used to identify independent predictors and nomograms were developed. Calibration, decision curves and area under the curve (AUC) were used to assess model performance. RESULTS: The multivariate logistic regression analysis screened out the four most significant factors, including age > 70 years (p = 0.001, OR = 2.516, 95% CI 1.452-4.360), elevated serum PT (p < 0.001, OR = 1.383, 95% CI 1.143-1.673), high viral load (p < 0. 001, OR = 1.496, 95% CI 1.290-1.735) and high level of serum urea (> 8.0 µmol/L) (p < 0.001, OR = 4.433, 95% CI 1.888-10.409). The AUC of the nomogram based on these four factors was 0.813 (95% CI, 0.758-0.868). The bootstrap resampling internal validation model performed well, and decision curve analysis indicated a high net benefit. CONCLUSIONS: The nomogram based on age, elevated PT, high serum urea level, and high viral load can be used to help early identification of SFTS patients at risk of fatality.

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.

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.

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.

The Association Between Elevated Myocardial Injury-Related Biomarker (TnI) and Increased Mortality in Patients With Severe Fever With Thrombocytopenia Syndrome.

OBJECTIVES: The objective of this study was to investigate the dynamic profiles of myocardial injury biomarkers and their association with mortality in patients with severe fever with thrombocytopenia syndrome (SFTS). DESIGN: A retrospective cohort study. SETTINGS: Union Hospital in Wuhan, China. PATIENTS: A total of 580 patients with SFTS, observed between May 2014 and December 2021, were included in the final analysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In total, 580 patients with SFTS were enrolled in the study, comprised of 469 survivors and 111 nonsurvivors, with a 21-day fatality rate of 19.1%. The elevation of troponin I (TnI) was observed in 61.6% patients (357/580) with SFTS upon admission, and 68.4% patients (397/580) developed an abnormal TnI level during hospitalization. Multivariate logistic regression identified age, viral load, platelet count, creatinine level, and TnI level as potential risk factors for mortality in patients with SFTS. The results of restricted cubic splines revealed that when the TnI level (baseline TnI: 1.55 [lg (ng/L+1)], peak value: TnI 1.90 [lg (ng/L+1)]) exceeded a certain threshold, the predicted mortality of patients with SFTS increased alongside the rise in TnI levels. Mortality rate surpassed 40% among patients with SFTS with TnI greater than or equal to 10 times the upper limit of normal at admission (43.8%) or during hospitalization (41.7%). Older age, a history of cardiovascular disease, and higher d -dimer levels were potential risk factors for elevated TnI levels in patients with SFTS. CONCLUSIONS: Elevated TnI levels were prevalent among patients with SFTS and were strongly associated with an increased risk of mortality.

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.

Fibrinogen-to-prealbumin and C-reactive protein-to-prealbumin ratios as prognostic indicators in severe fever with thrombocytopenia syndrome.

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

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.

Effect of fasting plasma glucose level in severe fever and thrombocytopenia syndrome patients without diabetes.

Hyperglycemia is correlated with worse in-hospital outcomes in acute infectious diseases such as coronavirus disease 2019 (COVID-19) and severe fever with thrombocytopenia syndrome (SFTS). This study assessed the relationship between fasting plasma glucose (FPG) levels and in-hospital mortality, disease type, and secondary infections among individuals with SFTS without preexisting diabetes. The clinical data and laboratory results upon admission of 560 patients with SFTS without preexisting diabetes meeting the inclusion criteria at Wuhan Union Hospital were collected. FPG levels in surviving patients with SFTS subjects were significantly lower than those in patients with SFTS who had died (P<0.0001). In multivariate Cox regression, high FPG level (≥11.1 mmol/L) was a risk factor independently associated with the in-hospital death of patients with SFTS without preexisting diabetes. Similarly, the FPG levels in general patients with SFTS were significantly lower than those in patients with severe SFTS (P<0.0001). Multivariate logistic regression identified high FPG level (7.0-11.1 mmol/L) as a risk factor independently associated with SFTS severity. While FPG levels were comparable between patients with SFTS with and without secondary infection (P = 0.5521), logistic regression analysis revealed that high FPG levels were not a risk factor for secondary infection in patients with SFTS without preexisting diabetes. High FPG level on admission was an independent predictor of in-hospital death and severe disease in individuals with SFTS without preexisting diabetes. FPG screening upon admission and glycemic control are effective methods for improving the prognosis of patients with SFTS.

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.

Suspected Transmission of Severe Fever with Thrombocytopenia Syndrome Virus from a Cat to a Veterinarian by a Single Contact: A Case Report.

A 67-year-old male veterinarian presented with fatigue, anorexia, and diarrhea. Although there were no tick bite marks, we suspected severe fever with thrombocytopenia syndrome (SFTS) due to bicytopenia, mild disturbance of consciousness, and a history of outdoor activities. Thus, we started immunoglobulin therapy immediately. A serum reverse transcription-polymerase chain reaction (RT-PCR) test for SFTS virus (SFTSV) was positive. The patient had treated a cat with thrombocytopenia 10 days prior to admission. The cat's serum SFTSV RT-PCR test result was positive, and the whole genome sequences of the patient's and cat's SFTSV were identical, suggesting the possibility of transmission from the cat to the patient. Other cases of direct cat-to-human SFTV transmission have been reported recently. Mucous membranes should be protected, including eye protection, in addition to standard precautions, when in contact with any cat with suspected SFTS.

IL-6 and IL-10 Levels, Rather Than Viral Load and Neutralizing Antibody Titers, Determine the Fate of Patients With Severe Fever With Thrombocytopenia Syndrome Virus Infection in South Korea.

Severe fever with thrombocytopenia syndrome (SFTS) is a new tick-borne viral disease, and most SFTS virus (SFTSV) infections occur via bites from the tick Haemaphysalis longicornis; however, SFTSV transmission can also occur through close contact with an infected patient. SFTS is characterized by acute high fever, thrombocytopenia, leukopenia, elevated serum hepatic enzyme levels, gastrointestinal symptoms, and multiorgan failure and has a 16.2 to 30% mortality rate. In this study, we found that age, dyspnea rates, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase, multiorgan dysfunction score (MODS), viral load, IL-6 levels, and IL-10 levels were higher in patients with fatal disease than in patients with nonfatal disease during the initial clinical course of SFTS. In addition, we found that IL-6 and IL-10 levels, rather than viral load and neutralizing antibody titers, in patients with an SFTSV infection strongly correlated with outcomes (for severe disease with an ultimate outcome of recovery or death).

Comparison of RT-PCR, RT-nested PCRs, and real-time PCR for diagnosis of severe fever with thrombocytopenia syndrome: a prospective study.

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.

Seroepidemiologic survey of emerging vector-borne infections in South Korean forest/field workers.

With global warming and lush forest change, vector-borne infections are expected to increase in the number and diversity of agents. Since the first report of severe fever with thrombocytopenia syndrome (SFTS) in 2013, the number of reported cases has increased annually in South Korea. However, although tick-borne encephalitis virus (TBEV) was detected from ticks and wild rodents, there is no human TBE case report in South Korea. This study aimed to determine the seroprevalence of TBEV and SFTS virus (SFTSV) among forest and field workers in South Korea. From January 2017 to August 2018, a total 583 sera were obtained from the forest and field workers in South Korea. IgG enzyme-linked immunosorbent assay (ELISA) and neutralization assay were conducted for TBEV, and indirect immunofluorescence assay (IFA) and neutralization assay were performed for SFTSV. Seroprevalence of TBEV was 0.9% (5/583) by IgG ELISA, and 0.3% (2/583) by neutralization assay. Neutralizing antibody against TBEV was detected in a forest worker in Jeju (1:113) and Hongcheon (1:10). Only 1 (0.2%) forest worker in Yeongju was seropositive for SFTSV by IFA (1:2,048) and neutralizing antibody was detected also. In conclusion, this study shows that it is necessary to raise the awareness of physicians about TBEV infection and to make efforts to survey and diagnose vector-borne diseases in South Korea.

Application of a decision tree model in the early identification of severe patients with severe fever with thrombocytopenia syndrome.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is a serious infectious disease with a fatality of up to 30%. To identify the severity of SFTS precisely and quickly is important in clinical practice. METHODS: From June to July 2020, 71 patients admitted to the Infectious Department of Joint Logistics Support Force No. 990 Hospital were enrolled in this study. The most frequently observed symptoms and laboratory parameters on admission were collected by investigating patients' electronic records. Decision trees were built to identify the severity of SFTS. Accuracy and Youden's index were calculated to evaluate the identification capacity of the models. RESULTS: Clinical characteristics, including body temperature (p = 0.011), the size of the lymphadenectasis (p = 0.021), and cough (p = 0.017), and neurologic symptoms, including lassitude (p<0.001), limb tremor (p<0.001), hypersomnia (p = 0.009), coma (p = 0.018) and dysphoria (p = 0.008), were significantly different between the mild and severe groups. As for laboratory parameters, PLT (p = 0.006), AST (p<0.001), LDH (p<0.001), and CK (p = 0.003) were significantly different between the mild and severe groups of SFTS patients. A decision tree based on laboratory parameters and one based on demographic and clinical characteristics were built. Comparing with the decision tree based on demographic and clinical characteristics, the decision tree based on laboratory parameters had a stronger prediction capacity because of its higher accuracy and Youden's index. CONCLUSION: Decision trees can be applied to predict the severity of SFTS.

Clinical effect and antiviral mechanism of T-705 in treating severe fever with thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging tick-borne virus with high fatality and an expanding endemic. Currently, effective anti-SFTSV intervention remains unavailable. Favipiravir (T-705) was recently reported to show in vitro and in animal model antiviral efficacy against SFTSV. Here, we conducted a single-blind, randomized controlled trial to assess the efficacy and safety of T-705 in treating SFTS (Chinese Clinical Trial Registry website, number ChiCTR1900023350). From May to August 2018, laboratory-confirmed SFTS patients were recruited from a designated hospital and randomly assigned to receive oral T-705 in combination with supportive care or supportive care only. Fatal outcome occurred in 9.5% (7/74) of T-705 treated patients and 18.3% (13/71) of controls (odds ratio, 0.466, 95% CI, 0.174-1.247). Cox regression showed a significant reduction in case fatality rate (CFR) with an adjusted hazard ratio of 0.366 (95% CI, 0.142-0.944). Among the low-viral load subgroup (RT-PCR cycle threshold ≥26), T-705 treatment significantly reduced CFR from 11.5 to 1.6% (P = 0.029), while no between-arm difference was observed in the high-viral load subgroup (RT-PCR cycle threshold <26). The T-705-treated group showed shorter viral clearance, lower incidence of hemorrhagic signs, and faster recovery of laboratory abnormities compared with the controls. The in vitro and animal experiments demonstrated that the antiviral efficacies of T-705 were proportionally induced by SFTSV mutation rates, particularly from two transition mutation types. The mutation analyses on T-705-treated serum samples disclosed a partially consistent mutagenesis pattern as those of the in vitro or animal experiments in reducing the SFTSV viral loads, further supporting the anti-SFTSV effect of T-705, especially for the low-viral loads.