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.

Severe fever with thrombocytopenia syndrome virus: a highly lethal bunyavirus.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel bunyavirus. Since 2007, SFTS disease has been reported in China with high fatality rate up to 30%, which drew high attention from Centre for Disease Control and Prevention and government. SFTSV is endemic in the centra l and eastern China, Korea and Japan. There also have been similar cases reported in Vietnam. The number of SFTSV infection cases has a steady growth in these years. As SFTSV could transmitted from person to person, it will expose the public to infectious risk. In 2018 annual review of the Blueprint list of priority diseases, World Health Organisation has listed SFTSV infection as prioritised diseases for research and development in emergency contexts. However, the pathogenesis of SFTSV remains largely unclear. Currently, there are no specific therapeutics or vaccines to combat infections of SFTSV. This review discusses recent findings of epidemiology, transmission pathway, pathogenesis and treatments of SFTS disease.

Clinical manifestations of death with severe fever and thrombocytopenia syndrome: A meta-analysis and systematic review.

Severe hemorrhagic fever disease is caused by severe fever with thrombocytopenia syndrome virus (SFTSV) infection, which belongs to the Phlebovirus genus in the Bunyaviridae family. A comprehensive literature search of PubMed, Web of Science, Embase, Cochrane Library, Chinese National Knowledge Infrastructure databases, Wan Fang Data, Sinomed Database, and VIP database was conducted for articles which have described the clinical manifestation of deceased patients. Data from selected studies were pooled by using STATA VERSION 15.0 software. Finally, 29 articles comprising 4717 laboratory-confirmed SFTSV cases were included in this analysis. We found there were significant differences between the two groups for fatigue, headache, underlying disease, vomiting, diarrhea, skin bleeding, neurological symptoms, arrhythmia, diffuse intravascular coagulation, and multiple organ failure. There were some significant differences between the fatal and nonfatal groups, and we need to pay more attention to the above symptoms to distinguish between fatal and nonfatal patients.

Clinical features of severe fever with thrombocytopenia syndrome and analysis of risk factors for mortality.

BACKGROUND: To understand the clinical characteristics of and explore the risk factors for mortality in patients with severe fever with thrombocytopenia syndrome (SFTS). METHODS: Data from SFTS patients diagnosed by laboratory examination at Chaohu Hospital affiliated with Anhui Medical University from June 2017 to January 2021 were retrospectively analysed. According to the clinical results, all confirmed patients were divided into the surviving group (80 patients) and non-surviving group (20 patients). The two groups were compared in terms of general characteristics, clinical symptoms and signs, laboratory indicators and other aspects. The independent risk factors for mortality in SFTS patients were analysed by multivariate binary logistic regression. RESULTS: Univariate analysis showed a significant difference in age and the incidence of consciousness disturbance, respiratory failure, haemorrhagic manifestations, renal dysfunction, shock, aspartate aminotransferase (AST) ≥400 U/L, creatine kinase (CK)≥1000 U/L, creatine kinase isoenzymes (CK-MB) ≥100 U/L, lactate dehydrogenase (LDH) ≥1000 U/L, serum creatinine ≥100 mmol/L, blood urea nitrogen ≥7.5 mmol/L and C-reactive protein ≥8 mg/L between the two groups (P < 0.05). CONCLUSIONS: Consciousness disorder, haemorrhagic manifestations, renal dysfunction, AST ≥ 400 U/L, and LDH ≥ 1000 U/L are independent risk factors for mortality in SFTS patients and merit close attention in clinical treatment to avoid fatal consequences.

One-year mortality and morbidities of severe fever with thrombocytopenia syndrome compared with other diseases: A nationwide cohort study in South Korea.

BACKGROUND: The long-term mortality and morbidity of patients with severe fever with thrombocytopenia syndrome (SFTS) remain unclear. METHODS: This retrospective cohort study was conducted using the National Health Insurance Service dataset on hospitalized patients with SFTS aged ≥20 years between 2016 and 2021 (n = 1,217). Each SFTS case was matched with three controls hospitalized for non-SFTS-related diseases using propensity score matching. The all-cause mortality of patients with SFTS was evaluated during the one-year follow-up and compared with that of controls. Post-discharge events were investigated to determine the effects of SFTS on post-acute sequelae. RESULTS: Finally, 1,105 patients with SFTS and 3,315 controls were included. Patients with SFTS had a higher risk of death during the one-year follow-up than that of controls (hazard ratio [HR], 2·26; 95% confidence interval [CI], 1·82-2·81). Thirty-day mortality was significantly higher in the SFTS group (HR, 3·99; 95% CI, 3·07-5·19) than in the control group. An increased risk of death after 31-365 days was observed among controls, though this difference was significant only among patients in their 80s (HR, 0·18; 95% CI, 0·06-0·57). For post-discharge events, patients in the SFTS group exhibited a higher risk of readmission (HR, 1·17; 95% CI, 1·04-1·32) and emergency room visit (HR, 2·32; 95% CI, 1·96-2·76) than those in the control group. CONCLUSION: SFTS induces a higher risk of short-term mortality and post-acute sequelae in hospitalized patients during a one-year follow-up than non-SFTS-related diseases. Our results provide guidance for the management of SFTS.

A nomogram to predict mortality in patients with severe fever with thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is an acute infectious disease caused by a novel Bunyavirus infection with low population immunity and high mortality rate. Lacking specific therapies, the treatment measures vary with the severity of the disease, therefore, a case control study involved 394 SFTS patients was taken to determine risk factors for mortality. Comparative clinical data from the first 24 h after admission was collected through the electronic medical record system. Independent risk factors for death of SFTS were identified through univariate and multivariate binary logistic regression analyses. The results of the logistic regression were visualized using a nomogram which was created by downloading RMS package in the R program. In our study, four independent mortality risk factors were identified: advanced age(mean 70.45 ± 7.76 years), MODS, elevated APTT, and D-dimer. The AUC of the nomogram was 0.873 (0.832, 0.915), and the model passes the calibration test namely Unreliability test with P = 0.958, showing that the model's predictive ability is excellent. The nomogram to determine the risk of death in SFTS efficiently provide a basis for clinical decision-making for treatment.

Pancreatic Injury Is Associated with Poor Prognosis in Severe Fever with Thrombocytopenia Syndrome.

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

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.

Effect of tocilizumab plus corticosteroid on clinical outcome in patients hospitalized with severe fever with thrombocytopenia syndrome: A randomized clinical trial.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral hemorrhagic fever with high fatality rates. The blockade of pro-inflammatory cytokines presents a promising therapeutic strategy. METHODS: We conducted a randomized clinical trial at the 154th hospital, Xinyang, Henan Province. Eligible patients with severe SFTS disease were randomly assigned in a 1:2 ratio to receive either a single intravenous infusion of tocilizumab plus usual care; or usual care only. The primary outcome was the clinical status of death/survival at day 14, while secondary outcomes included improvement from baseline in liver and kidney damage and time required for hospital discharge. The efficacy of tocilizumab plus corticosteroid was compared to those receiving corticosteroid alone. The trial is registered with the Chinese Clinical Trial Registry website (ChiCTR2300076317). RESULTS: 63 eligible patients were assigned to the tocilizumab group and 126 to the control group. The addition of tocilizumab to usual care was associated with a reduced death rate (9.5%) compared to those received only usual care (23.0%), with an adjusted hazard ratio (aHR) of 0.37 (95% confidence interval [CI], 0.15 to 0.91, P = 0.029). Combination therapy of tocilizumab and corticosteroids was associated with a significantly reduced fatality (aHR, 0.21; 95% CI, 0.08 to 0.56; P = 0.002) compared to those receiving corticosteroids alone. CONCLUSIONS: A significant benefit of reducing fatality in severe SFTS patients was observed by using tocilizumab. A combined therapy of tocilizumab plus corticosteroids was recommended for the therapy of severe SFTS.

Association of liver function and prognosis in patients with severe fever with thrombocytopenia syndrome.

OBJECTIVES: Severe fever with thrombocytopenia syndrome (SFTS) is an epidemic emerging infectious disease with high mortality rate. We investigated the association between liver injury and clinical outcomes in patients with SFTS. METHODS: A total of 291 hospitalized SFTS patients were retrospectively included. Cox proportional hazards model was adopted to identify risk factors of fatal outcome and Kaplan-Meier curves were used to estimate cumulative risks. RESULTS: 60.1% of patients had liver injury at admission, and the median alanine transaminase, aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBil) levels were 76.4 U/L, 152.3 U/L, 69.8 U/L and 9.9 µmol/L, respectively. Compared to survivors, non-survivors had higher levels of AST (253.0 U/L vs. 131.1 U/L, P < 0.001) and ALP (86.2 U/L vs. 67.9 U/L, P = 0.006), higher proportion of elevated ALP (20.0% vs. 4.4%, P < 0.001) and liver injury (78.5% vs. 54.9%, P = 0.001) at admission. The presence of liver injury (HR 2.049, P = 0.033) at admission was an independent risk factor of fatal outcome. CONCLUSIONS: Liver injury was a common complication and was strongly associated with poor prognosis in SFTS patients. Liver function indicators should be closely monitored for 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.

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.

Viral and Immunologic Factors Associated with Fatal Outcome of Patients with Severe Fever with Thrombocytopenia Syndrome in Korea.

Significant progress has been made on the molecular biology of the severe fever with thrombopenia virus (SFTSV); however, many parts of the pathophysiological mechanisms of mortality in SFTS remain unclear. In this study, we investigated virologic and immunologic factors for fatal outcomes of patients with SFTS. We prospectively enrolled SFTS patients admitted from July 2015 to October 2020. Plasma samples were subjected to SFTSV RNA RT-PCR, multiplex microbead immunoassay for 17 cytokines, and IFA assay. A total of 44 SFTS patients were enrolled, including 37 (84.1%) survivors and 7 (15.9%) non-survivors. Non-survivors had a 2.5 times higher plasma SFTSV load than survivors at admission (p < 0.001), and the viral load in non-survivors increased progressively during hospitalization. In addition, non-survivors did not develop adequate anti-SFTSV IgG, whereas survivors exhibited anti-SFTSV IgG during hospitalization. IFN-α, IL-10, IP-10, IFN-γ, IL-6, IL-8, MCP-1, MIP-1α, and G-CSF were significantly elevated in non-survivors compared to survivors and did not revert to normal ranges during hospitalization (p < 0.05). Severe signs of inflammation such as a high plasma concentration of IFN-α, IL-10, IP-10, IFN-γ, IL-6, IL-8, MCP-1, MIP-1α, and G-CSF, poor viral control, and inadequate antibody response during the disease course were associated with mortality in SFTS patients.

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.

Clinical Progress and Risk Factors for Death from Severe Fever with Thrombocytopenia Syndrome: A Multihospital Retrospective Investigation in Anhui, China.

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

A multicenter non-randomized, uncontrolled single arm trial for evaluation of the efficacy and the safety of the treatment with favipiravir for patients with severe fever with thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is a bunyavirus infection with high mortality. Favipiravir has shown effectiveness in preventing and treating SFTS virus (SFTSV) infection in animal models. A multicenter non-randomized, uncontrolled single arm trial was conducted to collect data on the safety and the effectiveness of favipiravir in treatment of SFTS patients. All participants received favipiravir orally (first-day loading dose of 1800 mg twice a day followed by 800 mg twice a day for 7-14 days in total). SFTSV RT-PCR and biochemistry tests were performed at designated time points. Outcomes were 28-day mortality, clinical improvement, viral load evolution, and adverse events (AEs). Twenty-six patients were enrolled, of whom 23 were analyzed. Four of these 23 patients died of multi-organ failure within one week (28-day mortality rate: 17.3%). Oral favipiravir was well tolerated in the surviving patients. AEs (abnormal hepatic function and insomnia) occurred in about 20% of the patients. Clinical symptoms improved in all patients who survived from a median of day 2 to day10. SFTSV RNA levels in the patients who died were significantly higher than those in the survivors (p = 0.0029). No viral genomes were detectable in the surviving patients a median of 8 days after favipiravir administration. The 28-day mortality rate in this study was lower than those of the previous studies in Japan. The high frequency of hepatic dysfunction as an AE was observed. However, it was unclear whether this was merely a side effect of favipiravir, because liver disorders are commonly seen in SFTS patients. The results of this trial support the effectiveness of favipiravir for patients with 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).

Hazardous alcohol consumption and aging synergistically increase the risk of death in patients with severe fever with thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high case fatality rate (CFR). Alcohol consumption which impairs host immunity and contributes to tissue damage in a variety of organs may be a predisposing factor of fatal outcome in SFTS. We aimed to determine the role of alcohol consumption on the fatal outcome of SFTS. Patients with laboratory-diagnosed SFTS who were admitted to the Jinan Infectious Disease Hospital, Jinan, China, between January 2011 and November 2018 were evaluated. Demographic, clinical, and laboratory data were recorded. Alcohol consumption was evaluated. The association between a fatal outcome and each demographic, clinical, and laboratory variable with alcohol consumption was assessed. A total of 694 patients with SFTS were identified during the study period. The overall CFR was 20.9 % (95 % CI: 17.9 %-23.9 %). The CFR in non/light drinkers (0-98 g/week) and moderate/heavy drinkers (>98 g/week) was 18.3 % and 35.6 %, respectively (P < 0.001). In age>60 years patients, the overall CFR in moderate/heavy drinker groups were as high as 53.4 % (95 % CI:40.2 %-66.7 %). Comparing to the age≤60y and non/light drinkers, age>60y and moderate/heavy drinkers was associated with increased risk of death with an odds ratio (95 % CI) of 9.9 (5.1-19.1). The interaction between age>60 and alcohol consumption was a significant determinant for death in both genders (F=10.18, P = 0.001). The clinical manifestation, laboratory parameters, and organ injury were significantly extensive and severe in moderate and heavy drinkers. In conclusion, hazardous alcohol consumption and aging synergistically increase the risk of death in patients with SFTS. In SFTS endemic areas, it is important for older individuals to minimize the exposure risks and abstain from alcohol.

Correlation between thrombocytopenia and host response in severe fever with thrombocytopenia syndrome.

Severe Fever with Thrombocytopenia Syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus, SFTS virus (SFTSV), with fatal outcome developed in approximately 17% of the cases. Thrombocytopenia is a hallmark feature of SFTS, and associated with a higher risk of fatal outcome, however, the pathophysiological involvement of platelet in the clinical outcome of SFTS remained under-investigated. In the current study, by retrospectively analyzing 1538 confirmed SFTS patients, we observed that thrombocytopenia was associated with enhanced activation of the cytokine network and the vascular endothelium, also with a disturbed coagulation response. The platelet phenotypes were also extensively altered in the process of thrombocytopenia development of SFTS patients. More importantly, all these disturbed host responses were related to the severity of thrombocytopenia, thus were considered to play in a synergistic way to influence the disease outcome. Moreover, the clinical effect of platelet transfusion was assessed by comparing two groups of patients with or without receiving this therapy. As a result, we observed no therapy effect in altering frequencies of fatal outcome, clinical bleeding development, or dynamic change of platelet count during the hospitalization. It's suggested that platelet supplementation alone acted a minor role in improving disease outcome, therefore new therapeutic intervention to regulate host response should be proposed. The current results revealed some evidence of interrelationship between platelet count and clinical outcome of SFTS disease from the perspective of activation of the cytokine network, the vascular endothelium, and the coagulation/fibrinolysis system. These evaluations might help to attain a better understanding of the pathogenesis and therapy choice in SFTS.