Severe Fever With Thrombocytopenia Syndrome Patients Research Articles

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.

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.

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

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. 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). 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. 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.

Risk factors for invasive pulmonary aspergillosis in patients with severe fever with thrombocytopenia syndrome: A multicenter retrospective study.

Invasive pulmonary aspergillosis (IPA) is a life-threatening complication in patients with severe fever with thrombocytopenia syndrome (SFTS), yet SFTS-associated IPA (SAPA)'s risk factors remain undefined. A multicenter retrospective cohort study across Hubei and Anhui provinces (May 2013-September 2022) utilized least absolute shrinkage and selection operator (LASSO) regression for variable selection. Multivariable logistic regression identified independent predictors of SAPA, Cox regression highlighted mortality-related risk factors. Of the 1775 screened SFTS patients, 1650 were included, with 169 developing IPA, leading to a 42-day mortality rate of 26.6% among SAPA patients. Multivariable logistic regression revealed SAPA risk factors including advanced age, petechia, hemoptysis, tremor, low albumin levels, elongated activated partial thromboplastin time (APTT), intensive care unit (ICU) admission, glucocorticoid usage, intravenous immunoglobulin (IVIG) and prolonged hospital stays. Cox regression identified predictors of 42-day mortality, including ecchymosis at venipuncture sites, absence of ICU admission, elongated prothrombin time (PT), vasopressor and glucocorticoid use, non-antifungals. Nomograms constructed on these predictors registered concordance indexes of 0.855 (95% CI: 0.826-0.884) and 0.778 (95% CI: 0.702-0.854) for SAPA onset and 42-day mortality, respectively. Lower survival rates for SAPA patients treated with glucocorticoids (p < 0.001) and improved 14-day survival with antifungal therapy (p = 0.036). Improving IPA management in SFTS-endemic areas is crucial, with effective predictive tool.

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.

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. 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. 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). 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.

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

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. 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. 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. 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.

Clinical value of coagulation parameters in predicting the severity of severe fever with thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus infection with a high lethality rate. The purpose of this study was to investigate the changes in coagulation parameters in patients with SFTS, aiming to provide clinical evidence for early diagnosis, treatment, and disease analysis. A total of 40 patients with SFTS attended from April 1, 2020 to May 21, 2022 in Nanjing Drum Tower Hospital were selected and grouped according to the duration of the disease, mild and severe disease, cure and death, with 50 healthy physical examiners as controls, and the risk of severe and death disease was predicted using ROC curves. Comparison between the healthy, mild and severe groups revealed that PT, INR, APTT, TT, D-D and vWF levels were higher than those in the healthy control group, and FII, FIX, FX, FXI, FXII, PC and PS levels were lower than those in the healthy control group, the differences were statistically significant (p < 0.05). Comparing the results of SFTS patients with different course times, the results of Fib, FV, FVII, FVIII, FIX, FX, FXI were statistically significant (p < 0.05). Among the survived and deceased patients, the PT, INR, DD and PS results of the deceased patients were higher than those of the survived patients, and the FVIII, FIX, FXI, FXII and PC were lower than those of the survived patients. The area under the ROC curve showed that D-D had higher predictive ability for the risk of severe disease (AUROC 0.93, sensitivity and specificity at a Cut-off value of 1.50 mg/L were 90.0 and 86.5%, respectively) and the risk of death occurring (AUROC 0.84, sensitivity and specificity at a Cut-off value of 3.39 mg/L were 87.5 and 80.0%, respectively). The monitoring of the coagulation parameters in patients with SFTS is great significance for identifying the severity and death of the patient's condition, and it is of great clinical value to provide early attention, timely intervention and maximum reduction of the mortality rate for patients at risk of severe disease.

Adenosine Deaminase as a Potential Diagnostic and Prognostic Biomarker for Severe Fever with Thrombocytopenia Syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is a serious infectious disease caused by the Dabie bandavirus, with a high mortality rate. Currently, there are no effective vaccines or specific treatments for SFTS. Early diagnosis and accurate severity assessment are crucial. This study included 171 cases of SFTS, COVID-19, and hepatitis B virus (HBV) patients and healthy controls. We compared the serum adenosine deaminase (ADA) activity across these groups. The diagnostic and prognostic efficiency of serum ADA for SFTS was evaluated by using receiver operating characteristic (ROC) curve analysis. We also examined the correlation between serum ADA in SFTS patients and clinical lab parameters as well as serum cytokines. SFTS patients had significantly higher serum ADA activity than those of COVID-19, HBV patients, and healthy controls. Nonsurvivor SFTS patients had notably higher ADA than survivors. ROC analysis indicated ADA as an effective SFTS diagnostic and prognostic biomarker. ADA correlated with prognosis, viral load, APTT, PT, AST, ferritin, negatively with HDL-c and LDL-c, and positively with cytokines like IL-6, TNF-α, and IL-1β. Multiorgan failure patients showed significant ADA increase. Elevated serum ADA activity in SFTS patients is linked with disease severity and prognosis, showing potential as a diagnostic and prognostic biomarker for SFTS.

Inhibition of SFTSV replication in humanized mice by a subcutaneously administered anti-PD1 nanobody

Severe fever with thrombocytopenia syndrome (SFTS) is a life-threatening disease caused by a novel bunyavirus (SFTSV), mainly transmitted by ticks. With no effective therapies or vaccines available, understanding the disease’s mechanisms is crucial. Recent studies found increased expression of programmed cell death-1 (PD-1) on dysfunctional T cells in SFTS patients. However, the role of the PD-1/programmed cell death-ligand 1 (PD-L1) pathway in SFTS progression remains unclear. We investigated PD-1 blockade as a potential therapeutic strategy against SFTSV replication. Our study analyzed clinical samples and performed in vitro experiments, revealing elevated PD-1/PD-L1 expression in various immune cells following SFTSV infection. An anti-PD-1 nanobody, NbP45, effectively inhibited SFTSV infection in peripheral blood mononuclear cells (PBMCs), potentially achieved through the mitigation of apoptosis and the augmentation of T lymphocyte proliferation. Intriguingly, subcutaneous administration of NbP45 showed superior efficacy compared to a licensed anti-PD-1 antibody in an SFTSV-infected humanized mouse model. These findings highlight the involvement of the PD-1/PD-L1 pathway during acute SFTSV infection and suggest its potential as a host target for immunotherapy interventions against SFTSV infection.

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

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

Lethal severe fever with thrombocytopenia syndrome virus infection causes systemic germinal centre failure and massive T cell apoptosis in cats.

Severe fever with thrombocytopenia syndrome (SFTS) is a fatal viral disease characterized by high fever, thrombocytopenia, leukopenia, and multi-organ haemorrhage. Disruption of the humoral immune response and decreased lymphocyte numbers are thought to contribute to the disease severity. These findings have been obtained through the analysis of peripheral blood leukocytes in human patients, whereas analysis of lymph nodes has been limited. Thus, in this study, we characterized the germinal centre response and apoptosis in the lymph nodes of cats with fatal SFTS, because SFTS in cats well mimics the pathology of human SFTS. Lymph node tissue sections collected during necropsy from seven fatal SFTS patients and five non-SFTS cases were used for histopathological analysis. Additionally, lymph node tissue sections collected from cats with experimental infection of SFTS virus (SFTSV) were also analysed. In the lymphoid follicles of cats with SFTS, a drastic decrease in Bcl6- and Ki67-positive germinal centre B cells was observed. Together, the number of T cells in the follicles was also decreased in SFTS cases. In the paracortex, a marked increase in cleaved-caspase3 positivity was observed in T cells. These changes were independent of the number of local SFTS virus-positive cell. Furthermore, the analysis of cats with experimental SFTSV infection revealed that the intrafollicular Bcl6- and CD3-positive cell numbers in cats with low anti-SFTSV antibody production were significantly lower than those in cats with high anti-SFTSV antibody production. These results suggest that dysfunction of the humoral response in severe SFTS was caused by the loss of germinal centre formation and massive apoptosis of T cells in the lymph nodes due to systemically circulating viruses.

Cardiac injury in hospitalized patients with severe fever and thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS), an emerging infectious disease with a high fatality rate. Cardiac injury in SFTS patients is a major concern. This study aimed to evaluate the prevalence of cardiac injury and its association with mortality in hospitalized patients infected with novel Bunyavirus. Cardiac injury was defined as the presence of any of the following abnormalities: (1) blood levels of cardiac biomarkers (creatine kinase-MB, troponin-I, B-type natriuretic peptide or N-terminal pro-B-type natriuretic peptide); (2) new abnormalities in electrocardiography. The 203 SFTS patients were included in the final analysis. The proportion of SFTS patients developing cardiac injury during hospitalization was 71.4% (145/203). Compared with the uninjured group, the cardiac injury group had the severity of cardiac injury was underscored by higher median hospital costs (31420 vs. 12911, p < 0.001), higher proportion of intensive care units admissions (13.1% vs. 3.4%, p = 0.041), and higher hospital mortality rate (33.8% vs. 6.9%, p < 0.001). Multivariable-adjusted Cox proportional hazards regression analysis showed that cardiac injury was associated with higher mortality during hospitalization (hazards ratio, 7.349; 95% CI: 2.352-22.960). Cardiac injury is common among hospitalized SFTS patients, and it is associated with higher risk of mortality.

Changes in Cytokine Levels in Patients with Severe Fever with Thrombocytopenia Syndrome Virus.

To characterize the cytokine profile of patients with severe fever with thrombocytopenia syndrome (SFTS) in relation to disease severity. 60 laboratory-confirmed SFTS patients and 12 healthy individuals from multi-centers in Shandong Province of China were included, and all patients were divided into fatal patients (9) and recovered patients (51) due to their final outcomes. Multiplex-microbead immunoassays were conducted to estimate levels of 27 cytokines in the sera of patients and controls. The results showed that levels of IL-2, IL-4, IL-6, IL-7, IL-8, IL-15, IL-1RA, G-CSF, GM-CSF, IFN-γ, TNF-α, basic FGF, PDGF-BB, RANTES, IP-10, MIP-1α, MIP-1β, MCP-1, and Eotaxin differed significantly among the SFTS fatal patients, recovered patients, and the healthy controls (all p<0.05). Compared to the healthy controls, the fatal patients and recovered patients had reduced levels of IL-2, IL-4, IL-7, PDGF-BB, RANTES, and Eotaxin, while the levels of PDGF-BB and RANTES were significantly lower in fatal patients compared to recovered patients. The increasing levels of IL-6, IL-8, IL-15, IL-1RA, G-CSF, GM-CSF, IFN-γ, TNF-α, basic FGF, IP-10, MIP-1α, MIP-1β, and MCP-1 were observed in fatal patients (all p<0.05), and the levels of IL-6, IP-10, MIP-1α, and MCP-1 were significantly higher than other two groups. The Spearman correlation analysis indicated a positive correlation between platelet count and PDGF-BB levels (p<0.05), while the white blood cell count had a negative correlation with MIP-1 level (p<0.05). The research exhibited that the SFTS virus (SFTSV) caused an atypical manifestation of cytokines. The levels of IL-6, IP-10, MIP-1α, and MCP-1 had been observed a positive association with the severity of the illness.

The pathogenic and clinical characteristics of severe fever with thrombocytopenia syndrome patients with co-infections.

The study aimed to comprehensively describe and evaluate the pathogenic and clinical characteristics of severe fever with thrombocytopenia syndrome (SFTS) patients with co-infections. We retrospectively collected clinical data and laboratory indicators of the SFTS patients at Tongji Hospital from October 2021 to July 2023. A total of 157 patients with SFTS virus (SFTSV) infection were involved in the analysis, including 43 co-infection and 114 non-co-infection patients. The pathogens responsible for co-infection were primarily isolated from respiratory specimens. Fungal infections, primarily Aspergillus fumigatus, were observed in 22 cases. Bacterial infections, with Klebsiella pneumoniae and carbapenem-resistant Acinetobacter baumannii as the main pathogens, were identified in 20 cases. SFTS patients with co-infection exhibited higher mortality (P=0.011) compared to non-co-infection patients. Among SFTS patients co-infected with both bacteria and fungi (8 cases) or specific drug-resistant strains (11 cases), the mortality rate was as high as 70% (14/19). In comparison with the non-co-infection group, SFTS patients with co-infection displayed significant alteration in inflammatory markers, coagulation function, and liver function indicators. The mortality rate of SFTS patients with co-infection is relatively high, underscoring the need for enhanced monitoring and timely, appropriate treatment to minimize the mortality rate.

The change of Siglec-9 expression in peripheral blood NK cells of SFTS patients can affect the function of NK cells

ObjectivesTo investigate the changes and mechanism of Siglec-9 on NK cells in peripheral blood of patients with severe fever with thrombocytopenia syndrome (SFTS). MethodsFirst, we used single-cell RNA sequencing to analyze the frequency of NK cells in Peripheral Blood Mononuclear Cells (PBMCs) of SFTS patients and healthy controls (HCs), as well as the differences in the genes on NK cells. Secondly, we analyzed the expression of Siglec-9 and other receptors on NK cells by flow cytometry. Thirdly, we analyzed the correlation between Siglec-9 on NK cells and DBV viral load in plasma. ResultsCompared with HCs, the frequency of NK cells in peripheral blood of SFTS patients was significantly decreased, and the activating receptors on NK cells were reduced. The expression of Siglec-9 on NK cells and the frequency of Siglec-9+NK cells decreased significantly in SFTS patients. The expression of Siglec-9 on CD16+CD56dim NK cells was negatively correlated with DBV viral load. In addition, Siglec-9+NK cells expressed higher levels of activating receptors and exhibited stronger effector functions than Siglec-9−NK cells. ConclusionsThe decreased expression of Siglec-9 on NK cells predicts NK cell dysfunction in SFTS patients, suggesting that Siglec-9 may be a potential marker for functional NK cell subsets in SFTS patients.

Kinetics and prognostic significance of laboratory markers in patients with severe fever with thrombocytopenia syndrome: insight from a comprehensive analysis.

Severe Fever with Thrombocytopenia Syndrome (SFTS) is an emerging infectious disease with significant mortality. Identifying prognostic factors that influence patient outcomes is crucial for effective clinical management. In this study, we assessed the dynamic changes of laboratory markers and their association with outcomes in 93 SFTS patients. We found that age and hypertension were significantly associated with poor outcomes in SFTS patients. The deceased group exhibited lower platelet counts, elevated liver and kidney function markers, coagulation profiles, inflammatory markers, and cytokines compared to the survival group. Kinetic analysis showed that these markers gradually normalized in the survival group, while they remained persistently abnormal in the deceased group. Furthermore, hypertension, elevated AST, PCT, and IL-10 were identified as independent risk factors for predicting poor prognosis of SFTS patients. These findings provide valuable insights into the prognostic significance of laboratory markers and highlight the importance of early identification of high-risk SFTS patients.

Clinical efficacy of immunoglobulin on the treatment of severe fever with thrombocytopenia syndrome: a retrospective cohort study

Optimal treatment strategy for severe fever with thrombocytopenia syndrome (SFTS) remained unknown. We aimed to evaluate the efficacy of intravenous immunoglobulin (IVIG) on SFTS. A retrospective cohort study was conducted based on medical records of the laboratory-confirmed SFTS patients hospitalized during 2010-2020 in the 154th hospital, China. A 1:1 propensity score matching with age, sex, the interval from symptom onset to admission, presence of chronic viral hepatitis, diabetes and disease severity was performed between Non-IVIG group (supportive therapy) and IVIG group (IVIG plus supportive therapy). The matching variables were adjusted to compare the case fatality rates (CFRs), viral load and laboratory parameters between the two groups. Risk ratio (RR) and 95% confidence interval (CI) were reported. Totally 2219 SFTS patients were recruited. CFRs were significantly higher in 1051 patients in IVIG group than 1168 patients in Non-IVIG group (19.0% vs. 4.6%, RR=4.30, 95% CI 3.12-5.93). The difference remained significant after matching (17.2% vs. 5.1%, RR=4.02, 95% CI 2.71-5.97). The CFR of IVIG group was significantly higher in all age groups, two IVIG therapy delay groups and two therapy duration groups compared to that of Non-IVIG group (all P<0.05). IVIG therapy was related to higher viral loads and reduced counts of lymphocytes, T cells, CD4+ T cells and natural killer cells in the blood (all P<0.05). No obvious efficacy of IVIG in saving life or improving outcome of SFTS was observed. Caution is needed for clinical physicians to continue prescribing IVIG for SFTS patients. Natural Science Foundation of China.

Self-assembling Gn head ferritin nanoparticle vaccine provides full protection from lethal challenge of Dabie bandavirus in aged ferrets.

Dabie bandavirus (DBV) is an emerging tick-borne virus that causes severe fever with thrombocytopenia syndrome (SFTS) in infected patients. Human SFTS symptoms progress from fever, fatigue, and muscle pain to the depletion of white blood cells and platelets with fatality rates up to 30%. The recent spread of its vector tick to over 20 states in the United States increases the potential for outbreaks of the SFTS beyond the East Asia. Thus, the development of vaccine to control this rapidly emerging virus is a high priority. In this study, we applied self-assembling ferritin (FT) nanoparticle to enhance the immunogenicity of DBV Gn head domain (GnH) as a vaccine target. Mice immunized with the GnH-FT nanoparticle vaccine induced potent antibody responses and cellular immunity. Immunized aged ferrets were fully protected from the lethal challenge of DBV. Our study describes the GnH-FT nanoparticle vaccine candidate that provides protective immunity against the emerging DBV infection.

Rapid and portable bunyavirus SFTSV RNA testing utilizing catalytic hairpin assembly coupled with lateral flow immunoassay.

Severe fever with thrombocytopenia syndrome (SFTS) is a prevalent, life-threatening, emergent infectious disease. Currently, reverse transcription-polymerase chain reaction is the gold standard for diagnosing SFTS virus (SFTSV) infection, which requires sophisticated equipment and professional personnel that are frequently unavailable in most SFTS endemic rural areas. Here, we reported a simple, rapid nucleic acid amplification system that combined the catalytic hairpin assembly (CHA) with a lateral flow immunoassay (LFIA) strip-based detection method for SFTSV detection. The detection of SFTSV RNA could be realized by generation of H1-H2 hybrid duplexes labeled with biotin and digoxin, which subsequently added to the LFIA test strips containing streptavidin conjugated with Alexa Fluor 647 as well as anti-digoxin antibodies. Our CHA-based LFIA assay offered high amplification efficiency and specificity with a detection limit of 1 aM. Crucially, this method enabled stable detection of 500 copies/mL of SFTSV within 30 min using clinical serum samples. Therefore, our CHA-based LFIA approach provided a potential useful tool to facilitate early and precise diagnosis of SFTS patients in poorly resourced SFTS endemic areas.IMPORTANCESevere fever with thrombocytopenia syndrome (SFTS) is an emerging and potentially fatal infectious disease prevalent in China. Here we report a simple, rapid nucleic acid amplification system, the catalytic hairpin assembly (CHA) in conjunction with a lateral flow immunoassay (LFIA) strip-based detection method for SFTS virus detection, which demonstrated high amplification efficiency and specificity with limit of detection of 1 aM. Most importantly, we also validate our CHA-based LFIA assay using the clinical serum samples, which was fully compatible with reverse transcription-PCR results. Therefore, our strategy provides a potential useful tool to facilitate early and precise diagnosis of SFTS patients especially in poorly resourced SFTS endemic areas.

Temporal Dynamics of Serum Perforin and Granzymes in Three Different Clinical Stages of Virus-Induced Severe Fever with Thrombocytopenia Syndrome.

Virus-induced severe fever with thrombocytopenia syndrome (SFTS) induces a cell-mediated immune response that likely contributes to virus control in SFTS patients. To identify the temporal changes of the cell-mediated immune response, we investigated the changes in serum levels of perforin and granzymes at early periods after illness onset in SFTS patients. We analyzed 32 SFTS patients and compared the temporal patterns of serum perforin and granzyme A and B to that of 20 healthy control adults using the Mann-Whitney U test. Compared with healthy controls, the mean level of perforin was significantly reduced by 81% (P < 0.01) during the first week after illness onset, whereas granzyme B significantly increased by 4.6-fold (P = 0.02) in the first week after illness onset and decreased to normal afterward. During the study period, there was no significant difference in serum perforin and granzyme. These findings indicate that perforin and granzyme B in serum can be considered possible serologic markers that reflect the clinical stage of SFTS. Additional study is warranted for tracking circulating perforin and granzyme in different ages and for an extended period after illness onset.