Severe Fever With Thrombocytopenia Syndrome Research Articles

Transcriptome Profiles Characteristics of the Peripheral Immune in Patients with Severe Fever with Thrombocytopenia Syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is an acute viral infection disease with a high mortality, but there are no specific effective drugs or vaccines available for use. To develop effective treatment methods, more basic researches are urgently needed to elucidate the response mechanisms of patients. Here, we conducted the transcriptomic analysis of peripheral immunity in 14 SFTS patients, ranging from moderate infection to severe and fatal disease. The results showed orderly cytokine signaling pathway modulation in moderate patients, cellular immunosuppression in severe patients, and significant dysregulation of the inflammatory response and coagulation dysfunction characteristic of deceased patients. In addition, WGCNA further showed a significant positive correlation between fatal outcomes and B cell and immunoglobulin mediated immune function modules, as well as a significant negative correlation with coagulation function modules. Overall, our research findings systematically observed potential immune mechanisms underlying clinical symptom heterogeneity and noteworthily revealed multiple signaling pathways leading to coagulation dysfunction in fatal outcomes, not just related to decreased platelet count, which can further elucidate the interaction between viruses and hosts and contribute to clinical treatment.

Two amino acid pairs in the Gc Glycoprotein of Severe Fever with Thrombocytopenia Syndrome Virus responsible for the enhanced virulence

Severe fever with thrombocytopenia syndrome (SFTS) is a significant public health concern, with a high fatality rate in humans and cats. In this study, we explored the genetic determinants that contribute to the different virulence of SFTS virus (SFTSV) based on Tk-F123 and Ng-F264 strains isolated from cats. Tk-F123 was 100% lethal in type I interferon receptor-knockout mice, whereas Ng-F264 exhibited no fatality. We identified a pair of amino acid residues in the Gc protein, glycine and serine, at residues 581 and 934, respectively, derived from Tk-F123, leading to a fatal infection. Those in Ng-F264 were arginine and asparagine. These results suggest that this pair of residues affects the Gc protein function and regulates SFTSV virulence. Our findings provide useful clues for the elucidation of viral pathogenicity and the development of effective live-attenuated vaccines and antiviral strategies.

Intravenous immunoglobulin‑based adjuvant therapy for severe fever with thrombocytopenia syndrome: A single‑center retrospective cohort study.

Intravenous immunoglobulin (IVIG) is frequently administered to patients with severe fever with thrombocytopenia syndrome (SFTS), particularly those with severe manifestations, although its efficacy remains controversial. The study retrospectively analyzed the effects of IVIG administration on SFTS patients in both mild and severe groups. The primary outcome measure was 28-day mortality. Inverse probability of treatment weighting (IPTW) with propensity score was used to account for baseline confounders. A total of SFTS patients with complete data enrolled from January 1, 2015, to August 1, 2023. Death at 28 days occurred for 68 (17.5%) patients. By unadjusted analysis, no difference was observed for 28-day mortality between the IVIG and non-IVIG groups in both the mild and severe groups. Similar results were found by propensity score matching and by IPTW analysis. Although IVIG is frequently used as adjuvant therapy for severe SFTS patients, no significant association was observed between IVIG treatment and reduced mortality in this patient population.

Multiple Genotypes and Reassortants of Severe Fever With Thrombocytopenia Syndrome Virus Co-Circulating in Hangzhou in Southeastern China, 2013-2023.

Severe fever with thrombocytopenia syndrome (SFTS), a tick-borne infectious disease caused by the SFTS virus (SFTSV), is becoming a significant public health threat due to its high mortality rate. Knowledge of SFTSV in southeastern coastal China is limited. The whole genomes of 66 SFTSV strains collected from 2013 to 2023 in Hangzhou, a coastal city in China, were amplified and sequenced to elucidate the geography-related genetic and pathogenic diversity. Hangzhou SFTSVs could be classified into five pure genotype groups (A, B-2, D, E, and F); genotype A was dominant, and genotype E was significantly associated with SFTS fatality. An unclassified sublineage of the L segment was proposed as a novel B-4 subgenotype. Seven types of genetic reassortants (abbreviated as B-3B-3B-1, CCA, B-2AB-2, B-2CB-2, DFD, B-4FF, and B-4B-2B-1 for the L, M, and S segments) were identified, including three novel forms. Six recombination events and ten amino acid substitutions were identified in the Hangzhou viruses. Collectively, our results demonstrated that all known SFTSV genotypes co-circulated in Hangzhou, leading to a gradual increase in genetic diversity and the generation of novel reassortants. Increased surveillance is urgently needed in Hangzhou, a critical region for SFTSV genetic exchange.

Adenovirus type 5-expressing Gn induces better protective immunity than Gc against SFTSV infection in mice.

Severe fever with thrombocytopenia syndrome (SFTS) is caused by the SFTS virus (SFTSV) with high morbidity and mortality. The major immunodominant region of SFTSV surface glycoprotein (G) remains unclear. In this study, we constructed adenovirus type 5 (Ad5) vectored vaccine candidates expressing different regions of SFTSV G (Gn, Gc and Gn-Gc) and evaluated their immunogenicity and protective efficacy in mice. In wild-type mice, compared with Ad5-Gc or Ad5-Gn-Gc, Ad5-Gn recruited/activated more dendritic cells and B cells in lymph nodes or peripheral blood, causing Th1-/Th2-mediated responses in splenocytes and triggered a greater level of SFTSV-neutralizing antibodies. In IFNAR Ab-treated mice, immunization of Ad5-Gn exhibited better protection against SFTSV challenge than Ad5-Gc or Ad5-Gn-Gc. Furthermore, passive immunization revealed complete protective immunity of Gn-specific serum rather than Gc. Collectively, our data demonstrated that Gn is the immunodominant fragment of SFTSV G and could be a potential candidate for SFTSV vaccine development.

Efficacy of CP-COV03 (a niclosamide-based inorganic nanohybrid product) against severe fever with thrombocytopenia syndrome virus in an in vitro model.

Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infectious disease caused by the SFTS virus (SFTSV). CP-COV03 is a novel antiviral candidate that significantly enhanced the bioavailability of niclosamide through inorganic-based drug delivery technology. The active pharmaceutical ingredient of CP-COV03, niclosamide, has been previously shown to possess broad-spectrum antiviral activity against over 30 different viruses in the in vitro tests. The aim of this study is to confirm the antiviral activity of CP-COV03 against the SFTSV in an in vitro model. Vero cells and SFTS viral stock NCCP43270, a 2015 Gangwon Province isolate, were used to obtain the 50% tissue culture infective dose of the virus. Vero cells seeded in 96-well plates were infected with SFTSV for 1 h. SFTSV-infected cells were treated with CP-COV03 at various concentrations of 0.1-100 μM and incubated for 7 days. On the seventh day of the culture, the cytopathic effect (CPE) of SFTSV was checked by microscopy and the cell viability was checked by using Cell Counting Kit-8 assay. The CPE reduced as the CP-COV03 concentration increased. The 50% inhibitory concentration (IC50) range of CP-COV03 was below 0.125 µM, as determined from the viral titers of culture supernatants collected on the third day posttreatment of CP-COV03. The plaque reduction assay showed that the IC50 of CP-COV03 was 1.893 µM, as determined from the percentage reduction of plaque counts for each drug concentration on the second day posttreatment with CP-COV03. This study suggests that CP-COV03 could be used as a potential antiviral agent for SFTS.IMPORTANCEWe demonstrated a concentration-dependent response and identified low a IC50 of CP-COV03. This result is comparable to other antiviral drugs used against viruses like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We believe that our study makes a significant contribution to the literature as our findings suggest that CP-COV03 may serve as a potential treatment for SFTS, highlighting its importance in the field of antiviral research.

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

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

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

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). A retrospective cohort study. Union Hospital in Wuhan, China. A total of 580 patients with SFTS, observed between May 2014 and December 2021, were included in the final analysis. None. 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. Elevated TnI levels were prevalent among patients with SFTS and were strongly associated with an increased risk of mortality.

Severe fever with thrombocytopenia syndrome (SFTS) in Thailand: using a one health approach to respond to novel zoonosis and its implications in clinical practice

Severe fever with thrombocytopenia syndrome (SFTS), a tick-borne disease caused by Dabie bandavirus (SFTSV) is an emerging infectious disease of substantial concern in East Asia. In 2019, Ongkittikul S et al. reported the first case of SFTS in Thailand. Our report describes a One Health investigation of SFTS zoonosis examining the index case and suspected animal reservoirs using real-time RT-PCR and immunoassays. We add to the report on the first confirmed case of SFTSV infection in a human in Thailand by conducting a limited but informative One Health surveillance study. Dogs and cats tested positive for SFTSV antibody using IgG ELISA. We conclude that domestic dogs and cats might serve as potential reservoirs for SFTSV spread due to their closer proximity to the index case than other non-domestic animals. Notably, we did not detect SFTSV in synanthropic cats or dogs—nor did we detect SFTSV in Rhipicephalus sanguineus ticks—using RT-PCR. We propose that One Health investigations coupling genomic and serologic assays in response to new SFTS cases could play a pivotal role in preventing and managing SFTS among humans and animals in East Asia. As such, we are establishing a collaborative response to SFTS in Thailand through human outbreak investigations that align with principles of One Health, through environmental surveys and animal RT-PCR and immunoassays. Our investigation highlights the importance of coupling RT-PCR with seroprevalence assays as principal elements of One Health surveillance for SFTS in order to shed light on potential animal reservoirs and track emerging zoonosis.

Enhancing Sensitivity in Detecting Severe Fever With Thrombocytopenia Syndrome Virus: Development of a Reverse Transcription-Droplet Digital Polymerase Chain Reaction.

Severe fever with thrombocytopenia syndrome (SFTS) is a highly fatal disease. Droplet digital polymerase chain reaction (ddPCR) presents unparalleled sensitivity and enables absolute quantification of viral load. In this prospective study, we enrolled 111 patients with SFTS and collected 259 continuous samples. Our findings unveil a robust reverse transcription (RT)-ddPCR method for SFTS with a limit of detection of 2.46 copies/µL (95% CI, 1.50-11.05), surpassing the sensitivity of RT-quantitative polymerase chain reaction at 103.29 copies/µL (95% CI, 79.69-216.35). Longitudinal cohort analysis revealed significantly higher RT-ddPCR detection rates at days 10 to 11, 13 to 14, and ≥15 of the disease course as compared with RT-quantitative polymerase chain reaction (P < .05). Positive RT-ddPCR results were associated with declined platelet and elevated aspartate aminotransferase and lactate dehydrogenase on the same day vs negative RT-ddPCR samples. RT-ddPCR exhibits commendable diagnostic efficacy in SFTS, and it remains detectable in blood samples from patients with an extended disease course. Furthermore, RT-ddPCR correlates with clinical laboratory tests, furnishing valuable reference data for clinical diagnosis.

Impact of Glucocorticoid Therapy on 28-Day Mortality in Patients Having Severe Fever with Thrombocytopenia Syndrome in an Intensive Care Unit: A Retrospective Analysis.

The high mortality rate associated with the critical stages of severe fever with thrombocytopenia syndrome (SFTS) does not have effective treatment. We aimed to evaluate the 28-day mortality and potential impact of glucocorticoid therapy in these patients. This retrospective observational study included participants from the intensive care unit between July 2019 and April 2023. The participants were categorized into glucocorticoid (GC) and non-GC groups. Propensity score matching (PSM) was employed to ensure comparability between groups. We used Cox proportional hazard models to examine mortality risk associated with GC use, Kaplan-Meier survival analyses for overall survival, stratified Cox proportional hazard models for subgroup analyses, and likelihood ratio tests to examine interactions between subgroups. Of 218 patients with SFTS (median age, 71 years; male, 49.1%), 61.9% required mechanical ventilation, 58.3% received GC treatment, and the 28-day mortality rate was 61.5%. After PSM, there were 58 patients in each group; post-PSM analysis revealed improved 28-day mortality rates with GC treatment, particularly for patients with Glasgow coma scale (GCS) score <13 (hazard ratio [HR], 95% confidence interval [CI] for GCS score: 9-12: 0.39, 0.17-0.88, p=0.024 and for GCS score: 3-8: 0.09, 0.02-0.35, p=0.001); lactate levels >2mmol/L (0.35, 0.15-0.83, p=0.017); and norepinephrine usage (0.26, 0.13-0.49, p<0.001). Combining antiviral (0.41, 0.22-0.78, p=0.006) or immunoglobulin therapy (0.22, 0.1-0.51, p<0.001) with GC treatment significantly decreased the 28-day mortality rates, compared with GC monotherapy. Using GCs reduced the high 28-day mortality rate in the patients, especially with low GCS score, high lactate levels, norepinephrine intake, and on antiviral or immunoglobulin therapy.

Molecular mechanism and structure-guided humanization of a broadly neutralizing antibody against SFTSV.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel tick-borne bunyavirus that causes severe fever with thrombocytopenia syndrome (SFTS), with a high mortality rate of up to 30%. The envelope glycoproteins of SFTSV, glycoprotein N (Gn) and glycoprotein C (Gc), facilitate the recognition of host receptors and the process of membrane fusion, allowing the virus to enter host cells. We previously reported a monoclonal antibody, mAb 40C10, capable of neutralizing different genotypes of SFTSV and SFTSV-related viruses. However, the specific neutralization mechanism is poorly understood. In this study, we elucidated the high-resolution structure of the SFTSV Gn head domain in complex with mAb 40C10, confirming that the binding epitope in the domain I region of SFTSV Gn, and it represented that a novel binding epitope of SFTSV Gn was identified. Through in-depth structural and sequence analyses, we found that the binding sites of mAb 40C10 are relatively conserved among different genotypes of SFTSV and SFTSV-related Heartland virus and Guertu virus, elucidating the molecular mechanism underlying the broad-spectrum neutralizing activity of mAb 40C10. Furthermore, we humanized of mAb 40C10, which is originally of murine origin, to reduce its immunogenicity. The resulting nine humanized antibodies maintained potent affinity and neutralizing activity. One of the humanized antibodies exhibited neutralizing activity at picomolar IC50 values and demonstrated effective therapeutic and protective effects in a mouse infection model. These findings provide a novel target for the future development of SFTSV vaccines or drugs and establish a foundation for the research and development of antibody therapeutics for clinical applications.

Identification of severe fever with thrombocytopenia syndrome virus isolates in the northwest of Hubei Province, China

Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne viral disease that is increasingly affecting human being worldwide. The clinical manifestations and mortality rates of SFTS can vary depending on the geographic region and the specific genotype of the SFTS virus (SFTSV). From July 2022 to August 2023, we collected serum samples from 83 patients with suspected SFTSV infection in the northwest of Hubei Province, China. From which, 13 patients tested positive for SFTSV. Phylogenetic analysis of the SFTSV L, M, and S gene segments was performed using the maximum likelihood method to determine the genetic diversity of the isolates. At least 2 SFTSV genotypes (A and F) were identified in the northwest of Hubei Province. The clinical manifestations and laboratory findings on the first day of admission were investigated. Results showed that bleeding and disturbance of consciousness, and significant elevated AST and APTT, are valuable for assessing the prognosis for SFTS patients. This study disclosed the genomic sequences and genotypes of SFTSV spreading in the northwest of Hubei Province for the first time, providing information of genetically etiology for SFTS in the local district. Furthermore, certain symptoms and/or laboratory findings may indicate adverse clinical outcomes, highlighting the importance of identifying the symptoms and monitoring specific laboratory markers. Future research is needed to investigate the threshold values of these markers and to closely observe the indicative symptoms in order to early identify and timely management of critically ill patients within clinical settings.

Development and Comparison of Time Series Models in Predicting Severe Fever with Thrombocytopenia Syndrome Cases - Hubei Province, China, 2013-2020.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by the SFTS virus, which has a high mortality rate. Predicting the number of SFTS cases is essential for early outbreak warning and can offer valuable insights for establishing prevention and control measures. In this study, data on monthly SFTS cases in Hubei Province, China, from 2013 to 2020 were collected. Various time series models based on seasonal auto-regressive integrated moving average (SARIMA), Prophet, eXtreme Gradient Boosting (XGBoost), and long short-term memory (LSTM) were developed using these historical data to predict SFTS cases. The established models were evaluated and compared using mean absolute error (MAE) and root mean squared error (RMSE). Four models were developed and performed well in predicting the trend of SFTS cases. The XGBoost model outperformed the others, yielding the closest fit to the actual case numbers and exhibiting the smallest MAE (2.54) and RMSE (2.89) in capturing the seasonal trend and predicting the monthly number of SFTS cases in Hubei Province. The developed XGBoost model represents a promising and valuable tool for SFTS prediction and early warning in Hubei Province, China.

Acute kidney injury as a prognostic marker in severe fever with thrombocytopenia syndrome

Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne illness with a notable morality risk that is becoming increasingly prevalent in East Asia (14–36%). Increasing evidence indicates a more direct role of the SFTS virus in renal impairment. However, few studies have explored the risk factors for and clinical outcomes of AKI in patients with SFTS. Therefore, in this study, we aimed to investigate risk factors and outcomes associated with AKI in patients with SFTS. In this retrospective cohort study, we included the data of 53 patients who were diagnosed with SFTS virus infection at Kangwon National University Hospital between 2016 and 2020. We incorporated laboratory data and medical information including comorbidities, complications, and mortality. Baseline characteristics, clinical features, laboratory parameters, and mortality rates of the non-AKI and AKI groups were compared. Patient survival of non-AKI and AKI groups were compared using the Kaplan–Meier method. To identify the population with poor prognosis, Cox regression analysis was used to identify the independent risk factors for in-hospital mortality in patients with SFTS. Of the 53 individuals, 29 (54.7%) were male, with an average age of 66.5 years. Nine patients (15.1%) died of SFTS. Twenty-seven (50.9%) patients exhibited AKI; the average time interval from fever onset to AKI occurrence was 3.6 days. Notably, 24 (88.9%) patients developed AKI within the first week of fever onset. Patients in the AKI group exhibited a significantly higher prevalence of diabetes and were older than those in the non-AKI group. The mortality rate was notably higher (29.6%) in the AKI group than in the non-AKI group (3.8%). Within the AKI cohort, advanced stages (stages 2 and 3) showed a 50% mortality rate, which was significantly higher than the 17.6% mortality rate in patients with stage 1 AKI. Additionally, Kaplan–Meier curves revealed lower survival rates among patients with AKI than among those without AKI (P = 0.017). Cox regression analysis identified leukopenia and elevated serum creatinine levels as significant risk factors for mortality. AKI is a common complication associated with SFTS. Moreover, the mortality rate was significantly higher in the patients who developed AKI than in those who did not. Our findings underscore the pivotal role of AKI as a prognostic marker of disease severity in patients with SFTS.

Severe Fever with Thrombocytopenia Syndrome in South Korea, 2016-2021: Clinical Features of Severe Progression and Complications.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infection with a high case fatality rate. The serious clinical features need to be further defined. We performed a retrospective analysis among SFTS patients in South Korea during 2016-2021 to update the current status. The basic epidemiology of all reported cases was analyzed, and the detailed clinical data of the subjects were further collected from study hospitals selected in terms of their geographic location and capability of SFTS care. Cases of SFTS were reported across the country and were greatly increased since the initial endemic phase, even under the passive surveillance system. The case fatality rate remained at approximately 16.8%. Coinfections at admission were present in 7.8% of the patients. Major complications included bleeding (15.2%), hemophagocytic lymphohistiocytosis (6.7%), bacteremia or candidemia (4.0%), and invasive pulmonary aspergillosis (1.7%). It took a median 4 days from the onset of illness to hospital admission. Rapid clinical deterioration was observed with a median 1 day for intensive care unit admission, 3 days for mechanical ventilation, 4 days for renal replacement therapy, and 5 days for death, all after the hospitalization. Multivariate analysis showed that the fatality was associated with older age, bacteremia, or candidemia during hospitalization, and the presence of several variables at admission such as fever, altered mentality, aspartate aminotransferase >200 IU/L, serum creatinine level >1.2 mg/dL, and prolonged prothrombin time and activated partial thromboplastin time. Treatment options to improve clinical outcomes are limited, despite best supportive care. Specific treatment is urgently needed to change the fatal course.

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.

Effect of Severe Fever With Thrombocytopenia Syndrome Virus Genotype on Disease Severity, Viral Load, and Cytokines in South Korea.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease caused by Bandavirus dabieense (SFTS virus [SFTSV]). Recently, at least 6 different genotypes of SFTSV have been identified, with genotypes A, D, and F dominant in China and B dominant in Japan and Korea. This study investigated the effect of SFTSV genotypes circulating in South Korea on disease severity, viral load, and cytokine profile. We prospectively enrolled 70 patients with SFTS from July 2015 to June 2022. Serial plasma samples were obtained during hospitalization and analyzed. Viral load was measured by real-time reverse-transcription polymerase chain reaction. Partial sequences of the viral genome were analyzed for genotyping. Plasma concentrations of 17 cytokines were measured by multiplex-bead immunoassay. Of 70 samples, 51 could be genotyped. Genotype B was predominant (80.4%) and other genotypes were uncommon. Intensive care unit admission rates (51.2% vs 50.0%) and mortality rates (26.8% vs 40.0%) did not show any significant differences between genotype B and non-B genotypes. The initial viral load did not show any significant differences (3.59 vs 3.64 log copies/μL), whereas viral load measured at hospital day 3-4 tended to be higher in genotype B than non-B genotypes (3.83 vs 1.83 log copies/μL, P = .07). Additionally, the plasma concentrations of interferon-α, interleukin 10, and interferon-γ-induced protein 10, which are closely related to mortality in cases of SFTS, did not show any significant differences. SFTSV genotype B was the prevalent genotype in South Korea, with no genotype-specific difference in clinical outcomes, initial viral load, or cytokine profiles.

Antiviral Activity of Selective Estrogen Receptor Modulators against Severe Fever with Thrombocytopenia Syndrome Virus In Vitro and In Vivo.

Severe fever with thrombocytopenia syndrome virus (SFTSV), also known as the Dabie Banda virus, is an emerging tick-borne Bunyavirus that causes severe fever with thrombocytopenia syndrome (SFTS). Currently, symptomatic treatment and antiviral therapy with ribavirin and favipiravir are used in clinical management. However, their therapeutical efficacy is hardly satisfactory in patients with high viral load. In this study, we explored the antiviral effects of selective estrogen receptor modulators (SERMs) on SFTSV infection and the antiviral mechanisms of a representative SERM, bazedoxifene acetate (BZA). Our data show that SERMs potently inhibited SFTSV-induced cytopathic effect (CPE), the proliferation of infectious viral particles, and viral RNA replication and that BZA effectively protected mice from lethal viral challenge. The mode of action analysis reveals that BZA exerts antiviral effects during the post-entry stage of SFTSV infection. The transcriptome analysis reveals that GRASLND and CYP1A1 were upregulated, while TMEM45B and TXNIP were downregulated. Our findings suggest that SERMs have the potential to be used in the treatment of SFTSV infection.

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

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