Application of blood purification technology in severe fever with thrombocytopenia syndrome

Objective To investigate of the risk factors for the death of severe fever with thrombocytopenia syndrome (SFTS), so as to set up SFTS critical score and evaluate its role in predicting the prognosis for patients with SFTS. Methods A total of 123 SFTS patients hospitalized in Ji′nan Hospital of Infectious Diseases affiliated to Shandong University from June 2011 to October 2014 were enrolled in this study. The univariate Logistic regression analysis was performed to analysis the risk factor for the death of SFTS. Then the SFTS critical score system was set up accordingly. The prognosis value of SFTS critical score was compared with the rapid emergency medicine score (REMS) and the acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) by using receiver operator characteristic curve (ROC). Results Among all the patients, 17 males and 14 females were in death group, and 45 males and 47 females were in survival group. The results of the univariate Logistic regression analyses indicated that the glasgow coma scale (GCS), lactate dehydrogenase, activated partial thromboplastin time, oxygen saturation were risk factors for the death of SFTS, with statistically significant difference (all P<0.05). All of the four parameters of SFTS critical scores in the death group were higher than those in the survival group, with statistically significant difference (all P<0.05). The REMS, APACHEⅡ score and SFTS critical score in the death group were significantly higher than those in the survival group (all P<0.01). The area under the curve (AUC) of REMS, APACHEⅡ scores and SFTS critical score were 0.734, 0.746 and 0.788, respectively. The Youden index of the SFTS critical scores was the highest among all three scores (P<0.01). If 15.0 was used as the cut off value of SFTS critical score, the specificity and the sensitivity for predicting the death risk for the hospitalized patient were 74.2% and 76.1%, respectively. Conclusion SFTS critical score, REMS and APACHEⅡ score can all effectively predict the prognosis for SFTS patients, among which, the SFTS critical score is the most convenient and has the best predictive value. Key words: Severe fever with thrombocytopenia syndrome; Critical score; REMS; APACHE; Receiver operating characteristic curve; Logistic models

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by SFTS virus (SFTSV) with a high fatality rate. But the immunofunction was still unclear. The objective of our study was to assess the immunofunction in SFTS patients. Immunofunction test with flow cytometry which contains CD3+, CD4+ and CD8+ T lymphocytes, B cells and NK cells would be used for detecting serum samples collected from 34 SFTS cases and 20 healthy donors. We found that CD3+ and CD4+ T lymphocytes were significantly diminished in SFTS compared to normal control. In contrast, the percentage of NK cells was elevated. Further analysis revealed that the number of CD3+ and CD4+ T lymphocytes showed that there was a more robust pattern of depression in acute phase and severe SFTS infection compared to the patients in recovery phase and mild SFTS infection. But NK cells were significantly increased in acute phase and severe SFTS. They reverted to the near normal levels in convalescent phase. Additionally, the levels of CD3+ and CD4+ T lymphocytes progressively decreased in death group when compared with the survival group, but the level of B cells was higher. The damages of immune system were obvious, and the immune dysfunction might be partly responsible for disease progression of patients with SFTSV infection.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease characterized by rapid progression and high mortality. Glucocorticoids (GCs) can be used as anti-inflammatory agents for SFTS, but no standardized protocols have been proposed. A total of 901 patients with SFTS diagnosed at two hospitals between July 2017 and October 2023 were included in this retrospective cohort study. Univariate and multivariate logistic regression were performed along with LASSO regression to identify independent risk factors of fatal outcomes and further develop mortality prediction model. A nomogram was used to visualize the predictive model. ROC curves, calibration curves, and DCA curves were conducted to assess model accuracy and clinical applicability. The efficacy of GC was assessed using survival analyses, and further subgroup analyses of the effects of different GC regimens on fatal outcomes and hospital-acquired infections (HAI) were performed. Propensity score matching (PSM) analyses were conducted to control confounding factors. Older age (age > 69 years), consciousness disturbance, decreased monocyte counts, prolonged activated partial thromboplastin time (APTT), and high viral load were identified as strong predictors of fatal outcomes in patients with SFTS. Patients were classified into mild and severe groups according to risk scores calculated by the nomogram (cut-off value = 121.43). Survival analyses showed that GCs treatment may reduce the mortality in severe patients (p = 0.004). Further subgroup analyses indicated that relatively high doses and early treatment with GCs may increase mortality in SFTS patients [OR = 2.292 (1.071, 5.066); OR = 3.693 (1.710, 8.345) respectively]. GCs treatment was associated with an elevated risk of HAI in patients both with mild and severe SFTS (p = 0.024; p = 0.015, respectively). Initiation of GCs therapy at a low level of aspartate aminotransferase (AST < 189.75 U/L) reduced the mortality before and after PSM (p<0.001; p = 0.004, respectively). A new nomogram based on five independent risk factors effectively predicts the prognosis of SFTS. Severe patients and those with low AST levels might benefit from GCs therapy while early and relatively high doses of GCs therapy should be used with caution.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by novel Bunyavirus. Due to the peculiarity of SFTS, accurate assessment is difficult to achieve with the current score systems. This study aimed to establish a new severity scoring system in predicting the prognosis of patients with SFTS. We included 123 patients with SFTS: 92 patients (45 males and 47 females), aged 59 ± 12 years, in survive group and 31 patients (17 males and 14 females), aged 61 ± 10 years, in death group. The lactate dehydrogenase (LDH), the activated partial thromboplastin time (APTT), the saturation of pulse oximeter oxygen (SpO2) and Glasgow Coma Scale (GCS) were measured. SFTS severity scoring system was set up based on the above four factors and compared with the Rapid Emergency Medicine Scores (REMS) and Acute Physiology and Chronic Health Evaluation (APACHE II) Scores. Four parameters in the death group were all significantly higher than survival group. The areas under the curves (AUC) of REMS, APACHE II scores and SFTS severity scores were 0.734, 0.746 and 0.780 respectively. The Youden index of the SFTS severity score was the highest among all the three scores (P < 0.01). If 15 was used as the cutoff value, the sensitivity and specificity of SFTS severity score in predicting the death risk for the patients were 74.2% and 76.1% respectively. The newly established SFTS severity scoring system is more efficient to predict the prognosis of patients with SFTS, compared with REMS and APACHE II.

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

Objective To investigate regional epidemiological and clinical characteristics of severe fever with thrombocytopenia syndrome (SFTS). Methods A total of 40 SFTS cases in Tiantai County People's Hospital from May 2012 to May 2018 were enrolled, and were divided into survival group (33 cases) and death group (7 cases) . Epidemiology, clinical and laboratory data, treatment and prognosis were systematically reviewed and statistically analyzed. Results Of 40 SFTS patients, 14 had history of tick bites. Fever was the first symptom in all the patients, followed by muscle ache (32 cases) , nausea and vomiting (25 cases), abdominal pain and diarrhea (20 cases) , lymphadenopathy (20 cases) , hemorrhage (14 cases) , neuropsychiatric symptoms(12 cases). The complications included pulmonary infection (6 cases) , atrial fibrillation (10 cases), heart failure (12 cases). Neuropsychiatric symptom, atrial fibrillation and heart failure occurred highly in the death group (χ2 =9.532, 6.984 and 12.864, P all <0.05) . PLT, ALT, AST, LDH, CK, Ca2+, Cr, ALB, APTT, TT and plasma D dimer during the 12th to 14th day of the disease were different from the fatal cases to the survivals (Z=1.977, 3.640, 6.250, 12.850, 16.940, 2.346, 2.108, 2.432, 21.820, 24.680 and 2.970, P all<0.05) . Conclusions From 2012 to 2018, SFTS cases were distributed sporadically in Tiantai. Occurrent neuropsychiatric symptom, atrial fibrillation and heart failure may reduce the survival rate. Several indexes in SFTS critical period might forebode a critical illness and worse prognosis. Key words: Bunyaviridae infections; Clinical features; Complication; Survival rate

Background: Severe fever with thrombocytopenia syndrome (SFTS) is a newly emerging infectious disease caused by SFTS virus (SFTSV). Immunologic factors have been proved to be related to the occurrence and development of SFTS; however, their role still remains to be further elucidated. Methods: Samples from 30 patients with laboratory-confirmed SFTS and 15 healthy controls were subjected to flow cytometry to detect the proportion of CD4+/total lymphocytes, CD4 + CD25+/CD4 + cells and CD4 + CD25+ Foxp3+/CD4 + CD25+ cells in circulating blood and to evaluate their potential function in the development of SFTS. Results: The data showed that a reduced proportion of CD4+/total lymphocytes and CD4 + CD25+/CD4 + cells was observed in patients with SFTS compared with healthy controls. In contrast, the percentage of CD4 + CD25+ Foxp3+/CD4 + CD25+ cells in the patients in the SFTS group was significantly elevated. Furthermore, we investigated the dynamic changes of the circulating regulatory T cells (Tregs) in patients with SFTS at different stages. The results showed that the proportion of CD4+/total lymphocytes and CD4 + CD25+/CD4 + cells in the non-severe group was prominently higher than that in patients with severe SFTS. Conversely, the proportion of CD4 + CD25+ Foxp3+/CD4 + CD25+ cells was lower in the non-severe group than in the severe group. Additionally, the circulating Tregs reverted to normal ranges during the convalescent phase of SFTSV infection. Moreover, the Tregs level correlated with various clinical parameters. Conclusion: We demonstrated that SFTSV infection resulted in a robust circulating Treg response in patients with SFTS. Our investigation suggested that the proportions of CD4+/total lymphocytes and CD4 + CD25+ Foxp3+/CD4 + CD25+ cells in circulating blood could serve as sensitive indices to evaluate the changes in Tregs in SFTS and predict the progression of SFTS.

Objective To analyze the differences of clinical manifestations and organ damage between patients with severe fever with thrombocytopenia syndrome(SFTS) and patients with tsutsugamushi disease, and to investigate the prognostic factors of SFTS. Methods The research was performed on 49 patients with SFTS and 16 patients with tsutsugamushi disease who visited the First Affiliated Hospital of Anhui Medical University from October 2014 to June 2017. The general information of patients including region, age, gender and clinical manifestations were evaluated. Blood routine, liver and kidney function, myocardial enzyme levels, lipase, amylase, electrolytes, C-reactive protein, procalcitonin, prothrombin time(PT) and activated partial thromboplastin time(APTT) were continuously monitored during the course of disease. T test was used for continuous variables of normal distribution, and non-parametric test was used for variables of non-normal distribution. Chi-square test was used for categorical variables. Results The mean age of SFTS patients was 62.1±15.5(ranging from 17 to 87 years) and the mean age of tsutsugamushi patients was 56.1±9.2 (ranging from 47 to 73 years). There was no significant difference between the two groups (t=1.47, P=0.147). There were 25 males(51%) in SFTS patients and 8 males (50%) in tsutsugamushi disease patients. There was no significant difference between the two groups (χ2=0.005, P=0.943). The incidences of headache, vomiting, superficial lymphadenectasis, disturbance of consciousness, proteinuria, hematuria, pulmonary infection, multiple organ dysfunction and acute pancreatitis in SFTS patients were all significantly higher than those in tsutsugamushi disease patients (χ2=8.82, 4.38, 8.71, 11.17, 7.88, 5.56, 4.35, 9.43, and 8.13, respectively, P<0.05 or 0.01). The counts of leukocytes (Z=2.73), neutrophils (Z=2.46), lymphocytes (Z=3.15), platelets (Z=4.25), albumin (Z=2.65) and sodium ion (t=2.10) in SFTS patients were all significantly lower than those in patients with tsutsugamushi disease (P<0.05 or 0.01). The levels of aspartate aminotransferase (Z=2.94), lactate dehydrogenase (Z=3.42), creatine kinase(CK)(Z=2.88), amylase (Z=2.77), lipase (Z=2.82), creatinine (Z=2.07) and urea nitrogen (Z=2.50) in fatal SFTS patients were all significantly higher than those in patients with tsutsugamushi disease (P<0.05 or 0.01). Among 49 SFTS patients, 16 patients died and 33 patients recovered finally. The age(t=3.33), platelet count (Z=2.55), alanine aminotransferase (ALT)(Z=2.10), aspartate aminotransferase (AST)(Z=2.22), lactate dehydrogenase (Z=2.26), CK(Z=3.50), CK-MB (Z=3.10), creatinine (Z=2.17), urea nitrogen (Z=2.36), and sodium (t=2.65) between the two subgroups had significant differences (P<0.05 or 0.01). Conclusions SFTS is more severe and has high mortality, while tsutsugamushi disease has a better prognosis. Early differential diagnosis and early rational treatment are important to reduce the mortality of patients with SFTS. Key words: Scrub typhus; Severe fever with thrombocytopenia syndrome; New bunyavirus; Organ damage

Severe Fever with Thrombocytopenia Syndrome (SFTS) is a zoonotic infectious disease with high mortality, in which coagulation dysfunction triggered by the virus serves as a critical factor in disease progression and patient death. This study comprehensively analyzed coagulation characteristics and the impact of concomitant Disseminated Intravascular Coagulation (DIC) on prognosis in 187 SFTS patients. Significant differences (p < 0.05) in coagulation parameters were observed among SFTS patients with varying disease severity and viral loads. The dynamic changes in coagulation parameters, especially activated partial thromboplastin time(APTT) and d-dimer (DD), differed significantly between the survival group and the death group. Prothrombin time(PT), International Normalized Ratio(INR), APTT, thrombin time(TT), and DD were identified as independent risk factors for death in SFTS patients. Furthermore, APTT ≥ 51.3 s (p = 0.001), TT ≥ 30.5 s (p = 0.023), and DD ≥ 2.39 µg/mL (p = 0.009) were shown to be effective predictors of patient mortality. Additionally, significant differences (p < 0.001) in admission coagulation parameters were found in SFTS patients complicated by DIC, among whom APTT was identified as an independent risk factor for death in this subgroup. Therefore, monitoring coagulation parameters aids in the early identification of high-risk patients, and intensive coagulation management may help improve patient prognosis.

CCHF in which the patient died of complications following surgical intervention for cerebral hemorrhage (8).

BackgroundHemorrhagic manifestations are highly prevalent in severe fever with thrombocytopenia syndrome (SFTS) patients and are significantly associated with fatal outcomes. In this study, we investigated the dynamic changes of activated partial thromboplastin time (APTT) and their association with mortality in SFTS patients.MethodsWe conducted a retrospective study analyzing clinical data from SFTS patients admitted to our hospital between April 2017 and June 2024. The dynamic changes of APTT and their association with clinical outcomes were analyzed.ResultsA total of 788 SFTS patients were enrolled in this study, among whom 96 (12.18%) died during hospitalization. Multivariate logistic regression identified prolonged APTT as an independent predictor of mortality, along with older age, neurological symptoms, higher viral load, and elevated creatinine levels. Prolonged APTT was observed in 568(72.08%) patients upon admission and was associated with the development of neurological symptoms, bleeding, intensive care unit (ICU) transfer, and mortality. APTT≥2.0 times the upper limit of normal (ULN) was associated with significantly higher mortality (55%) and an increased likelihood of ICU transfer (10%). Restricted cubic splines (RCS) analysis revealed that when the APTT level exceeded specific thresholds (49.86s upon admission and 53.61s at the peak during hospitalization), the predicted mortality of patients with SFTS increased with rising APTT levels. Kinetic analysis showed that APTT levels exhibited a declining trend during hospitalization and returned to the normal range by the 6th day in the survival group, while it gradually increased, reaching its peak on the 3rd day and then gradually decreased in the non-survival group.ConclusionProlonged APTT was prevalent among SFTS patients and was significantly associated with higher mortality. Monitoring APTT upon admission and its dynamic changes during hospitalization is recommended to enhance the management of SFTS patients.

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.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with a high mortality rate and is a public health concern. This study aimed to investigate the associations of serum interleukin 6 (IL-6) and interleukin 10 (IL-10) levels with the prognosis of SFTS patients. A total of 95 patients with confirmed SFTS were included. Clinical and laboratory data were compared between the survival and non-survival groups. Multivariate logistic regression analysis was used to assess independent risk factors for mortality. The predictive efficacies of laboratory markers were evaluated using receiver operating characteristic (ROC) curves. Survival analysis was performed using Kaplan‒Meier curves based on the log-rank test. The levels of IL-6 and IL-10 at admission were significantly greater in the non-survival group than in the survival group (p < 0.05). Multivariate logistic regression analysis indicated that the IL-6 and IL-10 levels, estimated glomerular filtration rate, and activated partial thromboplastin time (APTT) were independent risk factors for a poor prognosis in patients with SFTS. ROC curve analysis revealed that the IL-6 and IL-10 levels and the APTT had a greater predictive value than other measured laboratory markers. Kaplan-Meier survival analysis demonstrated that SFTS patients with IL-6 > 39.5 pg/mL or IL-10 > 45.2 pg/mL had significantly lower survival within a 30-day follow-up period. The levels of IL-6 and IL-10 at admission are the best markers for predicting in-hospital mortality of SFTS patients and have potential prognostic value in patients with SFTS.

BackgroundThis study aimed to identify a novel inflammatory index and construct a nomogram for predicting in‐hospital mortality due to severe fever with thrombocytopenia syndrome (SFTS).MethodsThis cohort included 610 patients with SFTS hospitalized in Wuhan Union Hospital between March 2017 and November 2022. The ratio of C‐reactive protein (CRP) to the prognostic nutritional index (PNI) was calculated and used to reflect patients' inflammatory status. Propensity score matching (PSM) was utilized to balance confounding factors between the low‐ and high‐CRP/PNI groups. SFTS individuals from Jinyinhu Hospital were used as the validation cohort.ResultsPatients with SFTS and high CRP/PNI were significantly correlated with a higher percentage of severe and critical SFTS types and higher in‐hospital mortality rates than those with low CRP/PNI. CRP/PNI was the potent risk indicator for in‐hospital mortality in individuals with SFTS. The CRP/PNI nomogram showed a good predictive value for in‐hospital mortality in patients with SFTS. After PSM, the predictive performance of CRP/PNI for 28‐day mortality was excellent. Finally, the CRP/PNI could still assess patients with SFTS at different risks based on SFTS data from another medical center.ConclusionThe CPR/PNI ratio exhibited a strong positive correlation with the SFTS disease type and could predict in‐hospital mortality in the early stages of SFTS. The CPR/PNI ratio could substantially help clinicians facilitate the early identification of patients with high‐risk SFTS and the timely initiation of intensive therapy.

Objective To summarize the clinical and laboratory characteristics of patients with severe fever with thrombocytopenia syndrome (SFTS) and to identify the related risk factors for mortality. Methods Clinical features and laboratory parameters were collected from 40 SFTS patients (7 deaths and 33 survivors). Dynamic changes of laboratory data were compared between the two groups, including white blood cell count (WBC), platelet count (PLT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase (CK), lactate dehydrogenase (LDH), prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT). Continuous variables with normal distribution were compared with t test, and those with non-normal distribution were compared with nonparametric test; categorical variables were compared with χ2 test. Univariate Logistic regression was used to evaluate the risk factors associated with death. Results For the deceased patients and the survivors, the APTT were 56.40 s and 44.45 s, respectively (Z=5.419, P=0.04) at day 1—7. Those were 66.25 s and 36.85 s, respectively (Z=10.112, P=0.009) at day 8—10, and (125.06±11.88) s and (33.44±6.50) s, respectively (t=45.760, P 15 s (OR=24.00, 95%CI: 1.99—289.60), APTT>70 s (OR=42.67, 95%CI: 3.54—514.85) and TT>120 s (OR=0.14, 95%CI: 0.02—0.88) were risk factors for the death of SFTS patients (all P<0.05). Conclusion Prolonged APTT, TT and PT at early stage and progressively increasing during the disease course suggest poor prognosis of SFTS. Key words: Severe fever with thrombocytopenia syndrome bunyavirus; Orthobunyavirus; Death; Risk factors