Discrimination of novel bunyavirus infection using routine laboratory test.

The wide epidemic and high case fatality rate have made severe fever with thrombocytopenia syndrome (SFTS) a significant public health problem. The diagnosis and discrimination of SFTS virus (SFTSV) infection at an early stage of the disease is important for treatment choice. A prospective study was performed in an SFTS reference hospital during 2011-2013. Suspected SFTS patients were recruited and prospectively observed. Comparison between SFTSV-positive and -negative patients was made to identify the parameters that were related to positive detection by discriminant and classification tree analysis. A total of 538 SFTSV-positive and 396 negative patients were recruited and observed. Multiple logistic regression models demonstrated the significant parameters associated with positive detection, including decreased platelet counts and elevated aspartate aminotransferase (AST) level during the first stage (1∼4 days), decreased white blood cell and platelet counts, elevated creatine kinase (CK) and AST levels during the second stage (5∼7 days), and older age, decreased consciousness and elevated CK and AST during the third stage (8-11 days). The classification trees disclosed that the significant predictors for positive SFTSV detection were AST >50.6 U/L and AST/alanine transaminase (ALT) >1.3 at the first stage, CK >257 U/L or 57.7 U/L < CK ≤98.5 U/L with AST/ALT >1.6 at the second stage, as well as CK >630.7 U/L or 114.3 U/L < CK ≤630.7 U/L with decreased consciousness at the third stage. In making the clinically probable diagnosis of SFTS, the supplementation of AST and CK evaluations might remarkably improve the diagnostic capacity of routine laboratory tests, while the leukopenia is of limited use.

Lu QB ，Yang ZD ，Wang LY ，Qin SL ，Cui N ，Wang HY ，Li H ，Liu K ，Hu JG ，Zhang XA ，Liu W ，Cao WC ... -  《-》

Clinical progression and predictors of death in patients with severe fever with thrombocytopenia syndrome in China.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease of which the clinical progression and factors related to death are still unclear. To identify the clinical progression of SFTS and explore predictors of fatal outcome throughout the disease progress. A prospective study was performed in a general hospital located in Xinyang city during 2011-2013. Confirmed SFTS patients were recruited and laboratory parameters that were commonly evaluated in clinical practice were collected. The clinical progression was determined based on analysis of dynamic profiles and Friedman's test. At each clinical stage, the laboratory features that could be used to predict fatal outcome of SFTS patients were identified by stepwise discriminant analysis. Totally 257 survivors and 54 deceased SFTS patients were recruited and the data of 11 clinical and laboratory parameters along their entire disease course were consecutively collected. Three clinical stages (day 1-5 post onset, day 6-11 post onset and day 12 to hospital discharge) were determined based on distinct clinical parameters evaluations. Multivariate discriminant analysis at each clinical stage disclosed the indicators of the fatal outcome as decreased platelet counts at early stage, older age and increased AST level at middle stage, and decreased lymphocyte percentage and increased LDH level at late stage. The significant indicators at three clinical stages could be used to assist identifying the patients with high risk of death. This knowledge might help to perform supportive treatment and avoid fatality.

Cui N ，Bao XL ，Yang ZD ，Lu QB ，Hu CY ，Wang LY ，Wang BJ ，Wang HY ，Liu K ，Yuan C ，Fan XJ ，Wang Z ，Zhang L ，Zhang XA ，Hu LP ，Liu W ，Cao WC ... -  《-》

Prognostic value of clinical and immunological markers in acute phase of SFTS virus infection.

SFTS virus (SFTSV) is a novel bunyavirus that causes severe fever with thrombocytopenia syndrome (SFTS), an emerging infectious disease that occurred in China in recent years, with an average case fatality rate of 10-12%. Intervention in the early clinical stage is the most effective measure to reduce the mortality rate of disease. To elucidate the natural course of and immune mechanisms associated with the pathogenesis of SFTSV, 59 laboratory-confirmed SFTS patients in the acute phase, who were hospitalized between October 2010 and September 2011, were enrolled in this study, and the patients sera were dynamically collected and tested for SFTSV viral RNA load, 34 cytokines or chemokines and other related laboratory parameters. All clinical diagnostic factors in the acute phase of SFTS were evaluated and assessed. The study showed that the severity of the disease in 11 (18.6%) patients was associated with abdominal pain (p 0.007; OR = 21.95; 95% CI, 2.32-208.11) and gingival bleeding (p 0.001; OR=122.11; 95% CI, 6.41-2328). The IP-10, TNF-α, IL-6, IL-10, granzyme B and HSP70 levels were higher over the 7-8 days in severe cases, accompanied by altered AST, CK and LDH levels. HSP70 (p 0.012; OR=8.29; 95% CI, 1.58-43.40) was independently correlated with the severity of the early acute phase of SFTSV infection. The severity of SFTS can be predicted based on the presence of symptoms such as abdominal pain and gingival bleeding and on the level of HSP70 in the acute phase of the disease.

Ding YP ，Liang MF ，Ye JB ，Liu QH ，Xiong CH ，Long B ，Lin WB ，Cui N ，Zou ZQ ，Song YL ，Zhang QF ，Zhang S ，Liu YZ ，Song G ，Ren YY ，Li SH ，Wang Y ，Hou FQ ，Yu H ，Ding P ，Ye F ，Li DX ，Wang GQ ... -  《-》

The AST/ALT Ratio (De Ritis Ratio) Represents an Unfavorable Prognosis in Patients in Early-Stage SFTS: An Observational Cohort Study.

Severe fever with thrombocytopenia syndrome (SFTS), a widely prevalent infectious disease caused by severe fever with thrombocytopenia syndrome virus (SFTSV) that carries with it a high mortality rate, has emerged to be a public health concern. This study aimed to investigate the epidemiological and clinical characteristics of patients infected with SFTSV, seeking novel prognostic risk factors for SFTS. In this retrospective and cross-sectional study, confirmed SFTS patients from the First Affiliated Hospital of Anhui Medical University were enrolled from September 1, 2019, to December 12, 2020. Cases were analyzed for epidemiological, demographic, clinical, and laboratory data. Logistic regression models were used to assess the association between predictors and outcome variables. A generalized additive mixed model (GAMM) was conducted to analyze the trending shift of aspartate aminotransferase/alanine transaminase-ratio (AST/ALT-ratio) and platelet (PLT) in SFTS patients treated with ribavirin. p values ≤ 0.05 were considered statistically significant. Clinical and laboratory results of 107 hospitalized patients with SFTSV infection were retrospectively described. The mean age at onset of disease was 60.38 ± 11.29 years old and the ratio between male and female was 1:1.2. Fever and thrombocytopenia are hallmark features of SFTS. Furthermore, multiple cases also experienced neurological complications, gastrointestinal/skeletal muscle symptoms together with other non-specific clinical manifestations; laboratory dataset outcomes reported dysregulated levels for routine blood biomarkers, coagulation function, and biochemistry. Overall, 107 patients were segregated into two groups according to patient condition at the clinical endpoint (survivors/non-survivors). SFTS survivors had a higher level of PLT- counts, total protein (TP), and estimated glomerular filtration rate (eGFR), while levels of activated partial thromboplastin time (APTT), thrombin time (TT), D-dimer (D-D), fibrinogen degradation products (FDP), ALT, AST, AST/ALT-ratio, creatinine (Cr), creatine phosphokinase (CK) and procalcitonin (PCT) was higher in non-survivors. Results from univariate Cox regression revealed that elevated levels of FDP, TT, AST/ALT-ratio, PCT, as well as decreased eGFR level and presence of central nervous system symptoms (CNS), were significant predictors for SFTS prognostic, results from multivariate logistic regression analysis in three adjusted models showed AST/ALT-ratio and PCT were independent risk factors for the prognosis of SFTS patients. Kaplan-Meier survival analysis showed that SFTS patients with AST/ALT-ratio >2.683 were associated with a shorter futime (means survival time), therefore indicating an unfavorable prognosis. Treatment with ribavirin could increase PLT count while decreasing AST/ALT-ratio within SFTS patients. SFTS is an emerging infectious disease, possibly leading to multiple-organ injury; AST/ALT-ratio was an independent risk factor for the prognosis of SFTS patients. Further investigation should be performed in order to gain more knowledge on this disease and guide clinical management.

Wang L ，Xu Y ，Zhang S ，Bibi A ，Xu Y ，Li T ... -  《Frontiers in Cellular and Infection Microbiology》

Severe fever with thrombocytopenia syndrome bunyavirus-related human encephalitis.

Severe Fever with Thrombocytopenia Syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus. Until recently, SFTSV-associated encephalitis remained largely uninvestigated. We made clinical investigation on SFTS patients who experienced encephalitis in one reference hospital in Henan Province from 2011 to 2013 to identify the risk factors for encephalitis occurrence and their fatal outcome development. Altogether 538 SFTS patients were included and 19.1% of them developed encephalitis. Fatal outcome occurred in 44.7% of the encephalitis patients. The risk factors associated with encephalitis occurrence and death included older age, longer delay between disease onset and hospital admission, pre-existing diabetes and myalgias, as well as the laboratory evaluations of higher virus load on admission, decreased WBC, PLT count, lymphocyte percentage and ALB, elevated neutrophils percentage, AST, ALT, LDH, CK, ALP, GGT, BUN and CREA. These parameters could be used as potential predictors referring to severe SFTS cases. One SFTSV strain was isolated from cerebrospinal fluid sample. Cytokine/chemokine assay revealed that blood EOTAXIN, IFN-γ, IL-15, IL-6, IP-10, TNF-α were remarkably elevated before clinical deterioration in the confirmed encephalitis patient. SFTSV is capable of infecting the central nervous system and screening for SFTSV in encephalitis of unknown reason should be performed in SFTS endemic regions. The encephalitis occurrence and fatal outcome could be potentially predicted by clinical and laboratory evaluations.

Cui N ，Liu R ，Lu QB ，Wang LY ，Qin SL ，Yang ZD ，Zhuang L ，Liu K ，Li H ，Zhang XA ，Hu JG ，Wang JY ，Liu W ，Cao WC ... -  《-》