Dynamic changes of laboratory parameters and peripheral blood lymphocyte subsets in severe fever with thrombocytopenia syndrome patients.

The aim of this study was to dynamically investigate laboratory parameters and peripheral blood lymphocyte subsets in severe fever with thrombocytopenia syndrome (SFTS) patients at different stages, to evaluate the significance of these changes in the infection process and its influence on prognosis. Case-control study was used in the research. Sixty-nine confirmed thrombocytopenia syndrome virus(SFTSV) infected patients were enrolled. They were divided into two groups, recovery group and poor prognosis group, according to the clinical prognosis of the diseases. The laboratory parameters were measured by matched fully-automatic detector. The dynamic lymphocyte subsets of each group were tested by flow cytometry. Independent-group Student's t-test, Bonferroni test and Nemenyi test were used to compare the mean value of every group. The clinical manifestations typically became worse on about the 7th day. Most of them had multi organ dysfunction, and part of them had hemophagocytic lymphohistiocytosis histiocytosis (HLH). The characteristic laboratory findings in the early stage were the drop of platelets (PLT), while the increase of alanine aminotransferase (ALT), aspartate amino transferase (AST), creatine kinase (CK), and lactate dehydrogenase (LDH). SFTSV viral loads reached the highest on Days 7-10 after onset of fever in SFTS patients. CD3+, CD3+CD4+ T cell counts were significantly reduced in poor prognosis group, more so on Days 7-10 after onset of fever. CD3-CD19+ (B cell) counts in SFTS patients were significantly higher than that of healthy controls. 11 days after illness onset, symptoms were improved, accompanied by resolution of laboratory abnormalities. These results indicated that SFTS had an acute onset and self-limited course. It was a systemic infection. The host immune response caused tissues and organs injury. The improvement of symptoms and laboratory tests was consistent with the elimination of the virus and recover of immune response. Further investigation should be done in order to reveal the mechanisms of SFTSV pathogenesis and guide the clinical treatment.

Liu J ，Wang L ，Feng Z ，Geng D ，Sun Y ，Yuan G ... -  《-》

Clinical and laboratory characteristics of severe fever with thrombocytopenia syndrome in Chinese patients.

Severe fever with thrombocytopenia syndrome (SFTS) associated with severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging infectious disease. 12 patients with severe fever with thrombocytopenia syndrome in our study were presented mainly with fever and severe malaise. The clinical manifestations typically became worse on the 6th or 7th day. The average fever time is 9.11 ± 1.54 days. Most of them had multiorgan dysfunction, and part of them had hemophagocytic lymphohistiocytosis histiocytosis (HLH). The characteristic laboratory findings in the early stage were the drop of white blood cells (WBC), platelets (PLT) and serum Ca++, while increase of aspartate amino transferase (AST), creatine kinase (CK), and lactate dehydrogenase (LDH). CD3+CD4+ were significantly decreased, while CD3-CD56+ were significantly increased, whereas CD3+CD8+ were constantly elevated throughout the disease course. Ten to 14 days after illness onset, symptoms were improved, accompanied by resolution of laboratory abnormalities. These results indicate that severe fever with thrombocytopenia syndrome has an acute onset and self-limited course. It is a systemic infection. The host immune response caused tissues and organs injury. The improvement of symptoms and laboratory tests is consistent with the elimination of the virus and recover of immune response. Further investigation should be done in order to better understand this disease and guide the clinical treatment.

Weng Y ，Chen N ，Han Y ，Xing Y ，Li J ... -  《-》

Decreased monocyte subsets and TLR4-mediated functions in patients with acute severe fever with thrombocytopenia syndrome (SFTS).

The role of a newly discovered bunyavirus, the severe fever with thrombocytopenia syndrome virus (SFTSV), in the pathogenesis of severe fever with thrombocytopenia syndrome (SFTS) is poorly understood. In this study, it was hypothesized that peripheral monocytes, which are constantly exposed to viral infection in the blood, are likely targeted by the causative virus in SFTS patients. Fifty-three patients and 25 healthy volunteers were enrolled in the study. Monocyte counts in the peripheral blood of all human subjects were monitored throughout the progress of the disease. SFTSV viral load and the expression of monocyte genes were investigated by real-time RT-PCR. Cytokine production of monocytes in SFTS patients upon lipopolysaccharide (LPS) stimulation was examined by ELISA. In comparison to SFTS patients in the convalescent stage and healthy controls, monocyte cell counts and percentages in patients at the acute stage were significantly lower. Decreased monocyte cell counts and subsets were positively correlated with SFTSV viral loads in the serum samples from SFTS patients. Despite their higher basal toll-like receptor 4 (TLR4) expression, monocytes from patients in the acute phase were shown to be compromised regarding the production of tumor necrosis factor alpha, but not interleukin 10, upon LPS stimulation. These data strongly suggest that monocytes could be a major target during SFTSV infection. The decreased population and dysfunction of monocytes in acute SFTS patients may contribute to the disease severity.

Peng C ，Wang H ，Zhang W ，Zheng X ，Tong Q ，Jie S ，Yang D ，Zhou Y ... -  《-》

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 ... -  《-》

Nucleocapsid protein-specific IgM antibody responses in the disease progression of severe fever with thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that is caused by the SFTS virus (SFTSV) and has a high fatality rate. SFTSV-specific antibody profiles among patients with different clinical outcomes are yet to be described. The nucleocapsid protein (NP) is the most immunogenic viral antigen of the SFTSV. This study, therefore, sought to determine NP-specific antibody responses among SFTS patients with different disease progressions. In the present study, 43 patients with confirmed SFTS were enrolled in our cohort, and 9 of them deceased. The clinical presentations and key laboratory parameters associated with SFTS fatality were also recorded. Serum samples from each patient were collected every 2 days during their hospitalization. NP-specific IgM and IgG responses as well as Gn or Gc-specific IgM responses were examined by enzyme-linked immunosorbent assay (ELISA), whereas, the dynamic viral loads of SFTSV RNA were quantified via real-time reverse transcription polymerase chain reaction (RT-PCR). First, 77% of patients generated positive NP-specific IgM antibody responses within two weeks since illness onset, defined as 'N-specific IgM-positive patients', while the rest of the patients were termed as 'N-specific IgM-delayed patients'. Only 17% of the patients generated NP-specific IgG responses. The absence of NP-specific humoral responses was strongly associated with a high risk of fatality and severity of SFTS. IgM-positive patients had significantly lower levels of viral loads, less disturbed coagulopathy, and hepatic and cardiac damage compared to IgM-delayed patients. Moreover, compared to severe or fatal SFTS patients, mild SFTS patients had significantly higher magnitudes of NP-specific IgM responses, but not NP-specific IgG, Gn-specific IgM, or Gc-specific IgM responses. The abundance of NP-specific IgM responses negatively correlated with viral loads, coagulation disturbances, and hepatic injuries among SFTS patients. Our data highlight distinct humoral profiles of NP-specific IgM responses among SFTS patients with different disease progressions and clinical outcomes.

Wang G ，Chang H ，Jia B ，Liu Y ，Huang R ，Wu W ，Hao Y ，Yan X ，Xia J ，Chen Y ，Wu C ... -  《-》