Risk Factors And Dynamic Changes In Lymphocyte Subsets For Severe Fever With Thrombocytopenia Syndrome

[Background]In recent years,Severe fever with thrombocytopenia syndrome(SFTS)is a newly discovered infectious disease in China,it is caused by severe fever with thrombocytopenia syndrome bunya virus(SFTSV).SFTS had no specific clinical manifestations at the early stage,it is often characterized by fever and fatigue for unknown reasons.laboratory examination with thrombocytopenia,leukopenia,serious illness can appear coma,shock,systemic diffuse vascular bleeding and multiple organ failure and death.At present,the fatality rate of SFTS is about 10%-30%,which has become a new emerging infectious disease that seriously threatens the health of Chinese people and public health.The pathogenesis of SFTSV infection in human body is still unclear,how to detect and identify these patients as early as possible and improve the cure rate of severe patients has become the focus of clinical and medical laboratories.By studying the laboratory indicators and peripheral blood lymphocyte subsets of SFTS,the project aims to detect severe patients in the early stage,which have great significance for revealing the pathogenesis,immune mechanism and improving the prognosis of severe patients.Part One.Analysis on the laboratory parameters and risk factors of severe fever with thrombocytopenia syndrome[Purpose]A retrospective study was conducted in SFTS patients with the clinical characteristics,laboratory indexes and epidemiological characteristics,which aimed at exploring the risk factors of severe patients and providing basis for improving cure rate.[Methods]From May 2016 to October 2017,we collected the hospitalized diagnosed 146 cases with SFTSV in Jinan infectious disease hospital of Shandong University.According to the prognosis,the SFTS patients were divided into normal group(114 cases)and severe group(32 cases).Descriptive epidemiology method was used to analyze medical records and single factor Logistic regression analysis for the severity of diagnosed cases with SFTSV.[Results]1.Compared with the normal group,the patient's age,ALT,AST,GLU,CK,CK-MB.LDH and a-HBDH,APTT,BUN,Cr,D-dimmer of the severe group were significantly higher,while the PLT count were significantly lower(all P<0.05).It has statistical significance.2.Analyzed by Logistic regression,it showed that the neuropsychiatric symptoms(OR=24.083,95%CI:6.064?95.642),skin bleeding point(OR=30.000,95%CI:6.936?]29.764),multiple organ dysfunction(OR=34.048.95%CI:7.740?149.782),medical history(OR=3.792,95%CI:1.284?11.200)and high levels of fasting glucose(OR=1.359,95%CI:1.106?1.668)could forecast effect to the disease severity.[Conclusions]The abnormality of the laboratory index,the special clinical manifestations and the previous medical history of SFTS patients were the important basis for judging the patient's serious condition.Elderly patients with previous underlying diseases,will progress rapidly and have poor prognosis when fasting blood glucose increases,neuropsychiatric symptoms,obvious bleeding tendency and multiple organ dysfunction occur.Part Two.Dynamic changes of peripheral blood lymphocyte subsets in patients of Severe fever with thrombocytopenia syndrome[Purpose]Dynamic observation of peripheral blood lymphocyte subsets in different stages of SFTS patients.To investigate the immunological status,pathogenesis and significance of SFTSV infection in disease progression.[Methods]Case-control study was used in the research,Clinical data of 79 SFTS inpatients with clinical diagnosis were collected in jinan infectious disease hospital affiliated to shandong university from June 2017 to October 2018.At the same time,30 healthy patients were selected as the healthy control group.According to the prognosis,SFTS inpatients were divided into the normal group(65 cases)and the severe group(14 cases).Real-time fluorescence quantitative PCR method was used to detect SFTSV nucleic acid in serum.Flow cytometry was used to detect CD3+T lymphocytes(T cells),CD3+CD4+T lymphocytes(Th cells),CD3+CD8+T lymphocytes(Tc cells),B cells,NK cells percentage and CD4+/CD8+ ratio in peripheral blood of healthy controls and SFTS patients at different disease stages.T-test statistical analysis was performed on the counts of lymphocyte subsets between the healthy control group and SFTS patients.Single factor ROC curve was used to analyze the predictive value of each index for the prognosis of patients.[Results]1.After SFTSV infection in human body,the percentage of CD3+T cells,CD3+CD4+T cells and CD4+/CD8+ ratio in peripheral blood of patients can be reduced,NK cells in peripheral blood decreased and B cells increased.2.Compared with normal group and severe group,the serum viral load of patients in the SFTS severe group was obviously higher than the normal group.Two groups of patients with Serum viral load were in II period(7?10d)peak.The percentage of CD3+T cells and CD3+CD4+T cells decreased significantly in the severe group.In addition,the percentage of B cells in both groups was significantly higher than the healthy control group,and the increase was more obvious in the severe group.3.In the normal group,CD3+T cells,CD3+CD8+T cell percentage in I period(3?6d)fell to the lowest,then began to rise and were higher than the healthy control group;CD3+CD4+T cells were decreased in the early stage,no significant difference in each stage.In the severe group,CD3+?CD3+CD4+and CD3+CD8+T cell percentage in ? period(7?10d)were significantly lower,the percentage of CD3+ and CD3+CD8+T cells in?period(?11d)begin to increase,but still lower than the healthy control group,while the percentage of CD3+CD4+T cells decreased continuously.4.Single factor ROC analysis showed that the percentage of CD3+T cells,CD3+CD4+T cells,CD4+/CD8+ ratio and the level of serum viral load have good predictive value in judging the prognosis of the disease.[Conclusions]SFTSV infection damage to cellular immunity and humoral immune function is relatively hyperactive,moderate cellular immune response is helpful for the recovery of diseases,while excessive cellular immune response and high viral load mean poor prognosis.Therefore,timely monitoring the dynamic changes of human peripheral blood lymphocyte subsets have great significance for clinical treatment and improving the prognosis of severe patients.