Clinical Risk Factors And The Study Of Pathogenic Mechanism In Patients With Severe Fever With Thrombocytopenia Syndrome

Backgrounds: Severe fever with thrombocytopenia syndrome (SFTS) is an emerginginfectious disease in our country in recent years. The current known pathogenic cause forthe disease is severe fever with thrombocytopenia bunyavirus (SFTSV). However, theclinical risk factors and underlying pathogenesis of SFTS are still unclear. Recent studieshave found that microvesicles (MVs), as previous ‘cellular dust’, can not only transportvirulence factors and other pathogenic components to host cells, but also can stimulate theimmune response, resulting in immunopathological damage. We aimed to assess the riskfactors for severe and death SFTS, and the roles of circulating MVs and immunofunctionfor the pathogenic mechanisms.Methods: The SFTS patients who were admitted to the department of infectious diseasesof Union Hospital, Tongji Medical College, Huazhong University of Science andTechnology between May2009and September2012were included. We collected theclinical data dynamically and analysed the risk factors with single factor logisticregression. Then we detected the concentration of MVs from circulating peripheral bloodof SFTS with Bicinchoninic acid (BCA) method and tested immunofunction with flowcytometry which contains CD3+, CD4+and CD8+T lymphocytes, B cells and NK cells.Results:1.78%of SFTS patients with MODS died within7days after admission and60%died within3days. Meanwhile, they had advanced age and lower platelet counts. Inaddition, we also observed that cumulative Marshall score was significantly higher in deathpatients than survival patients (P<0.001);2. The level of the circulating MVs in SFTSpatients was significantly higher than that of in the healthy control (P<0.005). Furtheranalysis showed that MVs level was associated with severity of the SFTS patients and thecirculating MVs of SFTS correlated with leukocyte counts (r=0.243, P<0.05), but had nocorrelation with platelet counts (r=0.193, P>0.05);3. The CD3+and CD4+T lymphocytes were significantly diminished in SFTS, compared to normal control(p<0.05).But NK cells were significantly higher in SFTS patients. Furthermore, the decline ofCD3+and CD4+was related to the clinical stage and severity of SFTS patients. TheCD3+and CD4+decreased intensely in death group, but the B cells were significantlyhigher than survival group.Conclusions: We proposed that advanced age, lower platelet counts and Marshall scorewere the main risk factors for the development of MODS for the first time, and they couldpredict mortality of SFTS patients. Simultaneously, the level of circulating MVs in SFTSpatients was high, and it was closely related to the severity of the disease and leukocytecounts. The immune system was inhibited obviously in SFTS patients, and it was moreserious in severe SFTS. Therefore, it has great value to detect the level of MVs andlymphocyte subsets counts in predicting the progression and prognosis of SFTSV infectionin circulating blood.