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Background Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne emerging infectious disease caused by SFTS virus (SFTSV). Mortality of SFTS estimated to be 21.8% in South Korea, and this disease is difficult differential diagnosis. Here, we analyzed clinical characteristics between SFTS positive group (SPG) and negative group (SNG) in a primary clinical setting. Methods In this prospective observational study, data were collected on patients with SFTS test performed at the single teaching hospital, in South Korea, between April 2013 and December 2018. The association between each demographic, climatic, clinical, and laboratory variable was assessed. All SFTS was confirmed at the KCDC by detecting the M segment gene of SFTSV RNA using reverse transcription-polymerase chain reaction (RT–PCR), and were confirmed at our laboratory by S segment gene of SFTSV RNA using RT–PCR about patient's family member and those with close contact. Results Of the 199 patients in the study periods, 61 (31%) were SPG and 138 (69%) were SNG. Mean age was 55.1 ± 20.3 years, and 103 (52%) patients were male. In SPG, the comorbidity score and history of tick bite were significantly higher compared with SNG. SPG and SNG were prevalent in summer and autumn, respectively (60.7% vs. 45.7%, P < 0.05). SPG was associated with mean outdoor temperature, humidity and rainfall compared with SNG (22.9°Cvs. 18.9 ℃; 78.8% vs. 70.6%; 12.6 mm vs. 8.5 mm, all P < 0.01). Dizziness, poor oral intake, nausea, and diarrhea were common in SPG. In laboratory findings, white blood cell counts, absolute neutrophil count, and C-reactive protein were significantly lower in SPG. Lymphocyte fraction, activated partial thromboplastin time, and creatinine phosphokinase were significantly higher in SPG. Case fatality of the SPG and SNG were 9.8% and 1.0%, respectively. In multivariate analysis, mean outdoor temperature, humidity, dizziness, and low CRP were predictive factors in SPG. Conclusion Early prediction of SFTS diagnosis is important because this emerging zoonotic disease was a high fatality in endemic areas. When a physician wants to do SFTS test, they would consider according to this predictive variable for differentiating SFTS in primary care settings. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]