Antiviral immunity of severe fever with thrombocytopenia syndrome: current understanding and implications for clinical treatment.

Dabie Banda virus (DBV), a tick-borne pathogen, was first identified in China in 2009 and causes profound symptoms including fever, leukopenia, thrombocytopenia and multi-organ dysfunction, which is known as severe fever with thrombocytopenia syndrome (SFTS). In the last decade, global incidence and mortality of SFTS increased significantly, especially in East Asia. Though previous studies provide understandings of clinical and immunological characteristics of SFTS development, comprehensive insight of antiviral immunity response is still lacking. Here, we intensively discuss the antiviral immune response after DBV infection by integrating previous ex- and in-vivo studies, including innate and adaptive immune responses, anti-viral immune responses and long-term immune characters. A comprehensive overview of potential immune targets for clinical trials is provided as well. However, development of novel strategies for improving the prognosis of the disease remains on challenge. The current review may shed light on the establishment of immunological interventions for the critical disease SFTS.

Clinical Update of Severe Fever with Thrombocytopenia Syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is an acute febrile illness characterized by fever, leukopenia, thrombocytopenia, and gastrointestinal symptoms such as diarrhea, nausea, and vomiting resulting from infection with the SFTS virus (SFTSV). The SFTSV is transmitted to humans by tick bites, primarily from Haemaphysalis longicornis, Amblyomma testudinarium, Ixodes nipponensis, and Rhipicephalus microplus. Human-to-human transmission has also been reported. Since the first report of an SFTS patient in China, the number of patients has also been increasing. The mortality rate of patients with SFTS remains high because the disease can quickly lead to death through multiple organ failure. In particular, an average fatality rate of approximately 20% has been reported for SFTS patients, and no treatment strategy has been established. Therefore, effective antiviral agents and vaccines are required. Here, we aim to review the epidemiology, clinical manifestations, laboratory diagnosis, and various specific treatments (i.e., antiviral agents, steroids, intravenous immunoglobulin, and plasma exchange) that have been tested to help to cope with the disease.

Effects of steroid therapy in patients with severe fever with Thrombocytopenia syndrome: A multicenter clinical cohort study.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an acute, febrile, and potentially fatal tick-borne disease caused by the SFTS Phlebovirus. Here, we evaluated the effects of steroid therapy in Korean patients with SFTS. METHODS: A retrospective study was performed in a multicenter SFTS clinical cohort from 13 Korean university hospitals between 2013 and 2017. We performed survival analysis using propensity score matching of 142 patients with SFTS diagnosed by genetic or antibody tests. RESULTS: Overall fatality rate was 23.2%, with 39.7% among 58 patients who underwent steroid therapy. Complications were observed in 37/58 (63.8%) and 25/83 (30.1%) patients in the steroid and non-steroid groups, respectively (P < .001). Survival analysis after propensity score matching showed a significant difference in mean 30-day survival time between the non-steroid and steroid groups in patients with a mild condition [Acute Physiology and Chronic Health Evaluation II (APACHE II) score <14; 29.2 (95% CI 27.70-30.73] vs. 24.9 (95% CI 21.21-28.53], P = .022]. Survival times for the early steroid (≤5 days from the start of therapy after symptom onset), late steroid (>5 days), and non-steroid groups, were 18.4, 22.4, and 27.3 days, respectively (P = .005). CONCLUSIONS: After steroid therapy, an increase in complications was observed among patients with SFTS. Steroid therapy should be used with caution, considering the possible negative effects of steroid therapy within 5 days of symptom onset or in patients with mild disease (APACHE II score <14).

Prognostic Factors of Severe Fever with Thrombocytopenia Syndrome in South Korea.

Severe fever with thrombocytopenia syndrome (SFTS), a tick-borne infectious disease, is difficult to differentiate from other common febrile diseases. Clinically distinctive features and climate variates associated with tick growth can be useful predictors for SFTS. This retrospective study (2013-2019) demonstrated the role of climatic factors as predictors of SFTS and developed a clinical scoring system for SFTS using climate variables and clinical characteristics. The presence of the SFTS virus was confirmed using reverse transcription polymerase chain reaction (RT-PCR) tests. In the univariate analysis, the SFTS-positive group was significantly associated with higher mean ambient temperature and humidity compared with the SFTS-negative group (22.5 °C vs. 18.9 °C; 77.9% vs. 70.7%, all p < 0.001). In the multivariate analysis, poor oral intake (Odds ratio [OR] 5.87, 95% CI: 2.42-8.25), lymphadenopathy (OR 7.20, 95% CI: 6.24-11.76), mean ambient temperature ≥ 20 °C (OR 4.62, 95% CI: 1.46-10.28), absolute neutrophil count ≤ 2000 cells/µL (OR 8.95, 95% CI: 2.30-21.25), C-reactive protein level ≤ 1.2 mg/dL (OR 6.42, 95% CI: 4.02-24.21), and creatinine kinase level ≥ 200 IU/L (OR 5.94, 95% CI: 1.42-24.92) were significantly associated with the SFTS-positive group. This study presents the risk factors, including ambient temperature and clinical characteristics, that physicians should consider when suspecting SFTS.

Why does activated partial thromboplastin time prolongation occur in severe fever with thrombocytopenia syndrome?

Severe fever with thrombocytopenia syndrome (SFTS) is caused by infection with SFTS virus and this mortality rate is 16.2% to 30%. An 85-year-old male patient presented to the emergency department of the hospital with primary complaints of fever and consciousness disturbance. Haemophagocytic syndrome and prolonged activated partial thromboplastin time (APTT) without associated prolonged prothrombin time were observed, suggesting SFTS, which was eventually diagnosed. APTT-only prolongation has been reported previously with SFTS, but the mechanism is unknown. The absence of coagulation factors was determined by a cross-mixing study. In addition, examination of intrinsic coagulation factors showed reduced factor XI activity. These results suggest that factor XI is causally related to APTT-only prolongation in SFTS.