Journal of Shandong University (Health Sciences) ›› 2026, Vol. 64 ›› Issue (8): 23-28.doi: 10.6040/j.issn.1671-7554.0.2026.0311

Previous Articles    

Research progress on therapeutic drugs for encephalitis associated with severe fever with thrombocytopenia syndrome

LIU Ping, ZHANG Xiaoguo, JI Shengwei, ZHANG Zhongfa   

  1. Department of Infectious Diseases, Public Health Clinical Center, Shandong University, Jinan 250100, Shandong, China
  • Published:2026-08-14

PDF (PC)

2

Abstract: Severe fever with thrombocytopenia syndrome-associated encephalitis(SFTSAE)is the most severe neurological complication of severe fever with thrombocytopenia syndrome(SFTS), with a mortality rate exceeding 40%. However, no specific therapeutic agent is currently available for SFTSAE, and existing treatment protocols are largely extrapolated from general SFTS management, failing to adequately address blood-brain barrier(BBB)penetration and neuro-targeting properties of drugs. This review systematically summarizes the current status and research progress of antiviral drugs, passive immunotherapy, immunomodulatory agents, and other potential therapeutic candidates in the treatment of SFTSAE from four aspects, with a focus on evaluating central nervous system(CNS)penetration and timing of immunomodulatory intervention. It integrates key evidence on how BBB penetrability and intervention timing affect therapeutic efficacy, and incorporates preliminary evidence on "drug repurposing" strategies, including JAK inhibitors, calcium channel blockers, and amodiaquine, into the assessment framework for SFTSAE treatment. This review aims to provide evidence-based guidance for precision pharmacotherapy in SFTSAE and highlights the need for future research on CNS pharmacokinetics and combination therapeutic strategies.

Key words: Severe fever with thrombocytopenia syndrome-associated encephalitis, Blood-brain barrier penetration, Antiviral drugs, Immunomodulatory therapy

CLC Number: 

  • R512.39
[1] Yu X J, Liang M F, Zhang S Y, et al. Fever with thrombocytopenia associated with a novel bunyavirus in China[J]. N Engl J Med, 2011: 1523-1532.
[2] Niu G Y, Li J D, Liang M F, et al. Severe fever with thrombocytopenia syndrome virus among domesticated animals, China[J]. Emerg Infect Dis, 2013, 19(5): 756-763.
[3] Lee M J, Kim K H, Yi J, et al. In vitro antiviral activity of ribavirin against severe fever with thrombocytopenia syndrome virus[J]. Korean J Intern Med, 2017, 32(4): 731-737.
[4] Cui N, Liu R, Lu Q B, et al. Severe fever with thrombocytopenia syndrome bunyavirus-related human encephalitis[J]. J Infect, 2015, 70(1): 52-59.
[5] Li H, Lu Q B, Xing B, et al. Epidemiological and clinical features of laboratory-diagnosed severe fever with thrombocytopenia syndrome in China, 2011-17: a prospective observational study[J]. Lancet Infect Dis, 2018, 18(10): 1127-1137.
[6] 余敏, 胡静, 刘小华, 等. 利巴韦林在新型冠状病毒肺炎治疗中的应用及注意事项[J]. 临床药物治疗杂志, 2020, 18(2): 71-79. Yu Min, Hu Jing, Liu Xiaohua, et al. Application and precautions of ribavairin in corona virus disease 2019[J]. Clinical Medication Journal, 2020, 18(2): 71-79.
[7] Dubey A, Kumar M, Tufail A, et al. Repurposing metal-based therapeutics for human metapneumovirus(HMPV): an integrative computational approach[J]. Bioinorg Chem Appl, 2025, 2025: 6680612. DOI:10.1155/bca/6680612
[8] Tani H, Fukuma A, Fukushi S, et al. Efficacy of T-705(favipiravir)in the treatment of infections with lethal severe fever with thrombocytopenia syndrome virus[J]. mSphere, 2016, 1(1): e00061-e00015.
[9] 彭俊侠, 王鑫, 杨佳月, 等. 法维拉韦治疗发热伴血小板减少综合征的临床观察[J]. 热带病与寄生虫学, 2024, 22(5): 271-276. Peng Junxia, Wang Xin, Yang Jiayue, et al. Clinical observation of faveravir for severe fever with thrombocytopenia syndrome[J]. Journal of Tropical Diseases and Parasitology, 2024, 22(5): 271-276.
[10] Yuan Y, Lu Q B, Yao W S, et al. Clinical efficacy and safety evaluation of favipiravir in treating patients with severe fever with thrombocytopenia syndrome[J]. EBioMedicine, 2021, 72: 103591. DOI:10.1016/j.ebiom.2021.103591
[11] Li H, Jiang X M, Cui N, et al. Clinical effect and antiviral mechanism of T-705 in treating severe fever with thrombocytopenia syndrome[J]. Sig Transduct Target Ther, 2021, 6(1): 145. DOI:10.1038/s41392-021-00541-3
[12] Li B, Qin X R, Qu J C, et al. Pair combinations of human monoclonal antibodies fully protected mice against bunyavirus SFTSV lethal challenge[J]. PLoSPathog, 2025, 21(1): e1012889. DOI:10.1371/journal.ppat.1012889
[13] Park S Y, Choi W, Chong Y P, et al. Use of plasma therapy for severe fever with thrombocytopenia syndrome encephalopathy[J]. Emerg Infect Dis, 2016, 22(7): 1306-1308.
[14] Yoo J R, Kim S H, Kim Y R, et al. Application of the-rapeutic plasma exchange in patients having severe fever with thrombocytopenia syndrome[J]. Korean J Intern Med, 2019, 34(4): 902-909.
[15] Wu S S, ji W J, Ren J Y, et al. Ruxolitinib concentrations in cerebrospinal fluid in patients with hemophagocytic lymphohistiocytosis and potential significance of central nervous system involvement[J]. Blood, 2025, 146: 1209. DOI:10.1182/blood-2025-1209
[16] Li W D, Wang W, Wang W, et al. Janus kinase inhibitors in the treatment of type I interferonopathies: a case series from a single center in China[J]. Front Immunol, 2022, 13: 825367. DOI:10.3389/fimmu.2022.825367
[17] Yamauchi N, Hongo T, Kawakami M, et al. Successful recovery from severe fever with thrombocytopenia syndrome and hemophagocytic lymphohistiocytosis with standard treatment and a calcium channel blocker of nicardipine hydrochloride[J]. Intern Med, 2023, 62(9): 1365-1369.
[18] Liu Y, Tong H W, He F, et al. Effect of intravenous immunoglobulin therapy on the prognosis of patients with severe fever with thrombocytopenia syndrome and neurological complications[J]. Front Immunol, 2023, 14: 1118039. DOI:10.3389/fimmu.2023.1118039
[19] Zhang S S, Du J, Cui N, et al. Clinical efficacy of immunoglobulin on the treatment of severe fever with thrombocytopenia syndrome: a retrospective cohort study[J]. eBioMedicine, 2023, 96: 104807. DOI:10.1016/j.ebiom.2023.104807
[20] Li Z F, Hu J L, Bao C J, et al. Activation of the NLRP3 inflammasome and elevation of interleukin-1β secretion in infection by sever fever with thrombocytopenia syndrome virus[J]. Sci Rep, 2022, 12: 2573. DOI:10.1038/s41598-022-06229-0
[21] Nakamura S, Azuma M, Maruhashi T, et al. Steroid pulse therapy in patients with encephalopathy associated with severe fever with thrombocytopenia syndrome[J]. J Infect Chemother, 2018, 24(5): 389-392.
[22] Kawaguchi T, Umekita K, Yamanaka A, et al. Corticosteroids may have negative effects on the management of patients with severe fever with thrombocytopenia syndrome: a case-control study[J]. Viruses, 2021, 13(5): 785. DOI:10.3390/v13050785
[23] Wang G, Xu Y L, Zhu Y, et al. Clinical efficacy of low-dose glucocorticoid therapy for critically ill patients with severe fever with thrombocytopenia syndrome: a retrospective cohort study[J]. Int J Infect Dis, 2023, 130: 153-160. DOI:10.1016/j.ijid.2023.03.015
[24] Shuto H, Komiya K, Usagawa Y, et al. Corticosteroid therapy for patients with severe fever with thrombocytopenia syndrome: a nationwide propensity score-matched study in Japan[J]. Open Forum Infect Dis, 2023, 10(8): ofad418. DOI:10.1093/ofid/ofad418
[25] Li H, Zhang L K, Li S F, et al. Calcium channel blockers reduce severe fever with thrombocytopenia syndrome virus(SFTSV)related fatality[J]. Cell Res, 2019, 29(9): 739-753.
[26] Ge Z R, Zhao C X, Xu Y L, et al. Analysis of the clinical efficacy of CCBs in patients with severe fever with thrombocytopenia syndrome combined with hypertension[J]. Virol J, 2025, 22(1): 184. DOI:10.1186/s12985-025-02818-3
[27] Sowndhararajan K, Deepa P, Kim M, et al. Neuroprotective and cognitive enhancement potentials of baicalin: a review[J]. Brain Sci, 2018, 8(6): 104. DOI:10.3390/brainsci8060104
[28] Baba M, Toyama M, Sakakibara N, et al. Establishment of an antiviral assay system and identification of severe fever with thrombocytopenia syndrome virus inhibitors[J]. Antivir Chem Chemother, 2017, 25(3): 83-89.
[29] Takayama-Ito M, Saijo M. Antiviral drugs against severe fever with thrombocytopenia syndrome virus infection[J]. Front Microbiol, 2020, 11: 150. DOI:10.3389/fmicb.2020.00150
[30] Boonyasuppayakorn S, Reichert E D, Manzano M, et al. Amodiaquine, an antimalarial drug, inhibits dengue virus type 2 replication and infectivity[J]. Antiviral Res, 2014, 106: 125-134. DOI:10.1016/j.antiviral.2014.03.014
[31] Kinoshita K, Matsumoto K, Kurauchi Y, et al. A Nurr1 agonist amodiaquine attenuates inflammatory events and neurological deficits in a mouse model of intracerebral hemorrhage[J]. J Neuroimmunol, 2019, 330: 48-54. DOI:10.1016/j.jneuroim.2019.02.010
[32] 陈广, 陈韬, 舒赛男, 等. 重症发热伴血小板减少综合征诊治专家共识[J]. 传染病信息, 2022, 35(5): 385-393. Chen Guang, Chen Tao, Shu Sainan, et al. Expert consensus on diagnosis and treatment of severe fever with thrombocytopenia syndrome[J]. Infectious Disease Information, 2022, 35(5): 385-393.
[1] Yuchen FAN. Current progress on prevention of mother to child transmission of hepatitis B virus [J]. Journal of Shandong University (Health Sciences), 2021, 59(5): 46-51,67.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Copyright 2018 © Editorial office of Journal of Shandong University (Health Sciences)
Supported by Beijing Magtech Co.Ltd