Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease with a high fatality rate, first identified in China in 2009¹. It is mainly endemic in central and eastern Asia, including China, Japan, South Korea, Vietnam and Myanmar². Although tick bites are the primary transmission route, only approximately 20% of patients report a definite tick exposure³. Other reported transmission routes include exposure to pets, livestock and wild animals such as dogs, cats, camels and foxes^4–7. In addition, human-to-human transmission via body fluids or aerosols has also been documented^8–10.

SFTS typically presents with fever, gastrointestinal symptoms, thrombocytopenia, and leukopenia. Severe cases may progress to neurological symptoms, shock, and multi-organ failure (MOF), with a mortality rate of approaching 30%¹¹. Due to the lack of effective treatments, the World Health Organization (WHO) has listed SFTS among the top 10 priority infectious diseases, emphasizing the urgent need for further research to elucidate transmission mechanisms and to develop effective therapeutic and preventive strategies¹².

In this case, a patient developed high fever, malaise, and diarrhea five days after a Mustela sibirica bite. SFTS was diagnosed by metagenomic next-generation sequencing (mNGS) one week after symptom onset. The epidemiologic and clinical characteristics of this SFTS patient suggests a possible transmission through a M. sibirica bite.

Sample collection and Metagenomic Next-Generation Sequencing

Peripheral blood and cerebrospinal fluid (CSF) samples were collected under sterile conditions and submitted for metagenomic next-generation sequencing (mNGS) to a certified third-party laboratory (Vision Medicals, Guangzhou, China), as part of routine clinical diagnostics. A target enrichment approach based on hybrid capture was used to enhance viral nucleic acid detection. After nucleic acid extraction, samples underwent fragmentation, reverse transcription, and ligation with barcoded adapters, followed by PCR amplification. Libraries were enriched using virus-specific biotinylated probes targeting a broad panel of human DNA and RNA viruses. Sequencing was performed on an Illumina platform, and data were analyzed using a validated bioinformatics pipeline that included quality filtering, subtraction of human host reads (aligned to GRCh38), and taxonomic classification against curated microbial reference databases. Pathogens were considered significant based on read number, genome coverage, and consistency with clinical findings.

On April 23, 2025 (day 0), a 55-year-old female farmer from Dalian, Liaoning Province, China, was bitten on the left hand by a M. sibirica (Fig. 1), resulting in bleeding and swelling. She received wound care, tetanus antitoxin and rabies vaccination at a local hospital. On day 5, she developed fever, malaise and diarrhea. Empirical antibiotics were administered followed by myalgia on day 6. With no other identifiable exposure, the M. sibirica was considered the most probable source of SFTSV infection.

On day 7, she was admitted to the Affiliated Hospital of Dalian Medical University with worsening symptoms including headache, nausea and vomiting. Laboratory tests showed thrombocytopenia (platelet count 35 × 10⁹/L) and elevated liver enzymes (AST 446 U/L, ALT 181 U/L). On day 12, mNGS of peripheral blood identified a novel bunyavirus (8,238 reads) (Table 1), and a diagnosis of SFTS was made based on clinical, epidemiological, and laboratory findings.

Then she was transferred to the emergency department of Peking Union Medical College Hospital and initiated on omadacycline. Due to recurrent seizures, she received etomidate and levetiracetam. On day 13, she was transferred to the ICU at Beijing Ditan Hospital due to worsening consciousness and delirium (Fig. 1). Laboratory tests on admission revealed leukocytosis (WBC 12.45 × 10⁹/L), severe thrombocytopenia (30 × 10⁹/L), elevated liver and cardiac enzymes (AST 229.8U/L, ALT 166.2U/L, TnI 6.041ng/ml), and impaired renal function (Cr 121umol/L).

Treatment was initiated with favipiravir, intravenous immunoglobulin, and dexamethasone, along with cefoperazone-sulbactam for possible bacterial co-infection (Fig. 1). However, her hemoglobin and platelet count continued to fall. On day 15, she required intubation due to seizures and impaired consciousness. SFTSV was detected in both blood (6.87 × 10⁵ copies/mL) and cerebrospinal fluid (10,730 reads), confirming central nervous system involvement (Table 1). Despite intensive support, her condition rapidly progressed to disseminated intravascular coagulation and circulatory failure. On day 20, the family withdrew treatment, and she was discharged against medical advice.

SFTS is a zoonotic disease caused by the SFTS virus, with an increasing number of cases reported across East Asia². The virus is primarily transmitted through vertical transmission among ticks and horizontal transmission from infected ticks to mammals. To date, SFTSV RNA or antibodies have been detected in 48 animal species², including both domestic and wild animals. While most infected animals remain asymptomatic, humans may acquire the infection through contact with viremic animals¹³.

According to the patient’s family, she lived in a rural area and had no history of tick exposure or contact with other animals, apart from a M. sibirica bite five days prior to symptom onset. The bite resulted in bleeding and was classified as a high-risk (Category III) exposure, potentially allowing direct transmission of SFTSV via saliva or blood. M. sibirica was thus considered the most likely source of infection. Previous studies have shown that ticks have been found on M. sibirica in China and Korea^14,15. Moreover, one study reported a seropositivity rate of 91.11% for SFTSV antibodies in this species¹⁶, further supporting our hypothesis that the patient may have acquired the infection directly from the M. sibirica, even though virological confirmation of SFTSV infection in the M. sibirica was not available.

Various zoonotic pathogens can be transmitted by ticks or M. sibirica, including tick-borne encephalitis (TBE) virus, Borrelia burgdorferi, and Coxiella burnetii, which can cause TBE, Lyme disease, and Q fever, respectively¹⁷. In addition, SFTS can also mimic other viral hemorrhagic fevers, such as hemorrhagic fever with renal syndrome (HFRS), severe dengue, and thrombotic thrombocytopenic purpura (TTP)¹⁸. In this case, the history of a M. sibirica bite and neurologic symptoms raised concern for rabies. However, SFTSV was detected by mNGS in both blood and cerebrospinal fluid samples, effectively ruling out other differential diagnoses.

The typical incubation period of tick-borne SFTS ranges from 5 to 14 days, with many severe cases resulting in death within two weeks due to MOF. As the first reported case of SFTS potentially transmitted through the bite of a M. sibirica, the clinical course was generally consistent with cases linked to other sick or viremic animals^{4–7,19–22}, as summarized in Table 2. This patient presented with a high viral load and progressed rapidly to MOF, including myocardial injury and encephalitis, within one week. Consistent with this case, several studies have identified high viral load and neurologic symptoms as predictors for poor prognosis^23,24. However, the prognostic significance of SFTSV transmission via M. sibirica remains to be further explored.

In this case, the patient developed SFTS shortly after a M. sibirica bite and rapidly progressed to MOF, resulting in a poor prognosis. Due to the difficulty of capturing wild animals, we were unable to perform pathogen testing on the offending M. sibirica. Although direct virological evidence of SFTSV in the M. sibirica was not obtained, this case highlights its possible and potential role in SFTSV transmission. This case provides novel insights into the potential zoonotic transmission of SFTSV and underscores the need for systematic surveillance of animal hosts in endemic regions to clarify transmission routes.