Severe Fever with Thrombocytopenia Syndrome in a 1-Year-Old Boy: A Rarely Reported Case with Coxiella burnetii Co‑Infection

The patient was a previously healthy 1-year-old boy with a history of tick exposure during outdoor activities in rural farmland in Lujiang, Hefei, China. Three days after the onset of fever and vomiting, he presented to a local hospital. Positive severe fever with thrombocytopenia syndrome virus (SFTSV) RNA detection in serum prompted his subsequent transfer to our hospital for further evaluation and standard treatment. The child had no underlying chronic diseases. Notably, the initially reported height and weight were incorrect; accurate anthropometric data were confirmed by telephone communication with the patient’s parents: height, 90.0 cm; weight, 12.5 kg. On admission, his vital signs were as follows: body temperature, 39.7 °C; blood pressure, 115/69 mmHg; heart rate, 95 beats/min; and room-air oxygen saturation, 99%. Physical examination revealed a visible tick bite lesion behind the right ear, accompanied by local erythema and swelling (Figure 1a). Immune profiling demonstrated that the SFTSV-induced cytokine storm was primarily characterized by elevated levels of interleukin (IL)-6, IL-8, IL-10, interferon (IFN)-α, and IFN-β, whereas no significant elevations were observed in IL-1, IL-12, tumor necrosis factor-α, IL-4, IL-5, or IL-17 (Figure 1b). No abnormal findings were noted in the head, chest, or extremities. Clinically, the patient exhibited high-grade fever, mild epigastric discomfort, intermittent nausea and vomiting, decreased appetite, and lethargy, with no neurological impairment or hemorrhagic symptoms observed throughout hospitalization. Consistent with the positive SFTSV nucleic acid result obtained at the local hospital, empirical treatment was initiated immediately upon admission, including ribavirin-based antiviral therapy, ceftazidime-based antibiotic therapy, intravenous immunoglobulin (Ig) infusion, and glutathione-mediated hepatoprotective supportive care. Comprehensive ancillary examinations were subsequently performed to establish the definitive diagnosis and assess the patient’s condition.

Figure 1.

(a and b) The infant patient's place of residence (a), tick bite sites (b), and recovered tick specimens. (c) Dynamic expression of multiple cytokines in the serum of patients clinically diagnosed with SFTS. (d and e) Dynamic counts of platelets (d) and neutrophils (e) in the blood of this young patient. (f) Dynamic change of body temperature in this young patient. (g) Whole-genome sequencing data derived from the child's peripheral blood specimens and tick isolates. (h) Expression of SFTSV nucleoprotein (NP) detected via Western blot analysis from the infant's PBMC and serum. (i) Sequence reads derived from the child's peripheral blood specimens and tick isolate. (j) Expression of SFTSV NP detected via immunofluorescence assay from the infant's serum and PBMC-infected 293T cells.

SFTSV, severe fever with thrombocytopenia syndrome virus; RNA, ribonucleic acid.

Initial laboratory tests revealed no significant anemia, leukopenia, or lymphopenia. However, marked reductions in neutrophil and platelet counts were identified (Figure 1c and d), accompanied by mild elevations in serum aspartate aminotransferase and lactate dehydrogenase levels. Further analysis of inflammatory biomarkers showed substantially elevated procalcitonin (PCT) levels, whereas C-reactive protein remained relatively normal, representing an inflammatory pattern distinct from that typically observed in adult SFTS patients. Repeat serum PCR testing confirmed persistent SFTSV RNA positivity, supporting the definitive diagnosis of SFTS (Table 1). No obvious abnormalities were detected in hepatic, renal, coagulation, or pancreatic function. Screening for common infectious pathogens, including Mycoplasma pneumoniae, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, influenza A/B virus, human rhinovirus, respiratory syncytial virus, and adenovirus, yielded negative results. The patient’s blood type was B, RhD-positive, and routine stool and urine examinations were unremarkable. During hospitalization, the patient developed recurrent fever, with a maximum temperature of 39.0 °C (Figure 1e). Symptomatic antipyretic management included ibuprofen administration and physical cooling. Short-term intravenous hydrocortisone sodium succinate was administered on April 3 to alleviate intractable fever (Table 1).

TABLE 1. Timeline of the Patient’s Clinical Characteristics and Therapeutic Strategies from Admission to Discharge.

Date	3.29	3.31	4.2	4.3	4.4	4.5	4.6	4.7	4.8	4.9
Hospitalized time	-	-	1	2	3	4	5	6	7	8
Course of the disease	Bitedate	Symptom appear and positive  for SFTSV	Transferred toour hospital	-	-	Platelettransfusion	-	-	-	Discharged
Fever time	-	39.1	38.3	38.6	39.4	38.4	36.4	36.8	36.5	36.2
Vomiting	-	Yes	Yes	Yes	Yes	-	-	-	-	-
Diarrhea	-	-	-	-	-	Yes	Yes	Yes	-	-
Cough	-	-	Yes	Yes	Yes	Yes	Yes	-	-	-
SFTSV-RNA copies	-	Positive	Positive (65)	-	-	-	-	-	< 10	-
WBC	-	4.51	4.66	2.76	-	4.78	-	6.72	7.12	-
NEU	-	1.52	1.15	0.65	-	0.45	-	0.51	0.94	-
LYM	-	2.53	2.88	1.81	-	3.96	-	5.86	5.60	-
Hb	-	120	119	120	-	124	-	107	116	-
PLT	-	77	71	60	-	55	-	98	133	-
CRP	-	10.88	10.04	6.25	-	1.93	-	0.63	0.56	-
PCT	-	1.22	1.122	1.098	-	0.758	-	-	-	-
AST	-	61	-	-	-	63	-	59	-	-
TG	-	-	-	-	-	2.39	-	-	-	-
APTT	-	-	36.80	-	-	35.50	-	-	-	-
LDH	-	-	323	-	-	437	-	367.8	-	-
CK-MB	-	-	12	-	-	26	-	23.50	-	-
Antiviral(ribavirin)	-	-	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Antibiotic(ceftazidime)	-	-	Yes	Yes	Yes	-	-	-	-	-
Antibiotic (piperacillin sodium and sulbactam sodium)	-	-	-	-	-	Yes	Yes	Yes	Yes	Yes
Liver care (glutathione)	-	-	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Immunoglobulin	-	-	Yes	Yes	Yes	Yes	Yes	-	-	-
Thermoregulation	-	-	Ibuprofen	Ibuprofen	Ibuprofen	Cortisol succinate	-	-	-	-
Antidiarrheal	-	-	-	-	-	Montmorillonite	Montmorillonite	Montmorillonite	-	-

SFTSV, severe fever with thrombocytopenia syndrome virus; RNA, ribonucleic acid; WBC, white blood cell; NEU, neutrophil; LYM, lymphocyte; Hb, hemoglobin; PLT, platelet; CRP, C-reactive protein; PCT, procalcitonin; AST, aspartate aminotransferase; TG, triglyceride; APTT, activated partial thromboplastin time; LDH, lactate dehydrogenase; CK-MB, creatine kinase-myocardial band.

Follow-up laboratory tests on April 4 revealed further declines in neutrophil and platelet counts, with the platelet count decreasing to 55 × 10⁹/L. Although PCT levels decreased slightly, recurrent fever persisted, accompanied by new-onset productive cough and diarrhea. Following an urgent multidisciplinary consultation, the antimicrobial regimen was switched to piperacillin/sulbactam on April 5. Platelet transfusion was performed to correct thrombocytopenia, and intestinal supportive therapy, including montmorillonite powder and Bifidobacterium supplementation, was initiated to alleviate gastrointestinal symptoms and restore intestinal flora homeostasis. Chest computed tomography was recommended for further evaluation of the respiratory symptoms but was declined by the patient’s guardians.

To investigate the infectious source and etiological characteristics of this pediatric SFTS case, next-generation sequencing was performed on both the tick specimen and the patient’s peripheral blood mononuclear cells (PBMCs). Coexisting sequences of SFTSV and Coxiella burnetii (C. burnetii) were detected in both the tick vector and clinical samples, suggesting that tick vectors harboring multiple pathogens may increase the risk of coinfection in young children. Meanwhile, an indirect immunofluorescence assay performed on the patient’s serum demonstrated a reciprocal C. burnetii antibody titer of 1:32, supporting coinfection with C. burnetii (Figure 1f). In addition, viable SFTSV was successfully isolated and cultured from the patient’s PBMCs and serum (Figure 1g and h). Genetic analysis of the patient-derived SFTSV strain identified no mutations associated with increased virulence or altered phenotypes. These findings suggest that coinfection caused by ticks carrying multiple pathogens may complicate the clinical course of pediatric SFTS, warranting close clinical monitoring and individualized intervention. After 1 week of standardized comprehensive treatment, the patient’s fever and vomiting completely resolved, and his appetite significantly improved. Follow-up laboratory examinations demonstrated complete recovery of neutrophil and platelet counts, with SFTSV RNA becoming undetectable in peripheral blood. The patient was successfully discharged. Long-term clinical follow-up of this infant is ongoing.

Most previously reported infant and childhood cases were diagnosed based on positive SFTSV-specific IgM serology and/or viral nucleic acid detection and presented with mild clinical manifestations, including fever, fatigue, and gastrointestinal symptoms, without severe hemorrhagic or neurological complications.^{1, 2, 3} Notably, no fatalities have been reported in pediatric SFTS cohorts, which differs substantially from adult SFTS, in which the case fatality rate among severe cases can reach approximately 30%.⁴ Children and adults exhibit distinct immune developmental states and inflammatory response profiles.⁵ The infant immune system is immature and characterized by underdeveloped innate immunity, high immune plasticity, abundant naive T cells and regulatory T cells (Tregs), increased production of anti-inflammatory cytokines (e.g., IL-10 and TGF-β), and a Th2-biased immune phenotype. In contrast, adults possess mature adaptive immunity, extensive immune memory repertoires, reduced anti-inflammatory regulatory capacity, and age-related chronic low-grade inflammation, primarily manifesting as a Th1-dominant immune response.⁶ These age-dependent immunological differences fundamentally shape host immune responses to SFTSV infection. In children, restrained proinflammatory activation and effective inhibition of inflammatory cascade amplification may reduce the risk of excessive systemic inflammation and multiorgan damage. Conversely, adults may be more susceptible to immune overactivation, excessive release of proinflammatory mediators, and insufficient anti-inflammatory feedback, predisposing them to severe cytokine storm and adverse clinical outcomes.⁷ Therefore, age-related immune maturity and the magnitude of cytokine storm responses are critical determinants of SFTS severity and prognosis.

Unlike previously reported mild pediatric SFTS cases, the present patient developed a robust proinflammatory response characterized by marked elevations in IFN-α, IFN-γ, and IL-6. This atypical hyperinflammatory phenotype may be partially attributable to tick-borne coinfection, which may synergistically amplify SFTSV-triggered inflammatory injury. Accordingly, although pediatric SFTS is generally considered a mild disease with relatively blunted inflammatory responses, clinicians, public health workers, and CDC personnel should remain vigilant for severe disease progression in young children, particularly those exposed to ticks carrying multiple pathogens. A previous Korean study reported a clinical case of SFTS in a 10-year-old child; however, detailed cytokine profiles and coinfection status were not described in that report.³ Currently, standardized therapeutic guidelines and consensus recommendations for pediatric SFTS are lacking. Treatment strategies for reported pediatric cases are primarily formulated through multidisciplinary consultation and clinical experience, with dynamic adjustments based on laboratory and clinical changes. The previously reported Korean pediatric case received combination therapy with glucocorticoids, IVIG, and ribavirin.³ The present patient was initially treated with ribavirin-based antiviral therapy and empirical antibiotics. In addition, comprehensive multiorgan supportive care was administered to a Japanese child with SFTS and concomitant hepatic and renal dysfunction.⁸

Herein, we report a pediatric case of SFTS in Anhui Province, China. The patient achieved a favorable outcome following combined treatment with ribavirin, IVIG, and targeted antibiotics. Given the progressive disease course and persistent thrombocytopenia, platelet transfusion and adjunctive glucocorticoid therapy were additionally administered. These findings highlight the urgent need for age-specific diagnostic criteria and targeted therapeutic strategies for pediatric SFTS.

Although pediatric SFTS is a rare disease with a generally benign clinical course, concomitant coinfection with other tick-borne pathogens may aggravate disease progression in infants. This finding emphasizes the need for early recognition, close clinical monitoring, and timely, standardized intervention in high-risk pediatric SFTS cases.