mNGS Identifies Acute Q Fever Presenting as Sepsis with Multisystem Involvement in an Immunosuppressed Patient

A 68-year-old man with a five-year history of rheumatoid arthritis (搜索)搜索该疾病 (RA) and long-term immunosuppressive therapy developed acute Coxiella burnetii (搜索)搜索该靶点 infection presenting as sepsis with multisystem involvement and a concurrent cerebrovascular event. Peripheral-blood metagenomic next-generation sequencing (mNGS) identified the pathogen after conventional microbiological investigations remained unrevealing, prompting doxycycline查看药品详情-based targeted therapy and subsequent clinical improvement.

The patient was admitted to the Department of Rheumatology and Immunology on June 8, 2025, with a one-week history of progressive gait instability and dizziness. He had been receiving methotrexate查看药品详情 (12.5 mg/week) and leflunomide查看药品详情 (20 mg/day) for RA, with adequate disease control before admission. He was also a chronic hepatitis B virus carrier receiving entecavir (0.5 mg/day), and had a 40-year smoking history that he had stopped one year earlier. He denied hypertension, diabetes mellitus, cardiac disease, recent travel, or animal contact.

On admission, vital signs were stable (temperature 36.2 °C, pulse 90 beats/min, respiratory rate 20 breaths/min, blood pressure 124/73 mmHg). Initial laboratory tests showed pancytopenia and systemic inflammation, with white blood cell count 2.18 × 10⁹/L, absolute neutrophil count 1.32 × 10⁹/L, hemoglobin 98 g/L, platelet count 88 × 10⁹/L, C-reactive protein (CRP) 54.75 mg/L, and procalcitonin (PCT) 1.01 ng/mL. Hepatic involvement was suggested by elevated alanine aminotransferase (79.90 U/L) and aspartate aminotransferase (100.00 U/L), together with hypoalbuminemia (albumin 33.90 g/L). CT angiography of the head and neck revealed extensive occlusion of the right middle cerebral artery at the M1–M2 segment with patchy hypodensity in the right temporal lobe, consistent with cerebral infarction.

Clinical Deterioration and Diagnostic Challenge

The patient's condition deteriorated rapidly after admission. On hospital days 2–3, he developed recurrent high fever with a peak temperature of 40.5 °C, accompanied by chills and rigors, followed by progressive abdominal distension, abdominal pain, and bilateral lower-limb edema. Repeat testing showed worsening pancytopenia, persistently elevated inflammatory markers (CRP 61.16 mg/L), and markedly elevated ferritin (>1,500 ng/mL). Infection was considered the leading etiology, and empirical antimicrobial therapy with ceftizoxime was initiated.

Despite escalation to piperacillin-tazobactam plus ornidazole on hospital day 4, fever persisted. Blood cultures and respiratory pathogen tests remained negative. On hospital day 5, the patient deteriorated further with altered mentation, exertional dyspnea, and oliguria, with platelet count falling to 41 × 10⁹/L, CRP rising to 74.86 mg/L, and worsening hypoalbuminemia (albumin 27.30 g/L). He was considered at risk of progression to septic shock and multisystem dysfunction.

mNGS Identifies Coxiella burnetii

Because fever, pancytopenia, polyserosal effusions, lack of response to empirical antimicrobial therapy, and negative conventional microbiological testing persisted, peripheral blood was submitted for mNGS on hospital day 7. On hospital day 8, peripheral-blood mNGS (PACEseq, Hugobiotech (搜索)搜索该词条, Beijing, China) identified 1,940 C. burnetii-specific sequence reads, with a relative abundance of 95.28%. Low-level Epstein–Barr virus (72 specific reads) and cytomegalovirus (1 specific read) signals were also detected but were interpreted as low-level viral reactivation or background detection rather than active coinfection, given the low sequence counts and the immunosuppressed host background.

C. burnetii-specific antibody testing was positive, and targeted qPCR further supported C. burnetii nucleic acid detection. Taken together, the clinical presentation, mNGS findings, and confirmatory results supported a diagnosis of acute Q fever (搜索)搜索该疾病 with disseminated manifestations, presenting as sepsis with multisystem involvement of the hematopoietic system, liver, and serosal surfaces.

Targeted Therapy and Clinical Response

Empirical antibiotics were discontinued, and targeted therapy with doxycycline查看药品详情 (200 mg orally twice daily) was initiated based on clinical experience of the infectious disease center team. Given the combination of high fever, pancytopenia, and markedly elevated ferritin, hemophagocytic lymphohistiocytosis (HLH) could not be fully excluded, so a short course of methylprednisolone was added for immunomodulation, and eltrombopag (25 mg/day) was introduced to support platelet recovery.

Body temperature normalized within 24 hours of doxycycline查看药品详情 initiation and remained normal thereafter. On hospital day 12, the doxycycline dose was reduced to 100 mg twice daily. By hospital day 15, inflammatory markers had declined substantially, albumin had increased to 41.3 g/L, and platelet count had risen to 102 × 10⁹/L, with pleural and peritoneal effusions largely resolved. Echocardiography showed no valvular vegetations and only a trivial pericardial effusion, with no evidence of endocarditis.

The patient was discharged on hospital day 18, completing a 14-day doxycycline查看药品详情 course. At follow-up 20 days after discharge, white blood cell count (4.33 × 10⁹/L), CRP (8.68 mg/L), and platelet count (303 × 10⁹/L) had normalized, with no recurrent fever or other infectious symptoms.

Clinical Significance

This case illustrates the diagnostic challenges of recognizing Q fever (搜索)搜索该疾病 during severe acute infection. Blood cultures remained negative, consistent with the obligate intracellular nature of C. burnetii and its poor recovery on routine culture media. The absence of a clear epidemiological exposure history, including denied animal contact and recent travel, further complicated early recognition, consistent with reports of Q fever in patients without obvious occupational or recreational animal exposure.

The detection of 1,940 C. burnetii-specific reads at a relative abundance of 95.28% provided a clinically important diagnostic clue and allowed timely adjustment of antimicrobial therapy. This case suggests that, in selected immunocompromised patients with severe culture-negative sepsis of undetermined origin, earlier consideration of mNGS may help shorten the diagnostic interval and reduce exposure to ineffective empirical therapy.

The concurrent right middle cerebral artery occlusion with right temporal lobe infarction was considered more likely an independent cerebrovascular event on a background of presumed atherosclerotic disease, supported by the 40-year smoking history, rather than a manifestation of C. burnetii infection. No clinical, echocardiographic, or laboratory findings suggested Q fever (搜索)搜索该疾病 endocarditis or Q fever-related vascular pathology.

The report has several limitations. As a single case, the findings are not generalizable, and any causal inference regarding the contribution of immunosuppression to disease severity should remain cautious. Dynamic phase I and phase II serological data were not available because of local laboratory constraints. The cost-effectiveness of early mNGS use in this setting was not assessed, and whether the initial higher-dose doxycycline查看药品详情 regimen conferred benefit over standard dosing remains uncertain.