Clinical characteristics of sporadic acute Q fever diagnosed by metagenomic next-generation sequencing: a retrospective analysis and literature review in China

BACKGROUND: Acute Q fever manifests sporadically in mainland China, where its clinical spectrum and optimal diagnostic strategies remain under-recognized. This study aimed to delineate the clinical phenotype and antimicrobial prescribing patterns of sporadic acute Q fever diagnosed via metagenomic next-generation sequencing (mNGS). METHODS: We conducted a retrospective, single-center cohort study of adult patients with sporadic acute Q fever. A comprehensive literature review of all published sporadic cases across China was subsequently performed to delineate the national clinical spectrum of sporadic Q fever. RESULTS: The cohort comprised 22 male patients (mean age 36.7±13.5 years). All patients presented with high-grade pyrexia (>39°C) accompanied by a characteristic symptom constellation of headache, fatigue, myalgia, and hepatic involvement (100%, mean ALT 122.2±56.9 U/L). Pneumonia was observed in 2 patients (2/22, 9.1%). A distinct dissociation was observed between markedly elevated C-reactive protein (mean 67.4 ± 33.6 mg/L) and normal leukocyte counts. A pooled analysis of 94 published cases and 22 consecutive patients from our center yielded 116 confirmed Q fever cases (male-to-female ratio 11.9:1, the proportion of hepatitis and pneumonia:87.9% and 24.1%) The median interval from symptom onset to pathogen confirmation was 7.8 ± 2.8 days. mNGS yielded a diagnosis in 77.5 % of 116 patients, the remaining 22.5 % were identified by PCR and antibody testing. CONCLUSION: Acute Q fever in China predominantly affects young males, presenting as a systemic febrile illness with a distinctive hepatic phenotype (elevated liver enzymes) rather than prominent pneumonia. The clinical triad of high fever, influenza-like symptoms (headache/myalgia), and "WBC-CRP dissociation" (normal white cell count with elevated CRP) serves as a potential clinical indicator. Empiric doxycycline should be initiated promptly in suspected cases. mNGS is a valuable tool for definitive diagnosis, particularly when empiric therapy fails or in severe/complicated cases.