Plasma mNGS Q Fever Linked to Delayed Defervescence
Key Takeaways
- At a single hospital in Changsha, China, a mostly acute 44-patient Q-fever cohort identified by plasma mNGS plus clinical criteria (41 acute, 3 chronic) was predominantly middle-aged and male; fever occurred in 95.5%, headache in 45.5%, and pulmonary involvement in 51.2%.
- C-reactive protein and erythrocyte sedimentation rate were elevated in 97.7% and 90.9% of patients, respectively, while leukocytosis remained less common.
- Transient antiphospholipid antibody positivity was observed during acute infection, and all patients retested for antiphospholipid antibodies at 12 weeks were negative; ANA positivity was also observed in a subset during the acute phase.
- Fever lasting beyond 7 days after targeted therapy was associated with higher inflammatory markers, lower CD8+ and B-cell counts, and more frequent aPL positivity, while mNGS read counts were not significantly different.
In the Chen et al. retrospective cohort of plasma metagenomic next-generation sequencing (mNGS)-confirmed Q fever, investigators retrospectively reviewed 44 patients at the Second Xiangya Hospital, Central South University, in Changsha, China, between March 2021 and January 2026. Diagnosis required plasma mNGS detection of Coxiella burnetii plus compatible clinical manifestations and plausible exposure history, or compatible features plus exclusion of alternative infections when exposure history was unclear. Serology and organism-specific polymerase chain reaction (PCR) were not systematically available, and mNGS positivity alone was not considered sufficient for diagnosis. Plasma mNGS and conventional microbiological tests were performed concurrently, and the primary outcome was fever duration after doxycycline or alternative anti-rickettsial therapy, with prolonged fever prespecified as more than 7 days after treatment initiation. Analyses were exploratory, with descriptive p-values only and no multivariable model because of sample size.
Across the cohort, fever, headache, and pulmonary involvement were common, and C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were elevated in nearly all patients. Splenomegaly, pleural or peritoneal effusions, and elevated D-dimer also recurred in hospital presentations. All patients received doxycycline; median time to defervescence after targeted therapy was reported as 8 days, although the prolonged- versus non-prolonged-fever subgroup counts total 41 patients rather than the full 44-patient cohort.
In the prespecified prolonged-fever group, white blood cell counts were higher (9.04 vs 6.03 ×10^9/L, p=0.004), CRP was higher (74.35 vs 47.53 mg/L, p=0.045), and antiphospholipid antibodies (aPL) positivity was more frequent (100% vs 57%, p=0.023) than with earlier defervescence. ESR was also higher, CD8+ T-cell and B-cell counts were lower, and Coxiella burnetii-specific mNGS read counts did not differ significantly; age, sex, liver tests, platelet count, creatinine, D-dimer, and other assessed variables were not significantly different as a group.
Separately, aPL were positive in 15 of 19 tested patients, none had thrombotic events during the reported acute-phase assessment, all 12 retested at 12 weeks were negative, and antinuclear antibodies (ANA) were positive in 8 of 34 tested patients. Because this retrospective single-center cohort in Changsha, China, was drawn from selectively ordered plasma mNGS cases, it likely skewed toward diagnostically difficult, atypical, severe, or empiric-therapy-refractory presentations rather than all acute Q fever. Case classification relied on an integrated clinical-epidemiologic-microbiologic framework because independent serology or PCR confirmation was not routinely available. Small subgroup sizes, incomplete retrospective laboratory capture, no serial immune measurements, and no validation cohort left the prolonged-fever findings associative only, and North American clinicians should view the report as a description of a selectively tested hospital population rather than a direct estimate of local presentation patterns.
The authors interpreted delayed defervescence in this cohort as tracking more closely with inflammatory and lymphocyte patterns than with measured plasma mNGS read counts, a relationship that does not establish causality. Q fever in this Changsha cohort also appeared as a heterogeneous multisystem illness, with antiphospholipid antibody positivity that was transient on follow-up retesting and ANA positivity observed during the acute phase.
Clinician Questions
How was plasma mNGS-confirmed Q fever defined in the Changsha cohort?
Plasma mNGS-confirmed Q fever in the Second Xiangya Hospital cohort required Coxiella burnetii reads on plasma mNGS plus compatible clinical manifestations and plausible epidemiologic exposure, or compatible features plus exclusion of alternative infections when exposure history was unclear. Serology and organism-specific PCR were not systematically available, and mNGS positivity alone was not considered sufficient for diagnosis.
Which patients were represented in this acute Q fever cohort, and how might that limit applicability?
This cohort came from a single hospital in Changsha, China, and reflected patients selected for plasma mNGS after negative or inconclusive routine testing, atypical or severe presentation, or failure of empiric therapy. The findings therefore apply most directly to a diagnostically challenging hospital population rather than to all patients with acute Q fever.
What did transient autoantibody positivity look like in acute Q fever in this cohort?
aPL were detected during the acute phase in a subset of tested patients, no thrombotic events were reported during the acute-phase assessment, follow-up testing at 12 weeks turned negative in all patients who were retested, and ANA positivity was also observed in a subset. The authors interpreted this pattern as transient infection-associated autoimmunity rather than proof of antiphospholipid syndrome or systemic lupus erythematosus.