Severe mpox in an immunocompromised patient complicated by deep tissue infection: A case report.

Objectives: We report prolonged mpox (>14 weeks) in a patient with HIV complicated by deep tissue MPXV infection despite two courses of tecovirimat treatment.

Methods: MPXV-DNA levels in lesional swabs, blood and tissue were quantified by qPCR. Anti-MPXV antibodies were analyzed by IF and VNT. Infectivity was assessed by virus isolation. Sequencing was performed to assess for tecovirimat resistance mutations and quantitative results were obtained by digital SNP PCR (A288P).

Results: The patient's clinical condition improved significantly during both tecovirimat treatment courses (each 14 days), yet we observed persistent MPXV-DNA in lesions accompanied by viremia (mean 1.4 × 10 copies/ml) for >14 weeks. A deep tissue infection driven by MPXV complicated the clinical course (week 9). Presence of infectious virus within the tissue and high infectious titers (>10 PFU/ml) were observed. The VP37 protein sequence revealed A288P substitutions. Digital PCR showed 1 % and less abundance (A288P) during first treatment course (blood and swabs), with increasing proportion during second course (week 8-9; 28 % in blood and swabs), however the mutation was absent in samples from deep tissue infection and MPXV isolates (week 9) indicating compartimentalization. Morphological fully enveloped MPXV partices visualized by TEM in necrotic areas suggesting tecovirimat treatment failure in the deep tissue compartment.

Conclusion: Our data provide evidence that Tecovirimat treatment selects for compartimentalized viral mutations (A288P). While the patient clinically benefited from repeated tecovirimat course, emergence of viral muations and deep tissue infection emphasizes the challenge and importance of infectious disease monitoring in mpox patient management.