Case Report: Beyond conventional diagnostics: mNGS support in a complex immunocompromised patient diagnosis

Next-generation metagenomic sequencing (mNGS) enables the direct and unbiased detection of pathogens from clinical samples, overcoming the limitations of standard methods. It is particularly valuable in immunocompromised patients and in cases of complex infections. We report the case of a man in his 40s, born in North Africa, who was admitted with progressive skin and soft-tissue lesions after a minor foot trauma. The initially localized infection rapidly worsened, leading to bilateral pneumonia, acute respiratory failure, disseminated intravascular coagulation, and death. Histopathological examination revealed granulomatous inflammation with alcohol-resistant bacilli and an undiagnosed cutaneous T-cell lymphoma associated with hemophagocytic syndrome. Conventional microbiological tests identified multiple pathogens, including influenza A virus, herpes simplex virus 1 (HSV-1), Candida albicans, Enterococcus faecalis, Proteus mirabilis, and Pseudomonas aeruginosa; however, their heterogeneous distribution and isolation from non-sterile sites hindered etiological interpretation. Cultures and molecular assays for Mycobacterium species were negative despite findings of histological examination suggestive of granulomatous inflammation with alcohol-resistant bacilli. To clarify the diagnosis, mNGS was performed on blood, serum, and lymph node samples using host DNA depletion and Illumina sequencing. Bioinformatic analysis revealed a diverse microbial landscape, with the detection of Fusarium pseudograminearum, Mycobacterium canettii, and Ralstonia sp., alongside low-level viral sequences [Epstein–Barr virus (EBV) and HSV-1]. These results reflected the patient’s severe immune deficiency, characterized by a marked depletion of CD8+ T cells and NK cells. Although the results became available too late to influence treatment, mNGS provided crucial diagnostic insights, demonstrating its ability to uncover hidden or rare pathogens. Early application of mNGS could significantly improve diagnostic precision and therapeutic decisions in critically ill immunocompromised patients.