2.1 General condition of the patient prior to and upon the last admission

On June 25, 2023, a 29-year-old man presented with symptoms, including fever, peaking at 38.3°C, and muscle soreness. Subsequently, he developed scattered red papules on his face and around his penis, accompanied by itching and pain. As the rash worsened, he sought medical attention at a hospital in Shenzhen. Considering the patient's history of male-to-male sexual behavior, the hospital collected herpes fluid for mpox virus nucleic acid testing, which returned a positive result, confirming the diagnosis of mpox. On July 9, the patient was admitted to a specialized infectious disease hospital for further treatment.

The main clinical manifestations in this patient included facial and penile rashes as well as enlarged lymph nodes in the bilateral neck, axilla, and inguinal regions. During hospitalization, the patient experienced perianal pain, which was determined to be an anal abscess. Concurrently, the patient was diagnosed with HIV infection (HIV ≥ log6 IU/mL). Starting from July 20, the patient received bictegravir/emtricitabine/tenofovir propofol for HIV treatment. On July 22, the patient discharged himself from the hospital, as there was an improvement in the skin lesions. However, he returned on July 30 with right-eye swelling, tearing, and inability to open the eye. At this time, purulent discharge, conjunctival congestion in the right eye, and aggravated skin lesions on the face, head, perineum, anus, penis, and perianal region were observed (Figure 1b). Laboratory test results during this hospitalization showed HIV-RNA quantification of 7.02E+03 IU/mL and a CD4 T lymphocyte count of 103 cells/μL. The White Blood Cell (WBC) count, C-Reactive Protein (CRP), and Procalcitonin (PCT) were measured as 11.21 × 10⁹/L, 55.1 mg/L, and 0.24 ng/mL, respectively (Table 1).

2.2 Treatment process: Empirical systemic and local application of antimicrobial agents, along with symptomatic supports at the early stage

To address the severe skin, mucosal, and soft tissue infections, the medical team initiated empirical intravenous administration of metronidazole and piperacillin–tazobactam. Mupirocin was topically applied for the skin infection. Following consultation with ophthalmologists, ganciclovir ophthalmic gel and levofloxacin eye drops were administered to the right eye. In accordance with surgical consultation, compound huangbai liquid and potassium permanganate sitz bath were provided for the perianal lesions. Regrettably, the patient's skin and mucosal lesions did not exhibit significant improvement, and the perianal erosion worsened. This was confirmed by a perianal ultrasound, which revealed the presence of an abscess. On August 12, the patient developed a fever with a peak temperature of 38.6°C. At that time, the WBC count, CRP, and PCT were measured as 1.85 × 10⁹/L, 47.7 mg/L, and 0.21 ng/mL, respectively (Table 1). Blood culture yielded no positive findings, and there were no notable changes in inflammatory markers. Similarly, secretion cultures did not reveal any specific bacteria or fungal pathogens.

2.3 Treatment process: Mpox antiviral therapy

Polymerase chain reaction testing revealed the presence of mpox virus in samples obtained from pharyngeal swabs, blister fluid, anal swabs, and saliva, suggesting the presence of ongoing viral viremia. In response to this, the medical team commenced compassionate use of intravenous cidofovir on August 14 to August 21. Fortunately, no infusion-related adverse events were observed. However, the patient's fever persisted, reaching a peak temperature of 39.5°C, and the severity of the skin and mucosal lesions worsened.

2.4 Treatment process: Adjusted systemic application of antimicrobial agents

Considering the patient's immunodeficiency, concomitant skin infection, and the possibility of bloodstream infection, fungal infection could not be ruled out. Consequently, the antibiotic regimen was modified to include linezolid and ertapenem to cover both gram-positive cocci and gram-negative bacilli, along with voriconazole for antifungal treatment. A bone marrow puncture was subsequently performed to exclude hematological and neoplastic diseases. The bone marrow smear revealed no evidence of such conditions. Because of the extremely elevated levels of lactate dehydrogenase and ferritin, excisional biopsy of the right inguinal lymph nodes was performed. Lymph node pathology suggested there was reactive proliferation due to HIV-associated Cytomegalovirus (CMV) and Epstein–Barr virus infections (Figure 2). Despite the broad-spectrum antibiotic, antifungal, and antiviral treatments, the patient's fever persisted, and the skin and mucosal lesions on the face, perineum, anus, and penis showed no signs of improvement. On August 26, the patient received an immunoglobulin infusion, which unfortunately resulted in the development of erythematous maculopapular lesions on the face, anterior chest, and proximal upper limbs, indicating the possibility of a drug allergy. To address this, the medical team prescribed dexamethasone for anti-allergic treatment and discontinued all previous anti-infective medications, except fosfomycin, which was continued for treatment.

To further elucidate any potential unidentified pathogens, a high-throughput genetic test for pathogen detection was conducted on the patient's blood sample on August 27. The results revealed a large number of mpox virus sequences, as well as CMV and Leptospiral virus sequences. The skin secretion culture demonstrated the presence of Enterococcus faecium. Therefore, the medical team utilized foscarnet sodium and contezolamide for antimicrobial treatment.

2.5 Treatment process: Plasma therapy

Despite the patient's body temperature gradually returning to normal after September 1, the elimination of the mpox virus remained challenging because of the patient's severely compromised immune status and multiple concurrent infections. Furthermore, there was no discernible improvement in the systemic lesions. Following thorough consultation with the patient and the patient's family, a decision was made to explore compassionate treatment using plasma obtained from a healthy population that had been vaccinated against smallpox. To identify suitable plasma donors, the patient's blood type was determined, and plasma from volunteers born before 1975 who shared the same blood type and had received smallpox vaccination was selected. Subsequently, various plasma samples were evaluated for their inhibitory activity against the mpox virus using a cell infection model. Ultimately, the plasma sample with the highest inhibitory activity was chosen for treatment. A total of 20 plasma samples, each exhibiting high titers of neutralizing antibodies against the smallpox virus, were pooled together, pre-treated, and administered as three separate doses on September 3, September 4, and September 5. Importantly, no adverse events related to the plasma infusion were observed. Following the plasma infusion, subsequent testing revealed an upward trend in mpox virus nucleic acid cycle threshold (CT) values in the patient's blister fluid and anal swab (Figure 3).

2.6 Treatment process: Special care for skin lesions

To address the patient's severe and non-healing systemic skin lesions, a comprehensive treatment approach was implemented. Daily dressing changes, potassium permanganate sitz baths, and perianal irrigation were performed. The pressure sore team changed dressings every other day and carefully removed crusts from the face. Topical medications, such as human epidermal growth factor gel, polymyxin B ointment, and compound huangbai liquid, were applied to the skin lesions, while infrared irradiation was utilized to maintain dryness. For the lesion in the right eye, daily conjunctival sac irrigation was performed, and levofloxacin eye drops, sodium hyaluronate eye drops, and ganciclovir ophthalmic gel were administered. Additionally, the patient received a multivitamin supplement and active nutritional support. As a result of this comprehensive treatment approach, the patient's skin rash exhibited significant improvement, with some mpox skin lesions beginning to scab over and the red maculopapular rash subsiding (Figure 1).

On September 16, the patient experienced another episode of fever, although there were no significant clinical symptoms, and the skin rash and ulcers did not worsen. Chest CT revealed ground-glass opacities, suggesting the possibility of Pneumocystis pneumonia infection. Despite the challenge posed by a severe facial rash that covered the entire nasal cavity and hindered bronchoscopy examination, the medical team decided to initiate empirical treatment with sulfamethoxazole–trimethoprim and ganciclovir. Fortunately, the patient's body temperature returned to normal from September 20, and subsequent chest CT showed resolution of the lesions. Moreover, the skin rash on the face and trunk successfully scabbed over without any new rashes emerging. However, the patient continued to experience blurred vision in the right eye, leading to the introduction of sodium hyaluronate eye drops. Ultimately, the patient demonstrated marked improvement and was discharged on October 24.