A 93-year-old Chinese woman presented to the clinic with fever and shortness of breath for 1 day and was admitted for treatment of pneumonia to the outpatient chest X-ray (Fig. 1), with no previous history.
Diagnostic assessment
At baseline, the results of her diagnostic tests were: white blood cell count (WBC), 6.95×10^9/L; monocyte count (MONO), 0.22×10^9/L; neutrophil count (NEUT %), 82.1%; monocyte count (MONO), 2.8%; platelet count (PLT), 230×10^9/L; the levels of hemoglobin (Hb), 99 g/L; high-sensitivity C-reactive protein (hs-CRP), 78.35 mg/L; procalcitonin (PCT), 0.05 ng/ml; interleukin 6 (IL6), 122.66 pg/mL; myoglobin (myo), 149.0 ng/ml; D-dimer (fluorescence), 726 ng/mL; erythrocyte sedimentation rate (ESR), 86 mm/h; blood CMV IgG, 87.20 U/ml; urine CMV DNA detection < 10^3 IU/ml; HIV antibody/P24 antigen (luminescence method), 0.10 S/ CO, Treponema pallidum antibody (TP-AP), 0.08 S/ CO; normal liver and kidney functions; negative (bronchoalveolar lavage fluid) Xpert MTB/RIF (Xpert) results; (blood) negative T-spot results; CD4 cell count, 128 cells/mul; CD8 cell count, 52 cells/mul; CD3 cell count, 192 cells/mul. The sinus rhythm and T-wave abnormalities on electrocardiography were checked and chest computed tomography (CT) (Fig. 2) revealed bilateral lung infection, with slightly dilated bronchi in the middle lobe of the right lung and in the upper lobe of the left lung.
Therapeutic intervention
We empirically gave ceftriaxone for the infection. On the 5th day of admission, metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) revealed 5 CMV sequences, and a relative abundance of 100%. The patients were treated antivirally with ganciclovir and received human immunoglobulin 2.5g/d. The patient continued to have recurrent fever, and the symptoms of shortness of breath worsened from the 10th day of hospitalization. We rechecked some indicators of the patient, PCT < 0.04 ng/ml; blood CMV IgM 0.29 AU/ml; blood CMV IgG 103.00 U/ml; B-type natriuretic peptide (BNP) 79.2 pg/ml; WBC 5.71×10^9/L, NEUT % 80.0%, Hb 87 g/L, PLT 346×10 ^ 9/L, hs-CRP:43.91 mg/L. During this period, we adjusted ceftriaxone to moxifloxacin for antibacterial treatment of urinary tract infection. On day 13, the chest CT (Fig. 3) was reexamined, and the results showed that the pneumonia had progressed; therefore, diagnostic bronchoalveolar lavage under tracheoscopy was performed again. The BALF was sent for mNGS and pathogen cultures, and a lung biopsy was performed simultaneously. The mNGS test results for BALF showed Aspergillus flavus (number of sequences: 336863, confidence level: 99%), Aspergillus fumigatus (number of sequences: 126752, confidence level: 99%), CMV (number of sequences: 81, confidence level: 99%), and TTV-22 (number of sequences: 4, confidence level: 99%). At the same time, Aspergillus was cultured in the BALF. Histopathological examination of the lung (puncture tissue of the right upper lung) showed reactive hyperplasia of the alveolar epithelium with multiple histiocytes and some chronic inflammatory cells infiltrating the alveolar space, morphologically considered as chronic inflammatory changes (Fig. 4). Based on these results, we immediately changed the antifungal treatment to voriconazole. No drug-related adverse effects were observed during treatment.
Follow-up and outcomes
We initiated appropriate treatment measures in a timely manner (Table 1). Unfortunately, the patient suffered a sudden myocardial infarction seven days later and died the following day.