A 57-year-old female patient complained with edema for 1 year and ardent fever for 3 days. She was diagnosed with T2DM 10 year ago. Based on the onset of her symptoms and laboratory test results, the patient was performed renal biopsy and diagnosed with membranoproliferative glomerulonephritis (MPGN) 1 year ago. Cyclophosphamide (100 mg/day) and prednisone (60 mg/day) were administered together in a combination regimen then. Following a partial remission of PNS, the prednisone dosage was steadily decreased to 20 mg/day within 6 months. Yet, the patient returned to our hospital because of high fever and headache 3 days ago. Physical examination at admission displayed the following: temperature of 38.8°C, blood pressure of 160/100 mmHg, negative meningeal irritation sign. The primary laboratory examination conducted at our hospital is detailed in. The results of lung imaging indicated normal findings, and there was no evidence of microbes in her blood samples. Non-contrast CT scan of the brain showed no evidence of abnormalities. Nevertheless, the patient tested positive for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) through a nasopharyngeal swab reverse transcription-polymerase chain reaction (RT-PCR) test, leading to the initiation of treatment with dexamethasone and favipiravir for COVID-19. After 3 days, her fever showed no significant improvement and was accompanied by worsening headache. Physical examination revealed no apparent signs of meningeal irritation, so a neurologist was consulted to consider the possibility of meningitis. A lumbar puncture was performed for her and CM was diagnosed when a positive Cryptococcus culture was obtained in the cerebrospinal fluid (CSF) (). Further examination revealed her immune system compromised (). Cyclophosphamide for PNS were temporarily discontinued and prednisone was adjusted to 15 mg/day. Accordingly, amphotericin B liposome (60 mg, once a day) and fluconazole (200 mg, twice a day) were given for her then. We also administered symptomatic supportive treatment, which included improving her daily nutritional intake, giving her intravenous albumin and immunoglobulin, and managing her serum glucose and blood pressure levels. The patient continued to experience a persistent fever for 3 days, however, his body temperature gradually decreased and returned to normal after two weeks (). In addition, we also observed a significant decrease in the lymphocyte counts of the patient upon admission, which returned to normal levels after two weeks of treatment (). The patient’s hemoglobin A1c levels of admission were elevated, indicating her poor recent overall glucose control. Despite experiencing significantly elevated glucose levels upon admission, the patient’s glucose levels generally stabilized after receiving intensified glucose-lowering treatment. The results of the repeated lumbar puncture revealed a decrease in CSF pressure. The CSF appeared colorless and transparent, with no evidence of ink staining or fungal growth. Additionally, there was an improvement in the biochemical indicators of the CSF compared to previous results. Both the blood and CSF antigen titers for Cryptococcus neoformans were lower, indicating the effectiveness of the antifungal treatment for cryptococcosis. The patient experienced gastrointestinal adverse reactions during the antifungal medication process, including complaints of nausea and discomfort in the stomach. However, appropriate symptomatic treatment was provided, resulting in improvement. Then immunosuppressive agents were restarted at a low dosage due to her urinary proteins had obviously increased than before. Four weeks after discharge, her proteinuria was almost stable during the follow-up outpatient.