Case Description: A 64-year-old Caucasian male presented with acute worsening of progressive neurological decline with difficulty in vision and reading. The patient was diagnosed with Coronavirus disease 2019 (COVID-19). Following COVID-19 infection he started to have difficulty in maintaining balance, poor attention span and expressive aphasia.

Based on history, examination, CSF markers, histopathology, and T2/FLAIR MRI Brain at the time of presentation the patient was diagnosed with PML in a setting of no immunosuppression disorder.

In our literature review, it was seen that the average age of symptom presentation was 57.5 with predominance in males. Most of the patients presented with progressive neurological deficits with symptomology ranging from mild confusion, aphasia, anxiety to sensory disturbances with numbness, hemiparesis and hemianopsia. Out of the 21 cases, patients responded to mirtazapine and intravenous pulse methylprednisolone (IVMP). The mortality rate was close to 50% with 11 fatal cases and 10 non-fatal cases. None of the cases had any immunosuppressive conditions or underlying HIV, malignancy, solids organ or stem cell transplants and were not on immunosuppressive medications.