BACKGROUND Prion disease (PrD) is one of the rapidly progressive dementias. It typically requires several diagnostic criteria to fulfill a probable diagnosis, as definite diagnosis is based on isolated brain biopsy. There has been much debate on a possible infectious etiology of PrD. Viral infections are commonly pathologic in most neurodegenerative conditions. In PrD, misfolded proteins can be contagious and act as infective proteins, regardless of the pathologic agent. There is evidence that COVID-19 can result in neurologic manifestations, and neurodegeneration has been reported in the literature. There are several case reports describing parkinsonism after COVID-19, with Parkinson's disease in particular noted in COVID-19. Few cases of PrD were reported after COVID-19 infection. We identified 1 case of PrD in the setting of COVID-19 at our hospital. CASE REPORT We report the case of a 62-year-old man admitted to Mount Sinai Queens Hospital Center, who presented with rapidly progressive dementia along with difficulty walking and myoclonus. All workup results were negative. He underwent MRI brain, but results were not revealing. Due to the high clinical suspicion, CSF protein 14-3-3 testing was ordered and was positive. Clinically, he experienced worsening neurological function after having been COVID-19-positive on admission. The case fulfilled the probable diagnostic criteria for diagnosing PrD. The patient continued to deteriorate and died due to the rapid progression of his condition. CONCLUSIONS Our case demonstrates the potential correlation of COVID with neurodegenerative conditions, especially prion disorders. While such cases are highly likely to be due to COVID-19, there is no definite evidence beyond coincidental findings. Future studies might be required to establish this correlation.