Abstract

Persistent infections capable of causing central nervous system (CNS) complications months or years after the initial infection represent a major public health concern. This concern is particularly relevant considering the ongoing coronavirus disease 2019 pandemic, where the long-term neurological effects are still being recognized. Viral infections are a risk factor for the development of neurodegenerative diseases. In this paper, we provide an in-depth exploration of the prevalent known and suspected persistent pathogens and their epidemiological and mechanistic links to later development of CNS disease. We examine the pathogenic mechanisms involved, including direct viral damage and indirect immune dysregulation, while also addressing the challenges associated with detecting persistent pathogens. Viral encephalitis has been closely associated with the later development of neurodegenerative diseases and persistent viral infections of the CNS can result in severe and debilitating symptoms. Further, persistent infections may result in the development of autoreactive lymphocytes and autoimmune mediated tissue damage. Diagnosis of persistent viral infections of the CNS remains challenging and treatment options are limited. The development of additional testing modalities as well as novel antiviral agents and vaccines against these persistent infections remains a crucial research goal.

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