COVID-19, Neuropathology, and Aging: SARS-CoV-2 Neurological Infection, Mechanism, and Associated Complications

Abstract

The spectrum of health complications instigated by coronavirus disease 2019 (COVID-19, caused by the novel severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2) pandemic has been diverse and complex. Besides the evident pulmonary and cardiovascular threats, accumulating clinical data points to several neurological complications, which are more common in elderly COVID-19 patients. Recent pieces of evidence have marked events of neuro infection and neuroinvasion, producing several neurological complications in COVID-19 patients; however, a systematic understanding of neuro-pathophysiology and manifested neurological complications, more specifically in elderly COVID-19 patients is largely elusive. Since the elderly population gradually develops neurological disorders with aging, COVID-19 inevitably poses a higher risk of neurological manifestations to the aged patients. In this report, we reviewed SARS-CoV-2 infection and its role in neurological manifestations with an emphasis on the elderly population. We reviewed neuropathological events including neuroinfection, neuroinvasion, and their underlying mechanisms affecting neuromuscular, central- and peripheral- nervous systems. We further assessed the imminent neurological challenges in the COVID-19 exposed population, post-SARS-CoV-2-infection. Given the present state of clinical preparedness, the emerging role of AI and machine learning was also discussed concerning COVID-19 diagnostics and its management. Taken together, the present review summarizes neurological outcomes of SARS-CoV-2 infection and associated complications, specifically in elderly patients, and underlines the need for their clinical management in advance.

Keywords: COVID-19; SARS-CoV-2; aging; neurodegenerative disease; neuroinfection; neuroinvasion; neuropathology; pandemic.

Figure 1

Coronavirus disease 2019 (COVID-19) neuro-pathophysiology: COVID-19 clinical manifestations associated with diverse neuronal systems/organs including the peripheral nerve, parenchymal, cerebrovascular, meningeal, spinal cord, neuromuscular, and cranial nerve in SARS-CoV-2-infected patients.

Figure 2

Schematic diagram showing potential modes of SARS-CoV-2 neuroinfection via neuronal/nervous, epithelial-humoral, infected immune/lymphatic, and lymphatic-cerebrospinal fluid routes.