Long COVID, the Brain, Nerves, and Cognitive Function

Abstract

SARS-CoV-2, a single-stranded RNA coronavirus, causes an illness known as coronavirus disease 2019 (COVID-19). Long-term complications are an increasing issue in patients who have been infected with COVID-19 and may be a result of viral-associated systemic and central nervous system inflammation or may arise from a virus-induced hypercoagulable state. COVID-19 may incite changes in brain function with a wide range of lingering symptoms. Patients often experience fatigue and may note brain fog, sensorimotor symptoms, and sleep disturbances. Prolonged neurological and neuropsychiatric symptoms are prevalent and can interfere substantially in everyday life, leading to a massive public health concern. The mechanistic pathways by which SARS-CoV-2 infection causes neurological sequelae are an important subject of ongoing research. Inflammation- induced blood-brain barrier permeability or viral neuro-invasion and direct nerve damage may be involved. Though the mechanisms are uncertain, the resulting symptoms have been documented from numerous patient reports and studies. This review examines the constellation and spectrum of nervous system symptoms seen in long COVID and incorporates information on the prevalence of these symptoms, contributing factors, and typical course. Although treatment options are generally lacking, potential therapeutic approaches for alleviating symptoms and improving quality of life are explored.

Keywords: COVID-19; brain fog; long COVID syndrome; memory; neuroinflammation; neurologic sequelae; neuron.

Figure 1

Possible mechanisms underlying neurologic symptoms in long COVID. Multiple factors are postulated to contribute to neurologic manifestations of long COVID. Persistent systemic inflammation leads to cytokine production, immune system activation, and production of reactive oxygen species. Increased blood-brain barrier (BBB) permeability allows cytokines to penetrate the brain and induce neuroinflammation. A more porous BBB may also permit direct viral invasion of the brain. Tissue hypoxia may occur due to microclot formation. ↑ = increased.

Figure 2

Sensorimotor effects of long COVID. Long COVID can cause multiple symptoms in the periphery affecting nerves and muscles as depicted in this figure. Patients may experience nerve pain or paresthesias, most often due to involvement of small nerve fibers. Muscle pain and weakness and joint pain can also be part of long COVID syndrome. Causes of these manifestations are not completely understood, but may result from inflammation and infection-triggered immune system dysregulation. Vasculitis with microclots may also damage nerve and muscle.