The virus SARS-CoV-2 is primarily known for attacking the respiratory system, but evidence confirms its effects extend directly and indirectly to the central nervous system (CNS). Research has identified a spectrum of neurological symptoms and the biological pathways that lead to them. This article explores the specific types of neural injury seen during the acute illness and the persistent, long-term consequences affecting survivors.
Observed Neurological Manifestations
During the active phase of COVID-19, patients frequently present with a range of acute neurological symptoms. A common complaint is “brain fog,” characterized by difficulty with concentration, impaired memory, and mental sluggishness. This cognitive disruption can occur even in individuals who experience only a mild case of the respiratory illness. More severe manifestations include acute cerebrovascular events, specifically ischemic and hemorrhagic strokes, observed even in younger individuals. The temporary loss of smell (anosmia) and taste (ageusia) were among the earliest and most distinctive signs of neurological involvement, suggesting damage to the supporting cells in the olfactory epithelium or disruption of neural pathways.
Pathways of Neural Damage
The mechanisms by which SARS-CoV-2 causes neurological injury are complex, with indirect damage being the most prevalent.
Systemic Inflammation
One significant pathway involves systemic inflammation, often referred to as a cytokine storm, where the body’s overactive immune response releases an excessive amount of inflammatory proteins. These inflammatory mediators can cross the blood-brain barrier (BBB). Once inside the central nervous system, this neuroinflammation can lead to injury and dysfunction of neurons.
Vascular Injury
A second major mechanism is related to vascular injury and a hypercoagulable state within the body. SARS-CoV-2 has been shown to attack the endothelial cells that line the blood vessels, causing damage and promoting the formation of blood clots. This process leads to the formation of micro-clots, which restrict blood flow in the brain’s tiny vessels, depriving brain tissue of oxygen and causing microvascular damage.
Direct Neurotropism
The possibility of direct neurotropism, where the virus directly invades and infects brain cells, remains a topic of ongoing research and debate. While some studies have shown the virus’s ability to infect neurons, the consensus suggests that indirect damage from inflammation and vascular issues is the primary driver of neurological symptoms in humans. The virus’s spike protein binds to the ACE2 receptor, and evidence suggests a pathway for invasion via the olfactory bulb, though direct viral load in the brain is often low.
Persistent Cognitive and Neurological Sequelae
For many survivors, neurological issues extend far beyond the acute phase of the illness, leading to Post-Acute Sequelae of COVID-19 (PASC), or Long COVID. These are lasting effects that persist for weeks or months after the initial infection has cleared. PASC often includes a constellation of chronic cognitive and mental health issues.
Chronic Cognitive Impairment
The acute brain fog can evolve into a chronic cognitive impairment that is a hallmark of Long COVID. This sustained “Long COVID brain fog” involves measurable biological changes, rather than simply fatigue or psychological stress. Studies have linked this persistent cognitive deficit to a leaky blood-brain barrier, which allows inflammatory molecules to continually affect the brain. Research has also identified a molecular signature involving excessive activity of AMPA receptors, suggesting a disruption in neural signaling essential for learning and memory.
Mental Health Implications
The lasting impact of the infection also manifests as an increased incidence of mental health implications, including anxiety, depression, and post-traumatic stress disorder (PTSD). These neuropsychiatric symptoms are associated with the sustained neurobiological changes caused by the infection. Ongoing, low-grade neuroinflammation, indicated by markers like elevated inflammatory cytokines, is thought to interfere with neurogenesis and synaptic plasticity, contributing to both the cognitive and mood disturbances.