COVID-19, caused by the SARS-CoV-2 virus, is primarily known for its respiratory effects. However, its impact extends beyond the lungs, significantly affecting the brain and nervous system. Diverse neurological manifestations can occur, ranging from immediate, acute symptoms during infection to prolonged issues that can persist for months or even years. This highlights the complex interplay between the virus and the body’s neurological functions.
Acute Neurological Manifestations
During the active phase of COVID-19 infection, individuals can experience a range of neurological symptoms. Common acute neurological symptoms include loss of smell (anosmia) and taste (ageusia). Anosmia was reported in 5–35% of hospitalized patients. Headaches are also frequently reported, appearing in up to 8% of patients.
Fatigue and general malaise are widespread during the acute illness. Many patients describe “brain fog,” characterized by difficulty concentrating and impaired memory. Dizziness and lightheadedness are also common.
More severe, though less common, acute neurological events can also occur. These include cerebrovascular events, such as strokes, which have been observed in COVID-19 patients. Seizures and encephalopathy, a condition causing altered mental status, have also been reported during the acute phase of the disease. These severe manifestations show the virus’s potential to impact the central nervous system.
Mechanisms of Brain Involvement
The ways in which SARS-CoV-2 affects the brain and nervous system are complex, involving several biological pathways.
A prominent mechanism is the body’s inflammatory response, often called a “cytokine storm.” This state, characterized by an excessive release of immune signaling molecules (cytokines), can lead to widespread inflammation, including in the brain. Pro-inflammatory cytokines can cross the blood-brain barrier, which normally protects the brain, resulting in neuroinflammation and neuronal damage.
The virus can also impact the brain through vascular issues. COVID-19 can cause blood vessel damage, increasing the risk of blood clots and impaired blood flow within the brain. These microclots can block blood flow to neurons, potentially leading to microbleeds or ischemic injury. SARS-CoV-2 spike proteins can bind to endothelial cells lining brain blood vessels, making the blood-brain barrier more permeable and allowing inflammatory agents to enter the brain.
Hypoxia, or oxygen deprivation, is another significant contributor to neurological effects. Severe respiratory illness can lead to reduced oxygen levels in the blood, which can then deprive brain cells of adequate oxygen. Prolonged lack of oxygen can cause brain damage and contribute to cognitive impairment. Localized brain hypoxia has been observed in some post-COVID-19 patients, even with normal systemic oxygen levels.
Direct viral invasion of the brain is a possible, though less common, route. SARS-CoV-2 may enter the central nervous system via the olfactory nerve, which transmits smell signals, explaining the common loss of smell symptom. Evidence of viral particles has been detected in olfactory regions. The virus can directly infect nerve and glial cells, though this is not considered the primary mechanism for most neurological symptoms.
Autoimmune responses also play a role in neurological complications. The immune system, fighting the virus, may mistakenly attack the body’s own brain cells. This can occur through mechanisms like molecular mimicry, where viral components resemble self-proteins, leading to the production of autoantibodies that target nervous system tissues. Such autoimmune reactions are implicated in various neurological conditions observed after viral infections.
Persistent Neurological and Cognitive Impacts
Beyond the acute phase, many individuals experience long-lasting neurological and cognitive issues, often described as “Long COVID” or post-COVID conditions. These persistent symptoms significantly affect daily life and are distinct from the initial acute illness.
Chronic brain fog is a commonly reported symptom, affecting around 60% of individuals. This involves ongoing difficulties with memory, concentration, and executive functions. While most people with COVID-19-related brain fog recover within 6 to 9 months, some experience these cognitive difficulties for 18 months or more.
Chronic fatigue is another long-term symptom, reported by nearly half of individuals with Long COVID. This extreme tiredness is not alleviated by rest and can interfere with daily activities. It often presents with other symptoms, including muscle aches and sleep problems.
Persistent headaches and dizziness are also frequently reported long after the initial infection. Lingering sensory disturbances, such as changes in smell (parosmia) or phantom smells (phantosmia), can continue for extended periods. These altered perceptions of smell and taste negatively affect quality of life.
Psychiatric and mood changes represent a significant component of long-term impacts. Increased rates of anxiety and depression have been observed since the pandemic began. Symptoms of anxiety and depression were reported by 23% of patients in one study following hospital discharge. Post-traumatic stress disorder (PTSD) and psychosis can also develop. These mental health challenges stem from both the virus’s biological effects on the brain and the psychological stress of illness, isolation, and the pandemic.