How COVID Affects the Brain and Nervous System

SARS-CoV-2 can damage the brain and nervous system through several overlapping routes, from direct inflammation of blood vessels to immune overreaction to lingering viral proteins at the borders of the brain itself. The neurological toll ranges from familiar early symptoms like lost smell and headaches to longer-lasting problems with memory, concentration, and autonomic control that persist months or even years after the initial infection. What makes COVID unusual is not that a respiratory virus can affect the nervous system, but the sheer breadth of neurological complications it produces and the number of people affected.

Neurological Symptoms During Acute Infection

Even during the first days and weeks of illness, COVID frequently announces itself with neurological symptoms. Headache, dizziness, and the signature loss of taste and smell are among the most common, but the range extends to far more serious complications: encephalopathy (a broad disruption of brain function), encephalitis (outright brain inflammation), and stroke.¹ Early cohort data found encephalopathy in a significant minority of hospitalized patients and in the majority of those in intensive care. Stroke appeared in roughly two to six percent of hospitalized cases, and Guillain-Barré syndrome, a condition in which the immune system attacks peripheral nerves, was reported in dozens of early case series.²

These acute neurological events tend to be more common in severe illness, but milder infections are not exempt. Many people with otherwise unremarkable cases notice persistent headaches, concentration problems, or sensory disturbances that only become more noticeable once the fever and cough have cleared.

How the Virus Reaches the Brain

The brain is normally shielded by the blood-brain barrier, a tightly sealed lining of specialized cells that keeps most pathogens and large molecules out of the central nervous system. SARS-CoV-2 appears to breach this barrier primarily by passing through the endothelial cells themselves rather than squeezing between them. In animal studies, researchers found that the tight junctions holding barrier cells together remained intact, yet the virus still made it through, suggesting a transcellular route.³

Once the virus interacts with the blood-brain barrier, things escalate. Infected neurovascular cells ramp up enzymes that degrade the structural scaffolding of the barrier, and the resulting leakiness triggers a cascade of inflammatory signaling. This inflammatory surge recruits immune cells and activates the brain’s resident immune sentinels, astrocytes and microglia, compounding the damage.⁴ Separately, lab studies of human brain endothelial cells exposed to SARS-CoV-2 showed inflammatory activation through specific signaling pathways and changes in how the cells’ mitochondria function, further contributing to barrier breakdown and neuroinflammation.⁵

Why COVID Steals Your Sense of Smell

Loss of smell was one of the earliest recognized neurological hallmarks of COVID. The mechanism, however, is not what many people assume. The virus does not typically infect olfactory neurons directly. Instead, it targets the supporting cells that surround and sustain those neurons, called sustentacular cells. When these support cells become infected, the olfactory lining undergoes rapid and massive damage, and the immune response that follows disrupts the tissue’s normal architecture.⁶

This distinction matters for recovery. Because the neurons themselves are largely spared, most people eventually regain their sense of smell as the supporting tissue regenerates. A comprehensive review of the mechanisms confirmed that neuronal infection in the olfactory system is extremely rare, and that indirect effects on support cells are the primary driver of COVID-related smell loss.⁷ For a minority of people, however, full recovery takes many months, and some report persistent distortions like parosmia, where familiar odors smell wrong or unpleasant.

Brain Fog and Lasting Cognitive Problems

The neurological story of COVID does not end when the infection clears. The cluster of symptoms people call “brain fog” includes difficulty concentrating, slowness in processing information, trouble retrieving words, and a general feeling that thinking requires unusual effort. Systematic reviews consistently find that executive function, memory, attention, and processing speed are the cognitive areas most affected in long COVID.⁸

Within executive function, the most consistently impaired abilities include mental flexibility, the capacity to switch between tasks, and working memory, which is the ability to hold and manipulate information in your mind while using it. Inhibitory control, the capacity to resist impulsive responses and stay focused, also shows measurable deficits in testing.⁹ One study found that mental flexibility was affected in over a third of participants who had recovered from COVID, even though most scored normally on a basic screening tool for general cognitive function.¹⁰

The neuroinflammatory response driven by microglia, the brain’s immune cells, is a leading candidate for why these cognitive symptoms persist. Even if the virus does not directly infect many brain cells, the inflammatory aftermath can linger and disrupt normal neural function. Current evidence suggests that aberrant microglial activity after infection may put people at higher risk for memory issues and other neuropsychiatric complications.¹¹

Changes Visible on Brain Imaging

Structural brain changes after COVID are not just a matter of subjective complaints. MRI studies of young, otherwise healthy adults who recovered from mild infections have found measurable reductions in cortical thickness and in the volume of deeper brain structures compared with matched controls. In one study, the COVID group also had smaller olfactory bulbs on the right side, consistent with the virus’s known effects on the smell-processing regions of the brain.¹²

These findings are striking because the participants were young and their infections were mild. It remains unclear whether these structural changes reverse over time or what they mean for long-term brain health, but they provide an objective marker that even uncomplicated COVID infections leave a physical trace on brain tissue.

Spike Protein Lingering at the Brain’s Borders

One of the more unsettling discoveries has been that SARS-CoV-2 spike protein can persist in tissues at the boundary of the brain long after the active infection is gone. Researchers using advanced imaging on post-mortem samples found spike protein in the skull bone marrow, the meninges (the membranes surrounding the brain), and in the brain’s frontal cortex. In many of these samples, no active viral RNA was detectable, yet the protein remained. Spike protein was found in the skull marrow of patients who had died from unrelated causes months after their COVID infection had resolved.¹³

The presence of spike protein in these areas was associated with activation of immune cells and microbleeds in the brain tissue. The implication is that even after the body clears the live virus, leftover viral proteins at the skull-meninges-brain axis may continue to provoke inflammation and could contribute to the neurological symptoms people experience months down the line.¹⁴

Adding to the concern, a separate study of post-mortem brains found abnormal accumulation of a hallmark Alzheimer’s-associated protein, hyperphosphorylated tau, in the hippocampus and nearby regions within four to thirteen months of recovery from acute COVID. Prolonged activation of glial cells and elevated inflammatory markers were present even though the virus itself could not be detected in those brain regions.¹⁵ This does not mean COVID causes Alzheimer’s disease, but it raises the possibility that the infection could accelerate neurodegenerative processes already underway, particularly in older adults.

Blood Biomarkers and What They Tell Us

Researchers have been searching for blood-based markers that could objectively measure nervous system injury from COVID. Two proteins have gotten the most attention: neurofilament light chain (NfL), which is released when nerve fibers are damaged, and GFAP, which is released when a particular type of brain support cell becomes activated. In post-mild COVID patients, blood levels of both NfL and GFAP were significantly elevated compared to healthy controls. Those with the worst self-reported cognitive failures had the highest levels of both markers.¹⁶

In critically ill COVID patients studied at follow-up, GFAP levels were higher in those who showed cognitive dysfunction compared to those who did not.¹⁷ However, the picture is not perfectly clear. A more recent study that carefully adjusted for confounders like age, sex, and kidney function found that initial group differences in these biomarkers between long COVID patients and recovered controls largely disappeared after adjustment.¹⁸ In other words, these biomarkers show promise for tracking acute injury but may be less useful as standalone diagnostic tools for long COVID’s neurological effects once you account for individual differences.

Autonomic Dysfunction and POTS

COVID does not only affect the brain. The autonomic nervous system, which controls heart rate, blood pressure, digestion, and other functions you do not have to think about, is a frequent casualty. The most common expression is postural orthostatic tachycardia syndrome, or POTS, in which standing up triggers an exaggerated spike in heart rate along with dizziness, lightheadedness, and fatigue. In a large cohort of highly symptomatic long COVID patients, about a third met the diagnostic criteria for POTS. Those affected tended to be younger and were overwhelmingly female, and their physical activity levels were significantly lower than patients without POTS.¹⁹

The mechanisms behind post-COVID POTS are still being worked out, but likely involve autoimmune damage to autonomic nerve fibers and disrupted regulation of adrenaline-related hormones. Some patients have shown normalization of their catecholamine levels after infection, and individual cases have documented clinical improvement over time.²⁰

Peripheral Nerve Damage

The peripheral nervous system, which lies outside the protective confines of the blood-brain barrier, has been particularly vulnerable to post-COVID complications. COVID has been linked to Guillain-Barré syndrome, myasthenia gravis, and small fiber neuropathy, the latter causing burning pain, tingling, and abnormal sensations in the hands and feet.²¹ In one case-control study, patients diagnosed with small fiber neuropathy on skin biopsy after COVID were predominantly female, with a median age of 47.²²

Small fiber neuropathy is easy to miss because standard nerve conduction studies do not detect it. Diagnosis requires a skin biopsy to count the density of small nerve fibers. If you are dealing with unexplained burning, tingling, or pain in your extremities after COVID, this is worth raising with your doctor, because the standard tests they run first may come back normal.

Autoimmune Attacks on the Nervous System

COVID can also trigger the immune system to turn on the nervous system itself. Autoantibodies directed against neural targets have been identified in the blood and spinal fluid of patients with severe COVID-related neurological symptoms. These include antibodies against NMDA receptors, myelin (the insulating coating on nerve fibers), and other neuronal proteins.²³ SARS-CoV-2 has been shown to induce production of anti-NMDA receptor autoantibodies, which can cause autoimmune encephalitis, a serious and treatable condition that produces confusion, psychosis, seizures, and movement abnormalities.²⁴

This autoimmune dimension is important because it means some of the most dramatic neurological complications of COVID are potentially responsive to immunotherapy. Recognizing autoimmune encephalitis, for instance, changes the treatment approach entirely compared with assuming the brain dysfunction is purely from the viral infection.

Neuropsychiatric Effects

Depression, anxiety, and insomnia frequently accompany the neurological damage from COVID. Over 30 percent of patients hospitalized with COVID showed cognitive impairment, depression, or anxiety persisting for months after discharge, with even higher rates among those who had been in intensive care.²⁵ A two-year prospective study found that at follow-up, roughly one in ten had clinically relevant anxiety or depression, while nearly four in ten still reported clinically significant fatigue. People who had headache or breathing difficulty at the time of their initial infection had roughly two and a half times the odds of anxiety at follow-up.²⁶

Large population-level data from South Korea and Japan confirmed that both the short-term and long-term risks of developing neuropsychiatric conditions were elevated in COVID patients compared with the general population and those with other respiratory infections. The list of conditions showing increased long-term risk included cognitive deficits, insomnia, anxiety, mood disorders, and stroke.²⁷ The fact that COVID’s neuropsychiatric risks outpaced those from other respiratory infections suggests this is not simply the psychological toll of being seriously ill; there is likely a biological component driven by the neuroinflammation and vascular damage described earlier.

Children Are Not Immune

Neurological complications in children were initially underappreciated, but large studies have since documented them in detail. Among children hospitalized with acute SARS-CoV-2 infection, about 18 percent had a severe neurological event, including encephalopathy, seizures, or delirium. The rate was even higher, roughly 25 percent, among those hospitalized with multisystem inflammatory syndrome in children (MIS-C), a post-infectious inflammatory condition.²⁸

Among survivors with severe neurological events, roughly 28 percent left the hospital with new neurocognitive or functional problems they did not have before admission. Children with severe neurological manifestations had roughly double the odds of new morbidity at discharge compared with those who were hospitalized but did not experience neurological complications.²⁹ The longer-term neurodevelopmental consequences of COVID in children remain poorly understood, and this is an area where research is still catching up.³⁰

Does Vaccination Help Protect the Brain?

The relationship between vaccination and COVID’s neurological effects is more nuanced than a simple yes or no. A large U.S. study found that people who received a bivalent booster had about 40 percent lower risk of developing long COVID with multiple symptoms at six months, with the reduction driven largely by neurological and general symptoms like fatigue.³¹ Separately, a survey of people already living with long COVID found that about 58 percent reported overall symptom improvement after vaccination, with average symptom scores improving by roughly 22 to 31 percent depending on the vaccine received.³²

However, one study specifically examining neurological manifestations in long COVID patients found that vaccination before infection did not significantly alter the neurological profile of those who went on to develop long COVID anyway.³³ The takeaway: vaccination appears to reduce your chances of developing long COVID in the first place, and may help if you already have it, but if long COVID with neurological features does develop in a vaccinated person, the pattern of neurological symptoms looks similar to that in unvaccinated patients.

Treatment Approaches for Brain Fog and Neurological Symptoms

Approved treatments specifically targeting long COVID’s neurological effects remain elusive, a point that multiple recent reviews have underscored.³⁴ That said, several interventions have shown promise in early studies. Noninvasive brain stimulation and hyperbaric oxygen therapy have both been associated with improvements in brain fog, with evidence suggesting they may work by improving blood flow to the brain and adjusting cortical activity levels. Rehabilitation strategies, including structured cognitive rehabilitation programs, have also shown benefit.³⁵

On the pharmacological side, researchers are exploring compounds targeting mitochondrial energy production and inflammation in the brain’s blood vessels, drawing on what has been learned from chronic fatigue syndrome and other conditions with overlapping symptoms. But much of this evidence is still indirect, coming from related conditions rather than dedicated long COVID trials.³⁶ For now, the practical advice is to work with a neurologist or rehabilitation specialist who is familiar with long COVID, since the management typically involves combining cognitive rehabilitation with symptom-specific treatments for issues like sleep disruption, autonomic dysfunction, and pain.

Impact on Work and Daily Functioning

The cognitive effects of COVID translate directly into problems at work and in everyday life. In a study of non-hospitalized patients, three-quarters reported reduced quality of life at work within the first four weeks of infection, and over half still reported it more than twelve weeks later. The strongest predictors of workplace impairment were trouble with multitasking and difficulty recalling previously learned information.³⁷ People with long COVID also showed measurably lower physical and mental quality of life scores, along with a 26 percent higher mental disability score, compared to those who recovered without long-term symptoms.³⁸

The difficulty answering questions clearly and the impaired ability to juggle multiple tasks can be especially devastating for people in knowledge-work or client-facing roles. These are not vague complaints but measurable deficits that persist well beyond the acute illness, and they underscore why long COVID has become a significant occupational health concern. For individuals navigating this reality, neuropsychological testing can help document the specific areas of difficulty, which in turn can support workplace accommodations and disability claims where needed.