When COVID-19 Breaches the Brain

COVID-19 has ravaged the world population for over a year, and most still think of the disease as a respiratory infection. However, while it starts in the airways, the virus that causes COVID-19, SARS-CoV-2, can affect other body systems—the heart, the skin, the blood vessels, and, yes, even the brain.

In the acute and severe stage, the most common effect on the brain is a temporary condition known as delirium. People hospitalized with
COVID-19 are at high risk for developing the disorder, which is characterized by fluctuating attention and disorientation, emotional extremes, agitation, hallucinations, and paranoia—or sometimes the opposite, a very flat emotional expression.

The sleep-wake cycle is usually disrupted, and the delirium classically gets worse as the day progresses. In the hospital it’s not uncommon to see a patient who is perfectly alert and aware in the morning become confused and hallucinating by the afternoon.

Typically, delirium affects 10 to 15 percent of hospitalized patients on the general medical floors and 50 to 70 percent of patients in the ICU. It can be caused by all sorts of things—infections, medications, withdrawal, surgery—and seems to be a common brain reaction to serious illness or consciousness-altering medications. Delirium is associated with longer hospital stays, more complications, and a higher risk of death.

In the context of COVID-19, much longer than normal ICU stays under heavy sedation and restrictions on family visitation mean delirium is extremely likely for very ill patients. In the elderly or in others with pre-existing brain conditions, delirium can sometimes be the first symptom of illness. Alteration of consciousness and behavioral disruption are sometimes the reason families bring their loved ones to the emergency room, only to have them diagnosed with COVID-19.

Delirium can be frightening and even dangerous. Patients, in fear and confusion, can try to escape, pull out IVs, catheters, and breathing tubes, and even attack family or staff.

However, delirium is temporary. Symptoms tend to improve with time, the treatment of underlying causes, minimal disruption of sleep, and the presence of familiar items like family photos at the bedside. The condition does not lead to lasting psychosis, although sometimes there can be psychiatric consequences, such as anxiety or flashbacks.

An Unflagging Fog

But SARS-CoV-2 can have other direct effects on the brain and nervous system. There have been documented cases of encephalitis (brain infection), spinal cord infection, seizures, nerve damage, neurodegeneration, and neuroinflammation. SARS-CoV-2 particles have been found in the brain, proving it can be a target of infection.

High levels of brain inflammation can lead to such symptoms as memory loss, cognitive fog, and/or depression, which, after already lasting as long as ten months, could continue indefinitely after the acute disease. Up to 45 percent of patients in the hospital experience some sort of neurological symptom—headache, loss of taste or smell, stroke, or confusion.

While most COVID-19 patients are never hospitalized and have full recovery, there is a growing cohort of “long-haulers”—people who are still unwell months after the initial infection. Many of these patients were never ill enough to be hospitalized but nevertheless experience long-term fevers, crippling fatigue, cognitive fog, fluctuations in vital signs such as tachycardia (high heart rate), and/or inability of the body’s blood pressure regulation system to compensate for postural changes, leading to dizziness on standing or changing position.

In one study, 69 percent of “long-COVID” patients described abnormal levels of fatigue, with 15 percent acknowledging symptoms of clinical depression when assessed nearly two months after discharge. Mady Hornig, a psychiatrist at Columbia University’s School of Public Health who has long studied the role of infectious factors in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), was left with chronic fatigue herself after a presumed COVID-19 infection in March. For weeks after becoming ill, she was often so tired that she says, “I felt as though I could not do anything further—my brain was just empty.”

The common cognitive fog is described as difficulty thinking, remembering details, or making decisions. The cause is unknown, but is thought to be related to the body’s immune response to the inflammatory effects (also known as inflammation) of the virus on the blood vessels in the brain. For many, these symptoms have lasted for months with no end in sight.

Some scientists have undertaken specific measures of cognitive functioning in people who have been ill with COVID-19. One team of researchers examined over 84,000 patients who had participated in the Great British Intelligence Test. They repeated the cognitive testing, making note of those who had suffered COVID-19 in the meantime and of how serious the illness was. Patients took the second test only after they had recovered from the acute symptoms of their infection.

In the post-COVID-19 participants, researchers found reductions in cognitive function, including greater difficulties in problem-solving, visual attention, and spatial working memory. The deficits seemed to track with how ill the subjects had been with coronavirus infection; those who were able to recover at home and needed no oxygen were less affected than those who remained home but needed oxygen.

The greatest cognitive changes were recorded in those who had been hospitalized and needed the assistance of a ventilator. The most severely affected experienced the equivalent of 10 years of cognitive aging and an 8.5 point drop in IQ. The researchers don’t know how long the deficits last—or whether they are permanent.

In the past, cognitive testing done pre- and post-illness of people with respiratory infections severe enough to require ventilator use also showed new intellectual problems that lasted as long as five years. What was a surprise to the British researchers, however, were the milder deficits in people who had COVID-19 but were never sick enough to need hospitalization. They suspect that even in those with a mild illness, COVID-19 affects oxygen levels in ways that may be responsible for some injury to the brain.

Sudden Psychosis

Another psychiatric manifestation of COVID-19 is rare but frightening—the development of new-onset psychosis. This disorder of thinking can include delusions, hallucinations, and/or disorganization of thought or behavior. Hallucinations in psychiatric disorders tend to be auditory (hearing voices or conversations that don’t exist), but they can also be tactile (such as feeling bugs crawling over the skin during severe alcohol withdrawal), visual, or even olfactory (much more likely to have a neurologic cause, like a seizure).

Delusions are a false, fixed belief—for example, that the government has hired the neighbors to spy on you as they walk their dogs. The “disorganization” entails sometimes being so out of touch with reality that it is difficult to eat, change clothes, or dress, and speech can become fragmented or even mute. Psychosis can be caused by drug or alcohol intoxication and withdrawal, medical illness, high fever, cancer, tumors, steroids, and primary psychiatric disorders, among other things.

Psychotic symptoms are known to occur often with serious illness, strokes, and seizures. COVID-19 can be complicated with strokes and even inflammation/infection of the brain itself, making neurological complications, including new psychotic symptoms, along with delirium, expected. Dramatic as they are, such symptoms become especially concerning when millions of people are sick at the same time.

A young person with no psychiatric history and no other signs of COVID-19 might suddenly brandish a knife at a family member in the psychotic belief that the relative is about to kill him. Psychiatrists know that such symptoms can occur with other infections, particularly viruses that can enter the brain.

It’s not their novelty that makes such phenomena notable—but that the sheer fact of mass infection magnifies what is otherwise a rare if alarming presentation. Just as respiratory infections can cause gastrointestinal distress and skin rashes, they can also trigger neurologic and psychiatric symptoms.

Other patients start out with signs of mild COVID-19 infection—perhaps a few minor neurologic symptoms, such as headache or loss of smell—then weeks or months later present with florid psychosis. As The New York Times reported: “The patient, a 42-year-old…mother of four young children, had never had psychiatric symptoms or any family history of mental illness. Yet there she was, sitting at a table in a beige-walled room at South Oaks Hospital…sobbing and saying that she kept seeing her children, ages 2 to 10, being gruesomely murdered and that she herself had crafted plans to kill them.”

It’s highly unusual for a 42-year-old otherwise healthy person with no psychiatric history to suddenly show up with psychosis in the absence of drugs or a brain tumor. Schizophrenia tends to begin in the late teens to early thirties, and paranoia associated with dementia commonly presents in later years. But this illness does happen; it’s called delusional disorder.

The delusions occur with neither the memory loss and the gradual cognitive decline seen in dementia nor the hallucinations and disorganization typical of schizophrenia. Often there is no known cause, but there are case reports of their happening after celiac disease, treatment with acne medication, or, along with other psychotic symptoms, after herpes encephalitis.

Delusional disorder can usually be treated with medication, but sometimes it lasts indefinitely. Although it is not a well-studied phenomenon, it is likely that the disorder has some sort of metabolic, infectious, or medication origin, one that may be quite minor—perhaps a virus that caused a headache months earlier. Again, it is not surprising that such rare cases are manifesting with COVID-19—what is remarkable is that there are so many of them right now because so many people are infected by the pandemic—well over 200,000 cases a day in the U.S. at the time of writing.

It Won’t Be Over When It’s Over

The vast majority of people will recover from COVID-19 and be fine. But some previously healthy people with mild illness will still struggle with long-haul symptoms of brain fog and fatigue.

Most of the worst complications, including psychiatric and cognitive problems, will predictably affect only those most seriously ill. Given the vast number of people requiring hospitalization, however, we can expect serious disabilities from COVID-19—both physical and mental—to follow our society for years to come.

Scientists are actively studying how COVID-19 affects the brain. That information will help in treating those afflicted with the psychiatric sequelae of the disease.

For now, the best course is to prevent infection in the first place. Mass vaccinations and nonpharmacologic interventions such as masking and social distancing are as important for the health of the brain as they are for our lungs and blood vessels.