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Long COVID Now Looks like a Neurological Disease, Helping Doctors to Focus Treatments
The causes of long COVID, which disables millions, may come together in the brain and nervous system
By Stephani Sutherland on February 14, 2023
Scientific American February 2023 Issue
Tara Ghormley has always been an overachiever. She finished at the top of her class in high school, graduated summa cum laude from college and earned top honors in veterinary school. She went on to complete a rigorous training program and build a successful career as a veterinary internal medicine specialist. But in March 2020 she got infected with the SARS-CoV-2 virus—just the 24th case in the small, coastal central California town she lived in at the time, near the site of an early outbreak in the COVID pandemic. “I could have done without being first at this,” she says.
Almost three years after apparently clearing the virus from her body, Ghormley is still suffering. She gets exhausted quickly, her heartbeat suddenly races, and she goes through periods where she can't concentrate or think clearly. Ghormley and her husband, who have relocated to a Los Angeles suburb, once spent their free time visiting their “happiest place on Earth”—Disneyland—but her health prevented that for more than a year. She still spends most of her days off resting in the dark or going to her many doctors' appointments. Her early infection and ongoing symptoms make her one of the first people in the country with “long COVID,” a condition where symptoms persist for at least three months after the infection and can last for years. The syndrome is known by medical professionals as postacute sequelae of COVID-19, or PASC.
People with long COVID have symptoms such as pain, extreme fatigue and “brain fog,” or difficulty concentrating or remembering things. As of February 2022, the syndrome was estimated to affect about 16 million adults in the U.S. and had forced between two million and four million Americans out of the workforce, many of whom have yet to return. Long COVID often arises in otherwise healthy young people, and it can follow even a mild initial infection. The risk appears at least slightly higher in people who were hospitalized for COVID and in older adults (who end up in the hospital more often). Women and those at socioeconomic disadvantage also face higher risk, as do people who smoke, are obese, or have any of an array of health conditions, particularly autoimmune disease. Vaccination appears to reduce the danger but does not entirely prevent long COVID.
The most common, persistent and disabling symptoms of long COVID are neurological. Some are easily recognized as brain- or nerve-related: many people experience cognitive dysfunction in the form of difficulty with memory, attention, sleep and mood. Others may seem rooted more in the body than the brain, such as pain and postexertional malaise (PEM), a kind of “energy crash” that people experience after even mild exercise. But those, too, result from nerve dysfunction, often in the autonomic nervous system, which directs our bodies to breathe and digest food and generally runs our organs on autopilot. This so-called dysautonomia can lead to dizziness, a racing heart, high or low blood pressure, and gut disturbances, sometimes leaving people unable to work or even function independently.
The SARS-CoV-2 virus is new, but postviral syndromes are not. Research on other viruses, and on neurological damage from the human immunodeficiency virus (HIV) in particular, is guiding work on long COVID. And the recognition that the syndrome may cause its many effects through the brain and the nervous system is beginning to shape approaches to medical treatment. “I now think of COVID as a neurological disease as much as I think of it as a pulmonary disease, and that's definitely true in long COVID,” says William Pittman, a physician at UCLA Health in Los Angeles, who treats Ghormley and many similar patients.
Although 16 million U.S. sufferers is a reasonable estimate of the condition's toll, there are other, more dire assessments. A meta-analysis of 41 studies conducted in 2021 concluded that worldwide, 43 percent of people infected with SARS-CoV-2 may develop long COVID, with about 30 percent—translating to approximately 30 million people—affected in the U.S. Some studies have offered more conservative numbers. A June 2022 survey reported by the U.S. National Center for Health Statistics found that among adults who had had COVID, one in five was experiencing long COVID three months later; the U.K. Office for National Statistics put the estimate at one in 10. Even if only a small share of infections result in long COVID, experts say, they will add up to millions more people affected—and potentially disabled.
Most of the first recognized cases of long COVID were in patients who needed extended respiratory therapy or who had obvious organ damage that caused lasting symptoms. People reporting neurological symptoms were often overlooked or dismissed as traumatized by their initial illness and hospitalization. But as 2020 came to an end, says Helen Lavretsky, a psychiatrist at the University of California, Los Angeles, “we started getting to a place of sorting through what was really going on ... and it became very evident at that time that neuropsychiatric symptoms were quite prevalent,” most commonly fatigue, malaise, brain fog, smell loss and post-traumatic stress disorder, as well as cognitive problems and even psychosis.
Ghormley was in her late 30s and relatively healthy when she caught the virus, but she had underlying conditions—including rheumatoid arthritis and asthma—that put her at risk for severe COVID. She spent several days at home, struggling to breathe, and then she went to the hospital, where her blood pressure soared and her blood glucose dropped precipitously. She mostly recovered from this acute phase within a few weeks, but, she says, “I never really got better.”
