Early on, patients with both mild and severe Covid-19 say they can’t breathe. Now, after recovering from the infection, some of them say they can’t think.
Even people who were never sick enough to go to a hospital, much less lie in an ICU bed with a ventilator, report feeling something as ill-defined as “Covid fog” or as frightening as numbed limbs. They’re unable to carry on with their lives, exhausted by crossing the street, fumbling for words, or laid low by depression, anxiety, or PTSD.
As many as 1 in 3 patients recovering from Covid-19 could experience neurological or psychological after-effects of their infections, experts told STAT, reflecting a growing consensus that the disease can have lasting impact on the brain. Beyond the fatigue felt by “long haulers” as they heal post-Covid, these neuropsychological problems range from headache, dizziness, and lingering loss of smell or taste to mood disorders and deeper cognitive impairment. Dating to early reports from China and Europe, clinicians have seen people suffer from depression and anxiety. Muscle weakness and nerve damage sometimes mean they can’t walk.
“It’s not only an acute problem. This is going to be a chronic illness,” said Wes Ely, a pulmonologist and critical care physician at Vanderbilt University Medical Center who studies delirium during intensive care stays. “The problem for these people is not over when they leave the hospital.”
Doctors have concerns that patients may also suffer lasting damage to their heart, kidneys, and liver from the inflammation and blood clotting the disease causes.
No one can yet tell patients with neurological complications when, or if, they’ll get better, as doctors and scientists strive to learn more about this coronavirus with each passing day. Their guideposts are the experience they’ve gained treating other viruses and delirium after ICU stays, sparse results from brain autopsies, and interviews with patients who know something is just not right.
“We would say that perhaps between 30% and 50% of people with an infection that has clinical manifestations are going to have some form of mental health issues,” said Teodor Postolache, professor of psychiatry at the University of Maryland School of Medicine. “That could be anxiety or depression but also nonspecific symptoms that include fatigue, sleep, and waking abnormalities, a general sense of not being at your best, not being fully recovered in terms of the abilities of performing academically, occupationally, potentially physically.”
John Bonfiglio, 64, counts himself among the fortunate ones. He remembers nothing between sitting in Newton-Wellesley Hospital’s emergency department with a fever and waking up 17 days later in the Massachusetts hospital’s ICU. He’d been on a ventilator, lying prone until his failing kidneys meant he needed to be flipped over onto his back for dialysis. Weak and confused from his ordeal after moving to a regular hospital floor, he tried to slip around his bed’s guardrails and slid to the floor. Nurses would routinely ask his name and if he knew where he was. One day he answered “Las Vegas.”
Bonfiglio chalks that up to post-ICU disorientation that included his feeling more emotional. Ordinarily “not a crier,” as he put it, he would choke up sometimes. More troubling were the persistent dizziness, muscle weakness, and tremors in his hands that made it impossible to put his contact lenses in his eyes.
He was discharged to Spaulding Rehabilitation Hospital in nearby Charlestown, Mass., where he spent the balance of his 51-day hospitalization — during which he saw no family members since suggesting to his daughter that she go home from the emergency room that night in April.
From his early days in rehab, when sitting up in bed was exhausting, to learning how to walk again with a walker, to finally going home to Waltham, Mass., Bonfiglio lost 40 pounds — “all muscle.” He’s regained some of his strength, and weight, now. His dizziness and tremors are gone. And his mind is clear.
He’s back driving part-time for a food-delivery service, and he jokes that being in a drug-induced coma meant he missed the pandemic’s surge in Massachusetts. When he visited the Newton-Wellesley ICU after a checkup, he couldn’t remember any of the staff there. He does remember what one nurse said as he was leaving the hospital for Spaulding: “‘You are the first person that is going to rehab and not to hospice,’ she told me. So I feel extremely lucky, you know, just making it through.”
Vanderbilt’s Ely worries about patients who emerge from the ICU with more serious problems than Bonfiglio’s, including delirium caused by high-potency drugs like benzodiazepines and nerve damage from low oxygen levels.
“And then they’re getting isolated. When they’re isolated and away from family, it makes it worse,” Ely said. Later, “they’re having either post-traumatic stress disorder, anxiety disorder, depression, or cognitive impairment, and some combination of all of that. So these people are really in for some neurologic and mental health problems.”
Right now, there is little that researchers can say definitively about how best to prevent and treat neuropsychological manifestations of Covid-19. Nor do they know for certain why the brain is affected.
“It’s sort of like you’re trying to put out the fire and then a little bit later, you go look at the nervous system as the embers,” said Victoria Pelak, professor of neurology and ophthalmology at the University of Colorado School of Medicine. “Because you are so concerned with the raging fire, you haven’t really been able to pay attention to the nervous system as much as you normally would.”
She and others are piecing the story together. So far the virus appears to cause its damage to the brain and nervous system not as much through direct infection as through the indirect effects of inflammation. Pieces of the virus, not actual viruses multiplying, can trigger an inflammatory response in the brain, said Lena Al-Harthi, chair of the Department of Microbial Pathogens and Immunity at Rush Medical College.
“If you have an uncontrolled level of inflammation, that leads to toxicity and dysregulation,” she said. “What I am concerned about is long-term effects, obviously in the people who have been hospitalized, but I think it’s definitely time to understand long-term sequelae for those individuals who have never been hospitalized. They’re young, too. We’re not talking about [only] older individuals, but people that are 30.”
Fred Pelzman, who practices internal medicine in New York City, fell sick with Covid-19 in March but has yet to recover fully. He doesn’t have his wind back, or his normal sense of taste and smell. His patients who have had Covid-19 are suffering from varying degrees of depression, anxiety, or Covid fog. One can’t do simple math calculations in her head any more. Others don’t feel as mentally sharp, struggling to find the right words to say. His colleagues tell him their patients, too, dread being reinfected with the virus.
“It’s hard to separate the physical from the psychological score, and we know they are intimately related,” he said. “It’s hard to separate the Covid-19 signal from the social justice upheaval and global warming and politics and the pandemic and anxiety of just being, you know, isolated and working at home and economic turmoil and all the rest.”
Neurocognitive testing, psychiatric evaluation, and diagnostic imaging might help determine the cause for these problems, Pelzman said, but not having a baseline for comparison could make that challenging, especially when hospitals are racing to keep patients breathing and prevent blood clots from forming and clogging blood vessels or triggering strokes — common problems caused by Covid-19.
“Strokes are larger, potentially more damaging with this disorder. Once inflammation or blood vessel problems occur within the nervous system itself, those people will have a lot longer road to recovery or may die from those illnesses,” Colorado’s Pelak said.
Doctors are also watching for a syndrome called demyelination, in which the protective coating of nerve cells is attacked by the immune system when there is inflammation in the brain. As in the autoimmune disease multiple sclerosis, this can cause weakness, numbness, and tingling. It can also disrupt how people think, in some cases spurring psychosis and hallucinations. “We’re just not sure if this virus causes it more commonly than other viruses,” Pelak said.
In Italy, three Covid-19 patients with no previous history of neurologic or autoimmune disorders developed myasthenia gravis, a disease that weakens the arm and leg muscles, causes double vision, and leads to difficulties speaking and chewing. While such symptoms could follow the viral infection of nerve cells, it’s also possible that an autoimmune mechanism — the body attacking healthy cells — is at work, the group reporting these cases said.
Recovery from Covid-19 often begins in rehab. Ross Zafonte, chief medical officer at Spaulding, said he is seeing some patients’ cognitive and brain-related issues last for much longer than expected. That includes depression, memory disorders, and PTSD, as well as muscle and peripheral nerve damage that makes mobility difficult. For some patients, their mental awareness has been slow to recover.
“We’re trying to follow people long term and do a longitudinal study to see what are the comorbid factors,” he said. “What are the characteristics of people who don’t get back to normal? How can early intervention try to deal with that? Are there some biomarkers of risk? Can we try to define better targets for early intervention?”
Maryland’s Postolache thinks Covid-19 infection might act as a “priming event” for problems to resurface in the future. Psychological stress could reactivate behavioral and emotional problems that were initially triggered by the immune system responding to the virus. “What we call psychological versus biological may actually be quite biological,” he said. “We don’t really say this is permanent … but considering all complexities of human life, it’s unavoidable.”
Ely of Vanderbilt suggests three things to do now.
“We can open the hospitals back up to the families. That’s important,” he said. “We can be aware of these problems and tell the families about them so that the families will know that this is coming. [And] we can do counseling and psychological help on the back end.”