Post by Nadica (She/Her) on Oct 3, 2024 1:43:43 GMT
Some Boston doctors are starting to unravel the mysteries of long COVID and find improved treatments for patients - Published Oct 2, 2024
By Adam Piore
There’s still no cure for the debilitating condition. But some front-line clinicians are finding ways to help patients feel better.
Until Elizabeth Kenny shuffled into Dr. David M. Systrom’s clinic at Brigham and Women’s Hospital in May 2022, she’d pretty much given up hope.
Two years earlier, the 50-something actress took to her bed with COVID-19, feverish and exhausted, to wait for her body to repair itself. Instead, Kenny’s 101-degree fever lasted 70 days and left behind a series of life-altering symptoms that perplexed every doctor she’d consulted. She’d stopped sweating. Her body fluctuated between feeling hot and freezing cold. She had so much trouble digesting food that she became malnourished. She developed a stutter. Bright lights made her vision blur. The back of her head often felt like someone had whacked it with a frying pan. Her heart raced. But the worst part was the relentless, soul-crushing exhaustion.
Systrom, she recalls, “was the first person that when I was describing my symptoms, wasn’t going ‘weird,’” said Kenny, who lives in Arlington. “He was like, ‘yep.’ And then asking me questions that nobody had asked.”
Systrom told her that “obviously” Kenny had long COVID. Then he introduced her to a series of unfamiliar words that she would come to know intimately in the weeks that followed: “dysautonomia,” “small fiber neuropathy,” and “mast cell disorder.” It was the beginning of a new phase in her illness. One with hope.
The US Centers for Disease Control and Prevention estimates almost 7 percent, or close to 18 million Americans, are afflicted with the mysterious condition known as long COVID, a syndrome that is so heterogenous, elusive, and difficult to treat, it took a year for some doctors to even acknowledge it was real. In the years that followed, the federal government has doled out more than $1.6 billion to study it, helping to make it one of the most researched diseases in any four years of recorded history. Yet we have little to show for it.
In July, the National Academies of Science, Engineering, and Medicine, at the behest of the Biden administration, published an official definition of the condition. Long COVID occurs after a COVID-19 infection, lasts for at least 3 months, affects one or more organ systems, and includes hundreds of possible symptoms and diagnosable conditions, scientists wrote. But there are still no approved blood tests to diagnose long COVID, no clinically validated treatments, and no cure.
The news is not all bad. Five years in, a small but growing cadre of front-line clinicians such as Systrom are beginning to unravel some of long COVID’s most vexing mysteries. In the process, they are achieving something that once seemed impossible: they are finding ways to help patients, including Kenny, get their lives back.
Doing so requires improvisation, experimentation, and a willingness to work at the edge of medical knowledge. Systrom and his colleagues discuss promising scientific papers and trade tips at conferences, on Zoom calls, and in email chains. Their growing well of anecdotal experience is pointing the way toward the groundbreaking research and clinical trials that will be needed to develop a standard of care in the years ahead as we grapple with a slow-burning public health crisis that shows no sign of abating. While the incidence of long COVID has dropped from roughly 10 percent at the peak of the pandemic to about 3.5 percent among the vaccinated, only about 25 percent of those who develop the condition recover, according to Systrom and other front-line clinicians.
In September 2021, Systrom was among the first clinicians in the nation to demonstrate a measurable change in the physiology of patients suffering from long COVID — and explain how those changes might account for the crushing fatigue that is among its most debilitating symptoms. The study helped establish long COVID as a legitimate condition and overcome the skeptics, said Dr. David Putrino, who runs a long COVID clinic at New York’s Mt. Sinai Hospital.
The study grew out of his experiences with patients: Prior to the arrival of COVID-19, Systrom, a critical care physician who runs a pulmonary clinic at Brigham and Women’s Hospital, had spent years studying chronic fatigue syndrome, also known as myalgic encephalomyelitis, an illness afflicting more than 3 million Americans. When Systrom saw his first long COVID patients — before the condition even had a name — he recognized their symptoms immediately. They were similar if not identical to those reported by patients with chronic fatigue.
To prove it, Systrom had 10 patients don masks and threaded thin, flexible tubes into their jugular veins and major arteries in the forearm to measure the concentration of oxygen absorbed into the lungs, passed into the bloodstream, and taken up by the body’s muscles as they underwent rigorous workouts on stationary bicycles.
Patients who reported symptoms of long COVID absorbed just as much oxygen into their lungs as those without it. But the amount reaching their muscles — oxygen needed to produce the energy required by the exercise — was dramatically reduced, Systrom found.
A growing body of research suggests that both long COVID and chronic fatigue are post-viral syndromes that result in chronic, low-grade inflammation that can damage healthy tissue and, in some cases, the production of auto-antibodies that can attack it.
Systrom and others have begun to catalog the scope of the microscopic carnage caused by the immune system’s friendly fire. Using skin biopsies, Systrom has identified damage to the vast microscopic network of small nerve fibers responsible for sending a wide array of sensory information to the brain. The brain uses that information to regulate involuntary physiologic processes including heart rate, blood flow, temperature, breathing, digestion, and sexual arousal. The result is a condition called “dysautonomia,” a failure of the autonomic nervous system often associated with diabetes as well as autoimmune and degenerative nerve disorders.
They have also identified reductions in mitochondria, the microscopic powerhouses that produce the chemical energy needed to perform basic cellular functions.
For many patients, these findings have been a revelation.
“He’s taken me from feeling completely lost in the woods to at least now just being on the edge of the woods,” Kenny said. “At least now I have a partial understanding of what’s happening to me.”
Perhaps more important, Systrom and others have begun to find ways to blunt the condition’s most debilitating symptoms.
Most front-line treatments are still “anecdotal, based on our hunch and experience that we’ve amassed in the clinic over the past several years,” said Ziyad Al-Aly, a clinical epidemiologist at Washington University in St. Louis and leading long COVID researcher, who runs a long COVID clinic.
To tamp down the toxic low-level inflammation, Systrom often prescribes a low dosage of naltrexone, an anti-addiction drug. He and others recently launched a randomized clinical trial to demonstrate the success they have seen in the clinic. He uses Midodrine, a drug that can cause blood vessels to tighten, to increase blood pressure, which can fall dangerously low due to the problems with autonomic nerve signaling. And he offers Mestinon, approved to treat a chronic autoimmune neuromuscular disease called myasthenia gravis, to improve communication between the small nerve fibers and the brain.
Other promising off-label therapies listed by Al-Awy, Putrino, and others include emergency opioid medications that seem to attenuate brain fog, transdermal patches that deliver mitochondrial supplements, and antihistamines, which can be used to tamp down the overactivation of the immune system’s mast cells in tissues.
These treatments have not been validated by the Food and Drug Administration and the success rate varies by patient type, symptoms, and clinical practice. While Putrino and Systrom both believe the transdermal patches have helped their patients with mitochondrial dysfunction, for instance, Al-Awy has less confidence in their efficacy and is thus far less likely to prescribe them.
For Kenny, these medications make a difference. Today, she can move around her house and do things for five hours a day, instead of just two. Her brain fog has lifted enough that she can write for small windows of time.
She no longer suffers from intestinal distress so severe she has to use the bathroom five times a day.
Her disease feels like a disability, not a death sentence.
“There’s this huge difference depending on which doctor you end up with,” she said. “I could have just as easily been put with a different doctor who doesn’t have Systrom’s background, who would give me that speech: ‘This is a brand new disease. We don’t know anything. This is all emerging. We still don’t know.’ I got lucky.”
By Adam Piore
There’s still no cure for the debilitating condition. But some front-line clinicians are finding ways to help patients feel better.
Until Elizabeth Kenny shuffled into Dr. David M. Systrom’s clinic at Brigham and Women’s Hospital in May 2022, she’d pretty much given up hope.
Two years earlier, the 50-something actress took to her bed with COVID-19, feverish and exhausted, to wait for her body to repair itself. Instead, Kenny’s 101-degree fever lasted 70 days and left behind a series of life-altering symptoms that perplexed every doctor she’d consulted. She’d stopped sweating. Her body fluctuated between feeling hot and freezing cold. She had so much trouble digesting food that she became malnourished. She developed a stutter. Bright lights made her vision blur. The back of her head often felt like someone had whacked it with a frying pan. Her heart raced. But the worst part was the relentless, soul-crushing exhaustion.
Systrom, she recalls, “was the first person that when I was describing my symptoms, wasn’t going ‘weird,’” said Kenny, who lives in Arlington. “He was like, ‘yep.’ And then asking me questions that nobody had asked.”
Systrom told her that “obviously” Kenny had long COVID. Then he introduced her to a series of unfamiliar words that she would come to know intimately in the weeks that followed: “dysautonomia,” “small fiber neuropathy,” and “mast cell disorder.” It was the beginning of a new phase in her illness. One with hope.
The US Centers for Disease Control and Prevention estimates almost 7 percent, or close to 18 million Americans, are afflicted with the mysterious condition known as long COVID, a syndrome that is so heterogenous, elusive, and difficult to treat, it took a year for some doctors to even acknowledge it was real. In the years that followed, the federal government has doled out more than $1.6 billion to study it, helping to make it one of the most researched diseases in any four years of recorded history. Yet we have little to show for it.
In July, the National Academies of Science, Engineering, and Medicine, at the behest of the Biden administration, published an official definition of the condition. Long COVID occurs after a COVID-19 infection, lasts for at least 3 months, affects one or more organ systems, and includes hundreds of possible symptoms and diagnosable conditions, scientists wrote. But there are still no approved blood tests to diagnose long COVID, no clinically validated treatments, and no cure.
The news is not all bad. Five years in, a small but growing cadre of front-line clinicians such as Systrom are beginning to unravel some of long COVID’s most vexing mysteries. In the process, they are achieving something that once seemed impossible: they are finding ways to help patients, including Kenny, get their lives back.
Doing so requires improvisation, experimentation, and a willingness to work at the edge of medical knowledge. Systrom and his colleagues discuss promising scientific papers and trade tips at conferences, on Zoom calls, and in email chains. Their growing well of anecdotal experience is pointing the way toward the groundbreaking research and clinical trials that will be needed to develop a standard of care in the years ahead as we grapple with a slow-burning public health crisis that shows no sign of abating. While the incidence of long COVID has dropped from roughly 10 percent at the peak of the pandemic to about 3.5 percent among the vaccinated, only about 25 percent of those who develop the condition recover, according to Systrom and other front-line clinicians.
In September 2021, Systrom was among the first clinicians in the nation to demonstrate a measurable change in the physiology of patients suffering from long COVID — and explain how those changes might account for the crushing fatigue that is among its most debilitating symptoms. The study helped establish long COVID as a legitimate condition and overcome the skeptics, said Dr. David Putrino, who runs a long COVID clinic at New York’s Mt. Sinai Hospital.
The study grew out of his experiences with patients: Prior to the arrival of COVID-19, Systrom, a critical care physician who runs a pulmonary clinic at Brigham and Women’s Hospital, had spent years studying chronic fatigue syndrome, also known as myalgic encephalomyelitis, an illness afflicting more than 3 million Americans. When Systrom saw his first long COVID patients — before the condition even had a name — he recognized their symptoms immediately. They were similar if not identical to those reported by patients with chronic fatigue.
To prove it, Systrom had 10 patients don masks and threaded thin, flexible tubes into their jugular veins and major arteries in the forearm to measure the concentration of oxygen absorbed into the lungs, passed into the bloodstream, and taken up by the body’s muscles as they underwent rigorous workouts on stationary bicycles.
Patients who reported symptoms of long COVID absorbed just as much oxygen into their lungs as those without it. But the amount reaching their muscles — oxygen needed to produce the energy required by the exercise — was dramatically reduced, Systrom found.
A growing body of research suggests that both long COVID and chronic fatigue are post-viral syndromes that result in chronic, low-grade inflammation that can damage healthy tissue and, in some cases, the production of auto-antibodies that can attack it.
Systrom and others have begun to catalog the scope of the microscopic carnage caused by the immune system’s friendly fire. Using skin biopsies, Systrom has identified damage to the vast microscopic network of small nerve fibers responsible for sending a wide array of sensory information to the brain. The brain uses that information to regulate involuntary physiologic processes including heart rate, blood flow, temperature, breathing, digestion, and sexual arousal. The result is a condition called “dysautonomia,” a failure of the autonomic nervous system often associated with diabetes as well as autoimmune and degenerative nerve disorders.
They have also identified reductions in mitochondria, the microscopic powerhouses that produce the chemical energy needed to perform basic cellular functions.
For many patients, these findings have been a revelation.
“He’s taken me from feeling completely lost in the woods to at least now just being on the edge of the woods,” Kenny said. “At least now I have a partial understanding of what’s happening to me.”
Perhaps more important, Systrom and others have begun to find ways to blunt the condition’s most debilitating symptoms.
Most front-line treatments are still “anecdotal, based on our hunch and experience that we’ve amassed in the clinic over the past several years,” said Ziyad Al-Aly, a clinical epidemiologist at Washington University in St. Louis and leading long COVID researcher, who runs a long COVID clinic.
To tamp down the toxic low-level inflammation, Systrom often prescribes a low dosage of naltrexone, an anti-addiction drug. He and others recently launched a randomized clinical trial to demonstrate the success they have seen in the clinic. He uses Midodrine, a drug that can cause blood vessels to tighten, to increase blood pressure, which can fall dangerously low due to the problems with autonomic nerve signaling. And he offers Mestinon, approved to treat a chronic autoimmune neuromuscular disease called myasthenia gravis, to improve communication between the small nerve fibers and the brain.
Other promising off-label therapies listed by Al-Awy, Putrino, and others include emergency opioid medications that seem to attenuate brain fog, transdermal patches that deliver mitochondrial supplements, and antihistamines, which can be used to tamp down the overactivation of the immune system’s mast cells in tissues.
These treatments have not been validated by the Food and Drug Administration and the success rate varies by patient type, symptoms, and clinical practice. While Putrino and Systrom both believe the transdermal patches have helped their patients with mitochondrial dysfunction, for instance, Al-Awy has less confidence in their efficacy and is thus far less likely to prescribe them.
For Kenny, these medications make a difference. Today, she can move around her house and do things for five hours a day, instead of just two. Her brain fog has lifted enough that she can write for small windows of time.
She no longer suffers from intestinal distress so severe she has to use the bathroom five times a day.
Her disease feels like a disability, not a death sentence.
“There’s this huge difference depending on which doctor you end up with,” she said. “I could have just as easily been put with a different doctor who doesn’t have Systrom’s background, who would give me that speech: ‘This is a brand new disease. We don’t know anything. This is all emerging. We still don’t know.’ I got lucky.”