Months-long waits at long-covid clinics combined with the sluggish pace of research have left vulnerable patients clamoring for immediate care as manufacturers bring novel remedies to market, often with little data behind them.
“I have tried, I would say, as many different things as anyone could do in my situation,” said Donna Davis-Doneghy, a 62-year-old accountant with Hearthside Food Solutions in London, Ky., who has been tormented by headaches since coming down with covid in November 2020.
“People will say to me, ‘Here’s a phone number,’ and off I go chasing something different,” said Davis-Doneghy, whose treatment regimen has ranged from acupuncture and Botox to nerve-block injections and vitamin infusions.
Long covid has taken to new heights a medical conflict that shows up with cancer and other dire diagnoses: the tension between the desire for evidence and the pressing needs of patients who are suffering. In their rush for relief, patients are turning to unproven treatments, putting them at risk of potentially harmful health effects as well as having their hopes dashed and their wallets emptied. Doctors often follow the practice of prescribing drugs off-label, not for the purpose the Food and Drug Administration originally approved them for.
“You want to protect people from charlatans,” said Harlan Krumholz, a professor of medicine at the Yale School of Medicine. “We need to resist the temptation to adopt tests and treatments without sufficient evidence to justify their use.”
But until researchers discover the mechanism — or, more likely, mechanisms — that cause long covid, clinicians are having to rely on their experience treating other illnesses.
“We’re kind of stuck,” said Michelle Haddad, a neuropsychologist who runs a long-covid clinic at Emory Rehabilitation Hospital in Atlanta. “I can define areas where you have impairments and how impaired you are. I can tell you what works in other, similar conditions. But I don’t have a magic pill.”
The scale of the problem — and opportunities for profiteering — are increasing as the number of Americans reporting long-lasting symptoms ramps up to as many as 15 million adults. Data released this summer by the Centers for Disease Control and Prevention suggests that almost 15 percent of the population has had long covid, or symptoms that lasted three months or longer after the acute infection.
Many long-haulers describe being devastated by disabilities that range from fatigue to brain fog and body-wracking tremors. Facing disbelief from their families and physicians, and frustrated by the slow pace of science, they are turning to social media to share ideas for relief.
While some patients report getting insurance coverage for the treatment of some symptoms, such as migraines, many end up spending thousands of dollars, out of pocket. Robert Harris, a 48-year-old veteran in Texas, estimates he has paid $25,000 for treatments, from over-the-counter supplements to the horse dewormer ivermectin and hyperbaric oxygen. “I can’t figure out what research is being done, what treatments have been approved,” he said.
The $1.15 billion Recover program, awarded nearly two years ago to the National Institutes of Health, is aimed at understanding the biological basis of long covid. Establishing the safety and efficacy of potential treatments involves a further step — setting up randomized controlled trials. Although NIH recently announced its intent to investigate the potential impact of the antiviral Paxlovid, results are not expected until 2024, reinforcing some scientists’ argument for a more agile research model to match the urgency of the moment.
“Government-sponsored and government-funded mechanisms are designed for incremental innovation — for steady and safe discoveries,” said David Putrino, director of rehabilitation innovation for Mount Sinai Health System in New York.
Under the swiftly changing circumstances of the pandemic, smaller research teams, advocacy groups and private companies with a variety of standards have stepped in — often without robust scientific evidence that the products actually work.
“We are the ETSY of long covid — DIY but giving you something the establishment can’t,” tweeted Ram Yogendra, an anesthesiologist with the California company IncellDx, referring to the company’s do-it-yourself approach, modeled on the online craftsmanship marketplace. IncellDx purports to have developed a diagnostic blood test for long covid.
Using machine learning to identify what is unusual in long-haulers’ blood, IncellDx claims to have found an immune signature or “cytokine profile” for the condition. The company, which has received a patent for using the HIV drug maraviroc to treat coronaviruses, has published three studies, enrolling more than 700 patients.
Krumholz said immune signatures are likely to become important for diagnosis and treatment. But after reviewing the data on the IncellDx website, he warned about the dangers of researchers rushing to adopt tests before the evidence is sufficient. “The evidentiary standards need to be much higher and the transparency about the science much greater than we have today to justify widespread use,” he said.
The $415 diagnostic test has been used by about 10,000 people, creating a “tremendous database,” according to Bruce Patterson, the former Stanford virologist who leads the company. The results, Patterson said, can be used to inform personalized treatment protocols typically administered by the patients’ primary care providers. A company spokeswoman said many long-haulers pay an additional $250 for a follow-up consultation and buy additional tests to check how the therapy is working. She said the company recognizes that the data need to “evolve” and said that IncellDX is helping people in the meantime.
Patterson, who said he is working on contracts for clinical trials of a “drug combination that we think works,” said it is up to patients and their doctors to decide how to proceed with treatment. “We do what clinical pathologists should do: ‘Here is a test report, you treat accordingly,’” he said. Company doctors are available to offer guidance, Patterson said.
But Alba Azola, a physical medicine and rehabilitation specialist at Johns Hopkins Medicine, said she has treated patients who report having spent hundreds of dollars for the tests and then don’t know what to make of the results.
“They bring it to me, like, ‘Look at this,’” Azola said. “And I’m, ‘I don’t know what to do with that.’”
Other long-haulers, including Harris, have paid for treatments promoted by groups linked to vaccine hesitancy and anti-science messaging.
Among them is the Front Line Covid-19 Critical Care Alliance, a nonprofit that promotes the anti-parasitic ivermectin not only for the prevention and treatment of acute covid but also as part of its long-covid protocol. The alliance publishes a list of pharmacies that will supply ivermectin, approved by the FDA to treat some parasitic worms, head lice and skin conditions like rosacea in humans. But the drug has not been shown to be effective in the treatment of acute covid illness. The American Medical Association and other professional groups oppose using the drug for covid outside of clinical trials because of its potential toxicity.
The alliance was co-founded by Pierre Kory, a critical-care physician who touted ivermectin as a “miracle drug” in Senate testimony and also runs a private telemedicine practice where he treats long-haulers. Kory, who charges $1,650 for an initial video consultation, follow-ups and check-in calls according to patients’ needs, said the drugs he prescribes, including ivermectin, steroids and anti-inflammatories, are safe.
In an interview, Kory said he does not follow the AMA’s position on ivermectin because the association provides general guidance but does not treat people. Other researchers say that the risks of the drug are known and that its benefits have not been shown.
“Based on the lack of effectiveness in acute covid, combined with what we know about long covid, it is extremely unlikely that ivermectin would be beneficial for someone suffering from long covid,” said Francesca Beaudoin, head of the Brown University School of Public Health’s Long Covid Initiative.
Kory also criticized the research community for being too slow to keep up with patient needs.
“We’re stuck right now trying to help patients with trial and error until the science evolves,” he said. “All of my patients get better to some extent.”
Among the most common online offerings are dietary supplements, which do not have to meet the same regulatory standards as pharmaceuticals. While drugs must be shown to be safe and effective before they reach the consumer, there are no such provisions for the FDA to regulate vitamins, herbs and amino acids.
One of the most widely touted supplements among long-haulers is Vedicinals-9, a new herbal suspension that purports to support “the human organism in the recovery phase from viral infections.”
The nutraceutical is made in India, where it is regulated as a food for special medical purpose, or FSMP, and then shipped around the world. A 42-day supply costs $95, according to the product website.
Harris said he bought several boxes but that the solution didn’t reduce the muscle spasms and pain he has suffered since testing positive 10 months ago. Other patients have reported benefits.
The company’s founder, retired German businessman Joachim Gerlach, said he had long been interested in finding natural remedies for chronic illness, which he has witnessed among family members. He turned his attention to acute covid in early 2020, Gerlach said, hoping, as long covid emerged, to find a common approach that would help large numbers of people. He believes that many symptoms stem from an imbalance of the gut bacteria that can help combat disease.
Gerlach, who has reached out to prominent long-covid researchers around the world to plan research next year, said his progress on long covid was “lacking a little bit on the side of publishing.” But by financing Vedicinals out of his own pocket, he said, he can “act fully in the patient’s interest” without pressure from shareholders.
New tests and products keep cropping up.
Earlier this month, QMC Health, a diagnostic testing technology company, announced its intention to produce a long-covid rapid test, based on blood biomarkers.
MDHyperbaric, a company in New York, offers oxygen therapy for a variety of conditions, from healing bones to slowing aging and improving long-covid symptoms, saying it plans to measure long-hauler outcomes.
And in October, Norman B. Gaylis, a Miami-based rheumatologist, collaborated with Tel Aviv researchers to release an “all-natural, patented formula RESTORE,” described on the company’s website as “proven by clinical study” to improve symptoms of covid long-haulers.
That study, published in Frontiers in Nutrition, involved 51 patients with positive coronavirus tests who reported lingering symptoms three to 11 months after infection. On average, the participants reported that their symptoms were milder after two weeks and better still after four, according to the study.
The study is small and lacked a control group to assess whether the patients’ symptoms would have improved anyway over time or whether their self-reported improvements resulted from a placebo effect.
“Obviously, a double-blind control is more valuable,” Gaylis said in a telephone interview. “Between time and cost and urgency, these things take so long, we felt it was sufficient.” The biggest endorsement of the product, he said, was that so many people who took part in the study asked to buy it.
Without solid data about treatments, some primary care physicians have fallen into a “kitchen-sink approach,” according to Haddad, the rehabilitation specialist at Emory.
Haddad saw one patient who had been prescribed Benadryl and several other sedating drugs in addition to an antidepressant that she was already taking. When the patient complained of brain fog, her doctor added Adderal, a stimulant — a little like chasing shots of hard liquor with double espressos.
“They kept throwing things at the post-covid,” Haddad said. “They didn’t step back and ask, ‘Could medications be part of the culprit?’”
Meanwhile, clinicians who are running long-covid clinics at major medical centers are drawing on their experience treating conditions with similar symptoms, such as ME/CFS, or chronic fatigue syndrome; POTS, a blood circulation disorder that causes a rapid heartbeat; and what’s known as post-ICU syndrome.
“We’re using a lot of experience, anecdotal evidence and related evidence with other conditions,” said Benjamin Abramoff, director of the Post-COVID Assessment and Recovery Clinic at Penn Medicine. “A lot of the things we do have not gone through trials.”
Many rehab experts have been meeting at CDC-funded monthly webinars to pool the expertise they are gaining and come up with guidance published by the American Academy of Rehabilitation and Physical Medicine.
There are likely to be therapeutic benefits to some of the treatments long-haulers are trying. A few small studies have suggested hyperbaric oxygen may provide relief. The spice turmeric, or curcumin — an ingredient found in Vedicinals and the Front Line Covid-19 Critical Care Alliance’s protocols — has anti-inflammatory properties. The key, clinicians say, is to evaluate the risk/benefit ratio for every therapy, including potentially detrimental interactions with other medications.
“For things patients are interested in trying, I won’t dissuade them if the risk of harm is low,” said Jeffrey Fine, director of rehabilitation medicine at NYU Langone Hospital, who said he tries “to meet patients where they are.”
In the meantime, patients continue their own research, through online resources such as Twitter.
“It’s my social life, my family, my research library,” said Molly Gordon, a 69-year-old executive coach in Washington state who gradually pieced together a self-diagnosis of mast cell activation syndrome — a condition akin to allergic reactions — that she believes came from long covid. Gordon said she is putting about $500 a month of her retirement savings toward supplements and cannabis.
Those networks have turned long-covid care into an international free-for-all, as patients search for therapies overseas, often with little idea of the regulatory oversight — or lack thereof.
Laura Wright, 45, a reflexologist in England, joined Twitter to glean information from fellow sufferers around the world about how to combat the fatigue that has plagued her since she came down with covid a year ago. She tried hyperbaric oxygen and began taking “every supplement under the sun and adding new ones every month,” Wright said, including garlic, hawthorn, B-12 and magnesium, until she began wondering whether they were doing her more harm than good.
She went cold turkey. With one exception: Boluoke.
Wright has pinned her hopes on the earthworm extract that is thought to promote circulatory health. A bottle of 30 capsules, which she imports from Canada, costs about $55.
“If I can get back to working again, then it will be worth it,” Wright said.