When Liza Fisher’s body became racked by tremors shortly after she was hospitalized with COVID-19 in 2020, she began an 18-month medical odyssey, consulting immunologists, cardiologists, neurologists and countless other -ologists in the hope they would know how to treat the crippling convulsions.
“They had no experience,” said Fisher, 38, a former flight attendant and part-time yoga instructor who now uses a wheelchair. So Fisher sought out fellow sufferers online, joining an increasingly vocal group of citizen scientists in their bid for research targeted at treating long COVID.
Fisher’s experience—and those of her fellow sufferers—is advancing a revolution in research not just for COVID but also many other conditions, experts say. Patients, who have typically been only subjects in the research process, are becoming partners in it.
They are documenting their symptoms online in real time, as well as helping to come up with questions and strategies for surveys and, eventually, to disseminate results.
Think of it as the guinea pigs working alongside the scientists.
“We bring experiential knowledge and have enough of an outsider’s perspective to see inefficiencies that people enmeshed in the system can’t see,” said Diana Zicklin Berrent, founder of Survivor Corps, a patient advocacy group that has been collaborating with researchers at Yale and other medical centers.
It is the latest step in the growing understanding that partnering with patients is not only the just and equitable thing to do but also that it can improve research. In the late 1980s, as the HIV/AIDS epidemic gained momentum, ACT UP and other groups successfully pushed to move drugs more quickly through the development pipeline. In 2010, the Affordable Care Act injected funding into patient-centered research.
All the while, advances in technology have mobilized patients to share emotional support, as well as real-time data about their symptoms online. Those forces have coalesced around long COVID, prompting studies at major medical centers such as the University of South Carolina and Yale University that involve patients in every stage of research.
In many cases, experts say, researchers’ scientific goals differ from those of patients, particularly during a pandemic in which large numbers of patients prioritize finding immediate treatments.
“What is relevant to policymakers and clinicians is not always what is most important for patients,” said Nabil Natafgi, an assistant professor in the department of health services policy at the University of South Carolina’s Arnold School of Public Health. Natafgi said the pandemic has forced researchers to rethink how best to engage patients in research and make it more relevant for them.
Natafgi’s colleagues recently enrolled 15 patient experts as part of a virtual “patient engagement studio” that will include patient experiences in all stages of research. Martha Griffin, a school science coordinator in Austin who retired in 2020 after developing long COVID, is one of them. She has been frustrated by recent research that focused on the virus itself and failed to take into account the human cost of living with fatigue and brain fog that makes even small tasks, like filling in researchers’ surveys, daunting.
“I would like for researchers to understand: What are the clues that would help our quality of life?” said Griffin, 62. “And not in five years. We need something right now.”
The need to find treatments for long COVID has become increasingly urgent as the country shifts toward accepting the coronavirus as a constant lower-level threat. The government estimates that between 7.7 and 23 million people may already have long COVID. Last month Sen. Tim Kaine, the Democrat of Virginia, who still experiences tingling after a 2020 bout of COVID, introduced a bill with the support of patient advocacy groups to expand treatment resources for people experiencing long-term effects.
That, experts say, requires involving from the earliest phases people who have intimate knowledge of living with long COVID. The approach upends the traditional top-down process, in which clinical trials are designed by researchers at major academic medical centers and require patients to play largely by their rules: Volunteers typically show up in person at labs to give samples or for other kinds of in-person evaluations. The results are often published in densely written academic journals, aimed primarily at answering scientific questions rather than immediate patient concerns.
Only gradually have researchers and regulators come to recognize the importance of patient input, according to Mark Wolff, chief health analytics strategist at the global data analytics company SAS. Along with evaluating the safety and efficacy of a new drug or treatment, in recent years regulators began to include patients’ evaluations of what level of risk they might be willing to accept as part of that evaluation.
Katherine R. Tuttle, a nephrologist at the University of Washington, has seen how patient perspectives can alter the way researchers do their work. She recalled a lab scientist who was so moved by speaking with patients that he vowed never again to throw away unused tissue. Only later did he discover that the frozen samples would prove key to advances in his work.
Tuttle, an intern in Chicago in the 1980s, and other researchers look back on the HIV/AIDS epidemic as a pivotal moment for patient advocacy. Steven Epstein, author of “Impure Science: AIDS, Activism, and the Politics of Knowledge,” recalls how groups such as ACT UP began to use their shared experiences to advance the development of drugs. They challenged investigators who wanted to exclude participants already taking other medications, forcing scientists to work instead with populations that looked more like the real world even if the data from such a study might end up being less clear-cut.
The activists “learned expert knowledge so people took them seriously,” Epstein said, foreshadowing the online advocacy that has developed around long COVID. “They had this other kind of experiential knowledge, and then they were able to gain allies among groups of experts.”
By 2012, the government was in on the game, establishing PCORI, or the Patient-Centered Outcomes Research Institute, an independent nonprofit, under the Affordable Care Act that calls for all stakeholders, including patients, to be involved throughout the research process.
Then along came COVID—and long COVID.
Pandemic restrictions precipitated a new “all-hands-on-deck approach” to research, recalled Tuttle, with scientists turning to couriers to deliver study drugs and patients collecting samples and monitoring their symptoms at home.
At the same time, the virus threw up surprises, from the breadth of symptoms it produced to the growing awareness that some patients didn’t fully recover or developed new symptoms—like Fisher.
Without a long COVID medical playbook to fall back on, Cindy Ivanhoe, a specialist in neurological rehabilitation at UTHealth Houston/TIRR Memorial Hermann who oversees Fisher’s treatment, said she had to draw on her experience with a condition with which she was already familiar: dysautonomia, or the dysfunction of the nerves regulating involuntary functions such as heart rate, blood pressure and sweating.
From the researcher’s point of view, that very lack of accumulated medical science has created new possibilities.
“There were no specialists,” said Harlan Krumholz, a cardiologist at Yale who has long believed in empowering patients in the research process. “The people who had the wisdom [about long COVID] were the people experiencing it.” And that Krumholz, said “opened a lot of people’s eyes to a different way of doing research.”
Research is often impaired by patients dropping out of studies or not following the scientists’ protocols closely, Krumholz said. And who better to come up with research questions than the people who have a vested interest in finding a cure? Who better understands the challenges of showing up to submit samples? And who is better equipped to disseminate the results of a study than a group of fellow sufferers?
Krumholz and his wife, Leslie, are using a for-profit platform they developed to test the patient-first philosophy, using technology to gather data from patients.
Hugo Health allows patients to link health-related data from electronic health records, their pharmacy and smartwatch, while promising not to share the data unless patients give permission. The first Hugo study in 2016 examined readmission and emergency department use after a patient was discharged from hospital.
The platform is hosting a COVID-specific community, Kindred, where patients can get peer support and expert information as well as answering surveys and polls, closing the gap between real-time patient experience and academic research. Harlan Krumholz and his Yale colleague immunologist Akiko Iwasaki plan to launch a study using data from the community to link people with similar symptom patterns with potential biological mechanisms, such as evidence of lingering virus in the body or changes in how the immune system is functioning.
Iwasaki collaborated with Survivor Corps for a previous study, drawing on the group’s membership to help with enrollment for a study that examines how vaccines might improve the symptoms of long COVID.
The approach contrasts with work at the National Institutes of Health, which more than a year ago received $1.15 billion from Congress to launch a four-year initiative to identify its causes.
The RECOVER initiative is composed largely of epidemiological and observational trials, enrolling tens of thousands of patients from all 50 states, as well as people who were not infected to serve as comparison.
“It will be a national treasure once it’s assembled,” said Bruce Levy, principal investigator of one part of the initiative, the Greater Boston COVID Recovery Cohort. “But it’s not really structured for quick answers, that’s for sure.”
The project does take a patient-driven approach, Levy said, putting an emphasis on including diverse patient groups. Levy, who described the support of patient advocacy groups as “extremely helpful, ” said their loud voices can sometimes drown out those less versed in online support groups. “Black and brown communities don’t have the same level of advocacy,” he said.
The scope of NIH initiative goes beyond long COVID, according to Walter Koroshetz, director of NIH’s National Institute of Neurological Disorders and Stroke and RECOVER’s co-chair. “It’s a ‘how do you get to the moon’ type of project,” he said, aimed at also understanding post-viral conditions such as chronic fatigue, or ME/CFS, that have mystified scientists for decades. “If there’s a quick answer and somebody from any country would get that answer it would be great,” he said.
But NIH’s sweeping ambition frustrates some physicians as well as patient advocates: What was the gold standard for collecting data on, say, heart attacks, which went through decades of research before clinicians came up with the best treatment, is poorly suited to a widespread emergency, they say.
“With heart disease, it wasn’t as if every 50-year-old had heart attacks,” said Kavita Patel, a primary care physician and health policy expert. “The difference this time is we have never had an entire globe suffering this much morbidity and devastation.”
Berrent believes that long COVID will change how research is done. “Once you’ve seen science move at warp speed, you’ll never go back,” she said.
She and Fisher are now listed along with fellow members of Survivor Corps and Yale and University of Pennsylvania researchers as co-authors of study that has not yet been peer reviewed on tremors among people with long COVID.
Using information from Survivor Corps’ approximately 200,000 members, the researchers were able to identify common themes in their descriptions of their symptoms as well as the responses from medical professionals.
Fisher never thought she would co-author a scientific study. But there’s little about the last two years that she could have anticipated.
“I came to terms with being a guinea pig when I was in hospital. It was a joke, and I came to realize it was not an actual joke,” Fisher said. “The way I get through it is: This will help others.”
By that, she means other people beyond the long COVID community who will stand to gain from patient-centered research.
“I don’t think this is just trending; this is transforming,” Fisher said.