Zach Ault is fitted with an EEG cap which uses...

Zach Ault is fitted with an EEG cap which uses electrodes to track the electrical activity of his brain, at the National Institutes of Health's hospital in Bethesda, Maryland, in November 2019. Ault had ME/CFS, what once was called "chronic fatigue syndrome," and was part of a study aiming to uncover clues to how the mysterious disease steals patients' energy. Credit: AP/Federica Narancio

If the pandemic feels endless to most healthy people, that sentiment is dramatically magnified for people living with long COVID. The suite of lingering symptoms can include debilitating fatigue, as well as lung, heart and neurological problems, and there are few treatments. Considering that as many as 40% of COVID patients go on to report symptoms at least one month after their diagnosis, millions of Americans may be suffering from a new type of chronic illness.

For people like JD Davids, long-COVID symptoms are eerily familiar. A 54-year-old trans organizer who lives with several chronic diseases, Davids has been deeply involved with health advocacy campaigns for decades. He cut his teeth on HIV/AIDS activism in the 1990s, serving in AIDS clinical trial groups that helped shape National Institutes of Health research and inform scientists working on treatments. Later, working with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) advocates, he saw that it took decades for perceptions of that disease to change and for patients to be taken seriously: Originally seen as a psychosomatic problem that mainly affected women, it's now recognized as a complex, chronic illness with clear biological markers.Having been plagued by symptoms of ME/CFS himself, and later developing symptoms of long COVID, the overlap between the two illnesses seemed apparent.

"That's the thing many of us experience with 'mild' cases [of COVID]. They are super life-changing," Davids said. "'Mild' is quite profound."

When Davids learned that the NIH was launching Recover, a massive $1.15 billion initiative to study long COVID, he was enthusiastic about the opportunity for patients to help shape the research in a way that looked more like the HIV/AIDS model than the ME/CFS one. They had certainly been trying: Since the first months of the coronavirus pandemic, people with "milder" symptoms who had expected to recover had been maintaining that infection can, and often does, lead to prolonged illness. Even the name "long COVID" — and the insistence that it deserved serious investigation — came directly out of patient testimonies that gathered momentum on social media. (Compare that with the name "chronic fatigue syndrome," established by the Centers for Disease Control and Prevention in 1988 in part to avoid linking the disease to a potential viral trigger and indicate that its cause was still unknown.)

As early as May 11, 2020, the Patient-Led Research Collaborative published a preliminary report on COVID-19 symptoms and recovery (or lack thereof) with 640 survey participants, followed by a survey with more than 3,700 participants released in December 2020. "What we have is a bunch of people who are newly ill or disabled who are struggling to help, who have very specific skills, some as data-oriented people or researchers," Davids says of long-covid patient advocates who want to partner with researchers for the NIH Recover Initiative. "We're trying our best to learn what's going on," he said, but the lack of communication and transparency has made it hard to know how the study is evolving.

In the best-case scenario, the NIH long-COVID research could be a glimpse into the future of how we study chronic diseases. It's an undeniable opportunity: a new disease that has a well-funded, interdisciplinary research program in Recover — and millions of patients who want to contribute their data and experiences.

But advocates say the program's success depends on whether patients have a meaningful role in shaping the questions researchers ask and the way they go about answering them. They fear that if experts spurn the research efforts and knowledge that longtime patients bring to the table, they will end up reinventing the wheel. And time lost means more and more Americans hobbled with an illness that could last a lifetime.

The Recover effort is ambitious and wide-ranging. The NIH has tasked four main institutions with organizing the research, collecting data and managing samples from cadavers. They've recruited more than 400 investigators who specialize in different organ systems. They plan on following 20,000 adults, plus 20,000 children paired with 20,000 caregivers, to answer some basic questions about long COVID: Who gets it, for what reasons, and what do its symptoms look like?

"If you're not feeling well and nobody understands why, that is a very bad place to be, even more so if your symptoms are disabling so that you can't function in a normal way," says Stuart Katz, a doctor at NYU Langone specializing in heart failure and a co-lead of clinical research for the Recover Initiative. Katz himself experienced COVID symptoms that lasted six months beyond his initial infection, and he hopes to find ways to provide relief for those still suffering.

But chronic-illness advocates like Davids express skepticism alongside hope: They see a disconnect between the initiative's promise to center patients and the organization of committees, which so far seem to offer little in the way of accountability to patient advocates. Even the name, Recover, suggests that it will help those suffering from long COVID, some of whom have been dealing with the illness for two years. Yet Recover is not about identifying treatments, for now; it's meant to define the disease and its symptoms.

As Davids knows, the success of government AIDS research came only after sustained, sometimes forceful pressure from advocates like himself.

"People literally broke into research meetings and said, 'You can't keep us out,'" he said. "It was the wisdom of some who were present who said, 'Okay, let's sit down and talk,'" which eventually led to research protocols like MIPA: the Meaningful Involvement of People with HIV/AIDS.

Other initiatives, like studies of ME/CFS, had a record of missteps and resistance when it came to working with patients.

In the 1980s, researchers largely viewed ME/CFS as a vague cluster of symptoms with no known biological basis. It was quickly labeled a psychosomatic illness, described as "yuppie flu" and "a fashionable form of hypochondria" in Newsweek in 1990. "There was a lot of dismissiveness and outright mockery of these patients within the CDC and NIH," says Maya Dusenbery, a journalist and author of the book "Doing Harm." This was compounded by the fact that the majority of sufferers were women, and "female" illnesses are historically more likely to end up underfunded and dismissed as psychological.

The CDC spent decades dragging its feet on research into ME/CFS. In 1999, the agency acknowledged that it had diverted millions of dollars meant for chronic fatigue syndrome research to other programs, after internal communications were published by journalist Hillary Johnson in her book-length exposé "Osler's Web." Meanwhile, when the NIH finally began to recognize and fund ME/CFS, it was initially housed in the Office of Women's Health, which had almost no funding.

Nevertheless, by 2010, researchers had identified markers associated with the condition, including more lactic acid in the brain and differences in the autonomic nervous system, the immune system, energy metabolism and oxidative stress. This was in part thanks to patient advocates and foundations that helped expose CDC mismanagement of funds and lobbied Congress for more money. It's these developments that advocates have in mind as they contemplate long-covid research today. When it comes to meaningfully incorporating patients into the research process, Davids said: "We have people who know how to do that. Why not have them involved?"

An initiative like Recover is rare in the world of nonlethal diseases. While cancer and heart disease tend to receive funding, lesser-known chronic illnesses frequently languish in terms of scientific advances. ME/CFS, for instance, was just allotted $35 million over the next five years by the NIH — pennies next to the four-year, $1.15 billion long-covid effort.

For that reason, researchers involved in Recover believe that the fruits of their endeavor will feed a better understanding of other chronic illnesses. "It's not like we've made great progress in ME/CFS. It's been pretty slow going," said Lucinda Bateman, founder and medical director of the Bateman Horne Center, a nonprofit dedicated to ME/CFS research. "Hopefully with the amount of funding put into long COVID, we'll make a lot faster progress."

But just how much progress depends on whether researchers have learned the lessons of other chronic diseases like ME/CFS, which can look like long COVID and may have similar underlying mechanisms. "The main concern that I have is that they are not building on the expertise of people who have been doing this for decades, those who have built their career specializing in post-viral illnesses like ME," said Alison Sbrana, a board member of Body Politic, a patient advocacy group, who has been sick with ME/CFS for eight years. Without ME/CFS specialists guiding the Recover efforts, she worries that researchers will spend precious time investigating dead ends that those experts have already identified.

It wasn't until 2015 that the Institute of Medicine (today the National Academy of Medicine) released a comprehensive report on the disease, which concluded that ME/CFS was chronically underfunded and woefully misunderstood, and that "more research is essential." Bateman, who was on the committee that produced the report, said it served as the evidence-based review that finally spurred the NIH to action: In 2017, the agency established a working group and several collaborative research centers to investigate ME/CFS further.

Tony Komaroff, a physician at Brigham and Women's Hospital who has treated ME/CFS for decades, believes that this larger narrative — the medical community first dismissing, then accepting, a mysterious chronic illness — helped pave the way for today's long-covid efforts. "I think the medical community remembered that it had been very skeptical about the importance of, or even the reality of, ME/CFS and fibromyalgia," he said. Like other researchers, he considers Recover to be complementary to the larger questions that other chronic-illness researchers have been asking.

Long COVID could also shine a light on the origins of other chronic illnesses. When patients with, say, lupus or ME/CFS first consult a doctor about their disease, they have often been sick for a decade or more. At that point, so many of the body's systems are affected that it's impossible to pinpoint any one cause. With long COVID, however, researchers know the initial illness and could establish biomarkers or specific pathways involved. Ignacio Sanz, an immunologist at Emory University, is optimistic that there will be a "full circle" effect. Given that "all the autoimmune diseases are almost a continuum," says Sanz, whose work on autoimmunity is partially funded by the Recover Initiative, probing these factors in COVID could help figure out how to treat other diseases.

At the same time, for researchers who have lobbied for the recognition of chronic illnesses for decades, it's understandably difficult that awareness has come at the cost of a pandemic. "It's been frustrating for everyone," said Bateman, "but we'll take whatever we can get."

The legacy of ME/CFS research isn't only that it laid the scientific groundwork for asking similar questions and looking into shared mechanisms. It's also influencing how patient advocates are engaging with the Recover Initiative and long-covid research more generally — and what they expect from researchers in return. Davids, Sbrana and other advocates worry that the NIH is ignoring much of what has been learned about ME/CFS and failing to truly incorporate patient feedback into its process.

But there are many examples of researchers who are listening to, and working with, patient advocates. For instance, Nisreen Alwan, who studies maternal and child health at the University of Southampton, was one of the first COVID long-haulers. Her experience led her to advocate for greater recognition of long COVID in the pages of Nature and the British Medical Journal, and to call on governments to begin counting long-covid patients so they wouldn't fall through the cracks. When she began working on long COVID, Nisreen drew on other long-hauler experiences and work that had been done on ME/CFS. "I now feel like it's not legitimate to produce research which is not actually involving people with lived experience right from the start," said Alwan.

Davids and Sbrana note that, while patient advocates have been included in some Recover meetings and have been named to task forces, there is no clear organizational structure for patient communication.. Davids was contacted late on the Thursday before the Martin Luther King Jr. Day holiday weekend, with questions about his availability for meetings the following week, and was expected to respond by that Monday — a difficult task for people who suffer from fatiguing illnesses.

"Rapidly launching a research effort of the size, scope, and scale of the Recover Initiative has placed time-sensitive demands upon everyone involved — researchers, NIH staff, and, yes, the patients/advocates that have been participating," said an NIH representative for Recover.

Groups including Body Politic, #MEAction, the Patient-Led Research Collaborative and the Long Covid Alliance have issued open letters to the NIH with concerns and concrete suggestions for how Recover could be improved. One criticism is that adult research participants must have been initially infected within the past 24 months to participate. But with recruitment still ramping up, those who became ill in the first wave in March 2020 worry that they'll be excluded.

"Imagine that you've been profoundly ill for two years and told you're excluded from a project literally called RECOVER . . . that you helped advocate and secure funding for," said Karyn Bishof, founder and president of the Covid-19 Longhauler Advocacy Project, in a recent news release. "Is anything planned for us, or are we excluded entirely?"

The leaders of Recover point to ways they've incorporated patient feedback — for one, they changed their criteria so that participants no longer need to have had a positive coronavirus test, since tests were in short supply early in the pandemic. They will also offer compensation for research participants and plan to target demographics such as African Americans and Latinos, who have been especially hard-hit by the virus.

Still, advocates point to what they see as lingering problems, such as the criteria for Recover's planned autopsy study, which will look at those who died in the aftermath of a COVID infection but not directly from COVID. The current format defines long-covid deaths as those that occurred 30 days or more after infection. But in a separate list of concerns, the Patient-Led Research Collaborative pointed out that deaths related to long COVID should be defined as occurring 30 or more days after hospital discharge, so as to more successfully exclude cases of death from acute COVID infections.

"We have a strong effort in patient engagement," said Walter Koroshetz, co-chair of the Recover Initiative, in response to the patient critiques.

"Patient, caregiver, and/or community representatives participate across the governance structure and provide input on the RECOVER Initiative," said an NIH representative. "RECOVER recognizes the important contributions of those affected by the condition, in this case, PASC, including long COVID, and supports their representation across the Initiative's governance structure."

For many of the patient advocates, what's at stake isn't just an improvement in their own health but a sea change in how medical research is conducted. If patients are treated as equal partners in the research process, as experts in their own illnesses, think what insights might be gained and how much faster treatments might be found. Recover might not only pave the way in long COVID; it could lay the groundwork for future research on infectious diseases and chronic illnesses.

Rachel E. Gross is a Brooklyn-based health and science writer and author of the book "Vagina Obscura: An Anatomical Voyage."

Lorraine Boissoneault is a Chicago-based science and history writer, and the author of "The Last Voyageurs: Retracing La Salle's Journey Across America."

Newsday LogoDON'T MISS THIS LIMITED-TIME OFFER1 5 months for only $1Save on Unlimited Digital Access