More than three years ago, the National Institutes of Health launched a $1 billion-plus initiative to find the root causes and potential treatments for long Covid, the chronic disease that has quickly changed the lives of millions of Americans.

But a lack of visible progress from the initiative, called RECOVER, has drawn months of criticism from patient advocates, researchers and lawmakers, including at a Senate hearing last week on the NIH’s budget. “We gave [the NIH] a chance and they bungled it,” said John Bolecek, who has lived with long Covid for two years and has closely followed RECOVER. The program has done nothing “to narrow down what’s actually going wrong with people,” or identify treatments, he said.

As the NIH assembled RECOVER, it selected three core institutions to lead most of the research: New York University, Massachusetts General Hospital and the North Carolina-based nonprofit Research Triangle International. Now, budget and other project documents obtained by The Sick Times, MuckRock and STAT News through the Freedom of Information Act show how decisions made early in this process likely contributed to RECOVER’s slow start.

The documents reveal how the NIH set up its flagship long Covid research initiative, including the scientific expertise that government reviewers prioritized in selecting research teams to lead RECOVER and the early goals and timelines of the program. Experts who reviewed the contracts and project documents say the agency set itself up for failure by not selecting scientists fluent in the post-infectious chronic diseases that predate the Covid-19 pandemic and are now commonly diagnosed alongside long Covid.

In NIH contracts with the institutions, the agency set up RECOVER’s goals: “It is a public health priority that we better understand and develop strategies to prevent and treat [long Covid] and that these strategies enable rapid innovation, evolution, and adaptation.”

These goals, as well as others outlined in the documents, are largely unrealized as the first round of funding has been mostly spent, experts say. RECOVER’s aims included estimating how many people in the U.S. are living with the disease as well as the risk of developing it after a coronavirus infection; identifying the disease’s underlying causes; and using feedback from patients in “shaping the research agenda.”

While many long Covid patient-advocates are disappointed with RECOVER’s progress so far, some say the NIH could turn this program around by using $515 million in additional funding, allocated earlier this year, to support high-impact biological research and clinical trials.

“I completely understand why [the long Covid community] is frustrated, I completely understand why they think we’re being slow,” said NIH Director Monica Bertagnolli in an interview. She said RECOVER’s pace was necessary to understand key aspects of long Covid, learn from patients and set up trials that will produce accurate results. “The infrastructure is now there,” she added, “And we are, with urgency, going to charge ahead as best we can.”

Further information from the NIH, sent in written responses to questions, defended many decisions made in RECOVER, including its selection of research teams to lead the program, inclusion of patient advocates in advisory groups, upcoming scientific publications and choices about clinical trials.

Among the problems identified by long Covid experts who reviewed the documents:

• The NIH failed to select scientists with “an established background in conducting research on post-acute infection syndromes” to lead the initiative, said David Putrino, Nash Family Director of the Cohen Center for Recovery from Complex Chronic Illness at Mount Sinai. In their applications, dozens of scientists from NYU and Mass. General shared details from their prior research that they believed were most relevant to the program; none mentioned the post-infectious chronic diseases that predate the Covid-19 pandemic and are now commonly diagnosed alongside long Covid, such as Myalgic Encephalomyelitis (ME) and Postural Orthostatic Tachycardia Syndrome (POTS).
  
  

• Instead, the NIH selected for leadership, as Putrino put it, “a bunch of biostatisticians and epidemiologists.” In their applications, the research teams highlighted their experience with collecting and utilizing electronic health records, clinical test results, genomics and other types of health data to answer biomedical questions. This focus aligns with a broader agency-level interest in “big data” under former NIH director Francis Collins, said Stephen Smith, a patient-advocate who closely follows research and runs the Twitter/X account Post-Viral Trials News. A “big data” approach is challenging for diseases like long Covid because standard medical tests and diagnostic codes often don’t capture the myriad complex symptoms that patients experience, Smith said. Oftentimes, expertise in post-infectious diseases is required to collect meaningful data, he said. Leora Horwitz, a principal investigator for RECOVER’s adult observational study at NYU, acknowledged this challenge and said the NIH program has addressed it through patient surveys that have been revised over time based on participant feedback.
  
  

• The NIH selected teams to lead RECOVER “based on a range of research expertise and the scientific merit of their proposals,” the agency said in a statement. Scientists and clinicians with expertise in post-infectious chronic diseases “informed the RECOVER Initiative design and continue to be involved” in different committees, the NIH said, sharing a list of involved experts. All but two of these experts are not part of RECOVER’s listed leadership, however, and one, Leonard Jason at DePaul University, said in an interview that he is no longer part of RECOVER after the advisory committee in which he participated was discontinued last year.
  
  

• Another original goal of RECOVER was to better define long Covid and identify how many people in the U.S. are living with the disease as well as the risk of developing it after a coronavirus infection. The initiative’s observational study has not produced these estimates, due in part to challenges with recruiting people who were not infected with Covid-19 early in the pandemic. According to the NIH’s contract with NYU, the observational study was set to have recruited 85% of its cohort by the end of its first year, in spring 2022, and to have a “working research-based definition” of long Covid in the same timeframe. The study had not met either goal by April 2023. RECOVER did share a working definition of long Covid in May 2023, with a paper published in the Journal of the American Medical Association. However, that paper quickly garnered criticism from the long Covid community, as patient-advocates and researchers questioned the symptoms it prioritized for diagnosis. “RECOVER posted a Q&A in response to concerns,” the NIH said. Acknowledging the criticism, Horwitz said that the paper affirmed a long Covid diagnosis for many people and “helped to convince the medical community that this is a legitimate syndrome.”
  
  

• NIH’s process for awarding grants suffers from some structural issues that impacted the RECOVER initiative, said experts who reviewed the documents. Unlike other agencies and research institutions that have adopted anonymity into their grant review process, the NIH continues to heavily weigh where researchers work and their prior records of NIH support. As a result, the NIH tends to award funding to researchers and institutions who have previously received NIH funding, creating an insular cycle that discourages unique innovation. This pattern creates a particular challenge for the researchers of post-infectious diseases best suited to study long Covid because the NIH has historically not funded large, ambitious research projects in this field, experts said. Bertagnolli acknowledged this challenge, saying that “the ME/CFS community has never had a real answer.”
  
  

• Another initial goal, as outlined in the applications and contracts, was that researchers would engage with long Covid patients as a central facet of the program through processes such as “patient engagement working groups” and platforms for patients to ask questions. While more than 50 patient-representatives are involved with advising RECOVER, their feedback is not as central as these documents suggest, particularly with designing the program’s clinical trials. Patient representatives are “there to check a box, they are not seen as experts,” said one of the representatives, who is not authorized to speak publicly. These concerns are not new, as patient organizations have shared criticisms going back to a fall 2021 letter written by the long Covid research organization Patient-Led Research Collaborative and signed by other research and advocacy groups. RECOVER has addressed some concerns but a lack of meaningful engagement at early stages of the program, as well as the lack of post-infectious chronic disease expertise, contributed to current problems with study design, said PLRC co-founder Lisa McCorkell. “Patient engagement was still forming” at the time of that letter, the NIH said.
  
  

• Despite a mandate from Congress for the NIH to identify treatments for long Covid, clinical trials run by RECOVER — particularly a pair of trials aimed to address exercise and exertion — have moved slowly and been fraught with criticism. The documents outlining NYU’s responsibilities make clear that clinical trials would start only after observational research was well underway, a decision that outside experts have questioned given extensive research going on outside the RECOVER program that could help set up such trials. RECOVER has revised its exercise and exertion trials to reduce the risk of harm to participants, but outside researchers and patient-advocates are frustrated that the trials are still moving forward when they are unlikely to “move the needle” on treatments, as Putrino put it, at the expense of more promising drugs that have not yet been tested. When asked about these trials, Bertagnolli said that the “first wave” of RECOVER’s trials aim to provide “definitive answers” about treatments that have preliminary evidence behind them already, while a coming “second wave” may test more novel options.
  

Experts and advocates acknowledge that some valuable parts of RECOVER should continue, such as pathobiology research with samples collected from patients in the observational study. Nita Jain, a biotech founder and patient representative working on upcoming scientific papers with RECOVER, thinks more in-depth examination of these samples could help answer questions about changes to the immune system and other biological changes that occur following Covid-19 infection.

RECOVER also provides an existing structure for longer-term research. The current observational study could be pared down to a smaller cohort that is tracked to study how symptoms change into future decades, some experts have suggested.

“I think this is an extraordinary cohort that cannot be replicated again,” Horwitz said of the observational study, pointing to the cohort’s size, diversity and the extensive surveys and medical testing conducted on its participants. This testing is currently slated to end in two years, and “it’s of public health importance that we not throw that away” by providing additional funding, she said.

RECOVER’s pediatric research provides one example of a more successful part of the program that should receive continued support, said Megan Carmilani, a patient representative and founder of long Covid Families. This research has identified how long Covid symptoms in children differ from adults and by age group, offering new information about this under-studied group of patients, she said. She has also found scientists leading this part of the program are more responsive to feedback from patient representatives like her than those leading the adult cohort, perhaps because this study started later, she said.

“There is no other study like RECOVER for pediatrics in the world,” Carmilani said. She would like to see RECOVER’s pediatric research gain additional funding to support clinical trials for children.

While recognizing that some parts of RECOVER should continue after the program’s initial four years, long Covid advocates are asking for new funding to largely be directed to other federal offices and agencies focused more on biomedical innovation, supporting clinical trials and improving medical care for people with long Covid. In requesting long Covid funding in the fiscal year 2025 budget, a proposed bill from Sen. Bernie Sanders (I-Vt.) and other efforts, advocates highlight the NIH Office of the Director, the Advanced Research Projects Agency for Health, the Agency for Healthcare Research and Quality, the Department of Defense, and Biomedical Advanced Research and Development Authority.

At a recent Senate hearing discussing the NIH’s fiscal year 2025 budget, agency director Bertagnolli said people with long Covid and related diseases “have taught us over the last two years what we needed to do, now we just need to deliver for them.”

When asked to elaborate on those comments in an interview, Bertagnolli said that due to the work done over the last two years, with patient engagement and observational research, “we are now ready to do the studies that are designed… to be what those people who are suffering need to see.” Delivering for people with long Covid means “trials, trials, trials,” she added, while fundamental biology work will also continue.

RECOVER has an opportunity to demonstrate a renewed commitment to this patient community using the $515 million that it received earlier in 2024, said Charlie McCone, a patient-advocate who has advised the program. According to the NIH, these funds will be used for additional clinical trials, extending observational research, additional clinical research studies, and managing RECOVER’s data and biospecimens along with real-world data.

McCone summarized many patient-advocates’ message for RECOVER: “If you don’t like our criticism, if you think you can do things better, demonstrate it with the $500 million.”