‘A slow-moving glacier’: NIH’s sluggish and often opaque efforts to study long Covid draw patient, expert ire

WASHINGTON — The National Institutes of Health is fumbling its first efforts to study long Covid.

Fifteen months ago, Congress showered the agency with a massive $1.2 billion to research the mysterious cases of patients who never fully recover from Covid-19 infections. But so far the NIH has brought in just 3% of the patients it plans to recruit.

Critics charge that the NIH’s missteps are even bigger: that it is acting without urgency, that it is taking on vague, open-ended research questions rather than testing out therapies or treatments, and that it is not being fully transparent with patient advocates and researchers.

This study “is a slow-moving glacier,” said Lauren Stiles, a former long Covid patient and a research assistant professor of neurology at the State University of New York at Stony Brook.“With a half-billion dollars, they could have run multiple clinical trials.”

Even the NIH admits the pace has been dissatisfying.

“I mean, everybody is frustrated about how slow things are,” said Walter Koroshetz, the director of the National Institute of Neurological Disorders and Stroke and a co-chair of the initiative, in an interview with STAT. He added, however, that while starting enrollment “took way too much time,” the NIH stood up the study “much faster than we’ve done anything else before,” pointing out the agency’s usual pace can be even slower.

And then there is the matter of the money — more than $1 billion of which was temporarily transferred out of NIH to help pay for the health department’s efforts to house unaccompanied children at the U.S. border with Mexico. (NIH, which quietly disclosed the transfer in an FAQ section on the study’s website, contends the transfer didn’t slow the research down at all.)

The success of the NIH’s research into long Covid will shape the trajectory of the long-term burden of the pandemic on health care systems around the world for years to come, as millions of patients grapple with debilitating symptoms. If researchers can find answers, it also could provide a once-in-a-lifetime chance to give hope to a host of patients with other post-viral illnesses that have been long misunderstood.

But the NIH will have to walk the fine line between responsibly designing large-scale research to provide the clearest answers, and making sure the effort doesn’t buckle under the weight of bureaucracy.

“The potential is huge. With that kind of investment, if the money is used wisely, it could be a huge leap in knowledge of post-viral disease,” said a long Covid researcher who spoke anonymously to avoid jeopardizing grants from the NIH. “That was the plan, and I hope it’s still going to be possible.”

Long Covid isn’t the first illness of its kind — one where a patient has an infection or sickness, but the symptoms never truly go away.

Researchers have struggled for years to understand post-viral diseases like myalgic encephalomyelitis/chronic fatigue syndrome and dysautonomia, a disorder of the autonomous nervous system. Currently there are no cures available. Patients with chronic, post-viral illnesses have often felt misunderstood and dismissed by the medical establishment.

The government’s massive investment in long Covid research — a sum that outstripped even what Congress put toward Biden’s request for an entire new agency designed to “end cancer as we know it” — gave post-viral patients and researchers hope that this could be their moment in the spotlight. This could be the resource-intensive push that could finally provide a breakthrough.

The circumstances of the pandemic make it a particularly rich research opportunity: Covid is a clearly defined, easily diagnosed illness, and millions of people recovered without long-term symptoms. It’s a remarkable natural experiment.

“This is your opportunity. If you can’t figure it out now, I think it’s going to be really hard to ever figure this out,” Koroshetz said.

To meet the moment, the NIH launched the four-year RECOVER initiative. Its primary goal at the moment is to enroll 40,000 adults and children to learn more about who gets long Covid, how prevalent it is, and to define its biological causes and symptoms. The project will also collect tissue samples from autopsies and real-world data.

The idea of the large-scale study is to avoid relying only on smaller trials that could be shots in the dark, the NIH’s Koroshetz explained.

“My worry has been that unless we take a broad but engineered approach to this problem, in the worst-case scenario, we run a lot of small studies that can never be validated, we learn nothing, and we have no treatments,” Koroshetz said.

Taking more time up front to ensure consistent research methods can also make the results more useful in the long run, said Juan Wisnivesky, who co-directs Mount Sinai’s first-in-the-nation long Covid clinic. Mount Sinai is also a RECOVER program site.

“Research has a slow pace, there is only so much you can push. I would say that the NIH is pushing very hard and very fast. If they were trying to do this faster, there might be more problems,” Wisnivesky said.

But there is a growing chorus that the study itself is far too broad and too focused on observing patients — and that the agency can make more of a difference if it studies treatments and therapeutics, too.

“It’s maddening that the NIH has decided to direct this massive amount of funding toward a four-year-long data collection project. … Their goals do not match the goals of people who are suffering,” said Diana Berrent, founder of the long Covid patient group Survivor Corps.

Researchers who have long worked to study post-viral illnesses are itching to speed up research into treatments, as well.

“Federal agencies, foundations, and other funding entities should look at early, real-world pragmatic pilots for treatments soon. We have got to move a little quicker,” said Ryan Hurt, the head of Mayo Clinic’s long Covid research and clinical efforts.

Even putting aside debate over the NIH study’s design, the enrollment numbers are minuscule. The study is meant to enroll 40,000 adults and children, but by March 18, it had signed up just 1,366 — 3% of the goal. And that’s after NIH gave nearly $470 million to New York University Langone Health in September to coordinate the recruitment effort.

But comparatively, long Covid clinics across the country that have been recruiting for their own internal studies are moving at a much faster clip.

A Mount Sinai standalone patient registry has recruited almost 1,600 patients since spring 2020. And the Mayo Clinic pulled in more than 200 patients since Jan. 2021, and expects another 100 by the end of April. The recruitment at these facilities is logistically limited to patients who can regularly travel to New York or to Minnesota.

The pace of recruitment for the NIH study has left patient advocates flummoxed.

JD Davids, a longtime patient advocate in the HIV/AIDS space, for example, caught Covid-19 in the first wave of the virus in March 2020 and still suffers from its effects. He signed up on the RECOVER website to receive more information about enrolling in the study, but never heard back. And due to a study design that says patients can’t participate if they had a Covid-19 infection more than two years before, he’s not sure he will be able to participate at all.

Even now, the NIH website doesn’t have a comprehensive listing of which sites are recruiting for the long Covid study. Though some sites began enrolling adults six months ago, there’s a placeholder note that tells interested patients, “Soon you’ll be able to see and choose study sites near you. When the studies begin enrolling, you can join a study.”

The pace is especially concerning for the NIH’s goals to recruit a diverse patient cohort, given that Covid-19 hit communities of color particularly hard — Black, Hispanic or Latino, and American Indian patients were all more likely than white patients to be hospitalized. The agency is aiming to overrepresent those patients in enrollment, and it’s unclear what the racial and ethnic makeup of the NIH’s enrollment is so far.

A group of two dozen Covid-19 experts recently released a report that excoriated the NIH’s progress as well, noting that recruiting for the study has been painfully slow. More than 200 long Covid studies were registered on a federal database as of February 2022, but only eight were NIH-funded, the experts noted.

“There is no urgency to get rapid answers to basic questions to guide public health and patient care decisions,” the group wrote.

The experts argued the Biden administration should create a long Covid task force to hold agencies accountable for progress, coordinate with existing studies, and launch a nationwide messaging campaign to encourage patients to enroll.

The funding for the NIH study has a complicated backstory.

Congress gave the NIH $1.15 billion in December 2020 for long Covid research. But in a little-noticed move last year, the Biden administration transferred the money for the study to pay for housing unaccompanied children at the U.S.-Mexico border.

The health department said it needed the money at the border because Covid-19 protocols required more social distancing and quarantine facilities. It had to set up emergency shelters and require testing and improve ventilation, according to a letter health secretary Xavier Becerra sent health industry stakeholders in January. Last April and May, the department was caring for a peak level of more than 20,300 children.

The NIH argues that its long Covid study wasn’t slowed down at all by the funding transfer because the money was replaced by funds from a Covid-19 testing and contact tracing program.

But the transfer makes it harder for outside experts to track how much is actually spent on long Covid research, especially during a time when the government is so strapped for pandemic response money.

The NIH’s Koroshetz said he hasn’t heard any inkling that the funding has been threatened. He said more than $700 million has been obligated so far, and he expects the rest to be spent once clinical trials begin. “I have not heard anything other than that all this money goes to post-Covid research,” he said.

Patient advocates have also grown increasingly worried that the NIH’s patient engagement efforts are subpar, and don’t live up to the high-minded rhetoric that the agency employs in public.

The study’s website says the NIH wants to include patients, caregivers, and community representatives to help make plans for and provide suggestions on research being done.

Then-NIH Director Francis Collins addressed the patient community in testimony before Congress in April 2021 — nearly a year ago. “I want to assure you: I hear you and I believe you. If you hear nothing else today, hear that we are working to get you answers,” Collins said.

But some prominent long Covid patient advocacy groups started raising concerns in November that the patient engagement efforts weren’t as robust as they had hoped. At the time, they were concerned by the lack of a comprehensive patient engagement structure, the dearth of involvement by experts involved in researching other post-viral illnesses, and little evidence that patient suggestions were actually being implemented.

For example, there was a call for patient participation that required attendance in multiple, multi-hour meetings in a single week; the invitation only went out the Friday before.

“When the [NIH] has invited us into some rooms, it feels like it’s purely to check a box,” the groups wrote.

In February, the groups wrote again, noting they still hadn’t seen a patient engagement infrastructure, a promised meeting with National Heart, Lung, and Blood Institute Director Gary Gibbons had never been scheduled, and patients advocating on behalf of children hadn’t seen draft parameters for upcoming studies. The concerns, in their view, put the study “in grave danger of failing to realize its goals.”

The NIH has since started the process of establishing several committees that include handpicked patient representatives nominated by researchers from study sites.

The process has been chaotic for Liza Fisher, a member of the Long Covid Alliance’s executive committee and a long Covid patient. Fisher was chosen to participate in a committee advising the program, but the panel’s focus was thrown into question after an abrupt reorganization.

“As it goes on, it seems to be an inefficient process, and there’s a lot of overlap,” Fisher said.

The membership of the different committees, besides the executive committee, is not public.

Beyond patient concerns about transparency, researchers have been frustrated too, and some have been afraid to speak out for fear of jeopardizing future NIH funding. The long Covid researcher called the initiative a “black box” that’s excluding subject matter experts.

“There needs to be more open access and discussion about who is being funded, and whether they can make data available. This is federal funding, and we should be able to share those things immediately,” the researcher said.

Much work still lies ahead for the NIH. It has to enroll the rest of the adult patients, and it hasn’t yet released research parameters for studying children with long Covid. And, as Koroshetz said, there are efforts in the works to begin clinical trials in additional to observational studies.

Even if the NIH can speed up the work, it may still have to fight against extraordinarily high expectations — an unlikely byproduct of its own triumph with the Covid-19 vaccines. The wildly successful public-private partnerships to accelerate the development of Covid-19 vaccines and treatments elevated the understanding of what the agency is capable of, said Alison Sbrana, a member of the board of the patient advocacy group Body Politic and a patient with post-viral chronic fatigue syndrome.

“Look, I get the way the NIH stuff usually works,” Sbrana said. “However, look what we were able to do with the vaccine. When there is an emergency that requires a response, they are able to move and make things happen.”

Elizabeth Cooney contributed reporting.