When the National Institutes of Health (NIH) launched a $1 billion dollar research effort in 2021 focused on long COVID, hopes were high that it would lead to some answers for the mysterious riddle of the complex condition. Now, more than 3 years later and with total funding of about $1.6 billion, critics contend the federal government has little to show for its efforts.
Disappointment runs high among long COVID specialists and patients, who cite poor scientific coordination, few treatments that go beyond symptom management, and a lack of clinical trials focused on pharmaceutical interventions.
Grace McComsey, MD, who leads one of the 15 nationwide long COVID centers funded by the federal Researching COVID to Enhance Recovery (RECOVER) Initiative in Cleveland, contended that RECOVER isn’t getting enough credit for what it’s trying to do, and critics need to be more realistic about how long things will take. If you look at long COVID through the lens of other diseases such as HIV, it took many years and many billions of dollars to find viable treatments, she said.
Righting the ship will not be easy, but for the 17 million Americans in desperate need of treatment for long COVID, there’s no other option, said Ziyad Al-Aly, MD, a global expert on long COVID and chief of research and development at the Veterans Affairs St. Louis Health Care System.
He argued that officials running the NIH program, known as the RECOVER Initiative, have been too defensive about the effort and not as open to helpful changes that would move it forward.
“Monday morning quarterbacking isn’t just about criticizing RECOVER, it’s about being constructive and providing the tools to make positive changes,” said Al-Aly. He added that those at the top have been defensive of criticism, which is making matters worse. “We can’t correct course if we don’t make changes. We’ll end up hitting the same wall again and again.”
First Step: Improve Coordination
Improving coordination among researchers of long COVID is a great place to start, Al-Aly said. “We all want to move the ball forward, so let’s put our heads together and do it,” he said.
He recommended establishing an advisory board that includes the nation’s top experts on long COVID. “Getting these people together in a room to discuss the best ways to allocate resources would help,” he said.
Long COVID has proven to be distressingly similar to other post-viral syndromes such as myalgic encephalomyelitis/chronic fatigue syndrome, according to a June 2023 article in the journal Frontiers of Medicine. Physicians who have worked on these conditions are also important resources for investigating the disease, he said. They shouldn’t be on the sidelines. Many of those at the top of RECOVER aren’t experts in these types of conditions, Al-Aly said.
Step Two: Move Beyond Symptom Management
Another overarching concern with RECOVER and with the condition as a whole is that researchers are still largely focused on symptom management rather than looking more deeply into the biological mechanisms driving this disease.
“We need to have large-scale research at the molecular level to find treatments that could lead to long-term sustained remission of long COVID rather than just managing symptoms,” said Nisha Viswanathan, MD, director of the Long COVID Program at UCLA Health. If we don’t develop a better understanding of the disease’s mechanism and how to diagnose it at a molecular level, we’re never going to truly be able to treat it, she said.
Step Three: More Clinical Trials
Another criticism of RECOVER is that it’s heavy on observational studies, which make up 47% of the budget thus far rather than prospective clinical trials. Observational studies don’t test potential treatments that could work for long COVID, rather, they follow participants on their current treatment regimen to see how they’re fairing.
Patients with long COVID such as Charlie McCone, 34, of San Francisco, are also pushing for more clinical trials. He’s a former marketing executive who lost his job due to long COVID in 2022. Now a patient advocate, he said that for the millions of patients like him depending on NIH to execute, the past 3 years have largely been a wash.
“The patient community needs clinical trials more than anything else. That’s the bread and butter here,” said McCone. He said a plethora of off-label pharmaceutical drugs such as antivirals, immunomodulators, antihistamines, and anticoagulants target the pathology of the disease, and NIH should be vigorously investigating them.
Case studies showed people improving on certain medications, but when patients go to their doctors to ask for them, they can’t get access because there are no clinical trials. One example is low-dose naltrexone for the treatment of extreme fatigue associated with long COVID, which was shown in a January 2024 article in the journal Clinical Therapeutics to improve symptoms in patients taking the medication. Patients want to know if these treatments will work on a larger scale.
Right now, RECOVER is only studying a few pharmaceutical medications, and one of them is Paxlovid, an antiviral medication that failed in its first trial to improve symptoms in patients with long COVID.
Viswanathan said that NIH should also avoid putting all researchers’ eggs in one bucket and rather start testing a variety of treatments to see what might show promise so that those can expand into larger trials. “We should be diversifying the things that we’re looking at to help manage our patient’s symptoms rather than doubling down on just a few options for helping them,” she said.
Step Four: Take the Focus Off ‘Soft Therapies’
Additionally, McCone said NIH needs to take the focus off of what he called soft therapies, using things such as melatonin. Last month, the agency announced it would be testing the over-the-counter sleep supplement as a potential treatment for sleep disturbances due to long COVID. Other treatments, such as exercise therapy, have also been criticized by patients as not taking the condition seriously enough or being ineffective.
“We need pharmaceutical interventions that have a plausible mechanism for intervening with the pathophysiology of this disease,” said McCone.
Still, some experts contend that constantly pointing the blame isn’t helping matters.
McComsey admitted things aren’t perfect but said that RECOVER has enrolled and retained nearly 20,000 people from an extremely diverse group of patients with nearly 18 papers that have been published or will be published soon. Clinical trials don’t happen overnight, said McComsey, because you have to design the studies, enroll patients, and ensure their safety. “No one else in the world is doing anything like this,” she said.
But for patients like McCone, who has now lived with long COVID for the entirety of his 30s, things aren’t happening fast enough, and his frustration is mounting. He’s lost his job, his hobbies, and is now largely a homebound millennial.
“For me and millions of people suffering like I am, the stakes for RECOVER couldn’t be higher,” he said.