Leadership Q&A: NIH to bolster RECOVER Long COVID research efforts
NIH RECOVER Initiative Co-Leaders Gary Gibbons, M.D., Walter Koroshetz, M.D., and Jeanne Marrazzo, M.D., M.P.H. share progress, and answer questions about investing an additional $515 million and what it means for the Initiative.
NIH RECOVER Initiative Co-Leaders Gary Gibbons, M.D., Walter Koroshetz, M.D., and Jeanne Marrazzo, M.D., M.P.H., talk in this Q&A about how the RECOVER initiative has helped patients, clinicians, and researchers so far – and what the new investment of $515 million will mean for them in the future. Dr. Gibbons is the director of the National Heart, Lung, and Blood Institute; Dr. Marrazzo is the director of the National Institute of Allergy and Infectious Diseases, and Dr. Koroshetz is the director of the National Institute of Neurological Disorders and Stroke.
NIH RECOVER Initiative Co-Leaders Gary Gibbons, M.D., Walter Koroshetz, M.D., and Jeanne Marrazzo, M.D., M.P.H.
What is RECOVER doing to help patients with Long COVID and the doctors that are trying to treat them?
Dr. Gibbons: Early in the pandemic we heard from many patients and providers about the many patients who were experiencing ongoing health issues long after having had COVID-19. We quickly recognized that these symptoms, which came to be known as Long COVID, were suggesting a new infection-associated syndrome, not entirely unfamiliar from other infection-associated chronic conditions. Knowing that tackling conditions like this have been unsuccessful to date, we immediately saw the need for an ambitious approach that would leave no stones unturned in addressing the suffering of patients with Long COVID.
The public investments in RECOVER have enabled a powerfully built, comprehensive, national research enterprise. It is unprecedented in its scale and scope and is already delivering findings that are helpful for clinicians. We now know that Long COVID can present with more than 200 symptoms that commonly cluster in relation to certain organ systems – for example, “brain fog” or symptoms affecting muscles and joints. This can be important in diagnosing the condition. We have also found what puts people at greater risk for developing Long COVID, and how vaccination appears to reduce that risk. Studies have even shown which communities experience a greater burden. Most importantly for advancing new treatment strategies, RECOVER research is illuminating how the SARS-Co-V2 virus maneuvers its way through bodily systems, resulting in different forms of this syndrome.
The RECOVER enterprise is unmatched by any other research effort in the number of study participants – nearly 90,000. And that doesn’t even include the more than 60 million whose electronic medical records are sharing important insights. The contributions of the thousands of people providing valuable data cannot be overlooked. We are grateful for each one of them.
Also exciting for RECOVER is its well-designed symptom-based treatment testing platforms – each addressing what patients feel are their most burdensome symptoms. So far, 13 treatment approaches are being tested, with many more in the queue to test in the months to come.
The new funds will enable us to maintain an important enterprise, one that’s never been seen for research on infection-associated chronic conditions. And we will continue to leverage it until we discover diagnostics and treatments that work.
Are there studies beyond RECOVER that NIH is conducting or funding in connection with Long COVID? If so, are we learning from them as well?
Dr. Marrazzo: Yes, in addition to the RECOVER studies, NIH is conducting other types of research with implications for Long COVID. For example, my Institute, NIAID, has funded immunology studies that have helped to reveal how severely COVID-19 may reprogram cells that impact inflammation up to 12 months after infection. In addition, several more studies are helping scientists understand how chronic viruses may potentially be reactivated after COVID-19. These important findings will help physician-scientists design improved clinical trials in the future to target some of the many symptoms present in Long COVID patients.
Do we know just how long, Long COVID lasts and if there is a risk for long-term disability in patients who have it?
Dr. Marrazzo: We know the potential for infection-associated chronic conditions to last for years. So, we shouldn’t underestimate the potential for Long COVID to do the same. This means that finding treatments and continuing to study our cohort of participants are both very important.
RECOVER must commit to both longer-term follow up studies of Long COVID patients to better understand the condition and find effective treatments for those who are suffering. We need to understand how and why some patients with Long COVID recover quickly, and why others continue to experience symptoms for a longer period. We also need to understand how reinfection with SARS-CoV-2 affects the development of Long COVID and its symptoms. As Dr. Gibbons noted, there are currently more than 200 symptoms that have been reported in association with Long COVID. A better understanding of the biological switches that turn Long COVID on and off, as well as its impacts on the human body, are critical to driving the research aimed at finding effective treatments.
Isn’t Long COVID just ME/CFS [myalgic encephalomyelitis/chronic fatigue syndrome] or another infection-associated condition? What’s the difference here and why not just study those syndromes?
Dr. Koroshetz: Yes, the similarities between Long COVID and ME/CFS are striking. But as Dr. Bertagnolli says in her statement, infection-associated chronic conditions like these have been notoriously difficult for us to solve. RECOVER is built to overcome the challenges that have thwarted our ability to understand and effectively treat the hundreds of thousands of persons suffering for decades with infection-associated chronic conditions. We’ve built a research engine that will hopefully succeed where we have failed before. More importantly, this engine, now focused on Long COVID, should serve to further our understanding and treatments of other such conditions.
One of the challenges in prior ME/CFS research has been lack of clarity about the specific infection or infections that trigger these conditions. In addition, gathering a large set of patients with the same infection, occurring at a known timepoint, and parceled into subgroups with a similar set of symptoms has not been possible. With Long COVID, we know that the culprit was the infection from the same virus or a variant of it. Given that millions were infected, we can conduct studies at a level and intensity that has previously evaded us with other conditions. We remain optimistic that RECOVER insights will help to provide answers leading to resolving the mystery and evolving treatments for the broader community of patients who continue experiencing infection-associated chronic conditions.
How long will it take before we see results from the clinical trials? And how many different treatments or interventions will the funds be able to support?
Dr. Koroshetz: The RECOVER treatment trials are now enrolling what will likely be just over 2,500 participants to test the first 13 interventions. Still, identifying the patients best suited for each will take a bit of time. Once recruited, the treatment studies should progress smoothly and render an understanding of what’s working to reduce bothersome symptoms.
More importantly, however, interventions that fail to show promise can be eliminated rather quickly. This will enable us to shift to another treatment candidate intervention for each symptom category. Many ideas for potential treatments and therapies to test have already come to NIH. And many more are likely to come as our research reveals more. RECOVER is designed to efficiently add other interventions to test to achieve our goal of identifying effective treatments.
Finally, Dr. Gibbons, just how will the additional $515 million in RECOVER funding help patients and doctors, and how will decisions be made for its use?
Dr. Gibbons: Since its inception, RECOVER has been learning and will remain in an adaptive learning posture. Important in this learning process is listening. Patients and their loved ones have been instrumental in helping the design of RECOVER. The lived experience and real-world insights from them and from clinicians have informed the research that is pointing us toward ways to truly diagnose and treat Long COVID – or surely address its many symptoms.
It goes without saying that a large portion of the new funds will be invested in diagnosing and finding promising treatments for Long COVID. Given its complexity, we will most assuredly need to identify many types and combinations of treatments. We will also need to continue following those thousands of participants currently providing critical data, as findings from these studies will provide knowledge about how the disease or diseases behave across the lifespan.
Studies of other infection-associated chronic conditions have shown us the importance of longer term follow up. We also will continue investing in ongoing studies on how the virus manifests within the body – including distinctions that can be gleaned because of the diversity of the participants taking part. As we further the plans for the allocations of these funds, we’re committed to working collaboratively with the researchers who are continuing to make discoveries, clinicians doing their best to find and inform treatment approaches, and most importantly patients – without whom this work could not be done.