Posted on by Gary Gibbons, M.D., National Heart, Lung, and Blood Institute; Walter Koroshetz, M.D., National Institute of Neurological Disorders and Stroke; Hugh Auchincloss, M.D., National Institute of Allergy and Infectious Diseases
“I connected with RECOVER to be a part of the answers that I was looking for when I was at my worst.” Long COVID patient and RECOVER representative, Nitza Rochez (Bronx, NY)
People, like Nitza Rochez, who are living with Long COVID—the wide-ranging health issues that can follow an infection with SARS-CoV-2, the coronavirus that causes COVID-19—experience disabling symptoms with significant physical, emotional and financial consequences.
The NIH has been engaging and listening to Nitza and others living with Long COVID even before the start of its Researching COVID to Enhance Recovery (RECOVER) Initiative. But now, with the launch of RECOVER, patients and those with affected family or community members have joined researchers, clinicians, and experts in their efforts to unlock the mysteries of Long COVID. All have come together to understand what causes the condition, identify who is most at risk, and determine how to prevent and treat it.
RECOVER is unprecedented in its size and scope as the most-diverse, deeply characterized cohort of Long COVID patients. We’ve enlisted the help of many patient volunteers, who have enrolled in observational studies designed to help researchers learn as much as possible about people who have Long COVID.
Indeed, thousands of research participants are now providing health information and undergoing in-depth medical evaluations and tests, enabling investigators to look for trends. Additionally, studies of millions of electronic medical records are providing insights about those who have received care during the pandemic. More than 40 studies are being conducted to identify the causes of disease, potential biomarkers of Long COVID, and new therapeutic targets.
In all, RECOVER’s research assets are voluminous. They involve invaluable contributions from many people and communities, including research volunteers, research investigators, and clinical specialists. In addition, millions of health records and numerous related tissues and specimens are being analyzed for possible leads.
At the center of it all is the National Community Engagement Group (NCEG). The NCEG is comprised of people living with Long COVID and those representing others living with the condition, and it is truly instrumental to the initiative’s progress in understanding how and why SARS-CoV-2 impacts people in different ways. It’s also helping researchers learn why some people recover while others do not.
So far, we’ve learned that people hospitalized with COVID-19 are twice as likely to have Long COVID than those who were not hospitalized for infection. We’ve also learned that members of racial and ethnic minority groups with Long COVID were more likely to have been hospitalized with COVID-19.
Similarly, disparities in Long COVID exist within those living in areas with particular environmental exposures , and those who were already burdened by other diseases and conditions—such as diabetes and chronic pulmonary disease . We’ve also discovered that the certain types of symptoms of Long COVID are consistent among patients regardless of which SARS-CoV-2 variant caused their initial infection. Yet, people infected with the earlier variants have a higher number of symptoms than those infected with more recent variants.
Patient experiences have guided and will continue to guide the study designs and trajectory of RECOVER. Now, fueled by the knowledge that we have gained, RECOVER is preparing to advance to the next phase of discovery—testing interventions in clinical trials to see if they can help people with Long COVID.
To prepare, we are beginning to identify potential clinical trial sites. This important step will help us to find the right places with the right staff and capabilities for enrolling the appropriate patient populations needed to implement the studies. We’ll ensure that the public knows when these upcoming clinical trials are ready to enroll.
Of course, the design of these RECOVER clinical trials will be critical, and insights gained from patients have been key in this process. Results from RECOVER study questionnaires, surveys, and discussions with people experiencing Long COVID identified symptom clusters considered to be the most significant and burdensome to patients. These include sleep disorders, “brain fog” (trouble thinking clearly), exercise intolerance and fatigue, and nervous system dysfunction affecting people’s ability to regulate normal body functions like heart rate and body temperature.
These patient observations have effectively guided the design of the clinical trials that will evaluate whether certain interventions and therapies can help alleviate symptoms that are part of these specific clusters. We’re excited to be advancing toward this phase of the initiative and, again, are very grateful to patient representatives like Nitza, quoted above, for getting us to this phase.
Effective evaluation of those treatments will be important, too. Early in the pandemic, while many clinical trials were launching, most were not large enough or did not have the appropriate objectives to define effective treatments for acute COVID-19. This left clinicians with few clear options when faced with patients needing help.
Learning from this experience, the RECOVER trials will be harmonized to ensure coordinated and efficient evaluation of interventions—in other words, all potential therapies will be using the same protocols platforms and the same data elements. This consistency accelerates our understanding and strengthens the certainty of findings.
Given the widespread and diverse impact that the virus has on the body, it is highly likely that more than one treatment will be needed for each kind of patient experience. Finding solutions for everyone—people of all races, ethnicities, genders, ages, and geographic locations—is paramount.
RECOVER patient representative, Juan Lewis, of San Antonio shared with us, “In April 2020, I was fighting for my life, and today I fight for my quality of life. COVID impacted me physically, mentally, socially, and financially.”
For people like Juan who are experiencing debilitating Long COVID symptoms, we know that finding answers as quickly as possible is critical. As we look ahead to the next 12 months, we’ll continue the studies evaluating the underlying causes, risk factors, and outcomes of Long Covid, and we anticipate significant scientific progress on research leading to Long COVID treatments.
Keep an eye on the RECOVER website for updates on our progress, and published findings.
 Identifying environmental risk factors for post-acute sequelae of SARS-CoV-2 infection: An EHR-based cohort study from the recover program. Zhang Y, Hu H, Fokaidis V, V CL, Xu J, Zang C, Xu Z, Wang F, Koropsak M, Bian J, Hall J, Rothman RL, Shenkman EA, Wei WQ, Weiner MG, Carton TW, Kaushal R. Environ Adv. 2023 Apr;11:100352.
 Identifying who has long COVID in the USA: a machine learning approach using N3C data. Pfaff ER, Girvin AT, Bennett TD, Bhatia A, Brooks IM, Deer RR, Dekermanjian JP, Jolley SE, Kahn MG, Kostka K, McMurry JA, Moffitt R, Walden A, Chute CG, Haendel MA; N3C Consortium. Lancet Digit Health. 2022 Jul;4(7):e532-e541.
NIH Builds Large Nationwide Study Population of Tens of Thousands to Support Research on Long-Term Effects of COVID-19, NIH News Release, September 15, 2021
Understanding Long-Term COVID-19 Symptoms and Enhancing Recovery, NIH Director’s Blog, October 4, 2022.
NIH RECOVER Research Identifies Potential Long COVID Disparities. NIH News Release, February 16, 2023.
NIH RECOVER Listening Session, June 2021 (NIH Videocast)
NIH RECOVER Listening Session: Understanding Long COVID Across Communities of Color and Those Hardest Hit by COVID, January 21, 2022 (NIH Videocast)
Note: Dr. Lawrence Tabak, who performs the duties of the NIH Director, has asked the heads of NIH’s Institutes, Centers, and Offices to contribute occasional guest posts to the blog to highlight some of the interesting science that they support and conduct. This is the 25th in the series of NIH guest posts that will run until a new permanent NIH director is in place.
Posted on by Lawrence Tabak, D.D.S., Ph.D.
It’s good for our health to eat right, exercise, and get plenty of rest. Still, many other things contribute to our sense of wellbeing, including making it a point to practice gratitude whenever we can. With this in mind, I can’t think of a better time than Thanksgiving to recognize just a few of the many reasons that I—and everyone who believes in the mission of the National Institutes of Health (NIH)—have to be grateful.
First, I’m thankful for the many enormously talented people with whom I’ve worked over the past year while performing the duties of the NIH Director. Particular thanks go to those on my immediate team within the Office of the Director. I could not have taken on this challenge without their dedicated support.
I’m also gratified by the continued enthusiasm and support for biomedical research from so many different corners of our society. This includes the many thousands of unsung, patient partners who put their time, effort, and, in some cases, even their lives on the line for the sake of medical progress and promising treatment advances. Without them, clinical research—including the most pivotal clinical trials—simply wouldn’t be possible.
I am most appreciative of the continuing efforts at NIH and across the broader biomedical community to further enable diversity, equity, inclusion, and accessibility within the biomedical research workforce and in all the work that NIH supports.
High on my Thanksgiving list is the widespread availability of COVID-19 bivalent booster shots. These boosters not only guard against older strains of the coronavirus, but also broaden immunity to the newer Omicron variant and its many subvariants. I’m also tremendously grateful for everyone who has—or soon will—get boosted to protect yourself, your loved ones, and your communities as the winter months fast approach.
Another big “thank you” goes out to all the researchers studying Long COVID, the complex and potentially debilitating constellation of symptoms that strikes some people after recovery from COVID-19. I look forward to more answers as this work continues and we certainly couldn’t do it without our patient partners.
I’d also like to express my appreciation for the NIH’s institute and center directors who’ve contributed to the NIH Director’s Blog to showcase NIH’s broad and diverse portfolio of promising research.
Finally, a special thanks to all of you who read this blog. As you gather with family and friends to celebrate this Thanksgiving holiday, I hope the time you spend here gives you a few more reasons to feel grateful and appreciate the importance of NIH in turning scientific discovery into better health for all.
Posted on by Lawrence Tabak, D.D.S., Ph.D.
As colder temperatures settle in and people spend more time gathered indoors, cases of COVID-19 and other respiratory illnesses almost certainly will rise. That’s why, along with scheduling your annual flu shot, it’s now recommended that those age 5 and up should get an updated COVID-19 booster shot [1,2]. Not only will these new boosters guard against the original strain of the coronavirus that started the pandemic, they will heighten your immunity to the Omicron variant and several of the subvariants that continue to circulate in the U.S. with devastating effects.
At last count, about 14.8 million people in the U.S.—including me—have rolled up their sleeves to receive an updated booster shot . It’s a good start, but it also means that most Americans aren’t fully up to date on their COVID-19 vaccines. If you or your loved ones are among them, a new study may provide some needed encouragement to make an appointment at a nearby pharmacy or clinic to get boosted .
A team of NIH-supported researchers found a remarkably low incidence of severe COVID-19 illness last fall, winter, and spring among more than 1.6 million veterans who’d been vaccinated and boosted. Severe illness was also quite low in individuals without immune-compromising conditions.
These latest findings, published in the journal JAMA, come from a research group led by Dan Kelly, University of California, San Francisco. He and his team conducted their study drawing on existing health data from the Veterans Health Administration (VA) within a time window of July 2021 and May 2022.
They identified 1.6 million people who’d had a primary-care visit within the last two years and were fully vaccinated for COVID-19, which included receiving a booster shot. Almost three-quarters of those identified were 65 and older. Nearly all were male, and more than 70 percent had another pre-existing health condition that put them at greater risk of becoming seriously ill from a COVID-19 infection.
Over a 24-week follow-up period for each fully vaccinated individual, 125 per 10,000 people had a breakthrough infection. That’s about 1 percent. Just 8.9 in 10,000 fully vaccinated people—less than 0.1 percent—died or were hospitalized from COVID-19 pneumonia. Drilling down deeper into the data:
• Individuals with an immune-compromising condition had a very low rate of hospitalization or death. In this group, 39.6 per 10,000 people had a serious breakthrough infection. That translates to 0.3 percent.
• For people with other preexisting health conditions, including diabetes and heart disease, hospitalization or death totaled 0.07 percent, or 6.7 per 10,000 people.
• For otherwise healthy adults aged 65 and older, the incidence of hospitalization or death was 1.9 per 10,000 people, or 0.02 percent.
• For boosted participants 65 or younger with no high-risk conditions, hospitalization or death came to less than 1 per 10,000 people. That comes to less than 0.01 percent.
It’s worth noting that these results reflect a period when the Delta and Omicron variants were circulating, and available boosters still were based solely on the original variant. Heading into this winter, the hope is that the updated “bivalent” boosters from Pfizer and Moderna will offer even broader protection as this terrible virus continues to evolve.
The Centers for Disease Control and Prevention continues to recommend that everyone stay up to date with their COVID-19 vaccines. That means all adults and kids 5 and older are encouraged to get boosted if it has been at least two months since their last COVID-19 vaccine dose. For older people and those with other health conditions, it’s even more important given their elevated risk for severe illness.
What if you’ve had a COVID-19 infection recently? Getting vaccinated or boosted a few months after you’ve had a COVID-19 infection will offer you even better protection in the future.
So, if you are among the millions of Americans who’ve been vaccinated for COVID-19 but are now due for a booster, don’t delay. Get yourself boosted to protect your own health and the health of your loved ones as the holidays approach.
 CDC recommends the first updated COVID-19 booster. Centers for Disease Control and Prevention. September 1, 2022.
 CDC expands updated COVID-19 vaccines to include children ages 5 through 11. Centers for Disease Control and Prevention, October 12, 2022.
 COVID-19 vaccinations in the United States. Centers for Disease Control and Prevention.
 Incidence of severe COVID-19 illness following vaccination and booster with BNT162b2, mRNA-1273, and Ad26.COV2.S vaccines. Kelly JD, Leonard S, Hoggatt KJ, Boscardin WJ, Lum EN, Moss-Vazquez TA, Andino R, Wong JK, Byers A, Bravata DM, Tien PC, Keyhani S. JAMA. 2022 Oct 11;328(14):1427-1437.
COVID-19 Research (NIH)
Dan Kelly (University of California, San Francisco)
NIH Support: National Institute of Allergy and Infectious Diseases