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.
The COVID-19 pandemic continues to present considerable public health challenges in the United States and around the globe. One of the most puzzling is why many people who get over an initial and often relatively mild COVID illness later develop new and potentially debilitating symptoms. These symptoms run the gamut including fatigue, shortness of breath, brain fog, anxiety, and gastrointestinal trouble.
People understandably want answers to help them manage this complex condition referred to as Long COVID syndrome. But because Long COVID is so variable from person to person, it’s extremely difficult to work backwards and determine what these people had in common that might have made them susceptible to Long COVID. The variability also makes it difficult to identify all those who have Long COVID, whether they realize it or not. But a recent study, published in the journal Lancet Digital Health, shows that a well-trained computer and its artificial intelligence can help.
Researchers found that computers, after scanning thousands of electronic health records (EHRs) from people with Long COVID, could reliably make the call. The results, though still preliminary and in need of further validation, point the way to developing a fast, easy-to-use computer algorithm to help determine whether a person with a positive COVID test is likely to battle Long COVID.
In this groundbreaking study, NIH-supported researchers led by Emily Pfaff, University of North Carolina, Chapel Hill, and Melissa Haendel, the University of Colorado Anschutz Medical Campus, Aurora, relied on machine learning. In machine learning, a computer sifts through vast amounts of data to look for patterns. One reason machine learning is so powerful is that it doesn’t require humans to tell the computer which features it should look for. As such, machine learning can pick up on subtle patterns that people would otherwise miss.
In this case, Pfaff, Haendel, and team decided to “train” their computer on EHRs from people who had reported a COVID-19 infection. (The records are de-identified to protect patient privacy.) The researchers found just what they needed in the National COVID Cohort Collaborative (N3C), a national, publicly available data resource sponsored by NIH’s National Center for Advancing Translational Sciences. It is part of NIH’s Researching COVID to Enhance Recovery (RECOVER) initiative, which aims to improve understanding of Long COVID.
The researchers defined a group of more than 1.5 million adults in N3C who either had been diagnosed with COVID-19 or had a record of a positive COVID-19 test at least 90 days prior. Next, they examined common features, including any doctor visits, diagnoses, or medications, from the group’s roughly 100,000 adults.
They fed that EHR data into a computer, along with health information from almost 600 patients who’d been seen at a Long COVID clinic. They developed three machine learning models: one to identify potential long COVID patients across the whole dataset and two others that focused separately on people who had or hadn’t been hospitalized.
All three models proved effective for identifying people with potential Long-COVID. Each of the models had an 85 percent or better discrimination threshold, indicating they are highly accurate. That’s important because, once researchers can identify those with Long COVID in a large database of people such as N3C, they can begin to ask and answer many critical questions about any differences in an individual’s risk factors or treatment that might explain why some get Long COVID and others don’t.
This new study is also an excellent example of N3C’s goal to assemble data from EHRs that enable researchers around the world to get rapid answers and seek effective interventions for COVID-19, including its long-term health effects. It’s also made important progress toward the urgent goal of the RECOVER initiative to identify people with or at risk for Long COVID who may be eligible to participate in clinical trials of promising new treatment approaches.
Long COVID remains a puzzling public health challenge. Another recent NIH study published in the journal Annals of Internal Medicine set out to identify people with symptoms of Long COVID, most of whom had recovered from mild-to-moderate COVID-19 . More than half had signs of Long COVID. But, despite extensive testing, the NIH researchers were unable to pinpoint any underlying cause of the Long COVID symptoms in most cases.
So if you’d like to help researchers solve this puzzle, RECOVER is now enrolling adults and kids—including those who have and have not had COVID—at more than 80 study sites around the country.
 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 May 16:S2589-7500(22)00048-6.
 A longitudinal study of COVID-19 sequelae and immunity: baseline findings. Sneller MC, Liang CJ, Marques AR, Chung JY, Shanbhag SM, Fontana JR, Raza H, Okeke O, Dewar RL, Higgins BP, Tolstenko K, Kwan RW, Gittens KR, Seamon CA, McCormack G, Shaw JS, Okpali GM, Law M, Trihemasava K, Kennedy BD, Shi V, Justement JS, Buckner CM, Blazkova J, Moir S, Chun TW, Lane HC. Ann Intern Med. 2022 May 24:M21-4905.
COVID-19 Research (NIH)
National COVID Cohort Collaborative (N3C) (National Center for Advancing Translational Sciences/NIH)
Emily Pfaff (University of North Carolina, Chapel Hill)
Melissa Haendel (University of Colorado, Aurora)
NIH Support: National Center for Advancing Translational Sciences; National Institute of General Medical Sciences; National Institute of Allergy and Infectious Diseases
Posted on by Dr. Francis Collins
There’s no question that vaccines are making a tremendous difference in protecting individuals and whole communities against infection and severe illness from SARS-CoV-2, the coronavirus that causes COVID-19. And now, there’s yet another reason to get the vaccine: in the event of a breakthrough infection, people who are fully vaccinated also are substantially less likely to develop Long COVID Syndrome, which causes brain fog, muscle pain, fatigue, and a constellation of other debilitating symptoms that can last for months after recovery from an initial infection.
These important findings published in The Lancet Infectious Diseases are the latest from the COVID Symptom Study . This study allows everyday citizens in the United Kingdom to download a smartphone app and self-report data on their infection, symptoms, and vaccination status over a long period of time.
Previously, the study found that 1 in 20 people in the U.K. who got COVID-19 battled Long COVID symptoms for eight weeks or more. But this work was done before vaccines were widely available. What about the risk among those who got COVID-19 for the first time as a breakthrough infection after receiving a double dose of any of the three COVID-19 vaccines (Pfizer, Moderna, AstraZeneca) authorized for use in the U.K.?
To answer that question, Claire Steves, King’s College, London, and colleagues looked to frequent users of the COVID Symptom Study app on their smartphones. In its new work, Steves’ team was interested in analyzing data submitted by folks who’d logged their symptoms, test results, and vaccination status between December 9, 2020, and July 4, 2021. The team found there were more than 1.2 million adults who’d received a first dose of vaccine and nearly 1 million who were fully vaccinated during this period.
The data show that only 0.2 percent of those who were fully vaccinated later tested positive for COVID-19. While accounting for differences in age, sex, and other risk factors, the researchers found that fully vaccinated individuals who developed breakthrough infections were about half (49 percent) as likely as unvaccinated people to report symptoms of Long COVID Syndrome lasting at least four weeks after infection.
The most common symptoms were similar in vaccinated and unvaccinated adults with COVID-19, and included loss of smell, cough, fever, headaches, and fatigue. However, all of these symptoms were milder and less frequently reported among the vaccinated as compared to the unvaccinated.
Vaccinated people who became infected were also more likely than the unvaccinated to be asymptomatic. And, if they did develop symptoms, they were half as likely to report multiple symptoms in the first week of illness. Another vaccination benefit was that people with a breakthrough infection were about a third as likely to report any severe symptoms. They also were more than 70 percent less likely to require hospitalization.
We still have a lot to learn about Long COVID, and, to get the answers, NIH has launched the RECOVER Initiative. The initiative will study tens of thousands of COVID-19 survivors to understand why many individuals don’t recover as quickly as expected, and what might be the cause, prevention, and treatment for Long COVID.
In the meantime, these latest findings offer the encouraging news that help is already here in the form of vaccines, which provide a very effective way to protect against COVID-19 and greatly reduce the odds of Long COVID if you do get sick. So, if you haven’t done so already, make a plan to protect your own health and help end this pandemic by getting yourself fully vaccinated. Vaccines are free and available near to you—just go to vaccines.gov or text your zip code to 438829.
 Risk factors and disease profile of post-vaccination SARS-CoV-2 infection in UK users of the COVID Symptom Study app: a prospective, community-based, nested, case-control study. Antonelli M, Penfold RS, Merino J, Sudre CH, Molteni E, Berry S, Canas LS, Graham MS, Klaser K, Modat M, Murray B, Kerfoot E, Chen L, Deng J, Österdahl MF, Cheetham NJ, Drew DA, Nguyen LH, Pujol JC, Hu C, Selvachandran S, Polidori L, May A, Wolf J, Chan AT, Hammers A, Duncan EL, Spector TD, Ourselin S, Steves CJ. Lancet Infect Dis. 2021 Sep 1:S1473-3099(21)00460-6.
COVID-19 Research (NIH)
Claire Steves (King’s College London, United Kingdom)
Posted on by Dr. Francis Collins
It’s become increasingly clear that even healthy people with mild cases of COVID-19 can battle a constellation of symptoms that worsen over time—or which sometimes disappear only to come right back. These symptoms are part of what’s called “Long COVID Syndrome.”
Now, a new study of relatively young, healthy adult healthcare workers in Sweden adds needed information on the frequency of this Long COVID Syndrome. Published in the journal JAMA, the study found that just over 1 in 10 healthcare workers who had what at first seemed to be a relatively mild bout of COVID-19 were still coping with at least one moderate to severe symptom eight months later . Those symptoms—most commonly including loss of smell and taste, fatigue, and breathing problems—also negatively affected the work and/or personal lives of these individuals.
These latest findings come from the COVID-19 Biomarker and Immunity (COMMUNITY) study, led by Charlotte Thålin, Danderyd Hospital and Karolinska Institutet, Stockholm. The study, launched a year ago, enlisted 2,149 hospital employees to learn more about immunity to SARS-CoV-2, the coronavirus that causes COVID-19.
After collecting blood samples from participants, the researchers found that about 20 percent already had antibodies to SARS-CoV-2, evidence of a past infection. Thålin and team continued collecting blood samples every four months from all participants, who also completed questionnaires about their wellbeing.
Intrigued by recent reports in the medical literature that many people hospitalized with COVID-19 can have persistent symptoms for months after their release, the researchers decided to take a closer look in their COMMUNITY cohort. They did so last January during their third round of follow up.
This group included 323 mostly female healthcare workers, median age of 43. The researchers compared symptoms in this group following mild COVID-19 to the 1,072 mostly female healthcare workers in the study (median age 47 years) who hadn’t had COVID-19. They wanted to find out if those with mild COVID-19 coped with more and longer-lasting symptoms of feeling unwell than would be expected in an otherwise relatively healthy group of people. These symptoms included familiar things such as fatigue, muscle pain, trouble sleeping, and problems breathing.
Their findings show that 26 percent of those who had mild COVID-19 reported at least one moderate to severe symptom that lasted more than two months. That’s compared to 9 percent of participants without COVID-19. What’s more, 11 percent of the individuals with mild COVID-19 had at least one debilitating symptom that lasted for at least eight months. In the group without COVID-19, any symptoms of feeling unwell resolved relatively quickly.
The most common symptoms in the COVID-19 group were loss of taste or smell, fatigue, and breathing problems. In this group, there was no apparent increase in other symptoms that have been associated with COVID-19, including “brain fog,” problems with memory or attention, heart palpitations, or muscle and joint pain.
The researchers have noted that the Swedish healthcare workers represent a relatively young and healthy group of working individuals. Yet, many of them continued to suffer from lasting symptoms related to mild COVID-19. It’s a reminder that COVID-19 can and, in fact, is having a devastating impact on the lives and livelihoods of adults who are at low risk for developing severe and life-threatening COVID-19. If we needed one more argument for getting young people vaccinated, this is it.
At NIH, efforts have been underway for some time to identify the causes of Long COVID. In fact, a virtual workshop was held last winter with more than 1,200 participants to discuss what’s known and to fill in key gaps in our knowledge of Long COVID syndrome, which is clinically known as post-acute sequelae of COVID-19 (PASC). Recently, a workshop summary was published . As workshops and studies like this one from Sweden help to define the problem, the hope is to learn one day how to treat or prevent this terrible condition. The NIH is now investing more than $1 billion in seeking those answers.
 Symptoms and functional impairment assessed 8 Months after mild COVID-19 among health care workers. Havervall S, Rosell A, Phillipson M, Mangsbo SM, Nilsson P, Hober S, Thålin C. JAMA. 2021 Apr 7.
 Toward understanding COVID-19 recovery: National Institutes of Health workshop on postacute COVID-19. Lerner A, et al. Ann Intern Med, 2021 March 30.
COVID-19 Research (NIH)
Charlotte Thålin (Karolinska Institutet, Stockholm, Sweden)