COVID-19 recovery
Understanding Long-Term COVID-19 Symptoms and Enhancing Recovery
Posted on by Walter J. Koroshetz, M.D., National Institute of Neurological Disorders and Stroke
We are in the third year of the COVID-19 pandemic, and across the world, most restrictions have lifted, and society is trying to get back to “normal.” But for many people—potentially millions globally—there is no getting back to normal just yet.
They are still living with the long-term effects of a COVID-19 infection, known as the post-acute sequelae of SARS-CoV-2 infection (PASC), including Long COVID. These people continue to experience debilitating fatigue, shortness of breath, pain, difficulty sleeping, racing heart rate, exercise intolerance, gastrointestinal and other symptoms, as well as cognitive problems that make it difficult to perform at work or school.
This is a public health issue that is in desperate need of answers. Research is essential to address the many puzzling aspects of Long COVID and guide us to effective responses that protect the nation’s long-term health.
For the past two years, NIH’s National Heart, Lung, and Blood Institute (NHLBI), the National Institute of Allergy and Infectious Diseases (NIAID), and my National Institute of Neurological Disorders and Stroke (NINDS) along with several other NIH institutes and the office of the NIH Director, have been leading NIH’s Researching COVID to Enhance Recovery (RECOVER) initiative, a national research program to understand PASC.
The initiative studies core questions such as why COVID-19 infections can have lingering effects, why new symptoms may develop, and what is the impact of SARS-CoV-2, the virus that causes COVID-19, on other diseases and conditions? Answering these fundamental questions will help to determine the underlying biologic basis of Long COVID. The answers will also help to tell us who is at risk for Long COVID and identify therapies to prevent or treat the condition.
The RECOVER initiative’s wide scope of research is also unprecedented. It is needed because Long COVID is so complex, and history indicates that similar post infectious conditions have defied definitive explanation or effective treatment. Indeed, those experiencing Long COVID report varying symptoms, making it highly unlikely that a single therapy will work for everyone, underscoring the need to pursue multiple therapeutic strategies.
To understand Long COVID fully, hundreds of RECOVER investigators are recruiting more than 17,000 adults (including pregnant people) and more than 18,000 children to take part in cohort studies. Hundreds of enrolling sites have been set up across the country. An autopsy research cohort will also provide further insight into how COVID-19 affects the body’s organs and tissues.
In addition, researchers will analyze electronic health records from millions of people to understand how Long COVID and its symptoms change over time. The RECOVER initiative is also utilizing consistent research protocols across all the study sites. The protocols have been carefully developed with input from patients and advocates, and they are designed to allow for consistent data collection, improve data sharing, and help to accelerate the pace of research.
From the very beginning, people suffering from Long COVID have been our partners in RECOVER. Patients and advocates have contributed important perspectives and provided valuable input into the master protocols and research plans.
Now, with RECOVER underway, individuals with Long COVID, their caregivers, and community members continue to serve a critical role in the Initiative. The National Community Engagement Group (NCEG) has been established to make certain that RECOVER meets the needs of all people affected by Long COVID. The RECOVER Patient and Community Engagement Strategy outlines all the approaches that RECOVER is using to engage with and gather input from individuals impacted by Long COVID.
The NIH recently made more than 40 awards to improve understanding of the underlying biology and pathology of Long COVID. There have already been several important findings published by RECOVER scientists.
For example, in a recent study published in the journal Lancet Digital Health, RECOVER investigators used machine learning to comb through electronic health records to look for signals that may predict whether someone has Long COVID [1]. As new findings, tools, and technologies continue to emerge that help advance our knowledge of the condition, the RECOVER Research Review (R3) Seminar Series will provide a forum for researchers and our partners with up-to-date information about Long COVID research.
It is important to note that post-viral conditions are not a new concept. Many, but not all, of the symptoms reported in Long COVID, including fatigue, post-exertional malaise, chronic musculoskeletal pain, sleep disorders, postural orthostatic tachycardia (POTS), and cognitive issues, overlap with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).
ME/CFS is a serious disease that can occur following infection and make people profoundly sick for decades. Like Long COVID, ME/CFS is a heterogenous condition that does not affect everybody in the same way, and the knowledge gained through research on Long COVID may also positively impact the understanding, treatment, and prevention of POTS, ME/CFS, and other chronic diseases.
Unlike other post-viral conditions, people who experience Long COVID were all infected by the same virus—albeit different variants—at a similar point in time. This creates a unique opportunity for RECOVER researchers to study post-viral conditions in real-time.
The opportunity enables scientists to study many people simultaneously while they are still infected to monitor their progress and recovery, and to try to understand why some individuals develop ongoing symptoms. A better understanding of the transition from acute to chronic disease may offer an opportunity to intervene, identify who is at risk of the transition, and develop therapies for people who experience symptoms long after the acute infection has resolved.
The RECOVER initiative will soon announce clinical trials, leveraging data from clinicians and patients in which symptom clusters were identified and can be targeted by various interventions. These trials will investigate therapies that are indicated for other non-COVID conditions and novel treatments for Long COVID.
Through extensive collaboration across the multiple NIH institutes and offices that contribute to the RECOVER effort, our hope is critical answers will emerge soon. These answers will help us to recognize the full range of outcomes and needs resulting from PASC and, most important, enable many people to make a full recovery from COVID-19. We are indebted to the over 10,000 subjects who have already enrolled in RECOVER. Their contributions and the hard work of the RECOVER investigators offer hope for the future to the millions still suffering from the pandemic.
Reference:
[1] 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.
Links:
COVID-19 Research (NIH)
Long COVID (NIH)
RECOVER: Researching COVID to Enhance Recovery (NIH)
“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.
Director’s Messages (National Institute of Neurological Disorders and Stroke/NIH)
Note: Dr. Lawrence Tabak, who performs the duties of the NIH Director, has asked the heads of NIH’s Institutes and Centers (ICs) to contribute occasional guest posts to the blog to highlight some of the interesting science that they support and conduct. This is the 18th in the series of NIH IC guest posts that will run until a new permanent NIH director is in place.
Breakthrough Infections Occur in Those with Lower Antibody Levels, Israeli Study Shows
Posted on by Dr. Francis Collins
To see how COVID-19 vaccines are working in the real world, Israel has provided particularly compelling data. The fact that Israel is relatively small, keeps comprehensive medical records, and has a high vaccination rate with a single vaccine (Pfizer) has contributed to its robust data collection. Now, a new Israeli study offers some insight into those relatively uncommon breakthrough infections. It confirms that breakthrough cases, as might be expected, arise most often in individuals with lower levels of neutralizing antibodies.
The findings reported in The New England Journal of Medicine focused on nearly 1,500 of about 11,500 fully vaccinated health care workers at Sheba Medical Center, Ramat Gan, Israel [1]. All had received two doses of the Pfizer mRNA vaccine. But, from December 19, 2020 to April 28, 2021, they were tested for a breakthrough infection due to a known exposure to someone with COVID-19 or possible symptoms of the disease.
Just 39 confirmed breakthrough cases were found, indicating a breakthrough infection rate of just 0.4 percent. That’s consistent with rates reported in previous studies. Most in the Israeli study who tested positive for COVID-19 had mild or no symptoms and none required hospitalization.
In the new study, researchers led by Gili Regev-Yochay at Sheba Medical Center’s Infection Control and Prevention Unit, characterized as many breakthrough infections as possible among the health care workers. Almost half of the infections involved members of the hospital nursing staff. But breakthrough cases also were found in hospital administration, maintenance workers, doctors, and other health professionals.
The average age of someone with a breakthrough infection was 42, and it’s notable that only one person was known to have a weakened immune system. The most common symptoms were respiratory congestion, muscle aches (myalgia), and loss of smell or taste. Most didn’t develop a fever. At six weeks after diagnosis, 19 percent reported having symptoms of Long COVID syndrome, including prolonged loss of smell, persistent cough, weakness, and fatigue. About a quarter stayed home from work for longer than the required 10 days, and one had yet to return to work at six weeks.
For 22 of the 39 people with a breakthrough infection, the researchers had results of neutralizing antibody tests from the week leading up to their positive COVID-19 test result. To look for patterns in the antibody data, they matched those individuals to 104 uninfected people for whom they also had antibody test results. These data showed that those with a breakthrough infection had consistently lower levels of neutralizing antibodies circulating in their bloodstream to SARS-CoV-2, the coronavirus that causes COVID-19. In general, higher levels of neutralizing antibodies are associated with greater protection and lower infectivity—though other aspects of the immune system (memory B cells and cell-mediated immunity) also contribute.
Importantly, in all cases for which there were relevant data, the source of the breakthrough infection was thought to be an unvaccinated person. In fact, more than half of those who developed a breakthrough infection appeared to have become infected from an unvaccinated member of their own household.
Other cases were suspected to arise from exposure to an unvaccinated coworker or patient. Contact tracing found no evidence that any of the 39 health care workers with a breakthrough infection passed it on to anyone else.
The findings add to evidence that full vaccination and associated immunity offer good protection against SARS-CoV-2 infection and severe illness. Understanding how SARS-CoV-2 immunity changes over time is key for charting the course of this pandemic and making important decisions about COVID-19 vaccine boosters.
Many questions remain. For instance, it’s not clear from the study whether lower neutralizing antibodies in those with breakthrough cases reflect waning immunity or, for reasons we don’t yet understand, those individuals may have had a more limited immune response to the vaccine. Also, this study was conducted before the Delta variant became dominant in Israel (and now in the whole world).
Overall, these findings provide more reassurance that these vaccines are extremely effective. Breakthrough infections, while they can and do occur, are a relatively uncommon event. Here in the U.S., the Centers for Disease Control and Prevention (CDC) has recently estimated that infection is six times less likely for vaccinated than unvaccinated persons [2]. That those with immunity tend to have mild or no symptoms if they do develop a breakthrough case, however, is a reminder that these cases could easily be missed, and they could put vulnerable populations at greater risk. It’s yet another reason for all those who can to get themselves vaccinated as soon as possible or consider a booster shot when they become eligible.
References:
[1] Covid-19 breakthrough infections in vaccinated health care workers. Bergwerk M, Gonen T, Lustig Y, Amit S, Lipsitch M, Cohen C, Mandelboim M, Levin EG, Rubin C, Indenbaum V, Tal I, Zavitan M, Zuckerman N, Bar-Chaim A, Kreiss Y, Regev-Yochay G. N Engl J Med. 2021 Oct 14;385(16):1474-1484.
[2] Rates of COVID-19 cases and deaths by vaccination status, COVID Data Tracker, Centers for Disease and Prevention. Accessed October 25, 2021.
Links:
COVID-19 Research (NIH)
Sheba Medical Center (Ramat Gan, Israel)
Study Finds 1 in 10 Healthcare Workers with Mild COVID Have Lasting Symptoms
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 [1]. 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 [2]. 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.
References:
[1] 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.
[2] Toward understanding COVID-19 recovery: National Institutes of Health workshop on postacute COVID-19. Lerner A, et al. Ann Intern Med, 2021 March 30.
Links:
COVID-19 Research (NIH)
Charlotte Thålin (Karolinska Institutet, Stockholm, Sweden)
Antibody Response Affects COVID-19 Outcomes in Kids and Adults
Posted on by Dr. Francis Collins
Doctors can’t reliably predict whether an adult newly diagnosed with COVID-19 will recover quickly or battle life-threatening complications. The same is true for children.
Thankfully, the vast majority of kids with COVID-19 don’t get sick or show only mild flu-like symptoms. But a small percentage develop a delayed, but extremely troubling, syndrome called multisystem inflammatory syndrome in children (MIS-C). This can cause severe inflammation of the heart, lungs, kidneys, brain, and other parts of the body, coming on weeks after recovering from COVID-19. Fortunately, most kids respond to treatment and make rapid recoveries.
COVID-19’s sometimes different effects on kids likely stem not from the severity of the infection itself, but from differences in the immune response or its aftermath. Additional support for this notion comes from a new study, published in the journal Nature Medicine, that compared immune responses among children and adults with COVID-19 [1]. The study shows that the antibody responses in kids and adults with mild COVID-19 are quite similar. However, the complications seen in kids with MIS-C and adults with severe COVID-19 appear to be driven by two distinctly different types of antibodies involved in different aspects of the immune response.
The new findings come from pediatric pulmonologist Lael Yonker, Massachusetts General Hospital (MGH) Cystic Fibrosis Center, Boston, and immunologist Galit Alter, the Ragon Institute of MGH, Massachusetts Institute of Technology, and Harvard, Cambridge. Yonker runs a biorepository that collects samples from kids with cystic fibrosis. When the pandemic began, she started collecting plasma samples from children with mild COVID-19. Then, when Yonker and others began to see children hospitalized with MIS-C, she collected some plasma samples from them, too.
Using these plasma samples as windows into a child’s immune response, the research teams of Yonker and Alter detailed antibodies generated in 17 kids with MIS-C and 25 kids with mild COVID-19. They also profiled antibody responses of 60 adults with COVID-19, including 26 with severe disease.
Comparing antibody profiles among the four different groups, the researchers had expected children’s antibody responses to look quite different from those in adults. But they were in for a surprise. Adults and kids with mild COVID-19 showed no notable differences in their antibody profiles. The differences only came into focus when they compared antibodies in kids with MIS-C to adults with severe COVID-19.
In kids who develop MIS-C after COVID-19, they saw high levels of long-lasting immunoglobulin G (IgG) antibodies, which normally help to control an acute infection. Those high levels of IgG antibodies weren’t seen in adults or in kids with mild COVID-19. The findings suggest that in kids with MIS-C, those antibodies may activate scavenging immune cells, called macrophages, to drive inflammation and more severe illness.
In adults with severe COVID-19, the pattern differed. Instead of high levels of IgG antibodies, adults showed increased levels of another type of antibody, called immunoglobulin A (IgA). These IgA antibodies apparently were interacting with immune cells called neutrophils, which in turn led to the release of cytokines. That’s notable because the release of too many cytokines can cause what’s known as a “cytokine storm,” a severe symptom of COVID-19 that’s associated with respiratory distress syndrome, multiple organ failure, and other life-threatening complications.
To understand how a single virus can cause such different outcomes, studies like this one help to tease out their underlying immune mechanisms. While more study is needed to understand the immune response over time in both kids and adults, the hope is that these findings and others will help put us on the right path to discover better ways to help protect people of all ages from the most severe complications of COVID-19.
Reference:
[1] Humoral signatures of protective and pathological SARS-CoV-2 infection in children. Bartsch YC, Wang C, Zohar T, Fischinger S, Atyeo C, Burke JS, Kang J, Edlow AG, Fasano A, Baden LR, Nilles EJ, Woolley AE, Karlson EW, Hopke AR, Irimia D, Fischer ES, Ryan ET, Charles RC, Julg BD, Lauffenburger DA, Yonker LM, Alter G. Nat Med. 2021 Feb 12.
Links:
COVID-19 Research (NIH)
“NIH effort seeks to understand MIS-C, range of SARS-CoV-2 effects on children,” NIH news release, March 2, 2021.
Lael Yonker (Massachusetts General Hospital, Boston)
Alter Lab (Ragon Institute of Massachusetts General Hospital, MIT, and Harvard, Cambridge)
NIH Support: National Institute of Allergy and Infectious Diseases; National Cancer Institute
Vast Majority of Pregnant Women with COVID-19 Won’t Have Complications, Study Finds
Posted on by Dr. Francis Collins
It’s natural and highly appropriate for women to be concerned about their health and the wellbeing of their unborn babies during pregnancy. With the outbreak of the pandemic, those concerns have only increased, especially after a study found last spring that about 30 percent of pregnant women who become infected with SARS-CoV-2, the coronavirus that causes COVID-19, needed to be hospitalized [1].
But that early study didn’t clearly divide out hospitalizations that were due to pregnancy from those owing to complications of COVID-19. Now, a large, observational study has taken a more comprehensive look at the issue and published some reassuring news for parents-to-be: the vast majority of women who test positive for COVID-19 during their pregnancies won’t develop serious health complications [2]. What’s more, it’s also unlikely that their newborns will become infected with SARS-CoV-2.
The findings reported in JAMA Network Open come from a busy prenatal clinic that serves women who are medically indigent at Parkland Health and Hospital System, affiliated with the University of Texas Southwestern, Dallas. Researchers there, led by obstetrician Emily Adhikari, followed more than 3,300 pregnant women, most of whom were Hispanic (75 percent) or African American (14 percent). From March through August of this year, 252 women tested positive for COVID-19 during their pregnancies.
At diagnosis, 95 percent were asymptomatic or had only mild symptoms. Only 13 of the 252 COVID-19-positive women (5 percent) in the study developed severe or critical pneumonia, including just six with no or mild symptoms initially. Only 14 women (6 percent) were admitted to the hospital for management of their COVID-19 pneumonia, and all survived.
By comparing mothers with and without COVID-19 during pregnancy, the researchers found there was no increase in adverse pregnancy-related outcomes. Overall, women with COVID-19 during pregnancy were not more likely to give birth early on average. They weren’t at increased risk of dangerous preeclampsia, a pregnancy complication characterized by high blood pressure and organ damage, or an emergency C-section to protect the baby.
The researchers found no evidence that the placenta was compromised in any way by the SARS-CoV-2 infection. In most cases, newborns didn’t get sick. Only 6 of 188 infants (3 percent) tested positive for COVID-19. Most of those infected were born to mothers who were asymptomatic or had only mild illness.
This is all encouraging news. However, it is worth noting that mothers who developed severe COVID-19 before reaching 37 weeks, or well into the third trimester of pregnancy, were more likely to give birth prematurely. More research is needed, but the study also suggests that diabetes may increase the risk for severe COVID-19 in pregnancy.
This study’s bottom line is that most women who become infected with SARS-CoV-2 during pregnancy will do just fine. That doesn’t mean, however, that anyone should take this situation casually. The finding that 5 percent of pregnant women may become severely ill is still cause for concern. Plus not all researchers come to the same conclusion—an update to the first study cited in this post recently found a greater risk for pregnant women becoming severely ill from COVID-19 and giving birth prematurely.
Taken together, while there’s no need to panic about COVID-19 infection during pregnancy, it’s still a good idea for pregnant women and their loved ones to take extra precautions to protect their health. And, of course, follow the three W’s: Wear a mask, Watch your distance, and Wash your hands.
References:
[1] Characteristics of women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status—United States, January 22–June 7, 2020. CDC COVID-19 Response Team. MMWR Morb Mortal Wkly Rep. 2020 Mar 27;69(12):343-346.
[2] Pregnancy outcomes among women with and without severe acute respiratory syndrome coronavirus 2 infection. Adhikari EH, Moreno W, Zofkie AC, MacDonald L, McIntire DD, Collins RRJ, Spong CY. JAMA Netw Open. 2020 Nov 2;3(11):e2029256.
Links:
Coronavirus (COVID) (NIH)
Combat COVID (U.S. Department of Health and Human Services, Washington, D.C.)
Data on COVID-19 during Pregnancy: Severity of Maternal Illness (Centers for Disease Control and Prevent, Atlanta)
COVID-19 Treatment Guidelines: Special Considerations in Pregnancy (NIH)
Emily Adhikari (University of Texas Southwestern Medical Center, Dallas)
Study Highlights Need for Continued Care of COVID-19 Survivors
Posted on by Dr. Francis Collins
The past several months have shown that most people hospitalized with COVID-19 will get better. As inspiring as it is to see these patients breathe on their own and converse with their loved ones again, we are learning that many will leave the hospital still quite ill and in need of further care. But little has been published to offer a detailed demographic picture of those being discharged from our nation’s hospitals and the types of community-based care and monitoring that will be needed to keep them on the road to recovery.
A recent study in the journal EClinicalMedicine helps to fill in those gaps by chronicling the early COVID-19 experience of three prominent hospitals in the Boston area: Massachusetts General Hospital, Brigham and Women’s Hospital, and Newton-Wellesley Hospital. These data were reported from a patient registry of 247 middle-aged and older COVID-19 patients. The patients were admitted over three weeks last March into one of these hospitals, which are part of New England’s largest integrated health network.
The data confirm numerous previous reports that COVID-19 disproportionately affects people of color. The researchers, led by Jason H. Wasfy and Cian P. McCarthy, Massachusetts General Hospital and Harvard Medical School, Boston, found a large number of their patients were Hispanic (30 percent) or Black (10 percent). Wasfy said these numbers could be driven by many factors, including a low income, more family members living in one home, greater difficulty accessing healthcare, presence of chronic illness (health disparities), and serving as essential workers during the pandemic.
The researchers also tracked the patients after discharge for about 80 days. About a third of patients left the hospital for a post-acute care facility to continue their rehabilitation. After discharge, many required supplemental oxygen (15 percent), tube feeding (9 percent), or treatment with medications including antipsychotics and prescription painkillers (16 percent). About 10 percent were readmitted to the hospital within weeks or months of their initial discharge.
Wasfy and colleagues also found:
· Many patients undergoing treatment were enrolled in Medicaid (20 percent) or both Medicaid and Medicare (12 percent).
· A substantial number also were retired (36 percent) or unemployed (8.5 percent), highlighting the role of non-occupational spread. Many others worked in the hospitality industry, healthcare, or public transportation.
· A large proportion (42 percent) of hospitalized patients required intensive care. The good news is that most of them (86 percent) ultimately recovered enough to be discharged from the hospital. Tragically, 14 percent—34 of 247 people—died in the hospital.
These findings represent hospitals in just one notable American city hard hit early in the pandemic. But they spotlight the importance of public health efforts to prevent COVID-19 among the most vulnerable and reduce its most devastating social impacts. These are critical points, and NIH has recently begun supporting community engagement research efforts in areas hardest hit by COVID-19. With this support and access to needed post-discharge care, we aim to help more COVID survivors stay on the road to a full recovery.
Reference:
[1] Early clinical and sociodemographic experience with patients hospitalized with COVID-19 at a large American healthcare system. McCarthy CP et al. EClinicalMedicine. August 19, 2020.
Links:
Coronavirus (COVID-19) (NIH)
Massachusetts General Hospital (Boston)
Brigham and Women’s Hospital (Boston)
Newton-Wellesley Hospital (Newton, MA)
Jason Wasfy (Massachusetts General Hospital)
COVID-19 Can Damage Hearts of Some College Athletes
Posted on by Dr. Francis Collins
There’s been quite a bit of discussion in the news lately about whether to pause or resume college athletics during the pandemic. One of the sticking points has been uncertainty about how to monitor the health of student athletes who test positive for SARS-CoV-2, the novel coronavirus that causes COVID-19. As a result, college medical staff don’t always know when to tell athletes that they’ve fully recovered and it’s safe to start training again.
The lack of evidence owes to two factors. Though it may not seem like it, this terrible coronavirus has been around for less than a year, and that’s provided little time to conduct the needed studies with young student athletes. But that’s starting to change. An interesting new study in the journal JAMA Cardiology provides valuable and rather worrisome early data from COVID-positive student athletes evaluated for an inflammation of the heart called myocarditis, a well-known complication [1].
Saurabh Rajpal and his colleagues at the Ohio State University, Columbus, used cardiac magnetic resonance imaging (MRI) to visualize the hearts of 26 male and female student athletes. They participated in a range of sports, including football, soccer, lacrosse, basketball, and track. All of the athletes were referred to the university’s sports medicine clinic this past summer after testing positive for SARS-CoV-2. All had mild or asymptomatic cases of COVID-19.
Even so, the MRI scans, taken 11-53 days after completion of quarantine, showed four of the student athletes (all males) had swelling and tissue damage to their hearts consistent with myocarditis. Although myocarditis often resolves on its own over time, severe cases can compromise the heart muscle’s ability to beat. That can lead to heart failure, abnormal heart rhythms, and even sudden death in competitive athletes with normal heart function [2].
The investigators also looked for more subtle findings of cardiac injury in these athletes, using a contrast agent called gadolinium and measuring its time to appear in the cardiac muscle during the study. Eight of the 26 athletes (31 percent) had late gadolinium enhancement, suggestive of prior myocardial injury.
Even though it’s a small study, these results certainly raise concerns. They add more evidence to a prior study, published by a German group, that suggested subtle cardiac consequences of SARS-CoV-2 infection may be common in adults [3].
Rajpal and his colleagues will continue to follow the athletes in their study for several more months. The researchers will keep an eye out for other lingering symptoms of COVID-19, generate more cardiac MRI data, and perform exercise testing.
As this study shows, we still have a lot to learn about the long-term consequences of COVID-19, which can take people on different paths to recovery. For athletes, that path is the challenge to return to top physical shape and feel ready to compete at a high level. But getting back in uniform must also be done safely to minimize any risks to an athlete’s long-term health and wellbeing. The more science-based evidence that’s available, the more prepared athletes at large and small colleges will be to compete safely in this challenging time.
References:
[1] Cardiovascular magnetic resonance findings in competitive athletes recovering from COVID-19 infection. Rajpal S, Tong MS, Borchers J, et al. JAMA Cardiol. 2020 September 11. [Published online ahead of print.]
[2] Eligibility and disqualification recommendations for competitive athletes with cardiovascular abnormalities: Task Force 3: Hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy and other cardiomyopathies, and myocarditis. Maron BJ, Udelson JE, Bonow RO, et al. Circulation. 2015;132(22):e273-e280.
[3] Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from Coronavirus Disease 2019 (COVID-19). Puntmann VO, Carej ML, Wieters I. JAMA Cardiol. 2020 Jul 27:e203557. [Published online ahead of print.]
Links:
Coronavirus (COVID-19) (NIH)
Heart Inflammation (National Heart, Lung, and Blood Institute/NIH)
Saurabh Rajpal (Ohio State College of Medicine, Columbus)
Months After Recovery, COVID-19 Survivors Often Have Persistent Lung Trouble
Posted on by Dr. Francis Collins
The pandemic has already claimed far too many lives in the United States and around the world. Fortunately, as doctors have gained more experience in treating coronavirus disease 2019 (COVID-19), more people who’ve been hospitalized eventually will recover. This raises an important question: what does recovery look like for them?
Because COVID-19 is still a new condition, there aren’t a lot of data out there yet to answer that question. But a recent study of 55 people recovering from COVID-19 in China offers some early insight into the recovery of lung function [1]. The results make clear that—even in those with a mild-to-moderate infection—the effects of COVID-19 can persist in the lungs for months. In fact, three months after leaving the hospital about 70 percent of those in the study continued to have abnormal lung scans, an indication that the lungs are still damaged and trying to heal.
The findings in EClinicalMedicine come from a team in Henan Province, China, led by Aiguo Xu, The First Affiliated Hospital of Zhengzhou University; Yanfeng Gao, Zhengzhou University; and Hong Luo, Guangshan People’s Hospital. They’d heard about reports of lung abnormalities in patients discharged from the hospital. But it wasn’t clear how long those problems stuck around.
To find out, the researchers enrolled 55 men and women who’d been admitted to the hospital with COVID-19 three months earlier. Some of the participants, whose average age was 48, had other health conditions, such as diabetes or heart disease. But none had any pre-existing lung problems.
Most of the patients had mild or moderate respiratory illness while hospitalized. Only four of the 55 had been classified as severely ill. Fourteen patients required supplemental oxygen while in the hospital, but none needed mechanical ventilation.
Three months after discharge from the hospital, all of the patients were able to return to work. But they continued to have lingering symptoms of COVID-19, including shortness of breath, cough, gastrointestinal problems, headache, or fatigue.
Evidence of this continued trouble also showed up in their lungs. Thirty-nine of the study’s participants had an abnormal result in their computed tomography (CT) lung scan, which creates cross-sectional images of the lungs. Fourteen individuals (1 in 4) also showed reduced lung function in breathing tests.
Interestingly, the researchers found that those who went on to have more lasting lung problems also had elevated levels of D-dimer, a protein fragment that arises when a blood clot dissolves. They suggest that a D-dimer test might help to identify those with COVID-19 who would benefit from pulmonary rehabilitation to rebuild their lung function, even in the absence of severe respiratory symptoms.
This finding also points to the way in which the SARS-CoV-2 virus seems to enhance a tendency toward blood clotting—a problem addressed in our Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership. The partnership recently initiated a trial of blood thinners. That trial will start out by focusing on newly diagnosed outpatients and hospitalized patients, but will go on to include a component related to convalescence.
Moving forward, it will be important to conduct larger and longer-term studies of COVID-19 recovery in people of diverse backgrounds to continue to learn more about what it means to survive COVID-19. The new findings certainly indicate that for many people who’ve been hospitalized with COVID-19, regaining normal lung function may take a while. As we learn even more about the underlying causes and long-term consequences of this new infectious disease, let’s hope it will soon lead to insights that will help many more COVID-19 long-haulers and their concerned loved ones breathe easier.
Reference:
[1] Follow-up study of the pulmonary function and related physiological characteristics of COVID-19 survivors three months after recovery. Zhao YM, Shang YM, Song WB, Li QQ, Xie H, Xu QF, Jia JL, Li LM, Mao HL, Zhou XM, Luo H, Gao YF, Xu AG. EClinicalMedicine.2020 Aug 25:100463
Links:
Coronavirus (COVID-19) (NIH)
How the Lungs Work (National Heart, Lung, and Blood Institute/NIH)
Computed Tomography (CT) (National Institute of Biomedical Imaging and Bioengineering/NIH)
Zhengzhou University (Zhengzhou City, Henan Province, China)
Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) (NIH)
Citizen Scientists Take on the Challenge of Long-Haul COVID-19
Posted on by Dr. Francis Collins
Coronaviruses are a frequent cause of the common cold. Most of us bounce back from colds without any lasting health effects. So, you might think that individuals who survive other infectious diseases caused by coronaviruses—including COVID-19—would also return to normal relatively quickly. While that can be the case for some people, others who’ve survived even relatively mild COVID-19 are experiencing health challenges that may last for weeks or even months. In fact, the situation is so common, that some of these folks have banded together and given their condition a name: the COVID “long-haulers.”
Among the many longer-term health problems that have been associated with COVID-19 are shortness of breath, fatigue, cognitive issues, erratic heartbeat, gastrointestinal issues, low-grade fever, intolerance to physical or mental activity, and muscle and joint pains. COVID-19 survivors report that these symptoms flair up unpredictably, often in different combinations, and can be debilitating for days and weeks at a time. Because COVID-19 is such a new disease, little is known about what causes the persistence of symptoms, what is impeding full recovery, or how to help the long-haulers.
More information is now emerging from the first detailed patient survey of post-COVID syndrome, also known as Long COVID [1]. What’s unique about the survey is that it has been issued by a group of individuals who are struggling with the syndrome themselves. These citizen scientists, who belong to the online Body Politic COVID-19 Support Group, decided to take matters into their own hands. They already had a pretty good grip on what sort of questions to ask, as well as online access to hundreds of long-haulers to whom they could pose the questions.
The citizen scientists’ group, known as the Patient-led Research for COVID-19, brought a lot of talent and creativity to the table. Members reside in the United States, Canada, and England, and none have ever met face to face. But, between their day jobs, managing time differences, and health challenges, each team member spends about 20 hours per week working on their patient-led research, and are now putting the final touches on a follow-up survey that will get underway in the next few weeks.
For their first survey, the group members faced the difficult decision of whom to contact. First, they needed to define long hauler. For that, they decided to target people whose symptoms persisted for more than 2 weeks after their initial recovery from COVID-19. The 640 individuals who responded to the survey were predominately white females between the ages of 30 to 49 who lived in the United States. The members said that the gender bias may stem from women being more likely to join support groups and complete surveys, though there may be a gender component to Long COVID as well. About 10 percent of respondents reported that they had ultimately recovered from this post-COVID syndrome.
Another important issue revolved around COVID-19 testing. Most long-haulers in the online group had gotten sick in March and April, but weren’t so sick that they needed to be hospitalized. Because COVID-19 testing during those months was often limited to people hospitalized with severe respiratory problems, many long-haulers with mild or moderate COVID-like symptoms weren’t tested. Others were tested relatively late in the course of their illness, which can increase the likelihood of false negatives.
The team opted to cast a wide investigative net, concluding that limiting its data to only people who tested positive for COVID-19 might lead to the loss of essential information on long-haulers. It turns out that half of the respondents hadn’t been tested for SARS-CoV-2, the virus that causes COVID-19. The other half was divided almost equally between those who tested positive and those who tested negative. Here are some highlights of the survey’s findings:
Top 10 Symptoms: Respondents were asked to rank their most common symptoms and their relative severity. From highest to lowest, they were: mild shortness of breath, mild tightness of chest, moderate fatigue, mild fatigue, chills or sweats, mild body aches, dry cough, elevated temperature (98.8-100), mild headache, and brain fog/concentration challenges. Highlighting the value of patient-led research, the team was able to assemble an initial list of 62 symptoms that long-haulers often discuss in support groups. The survey revealed common symptoms that have been greatly underreported in the media, such as neurological symptoms. These include brain fog, concentration challenges, and dizziness.
Making a Recovery: Of the 60 respondents who had recovered, the average time to recovery was 27 days. The respondents who had not recovered had managed their symptoms for 40 days on average, with most dealing with health problems for 5 to 7 weeks. The report shows that the chance of full recovery by day 50 is less than 20 percent.
Exercise Capacity: About 65 percent of respondents now consider themselves mostly sedentary. Most had been highly physically active before developing COVID-19. Many long-haulers expressed concern that overexertion causes relapses
Testing. Respondents who reported testing positive for SARS-CoV-2 were tested on average earlier in their illness (by day 10) than those who reported testing negative (by day 16). The team noted that their findings parallel those in a recent published scientific study, which found false-negative rates for current PCR-based assays rose as the time between SARS-CoV-2 infection and testing increased [2]. In that published study, by day 21, the false-negative rate reached 66 percent. Only two symptoms (loss of smell and loss of taste) occurred more frequently in respondents who tested positive; the other 60 symptoms were statistically the same between groups. The citizen scientists speculate that testing is not capturing a subset of COVID patients, and more investigation is required.
Since issuing their survey results on May 11, the team has met with staff from the Centers for Disease Control and Prevention and the World Health Organization. Their work also been mentioned in magazine articles and even cited in some papers published in scientific journals.
In their next survey, these citizen scientists hope to fill in gaps in their first report, including examining antibody testing results, neurological symptoms, and the role of mental health. To increase geographic and demographic diversity, they will also translate the survey into 10 languages. If you’re a COVID-19 long-hauler and would like to find out how to get involved, there’s still time to take part in the next survey.
References:
[1] “What Does COVID-19 Recovery Actually Look Like?” Patient-led Research for COVID-19. May 11, 2020.
[2] Variation in False-Negative Rate of Reverse Transcriptase Polymerase Chain Reaction-Based SARS-CoV-2 Tests by Time Since Exposure. Kucirka LM, Lauer SA, Laeyendecker O, Boon D, Lessler J. Ann Intern Med. 2020 Aug 18;173(4):262-267.
Links:
Coronavirus (COVID-19) (NIH)
