The amount of SARS-CoV-2 antigen measured in the blood of patients hospitalized with COVID-19 is associated with illness severity and other clinical outcomes, according to a new study published in the Annals of Internal Medicine. Following the ACTIV-3 trial of COVID-19 therapeutics in people hospitalized with COVID-19, researchers from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and their collaborators analyzed levels of SARS-COV-2 antigen in blood samples taken from study participants and assessed the association of those levels with disease progression. Higher levels of viral antigen in the blood, which could indicate ongoing SARS-CoV-2 replication, correlated with more severe disease. The authors suggest that SARS-CoV-2 antigen levels hold promise as a biomarker, or a measurable substance, to predict which patients hospitalized with COVID-19 have a higher risk of worse outcomes.
The ACTIV-3 trial enrolled people hospitalized with COVID-19 between August 2020 and November 2021. Participants contributed a baseline blood sample and were then randomized to receive either an experimental COVID-19 therapeutic or a placebo. All participants received the antiviral remdesivir unless contraindicated. In this follow-up analysis, the researchers examined 2,540 participant baseline blood samples for SARS-CoV-2 antigen levels.
The researchers assessed the relationship between each participant’s SARS-CoV-2 blood antigen levels and their time to discharge from the hospital, as well as their pulmonary symptoms at day five of the trial—whether they had stayed the same, worsened, or improved since enrollment. With all this information in hand, the researchers conducted statistical analyses to determine if plasma antigen levels were associated with the participants’ pulmonary function when they gave the blood sample—and whether they could predict how the participants would fare over time. In addition, the researchers examined the relationship between a number of participant and viral characteristics and antigen levels.
Researchers at the National Institutes of Health have found that a novel blood test can be used to easily evaluate disease severity in patients with pulmonary arterial hypertension (PAH) and predict survivability. PAH is a rare, life-threatening condition that causes unexplained high blood pressure in the lungs. In early clinical studies, the researchers showed the test to significantly improve upon conventional tests, some of which use invasive tools.
The new blood test measures DNA fragments shed by damaged cells. Researchers found that these fragments, called cell-free DNA, were elevated in the blood of patients with PAH and increase with disease severity. If future studies confirm the findings, this first-of-its-kind blood test for PAH patients could allow doctors to intervene faster to prevent or delay progression of the disease and possibly save lives. Cell-free DNA is a relatively new analytical technique that is growing in its potential medical uses, which include the early detection of heart- and lung-transplant rejection as well as early detection of cancer.
“Researchers have been actively searching for novel, less-invasive approaches to evaluate PAH severity, disease progression, and response to therapy for more than a decade. These cell-free DNA analyses represent progress toward that goal,” said study co-author Michael A. Solomon, M.D., M.B.A., who is part of the NHLBI Cardiovascular Branch and co-director of the NIH Clinical Center Pulmonary Arterial Hypertension Section.
Older adults who participate weekly in many different types of leisure time activities, such as walking for exercise, jogging, swimming laps, or playing tennis, may have a lower risk of death from any cause, as well as death from cardiovascular disease and cancer, according to a new study led by researchers at the National Cancer Institute, part of the National Institutes of Health.
The findings suggest that it’s important for older adults to engage in leisure time activities that they enjoy and can sustain, because many types of these activities may lower the risk of death, the authors wrote.
The findings appear Aug. 24 in JAMA Network Open.
Using data from 272,550 adults between ages 59 and 82 who had completed questionnaires about their leisure time activities as part of the NIH-AARP Diet and Health Study, the researchers looked at whether participating in equivalent amounts of seven different exercise and recreational activities — including running, cycling, swimming, other aerobic exercise, racquet sports, golf, and walking for exercise — was associated with lowered risk of death.
NIH study suggests poverty combined with crowded housing or parental separation pose highest risks
Poverty, combined with other types of adversity in early childhood, is associated with greater chances of premature death in adulthood, compared to other adverse childhood experiences, according to a study of more than 46,000 people by researchers at the National Institutes of Health.
Compared to children who did not experience early life adversity, childhood poverty combined with crowded housing was associated with a 41% higher risk for premature death, and early poverty combined with separation from a parent was associated with a 50% increase in premature death. Those who experienced parental harshness and neglect had a 16% higher risk of premature death, and those who experienced family instability had a 28% higher risk for premature death.
The findings build upon earlier studies that linked individual types of adverse childhood experiences to risk of death, as well as other studies that demonstrated that death risk rose as exposure to childhood adversity increased. The current study identifies links between combinations of early childhood adversity and the overall chances of premature death.
“Understanding how patterns of early childhood adversity are associated with shortened life expectancy helps us better understand the toll of early experiences on human health and the extent that this toll carries over from childhood through adulthood,” said the study’s senior author, Stephen E. Gilman, Sc.D., chief of the Social and Behavioral Sciences Branch at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). “In the long run, we hope that results such as ours can inform efforts to develop better interventions that would both reduce exposure to childhood adversity and reduce the health consequences of early adversity among exposed children.”
I am announcing today that I will be stepping down from the positions of Director of the National Institute of Allergy and Infectious Diseases (NIAID) and Chief of the NIAID Laboratory of Immunoregulation, as well as the position of Chief Medical Advisor to President Joe Biden. I will be leaving these positions in December of this year to pursue the next chapter of my career.
It has been the honor of a lifetime to have led the NIAID, an extraordinary institution, for so many years and through so many scientific and public health challenges. I am very proud of our many accomplishments. I have worked with — and learned from — countless talented and dedicated people in my own laboratory, at NIAID, at NIH and beyond. To them I express my abiding respect and gratitude.
Over the past 38 years as NIAID Director, I have had the enormous privilege of serving under and advising seven Presidents of the United States, beginning with President Ronald Reagan, on newly emerging and re-emerging infectious disease threats including HIV/AIDS, West Nile virus, the anthrax attacks, pandemic influenza, various bird influenza threats, Ebola and Zika, among others, and, of course, most recently the COVID-19 pandemic. I am particularly proud to have served as the Chief Medical Advisor to President Joe Biden since the very first day of his administration.
NIH study finds chemicals from Deepwater Horizon disaster associated with more wheeze
Researchers from the Gulf Long-term Follow-up Study (GuLF STUDY) found that workers involved in cleaning up the nation’s largest oil spill were 60% more likely than those who did not work on the cleanup to be diagnosed with asthma or experience asthma symptoms one to three years after the spill.
This ongoing study, led by the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health, is the largest study to look at the health of workers who responded to the 2010 Deepwater Horizon oil spill in the Gulf of Mexico.
“This is the first study to ever look at specific chemicals from oil spills and link them to respiratory diseases,” said Dale Sandler, Ph.D., chief of the NIEHS Epidemiology Branch and lead researcher for the GuLF STUDY. “If you were an oil spill cleanup worker in the gulf experiencing wheezing or other asthma-like symptoms, it would be good to let your healthcare provider know you worked on the oil spill.”
Researchers hope discovery leads to potential treatments for mitochondrial diseases
Researchers from the National Institutes of Health have developed a three-dimensional structure that allows them to see how and where disease mutations on the twinkle protein can lead to mitochondrial diseases. The protein is involved in helping cells use energy our bodies convert from food. Prior to the development of this 3D structure, researchers only had models and were unable to determine how these mutations contribute to disease. Mitochondrial diseases are a group of inherited conditions that affect 1 in 5,000 people and have very few treatments.
“For the first time, we can map the mutations that are causing a number of these devastating diseases,” said lead author Amanda A. Riccio, Ph.D., and researcher in the National Institute of Environmental Health Sciences (NIEHS) Mitochondrial DNA Replication Group, which is part of NIH. “Clinicians can now see where these mutations lie and can use this information to help pinpoint causes and help families make choices, including decisions about having more children.”
The new findings will be particularly relevant for developing targeted treatments for patients who suffer from mitochondrial diseases such as progressive external ophthalmoplegia, a condition that can lead to loss of muscle functions involved in eye and eyelid movement; Perrault syndrome, a rare genetic disorder that can cause hearing loss; infantile-onset spinocerebellar ataxia, a hereditary neurological disorder; and hepatocerebral mitochondrial DNA (mtDNA) depletion syndrome, a hereditary disease that can lead to liver failure and neurological complications during infancy.
Larger trials enrolling infants and children are underway in Mali and Kenya
One injection of a candidate monoclonal antibody (mAb) known as L9LS was found to be safe and highly protective in U.S. adults exposed to the malaria parasite, according to results from a National Institutes of Health Phase 1 clinical trial published in The New England Journal of Medicine. Additional clinical trials evaluating if L9LS can prevent malaria over six to 12 months against seasonal and perennial transmission are underway in infants and children in Mali and Kenya, where malaria is endemic. The trial was sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of NIH.
“These early clinical trial results demonstrating that a monoclonal antibody administered subcutaneously can protect people from malaria are highly encouraging,” said NIAID Director Anthony S. Fauci, M.D. “A one-time intervention that protects against malaria for six months to a year could significantly reduce morbidity and mortality among children in malaria-endemic regions and offer an effective preventive tool for health care workers, military personnel and travelers to these areas.”
Malaria is a mosquito-borne disease caused by Plasmodium parasites. The World Health Organization estimates that in 2020, about 240 million people had malaria and about 627,000 of them died. A disproportionate burden of malarial disease is seen in Sub-Saharan Africa, where children under age 5 account for approximately 80% of all malaria deaths. A vaccine to prevent malaria is now available; however, its variable efficacy underscores the need for new interventions that offer high-level protection against disease.
Discovery sets the stage for development of new therapies to treat vitelliform macular dystrophy
Using a new imaging technique, researchers from the National Eye Institute have determined that retinal lesions from vitelliform macular dystrophy (VMD) vary by gene mutation. Addressing these differences may be key in designing effective treatments for this and other rare diseases. NEI is part of the National Institutes of Health.
“The NEI’s long-term investment in imaging technology is changing our understanding of eye diseases,” said NEI Director Michael F. Chiang, M.D. “This study is just one example of how improved imaging can reveal subtle details about pathology in a rare eye disease that can inform the development of therapeutics.”
VMD is an inherited genetic disease that causes progressive vision loss through degeneration of the light-sensing retina. Genes implicated in VMD include BEST1, PRPH2, IMPG1, and IMPG2. Depending on the gene and mutation, age of onset and severity vary widely. All forms of the disease have in common a lesion in the central retina (macula) that looks like an egg yolk and is a build-up of toxic fatty material called lipofuscin. VMD affects about 1 in 5,500 Americans and there is currently no treatment for this condition.
Johnny Tam, Ph.D., head of the NEI Clinical and Translational Imaging Unit, used multimodal imaging to evaluate the retinas of patients with VMD at the NIH Clinical Center. Tam’s multimodal imaging uses adaptive optics — a technique that employs deformable mirrors to improve resolution — to view live cells in the retina, including the light-sensing photoreceptors, retinal pigment epithelial (RPE) cells, and blood vessels in unprecedented detail.
Loss of the protein pigment epithelium-derived factor (PEDF), which protects retinal support cells, may drive age-related changes in the retina, according to a new study in mice from the National Eye Institute (NEI). The retina is the light-sensitive tissue at the back of the eye, and aging-associated diseases of the retina, like age-related macular degeneration (AMD), can lead to blindness. This new finding could lead to therapies to prevent AMD and other aging conditions of the retina. The study was published in the International Journal of Molecular Sciences. NEI is part of the National Institutes of Health.
“People have called PEDF the ‘youth’ protein, because it is abundant in young retinas, but it declines during aging,” said Patricia Becerra, Ph.D., chief of NEI’s Section of Protein Structure and Function and senior author of the study. “This study showed for the first time that just removing PEDF leads to a host of gene changes that mimic aging in the retina.”
The retina is composed of layers of cells that function together to detect and process light signals, which the brain uses to generate vision. The retina’s light-sensing photoreceptors sit above the retinal pigment epithelium (RPE), a layer of support cells. The RPE nourishes photoreceptors and recycles pieces of the photoreceptor cells called 'outer segments,' which get used up and their tips shed each time photoreceptors detect light. If the RPE cannot provide recycled components of older outer segment tips back to photoreceptors, these cells lose their ability to make new segments, and eventually become unable to sense light. And without nutrients supplied by the RPE, photoreceptors die. In people with AMD or certain types of retinal dystrophies, senescence (aging) or death of RPE cells in the retina leads to vision loss.