The National Institutes of Health awarded nearly $470 million to build a national study population of diverse research volunteers and support large-scale studies on the long-term effects of COVID-19. The NIH REsearching COVID to Enhance Recovery (RECOVER) Initiative made the parent award to New York University (NYU) Langone Health, New York City, which will make multiple sub-awards to more than 100 researchers at more than 30 institutions and serves as the RECOVER Clinical Science Core. This major new award to NYU Langone supports new studies of COVID-19 survivors and leverages existing long-running large cohort studies with an expansion of their research focus. This combined population of research participants from new and existing cohorts, called a meta-cohort, will comprise the RECOVER Cohort. This funding was supported by the American Rescue Plan.
NIH launched the RECOVER Initiative to learn why some people have prolonged symptoms (referred to as long COVID) or develop new or returning symptoms after the acute phase of infection from SARS-CoV-2, the virus that causes COVID-19. The most common symptoms include pain, headaches, fatigue, “brain fog,” shortness of breath, anxiety, depression, fever, chronic cough, and sleep problems.
“We know some people have had their lives completely upended by the major long-term effects of COVID-19,” said NIH Director Francis S. Collins, M.D., Ph.D. “These studies will aim to determine the cause and find much-needed answers to prevent this often-debilitating condition and help those who suffer move toward recovery.”
Data from the RECOVER Cohort will include clinical information, laboratory tests, and analyses of participants in various stages of recovery following SARS-CoV-2 infection. With immediate access to data from existing, diverse study populations, it is anticipated researchers will be able to accelerate the timeline for this important research.
“This scientifically rigorous approach puts into place a collaborative and multidisciplinary research community inclusive of diverse research participants that are critical to informing the treatment and prevention of the long-term effects of COVID-19,” said Gary H. Gibbons, M.D., director of NIH’s National Heart, Lung, and Blood Institute and one of the co-chairs of the RECOVER Initiative.
Researchers, people affected by long COVID, and representatives from advocacy organizations worked together to develop the RECOVER master protocols that use standardized trial designs and research methods to enable uniform evaluation of study populations across studies and the ability to quickly pivot the research focus depending on what findings show. This approach allows for data harmonization across research studies and study populations. Data harmonization allows data to be compared and analyzed, which will facilitate the research process and provide more robust findings.
Studies will include adult, pregnant, and pediatric populations; enroll patients during the acute as well as post-acute phases of the SARS-CoV-2 infection; evaluate tissue pathology; analyze data from millions of electronic health records; and use mobile health technologies, such as smartphone apps and wearable devices, which will gather real-world data in real time. Together, these studies are expected to provide insights over the coming months into many important questions including the incidence and prevalence of long-term effects from SARS-CoV-2 infection, the range of symptoms, underlying causes, risk factors, outcomes, and potential strategies for treatment and prevention.
“Given the range of symptoms that have been reported, intensive research using all available tools is necessary to understand what happens to stall recovery from this terrible virus. Importantly, the tissue pathology studies in RECOVER will enable in depth studies of the virus’s effects on all body systems” said Walter J. Koroshetz, M.D., director of NIH’s National Institute of Neurological Disorders and Stroke and one of the RECOVER co-chairs.
Research opportunity announcements were issued in February 2021 and awards to launch the RECOVER Clinical Science Core and Data Resource Core were announced in June. An award in support of a RECOVER Biorepository Core has also been made to the Mayo Clinic for approximately $40 million to collect, curate, and distribute comprehensive sources of clinical samples for additional research studies. The Cores provide coordination and infrastructure for the RECOVER Initiative, including supporting the activities of the investigator consortium and ensuring that all data are harmonized and shared among researchers. In May and June, short-term awards were provided to more than 30 institutions to develop the master protocols.
These awards pave the path to gaining greater understanding of the long-term effects of SARS-CoV-2 infection and enabling researchers to identify potential interventions and preventive strategies.
About the National Institute of Neurological Disorders and Stroke (NINDS): NINDS is the nation’s leading funder of research on the brain and nervous system. The mission of NINDS is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease. For more information, visit www.ninds.nih.gov.
About the National Heart, Lung, and Blood Institute (NHLBI): NHLBI is the global leader in conducting and supporting research in heart, lung, and blood diseases and sleep disorders that advances scientific knowledge, improves public health, and saves lives. For more information, visit www.nhlbi.nih.gov.
About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
Genomics, the study of all of a person’s genes, is a growing field within health care and the burgeoning health technology space. Genomics is a complex competency and has been identified as a core trend shaping health care’s future. With the vast amount of information made available by genetic testing, data science, and advanced sequencing technologies, there is an increased need for nurses trained in genomics, who can interpret the information and translate it in a way that patients can understand.
The largest patient-facing workforce in health care, nurses play an integral role in the effective delivery of genomic health care for patients, their families, communities, and populations. Research over the past decade has shown that many nurses have knowledge gaps in the basics of human genetics, Connors said. Totaling nearly $700,000, the TIGER grant will enable Connors and her collaborators at Clemson University and Loyola University Chicago to increase the capacity and capability of doctoral nurses in genomics over the course of the grant’s timeline.
“We will deploy a ‘train the trainer’ model,” Connors said. “Our participants will take their skills back to their universities to serve as champions to incorporate genomics into curriculum, research, scholarship and clinical practice.
An advanced practice nurse in genetics, Connors aims to close the space between students with higher levels of proficiency in genomics and their educators. In her four years at Vanderbilt University School of Nursing, she has developed and implemented multiple genomic and oncology clinical-focused courses. Her specialty in genomics was sparked by looking deeper into hereditary predispositions to breast cancer during her time as an oncology nurse.
“Nursing is a profession where you are a lifelong learner,” Connors said. “Genomics has allowed me the opportunity to pursue new knowledge and to assist individuals and families in understanding their genetic risk assessment and risk of disease and what they can do about it.”
The training Connors is developing will begin with a half-day genomics course provided at the American Association of Colleges of Nursing annual doctoral conference in January, followed by monthly webinars posted to a learning management system from February to December 2022. To find out more information about this educational project, contact Connors at firstname.lastname@example.org.
Adolescent marijuana use and binge drinking did not significantly change during the COVID-19 pandemic, despite record decreases in the substances’ perceived availability, according to a survey of 12th graders in the United States. The study’s findings, which appeared online on June 24, 2021, in Drug and Alcohol Dependence, challenge the idea that reducing adolescent use of drugs can be achieved solely by limiting their supply. The work was led by researchers at the University of Michigan, Ann Arbor, and funded by the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health (NIH).
In contrast to consistent rates of marijuana and alcohol use, nicotine vaping in high school seniors declined during the pandemic, along with declines in perceived availability of vaping devices at this time. The legal purchase age is 21 for nicotine products and alcohol in all states, and for cannabis in states that have legalized nonmedical cannabis use.
“Last year brought dramatic changes to adolescents’ lives, as many teens remained home with parents and other family members full time,” said NIDA Director Nora D. Volkow, M.D. “It is striking that despite this monumental shift and teens’ perceived decreases in availability of marijuana and alcohol, usage rates held steady for these substances. This indicates that teens were able to obtain them despite barriers caused by the pandemic and despite not being of age to legally purchase them.”
The data for the study came from the annual Monitoring the Future (MTF) survey of substance use behaviors and related attitudes among adolescents in the United States. In a typical year, MTF surveys thousands of middle and high school students at more than a hundred schools across the country in the spring. MTF has been watching substance use trends for 46 years.
To assess the impact of the pandemic, the investigators issued a survey between mid-July and mid-August 2020, which 12th graders could complete outside of school. This summer survey followed up on investigators’ standard MTF spring survey, which gathered responses between mid-February and mid-March 2020 before stopping prematurely due to school closures caused by COVID-19. Of the 3,770 12th graders who responded in the spring, 582 submitted a follow-up survey in the summer. All data and statistical analyses used in the study were weighted to be nationally representative.
Analysis of the responses revealed that students perceived a sharp decrease in availability of marijuana and alcohol in the months after the onset of the pandemic. For marijuana, the fraction of students who reported “fairly” or “very” easy access dropped by 17 percentage points, from 76% in the spring before the pandemic to 59% during the pandemic, and for alcohol it dropped by 24 percentage points, from 86% to 62%. These were the largest year-to-year decreases in perceived availability of marijuana and alcohol ever recorded since the survey began in 1975. Prior to 2020, the largest recorded decreases were only two percentage points for marijuana, and one percentage point for alcohol. Between the spring and summer of 2020, there was also a sharp decrease in respondents who said they could “fairly” or “very” easily obtain a vaping device, going from 73% before the pandemic to 63% during the pandemic.
Despite the reported declines in marijuana and alcohol availability, the levels of use of these substances did not change significantly. Before the pandemic, 23% of students said they had used marijuana in the past 30 days, compared to 20% during the pandemic. For alcohol, 17% reported binge drinking in the past two weeks pre-pandemic, compared to 13% during the pandemic. However, there was a moderate and significant decrease in nicotine vaping – before the pandemic, 24% of respondents said they had vaped nicotine in the past 30 days, compared to 17% during the pandemic.
The study authors cite the wide availability of alcohol and marijuana, even during the pandemic, as a factor in the continued use of these substances. While pandemic-related restrictions limited social interactions, and even with record-breaking decreases in perceived availability among participants, most students said they still had access to marijuana and alcohol. In addition, the authors suggest that when the substances became less available, the students may have intensified their efforts to obtain them.
While a dip in the perceived supply of vaping devices may have contributed to the decline in nicotine vaping that occurred during the pandemic, there may have been other factors as well. The federal minimum age for tobacco product purchases, including vaping devices and liquids, rose from 18 to 21 years and went into effect in early 2020. News reports on vaping-induced lung injuries may have also had a chilling effect on usage.
“These findings suggest that reducing adolescent substance use through attempts to restrict supply alone would be a difficult undertaking,” said Richard A. Miech, Ph.D., lead author of the paper and team lead of the Monitoring the Future study at the University of Michigan. “The best strategy is likely to be one that combines approaches to limit the supply of these substances with efforts to decrease demand, through educational and public health campaigns.”
Monitoring the Future continues to survey respondents as they progress through adulthood, providing the researchers with the opportunity to explore the impact of the pandemic and the social changes it brought about on future substance use trends.
Researchers estimate nearly 17 million undiagnosed cases in the U.S. by mid-July 2020.
In a new study, National Institutes of Health (NIH) researchers report that the prevalence of COVID-19 in the United States during spring and summer of 2020 far exceeded the known number of cases and that infection affected the country unevenly. For every diagnosed COVID-19 case in this time frame, the researchers estimate that there were 4.8 undiagnosed cases, representing an additional 16.8 million cases by July alone. The team’s analysis of blood samples from people who did not have a previously diagnosed SARS-CoV-2 infection, along with socioeconomic, health, and demographic data, offers insight into the undetected spread of the virus and subgroup vulnerability to undiagnosed infection.
“This study helps account for how quickly the virus spread to all corners of the country and the globe,” said Bruce Tromberg, Ph.D., director of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), one of the NIH institutes who run the NIH SARS-CoV-2 Seroprevalence Project. “The information will be invaluable as we assess the best public health measures needed to keep people safe, as new—and even more transmissible—variants emerge and vaccine antibody response changes over time.”
In addition to NIBIB, the research team includes scientists from the National Institute of Allergy and Infectious Diseases (NIAID), the National Center for Advancing Translational Sciences (NCATS); and the Frederick National Laboratory for Cancer Research, sponsored by the National Cancer Institute (NCI). Their report in the June 22, 2021, early online issue of Science Translational Medicine represents the first data from the 12-month NIH study that was launched in April 2020.
“A hallmark of the coronavirus pandemic is that there are people infected with the virus that causes COVID-19 who have few or no symptoms,” said Matthew J. Memoli, M.D., M.S., director, Clinical Studies Unit, Laboratory of Infectious Diseases, NIAID. “While counting the numbers of symptomatic people in the United States is essential to contend with the impact of the pandemic and public health response, gaining a full appreciation of the COVID-19 prevalence requires counting the people who are undiagnosed.”
COVID-19 illness can range from short-lived cough, fatigue and fever to severe illness that could lead to hospitalization and death. Asymptomatic SARS-CoV-2 infection, which is rarely diagnosed, is a silent source of viral spread. While not causing overt signs of illness, undiagnosed infection poses a danger to the public and is a critical factor necessitating public health resources and strategies for addressing the pandemic.
The team recruited over 240,000 volunteers from across the country, then selected 8,058 individuals from that pool through quota sampling to ensure that their study cohort was representative of the U.S. population. Each participant received a sample kit to return to NIH with a dab of dried blood or had blood drawn at NIH, most of which they supplied in an 11-week span between May 10 and July 31. Participants also completed a questionnaire that enabled further analysis of the study results.
The researchers used an enzyme-linked immunosorbent assay to detect antibodies that recognize protein regions from the SARS-CoV-2 virus, referred to as antigens. Antibodies in a blood sample can bind to these antigens. The team found that 304 of the approximately 8,000 blood samples were seropositive, meaning that they contained antibodies against the SARS-CoV-2 virus. The researchers estimated that 4.6% of U.S. adults had undiagnosed COVID-19 during their study period. They determined that each diagnosed case of COVID-19 corresponds to an estimated 4.8 undiagnosed cases of the disease during this time frame.
The team observed that:
the youngest participants—those between the ages of 18 and 44—had the highest estimated seropositivity, at 5.9%,
estimated seropositivity was higher in females than in males (5.5% versus 3.5%, respectively),
participants in the Mid-Atlantic and Northeast regions had the highest rates (8.6% and 7.5%, respectively), and participants in the Midwest had the lowest rates (1.6%),
urban participants had a higher estimated seropositivity (5.3%) compared with rural participants (1.1%), and
Black/African American respondents had the highest estimated seropositivity rate (14.2%), followed by Native American/Alaska Native (6.8%), Hispanic (6.1%), white/Caucasian (2.5%), and Asian (2%) respondents.
“The estimate of COVID-19 cases in the United States in mid-July 2020, 3 million in a population of 330 million, should be revised upwards by almost 20 million when the percent of asymptomatic positive results is included,” said senior co-author Kaitlyn Sadtler, Ph.D., chief of the NIBIB Section on Immunoengineering. “This wide gap between the known cases at the time and these asymptomatic infections has implications not only for retrospectively understanding this pandemic, but future pandemic preparedness.”
The researchers are currently following up with the enrolled participants to evaluate the six- and 12-month status of seroprevalence; it will include new analyses to differentiate antibodies from infection versus antibodies from vaccination, as well as antibody reactivity to variants of concern.
The new report is part of the NIH SARS-CoV-2 Seroprevalence Project. The collaboration includes research groups led by Matthew J. Memoli, M.D., at NIAID; Matthew D. Hall, Ph.D., Early Translation Branch at NCATS; Dominic Esposito, Ph.D., Protein Expression Laboratory at the Frederick National Laboratory for Cancer Research; and Sadtler, Section on Immunoengineering, NIBIB.
This research was supported in part by the NIH Intramural Research Program, funded in part under contract number HHSN261200800001E, 75N91019D00024, Task Order No. 75N91019F00130, Clinical and Translational Science Awards Program grants UL1TR003096 (Robert P. Kimberly, M.D., University of Alabama at Birmingham) and UL1TR001857 (Steven E. Reis, M.D., University of Pittsburgh).
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