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.
Covid survivors are at risk from a separate epidemic of opioid addiction, given the high rate of painkillers being prescribed to these patients, health experts say.
A new study in Nature found alarmingly high rates of opioid use among covid survivors with lingering symptoms at Veterans Health Administration facilities. About 10% of covid survivors develop “long covid,” struggling with often disabling health problems even six months or longer after a diagnosis.
For every 1,000 long-covid patients, known as “long haulers,” who were treated at a Veterans Affairs facility, doctors wrote nine more prescriptions for opioids than they otherwise would have, along with 22 additional prescriptions for benzodiazepines, which include Xanax and other addictive pills used to treat anxiety.
Although previous studies have found many covid survivors experience persistent health problems, the new article is the first to show they’re using more addictive medications, said Dr. Ziyad Al-Aly, the paper’s lead author.
He’s concerned that even an apparently small increase in the inappropriate use of addictive pain pills will lead to a resurgence of the prescription opioid crisis, given the large number of covid survivors. More than 3 million of the 31 million Americans infected with covid develop long-term symptoms, which can include fatigue, shortness of breath, depression, anxiety and memory problems known as “brain fog.”
The new study also found many patients have significant muscle and bone pain.
The frequent use of opioids was surprising, given concerns about their potential for addiction, said Al-Aly, chief of research and education service at the VA St. Louis Health Care System.
“Physicians now are supposed to shy away from prescribing opioids,” said Al-Aly, who studied more than 73,000 patients in the VA system. When Al-Aly saw the number of opioids prescriptions, he said, he thought to himself, “Is this really happening all over again?”
Doctors need to act now, before “it’s too late to do something,” Al-Aly said. “We must act now and ensure that people are getting the care they need. We do not want this to balloon into a suicide crisis or another opioid epidemic.”
As more doctors became aware of their addictive potential, new opioid prescriptions fell, by more than half since 2012. But U.S. doctors still prescribe far more of the drugs — which include OxyContin, Vicodin and codeine — than physicians in other countries, said Dr. Andrew Kolodny, medical director of opioid policy research at Brandeis University.
Some patients who became addicted to prescription painkillers switched to heroin, either because it was cheaper or because they could no longer obtain opioids from their doctors. Overdose deaths surged in recent years as drug dealers began spiking heroin with a powerful synthetic opioid called fentanyl.
More than 88,000 Americans died from overdoses during the 12 months ending in August 2020, according to the Centers for Disease Control and Prevention. Health experts now advise doctors to avoid prescribing opioids for long periods.
The new study “suggests to me that many clinicians still don’t get it,” Kolodny said. “Many clinicians are under the false impression that opioids are appropriate for chronic pain patients.”
Hospitalized covid patients often receive a lot of medication to control pain and anxiety, especially in intensive care units, said Dr. Greg Martin, president of the Society of Critical Care Medicine. Patients placed on ventilators, for example, are often sedated to make them more comfortable.
Martin said he’s concerned by the study’s findings, which suggest patients are unnecessarily continuing medications after leaving the hospital.
“I worry that covid-19 patients, especially those who are severely and critically ill, receive a lot of medications during the hospitalization, and because they have persistent symptoms, the medications are continued after hospital discharge,” Martin said.
While some covid patients are experiencing muscle and bone pain for the first time, others say the illness has intensified their preexisting pain.
Rachael Sunshine Burnett has suffered from chronic pain in her back and feet for 20 years, ever since an accident at a warehouse where she once worked. But Burnett, who first was diagnosed with covid in April 2020, said the pain soon became 10 times worse and spread to the area between her shoulders and spine. Although she was already taking long-acting OxyContin twice a day, her doctor prescribed an additional opioid called oxycodone, which relieves pain immediately. She was reinfected with covid in December.
“It’s been a horrible, horrible year,” said Burnett, 43, of Coxsackie, New York.
Doctors should recognize that pain can be a part of long covid, Martin said. “We need to find the proper non-narcotic treatment for it, just like we do with other forms of chronic pain,” he said.
The CDC recommends a number of alternatives to opioids — from physical therapy to biofeedback, over-the-counter anti-inflammatories, antidepressants and anti-seizure drugs that also relieve nerve pain.
The country also needs an overall strategy to cope with the wave of post-covid complications, Al-Aly said
“It’s better to be prepared than to be caught off guard years from now, when doctors realize … ‘Oh, we have a resurgence in opioids,’” Al-Aly said.
Al-Aly noted that his study may not capture the full complexity of post-covid patient needs. Although women make up the majority of long-covid patients in most studies, most patients in the VA system are men.
The study of VA patients makes it “abundantly clear that we are not prepared to meet the needs of 3 million Americans with long covid,” said Dr. Eric Topol, founder and director of the Scripps Research Translational Institute. “We desperately need an intervention that will effectively treat these individuals.”
Al-Aly said covid survivors may need care for years.
“That’s going to be a huge, significant burden on the health care system,” Al-Aly said. “Long covid will reverberate in the health system for years or even decades to come.”
