Weeks or months after their coronavirus infection clears, many people diagnosed with COVID-19 still have debilitating symptoms such as fatigue, foggy thinking, and headaches. Today, the National Institutes of Health (NIH) announced a nearly $470 million grant to enroll up to 40,000 adults and children newly and previously infected with SARS-CoV-2 in a study that will probe the causes of these postinfection effects, dubbed Long Covid, and look for clues to treatments and prevention.
“The only way we’re going to sort this out is with very large studies that collect lots and lots of data about symptoms, physical findings, and laboratory measures,” NIH Director Francis Collins said at an online press briefing.
One prominent patient activist is disappointed the federal effort will largely enroll people who haven’t yet developed Long Covid, not the estimated millions now suffering from it. NIH’s large study, says Diana Berrent, founder of Survivor Corps, which represents people with Long Covid, is “smoke and mirrors. This doesn’t get us closer to any answers.”
Long Covid, or what NIH calls postacute sequelae of SARS-CoV-2 infection (PASC), can include pain, fatigue, “brain fog,” trouble sleeping, headaches, shortness of breath, fever, chronic cough, depression, and anxiety that linger or appear more than 4 weeks after an initial infection. Sometimes the symptoms are so severe that a person can’t work and struggles through daily tasks.
The Centers for Diseases Control and Prevention estimates 10% to 30% of COVID-19 patients develop Long Covid. Possible explanations include a hidden reservoir of SARS-CoV-2, a misfiring immune system, or a metabolic problem triggered by the infection, Collins said. But, he acknowledged, “We don’t know.”
NIH outlined its initial plans for a Long Covid research program in February, after Congress approved $1.15 billion over 4 years to study the condition. The program’s centerpiece study announced today, the Researching COVID to Enhance Recovery (RECOVER) Initiative, is funded with a $470 million grant to New York University (NYU) Langone Health. NYU will make subawards to more than 100 researchers at 35 institutions who will enroll patients using a common protocol.
Starting in October, the program will aim to enroll between 30,000 and 40,000 volunteers over 12 months from diverse populations in all 50 states. Although some people who already have Long Covid will be studied, the majority will have acute infections—that is, they will have just fallen sick with COVID-19, said NYU Grossman School of Medicine cardiologist Stuart Katz, the study’s principal investigator. The study will include hospitalized patients as well as those with milder COVID-19 cases—it’s not clear whether being sicker initially leads to more Long Covid.
Using electronic medical records and providing participants with wearable devices that monitor heart rates, sleep, and more, the study will compare the health of those who quickly recover with others whose symptoms persist, looking for risk factors and biological clues that may explain the different outcomes. Researchers will also explore questions such as whether getting a COVID-19 vaccination eases Long Covid symptoms, as some anecdotal reports suggest.
About one-half of those enrolled will be children, including some newborns, NIH officials hope. Even though children with COVID-19 usually have mild or no symptoms, concerns about long-term effects are growing because the number of cases in children is now “the highest it’s been throughout the entire pandemic,” Diana Bianchi, director of the National Institute of Child Health and Human Development, said on the Zoom call.
The study won’t itself test new treatments for Long Covid, Katz said. But its leaders will try to identify proteins or molecular processes that play a role in Long Covid and could be blocked with an existing drug. NIH hopes to find those targets within 18 months and then launch treatment trials using its remaining congressional funding for Long Covid research.
Lisa McCorkell, who is part of the Patient-Led Research Collaborative, a Long Covid group started by patients who are also researchers, says if the RECOVER study engages meaningfully with patients, it will be “a welcome step toward finding answers.”
But Berrent contends there’s a major flaw with the RECOVER plan to enroll newly infected people at a time when many people are vaccinated: The study may struggle to recruit participants. “The people who are just getting Long Covid now because they’re not vaccinated are not the same people who are going to enroll in an NIH longitudinal study,” she says.
She argues NIH should instead study those who already have Long Covid, including people with severe symptoms such as peripheral neuropathy and diabetes, which aren’t described in NIH’s press release. The announcement is “insulting” and “completely dismissive of the severity of the long-term sequelae of this virus, which is devastating,” she says.