Long COVID described as a 'syndrome of syndromes' in NIH funded research

The effort to pin down just what constitutes long COVID that might lead to more effective treatment of the symptoms associated with the condition seems to have gotten a boost by a recent study in JAMA Network that was funded by the National Institutes of Health (NIH).

Researchers with a myriad of institutions narrowed a field of 37 possible long COVID symptoms down to 12: changes in sexual desire or capacity, loss or change in smell or taste, being thirsty often, chronic coughing, chest pain, abnormal movements, exhaustion after exercise (or postexertional malaise), palpitations, fatigue, brain fog, dizziness and gastrointestinal illness.

NIH researchers concluded that the “definition of a classification rule for [long COVID] requires an updated algorithm that incorporates symptoms as well as biological features. Future analyses must consider the relationships among age, sex, race and ethnicity, social determinants of health, vaccination status after index date, comorbidities, and pregnancy status during infection on the risk of PASC and the distribution of PASC subgroups.”

That effort to pin down exactly what long COVID is and just how best to treat it doesn’t include the next step: How will those treatments be paid for?

Richard Stefanacci, D.O., of the Jefferson College of Population Health at Thomas Jefferson University, told Fierce Healthcare in an email that in terms of coverage for long COVID, insurers care mostly about two elements. The first is ensuring they only pay for care that is necessary.

“Payers want to know if they need to be proactive because of volume and science to support their blocking in inappropriate costly care,” Stefanacci said.

In addition, said Stefanacci, payers want to get an idea of what the long-term costs of coverage for long COVID might be. If long COVID care is needed, then payers want to be able to “adjust premiums appropriately as they work to cover and manage this new cost.”

NIH researchers mined data from 10,000 Americans in the NIH’s RECOVER program, an ongoing effort to define and treat long COVID. They found the condition to be more common among people who’d been infected before the omicron iteration of the disease hit the U.S. in late 2021 and among those who have never been vaccinated.

Corresponding author Andrea Foulkes, a professor at Harvard Medical School, said in a press release that “now that we’re able to identify people with long COVID, we can begin doing more in-depth studies to understand the biological mechanisms at play. One of the big takeaways from this study is the heterogeneity of long COVID: long COVID is not just one syndrome; it’s a syndrome of syndromes. Understanding this idea is a really important step for doing more research and ultimately administering informed interventions.”

Researchers noted that while many symptoms in many studies have been linked to long COVID, the retrospective design of those studies, reliance on electronic health records and a lack of an unaffected comparison group continue to fuel debate about the extent and severity of long COVID.

The RECOVER program, which began enrolling participants in October 2021, seeks to find a generally accepted definition of long COVID. The JAMA Network study relies on surveys of symptoms at 85 hospitals, health centers and community organizations in 33 states. More than 9,500 individuals took the survey, including uninfected adults.

Kevin Kavanagh, M.D., president and founder of the patient advocacy organization Health Watch USA, told Fierce Healthcare in an email that of the symptoms researchers focused on, exertional malaise and brain fog would be the most debilitating. He added that “of interest is that individuals in the ‘uninfected’ study arm were found to be more likely to be vaccinated. The best defense against long COVID is vaccination and not becoming infected with SARS-CoV-2 in the first place and if you do, seek immediate medical attention to determine if you qualify for antiviral medications.”

In the study, more than 20% of individuals who’ve had COVID were deemed to have long COVID because they exhibited these symptoms six months after the first time that they tested positive for the condition. However, a third of those individuals no longer suffered from long COVID at nine months.

Kavanagh said “there is growing evidence that the symptoms are not necessarily the result of past viral damage but ongoing damage from an abnormal immune system or viral reservoirs.”

Tanayott Thaweethai, Ph.D., an instructor at Harvard Medical School, said in the press release about the JAMA Network study that “this is a truly data-driven approach to defining long COVID as a new syndrome. We now have a definition for long COVID where there hasn’t been one previously, and we hope the ability to identify long COVID will enhance clinical awareness of this condition.”