Study details and key findings

For the study, researchers analyzed patient data from a symptoms survey distributed to 85 hospitals, health centers, and community centers in 33 states, Washington, D.C., and Puerto Rico.

In total, 9,764 participants were enrolled in the RECOVER adult cohort before April 2023 and completed a survey at least six months after their acute COVID-19 symptoms occurred or their original test date. Of these patients, 8,646 had a prior COVID-19 infection, and 1,118 were uninfected controls.

Most of the participants (71%) were female, and the median age was 47. Most participants were white while 16% were Hispanic or Latino and 15% were Black. Over half of the participants (58%) were fully vaccinated at the time of the survey, and uninfected participants were more likely to be fully vaccinated.

Overall, the researchers identified 37 self-reported symptoms that had a frequency of 2.5% or greater, as well as an odds ratio that was 1.5 or greater for infected participants compared to uninfected participants. Using statistical analyses, researchers then identified 12 "hallmark" symptoms of long COVID, including:

1.       Postexertional malaise

2.       Fatigue

3.       Brain fog

4.       Dizziness

5.       Gastrointestinal symptoms

6.       Heart palpitations

7.       Changes in sexual desire

8.       Loss of smell or taste

9.       Thirst

10.   Chronic cough

11.   Chest pain

12.   Abnormal movements

According to Leora Horwitz, one of the study's authors from the New York University Grossman School of Medicine, these 12 symptoms are not "the most common, or the most severe, or the most burdensome, or the most important to people," but they "are the ones that help us identify people who have long-term consequences" due to COVID-19.

Researchers assigned points to each of these 12 symptoms, which were used to give participants a post-acute sequelae of SARS-CoV-2 infection (PASC) score based on their different symptom combinations. In total, 23% of infected participants had a qualifying PASC score for long COVID compared to 3.7% of the controls.

In general, long COVID was more common and had more severe symptoms in participants who had been infected before the emergence of the omicron variant. In a subset of 2,231 participants who had been infected on or after Dec. 1, 2021, when omicron began circulating, only 10% had long COVID at six months.

According to NIH, these survey results are not final and will need to be validated against lab tests and imaging. The researchers also noted that the PASC score used to identify long COVID is operational and will need to be refined further before it can be used for larger populations.

Commentary

Andrea Foulkes, the director of biostatistics at Massachusetts General Hospital and one of the study's authors, said it's essential to precisely define long COVID and its symptoms before researchers can begin pursuing potential treatments. Without a way to distinguish patients with long COVID from those with other conditions, researchers won't be able to tell if a treatment is actually beneficial.

"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," Foulkes said. "Understanding this idea is a really important step for doing more research and ultimately administering informed interventions."

Going forward, Foulkes said she wants to continue following the study participants to learn more about how their symptoms evolve over time, particularly those who no longer met the definition of having long COVID at nine months.

In the study, around a third of participants who had long COVID at six months no longer met the criteria at nine months. Currently, it's too soon to tell if those who no longer met the criteria for long COVID at nine months are actually recovered or if their symptoms could return with time.

According to Horwitz, the study is the first in an "avalanche" of science that will soon come out about long COVID. "This is a hard disease," she said. "I think we will make a lot of progress with the science. I don't know how quickly we will come to treatment." (Weintraub, USA Today, 5/25; Dreher, Axios, 5/25; Hollowell, Becker's Hospital Review, 5/25; George, MedPage Today, 5/25; Thaweethai et al., JAMA, 5/25)

Three years after the COVID-19 pandemic began, experts are still struggling to understand what causes long Covid, how many people develop it, and how to treat it.