Credit: CDC
More than three years after the COVID-19 pandemic began, scientists have created a nationwide framework to detail the long-lasting effects of SARS-CoV-2 infection.
Results from RECOVER, one of the largest NIH studies ever funded, elucidate 12 defining symptoms of long COVID. The findings, published in JAMA, include a new scoring system for long COVID to help clinicians and researchers better define it and investigate treatments for patients.
“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,” said corresponding author Andrea Foulkes, ScD, Principal Investigator of the RECOVER Data Resource Core (DRC). “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."
Working with researchers at Mass General Brigham, RECOVER began enrolling participants in October 2021 as part of a prospective study. Previous long COVID studies were limited by a retrospective design, reliance on electronic health record entries and lack of an uninfected comparison group. Therefore, there was significant uncertainty over the definition of long COVID, including symptoms, commonality and severity. RECOVER sought to harmonize data acquisition and build a data-backed definition for long COVID.
Researchers distributed a symptoms survey at 85 hospitals, health centers and community organizations in 33 states, Washington, D.C., and Puerto Rico. More than 9,500 individuals completed the survey, including uninfected adults as well as individuals who were six months past infection with COVID-19.
Ultimately, 12 symptoms emerged as hallmarks of long COVID. In order of decreasing frequency among study participants, the symptoms include:
- post-exertional malaise (debilitating fatigue that is exacerbated by physical or mental activity)
- fatigue
- brain fog
- dizziness
- gastrointestinal symptoms
- palpitations
- changes in sexual desire or capacity
- loss of or change in smell or taste
- thirst
- chronic cough
- chest pain
- abnormal movements
According to study, correlating symptoms also include dry mouth, weakness, headaches, tremor, muscle and abdominal pain, fever/sweats/chills, and sleep disturbance. While the researchers found that some of the symptoms, like post-exertional malaise, are experienced by most people with long COVID, others, like loss of or change in smell and taste, are less common—but still important for identifying individuals with long COVID.
The research team also developed an algorithm to assess the 12 symptoms to generate an overall PASC—post-acute sequelae of SARS-CoV-2 cases—score. Using the full study cohort, the team attributed scores ranging from 1 to 8 to all 12 symptoms. The optimal PASC score threshold was 12 or greater—which was recorded in about 23% of participants. Among those with qualifying PASC scores, the most common symptoms were post-exertional malaise (87%), fatigue (85%), brain fog (64%), dizziness (62%), GI (59%) and palpitations (57%).
The result show PASC positivity was more common and associated with more severe manifestation in those infected with a pre-Omicron SARS-CoV-2 variant. The data also shows absence of vaccination is associated with a higher frequency and severity of long COVID.
“This is a truly data-driven approach to defining long COVID as a new syndrome,” said first author Tanayott Thaweethai, co-investigator for RECOVER DRC and an Associate Director at MGH Biostatistics. “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.”
Future studies from the RECOVER Consortium will analyze additional risk factors for long COVID, including social determinants of health. The researchers are also examining how long COVID may manifest in children, adolescents, and in people who were pregnant during SARS-CoV-2 infection.