What exactly is Long COVID? New UCLA research shows the answer depends on whom you ask

What is Long COVID?   Despite hundreds of published studies and millions affected worldwide, the medical field still lacks a clear answer.  

New research from UCLA finds that the definition of Long COVID varies so widely across published studies that the percentage of people identified as having the condition can differ dramatically, making it harder to treat patients and advance research.  

The study, published August 12 in JAMA Network Open, highlights just how much the lack of a standard definition is clouding our understanding of Long COVID. 

“The findings highlight the need for a standard definition for Long COVID,” said study lead Lauren Wisk, an assistant professor of medicine in the division of general internal medicine and health services research at the David Geffen School of Medicine at UCLA. “Up to one third of the variation in the published studies may stem from the fact that they use different definitions for Long COVID.”

Using data from 4,700 U.S. patients in the CDC-funded INSPIRE cohort, UCLA researchers applied five published Long COVID definitions from studies conducted in the US, U.K., Netherlands, Sweden, and Puerto Rico.  The result?   Depending on which definition was used, the estimated prevalence of Long COVID ranged from 15% to 42% - all in the same group of patients.

The five definitions assessed in the study differed by symptom duration (4 weeks to 6 months) and number of symptoms considered (9 to 44), resulting in reported prevalence of Long COVID that ranged from 2.6% to 61.9% in the original studies. When these different published definitions were applied to the INSPIRE cohort, these differences also created significant variation in who was labeled as having Long COVID.

Researchers also found that published definitions had only moderate sensitivity –the ability to correctly identify those with the disease— compared to participants’ own self-reported experience of Long COVID. While specificity of these definitions was better, none of the definitions reached an ideal level to be considered the optimal identification test. 

“If every study on Long COVID uses a different definition for identifying who has it, the scientific conclusions become harder to compare across studies and may lead to delays in our understanding of it,” Wisk said. “In the absence of an objective measure, like a blood test, or a uniform standard for measuring Long COVID, researchers and clinicians will need to decide which definition is best suited for their scientific question and be more transparent about the potential limitations of using a more vs less restrictive definition.”

These differences may lead researchers and physicians to miss some legitimate Long COVID cases and to label some patients as having Long COVID when they don’t, said Dr. Joann Elmore, professor of medicine in the division of general internal medicine and health services research at the David Geffen School of Medicine at UCLA and the study’s senior author.

 “Without a clinically usable and standardized research definition of Long COVID, it’s like every study is using a different measuring stick,” she said. “That makes it hard to compare results, develop treatments, or track progress.  Without a shared definition, we risk mislabeling patients and misguiding care.  This is more than an academic debate- it affects real people.”  

Study limitations include potential recall bias among participants; participant demographics that may have influenced prevalence were unexamined, and results may have differed had the researchers included more than the five published studies in their analysis.

Study co-authors are Michelle L’Hommedieu and Kate Diaz Roldan of UCLA, and others from the INSPIRE Group.  

INSPIRE was funded by the National Center of Immunization and Respiratory Diseases (75D30120C08008) in the Centers for Disease Control and Prevention.