By 2025, a consensus emerged among health experts regarding long Covid, now recognized as a biological disease. “I think everybody now agrees that long Covid is a biologic disease,” stated Igho Ofotokun, of Emory University School of Medicine, during the Long Covid International Conference. He emphasized, “It’s not in your mind. It’s real.” However, he pointed out that scientific progress is hindered by the absence of a gold-standard definition for long Covid, complicating clinical trial designs and outcome tracking.
The definitional challenges stem partly from the lack of definitive biomarkers—such as genes, antibodies, or unique physiological signatures—associated with long Covid. Researchers first need to identify patients believed to have the condition and then determine commonalities beyond reported symptoms. Establishing a biomarker can lead to targeted interventions, such as gene therapies and antivirals, and help differentiate those affected by long Covid from individuals experiencing similar symptoms due to other causes.
Scientific specialists lead the initiative to identify long Covid biomarkers, but the process hinges on how to classify individuals as having the condition. Patient advocates have notably influenced this classification. Determining inclusion criteria for long Covid studies necessitates a delicate balance; overly strict criteria may exclude some genuine patients, while relaxed criteria could incorrectly include those without the condition, each affecting the integrity of scientific findings.
For patient advocates, strict criteria present an additional concern as some individuals who believe they suffer from long Covid may not be classified officially as having it. This issue was prominent when, shortly after the pandemic began, the National Academies of Sciences, Engineering, and Medicine (NASEM) undertook the task of developing a “uniform, core definition” for long Covid. At that time, several fundamental questions remained unresolved: Is a prior positive SARS-CoV-2 test required? What symptoms should be included? How long must these symptoms persist?
In 2024, focusing on patient perspectives and interdisciplinary dialogue, the committee established an “intentionally inclusive” definition to ensure that those experiencing long Covid would be represented. The NASEM defined long Covid as “an infection-associated chronic condition that occurs after SARS-CoV-2 infection and is present for at least three months as a continuous, relapsing and remitting, or progressive disease state that affects one or more organ systems.” Symptoms may include shortness of breath, cough, persistent fatigue, post-exertional malaise, concentration difficulties, memory changes, recurring headaches, lightheadedness, tachycardia, sleep disturbances, taste or smell problems, bloating, constipation, and diarrhea.
According to the NASEM’s definition, a single symptom from this extensive list suffices for a diagnosis. The severity of symptoms can vary, and a previous positive test for Covid is not mandatory. Thus, an individual who experiences sleep troubles for three months, potentially linked to an unverified SARS-CoV-2 case, qualifies as having long Covid.
