By 2025, most experts had adopted the same position. “I think everybody now agrees that long Covid is a biologic disease,” said Igho Ofotokun, of Emory University School of Medicine, in his concluding comments at the Long Covid International Conference. “It’s not in your mind. It’s real.” Ofotokun also offered an explanation for the lack of scientific progress. “The big elephant in the room is just that we don’t have a gold-standard definition for long Covid. So it really makes it difficult to do all the things we want to do. Makes designing of clinical trials extremely difficult, following outcomes in clinical trials extremely challenging.”
Part of the definitional problem for long Covid is the absence of definitive biomarkers: genes, antibodies, any unique physiological signature of the illness. To discover biomarkers, researchers must first identify patients presumed to have a specific illness, then see what they have in common beyond their symptoms. Identifying a biomarker allows for the development of disease-targeting interventions—gene therapy, antivirals—and enables the sorting of people who have a particular condition from those whose symptoms mimic the condition but are caused by something else.
Scientific experts are in charge of the search for long Covid biomarkers. But their search depends on the essential question of how to classify someone as having long Covid in the first place, the answer to which has been strongly influenced by patient advocates. Deciding who to include in a study of long Covid requires a provisional set of exclusionary criteria. If the criteria are too strict, they will exclude people who have the condition; if they are too relaxed, they will include people who don’t have the condition. Each of these poses a risk to the accuracy of the science.
But for patient advocates, strict criteria have an additional risk. If they are implemented, some sufferers who believe they have long Covid won’t “officially” have it. This risk was front and center when, not long after the outbreak, the National Academies of Sciences, Engineering, and Medicine (NASEM) took on the challenge of producing a “uniform, core definition” of long Covid. At the time, basic questions remained unanswered: Does long Covid require a prior positive SARS-CoV-2 test? What symptoms are necessary? How long must they go on?
In 2024, with a “focus on the patient perspective and interdisciplinary dialogue,” the committee produced an “intentionally inclusive” definition, to “ensure that patients who experience long Covid will be included in the definition.” Long Covid, they decided, is “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.” Among the possible symptoms: shortness of breath, cough, persistent fatigue, post-exertional malaise, difficulty concentrating, memory changes, recurring headache, lightheadedness, fast heart rate, sleep disturbance, problems with taste or smell, bloating, constipation, and diarrhea.
According to the NASEM definition, a single symptom from the list is enough. It can be mild or severe. Previous infection “may have been recognized or unrecognized”—that is, a prior test for Covid is unnecessary. Put differently: If you start having trouble sleeping, on and off, for three months, and you attribute that to an unverified case of SARS-CoV-2, you have long Covid.
