By 2025, most experts have adopted the same position. “I think everyone now agrees that long Covid is a biological disease,” Igho Ofotokun of Emory University School of Medicine said in his closing remarks at the international Long Covid conference. “It’s not in your head. It’s real.” Ofotokun also provided an explanation for the lack of scientific progress. “The big elephant in the room is that we don’t have a gold standard definition of long Covid. That makes it really difficult to do everything we want. It makes designing clinical trials extremely difficult and tracking clinical trial outcomes extremely difficult.”
Part of the problem of defining Covid has long been the lack of definitive biomarkers: genes, antibodies, any unique physiological signature of the disease. To discover biomarkers, researchers must first identify patients who are thought to have a specific disease and then look for what they have in common beyond their symptoms. Identifying a biomarker allows for the development of disease-specific interventions – gene therapy, antiviral drugs – and can distinguish people with a specific disease from those whose symptoms mimic that disease but are caused by something else.
The search for long Covid biomarkers is being carried out by scientific experts. But their search hinges primarily on the fundamental question of how to classify a person as having had long-standing Covid, an answer to which patient advocates have had a major influence. Deciding who to include in a long Covid study requires an interim set of exclusion criteria. If the criteria are too stringent, people with the disease will be excluded; if they are too relaxed, they will include people who do not suffer from the disease. Each of these poses a risk to the accuracy of science.
But for patient advocates, stringent criteria carry additional risks. If implemented, some sufferers who think they have had Covid for a long time will not “officially” have it. This risk was a major theme when, shortly after the outbreak, the National Academies of Sciences, Engineering and Medicine (NASEM) took up the challenge of creating a “single baseline definition” of long Covid. Fundamental questions then remained unanswered: Does long Covid require a prior positive test for SARS-CoV-2? What symptoms are necessary? How long do they have to last?
In 2024, “focusing on the patient perspective and interdisciplinary dialogue”, produced by the committee a “deliberately inclusive” definition to “ensure that patients who experience long-term Covid are included in this definition.” They decided that Long Covid is “a chronic infection-related condition that occurs following SARS-CoV-2 infection and persists for at least three months as an ongoing, relapsing-remitting or progressive disease state that affects one or more organ systems.” Possible symptoms include: shortness of breath, cough, persistent fatigue, post-exertional malaise, difficulty concentrating, changes in memory, recurrent headaches, dizziness, rapid heartbeat, sleep disturbances, problems with taste or smell, flatulence, constipation and diarrhea.
According to the NASEM definition, one symptom from the list is enough. It may be subtle or severe. Previous infection “may have been recognized or undiagnosed” – meaning prior Covid testing is not necessary. In other words: if you start having trouble sleeping, on and off, for three months and attribute it to an unverified case of SARS-CoV-2, you already have long Covid.