The painful truth about long Covid

By 2025, most experts have adopted the same position. “I think everyone now agrees that long Covid is a biological disease,” Ego Ofotokun, of Emory University School of Medicine, said in his closing comments at the International Long Covid Conference. “It’s not in your mind. It’s real.” Ofotokun also gave an explanation for the lack of scientific progress. “The big problem in the room is that we don’t have a gold standard definition of long Covid. So, that makes it really difficult to do all the things we want to do. It makes designing clinical trials very difficult, and tracking results in clinical trials is very difficult.”

Part of the problem with defining long Covid is the absence of specific biomarkers: genes, antibodies, any unique physiological marker of disease. To discover biomarkers, researchers must first identify patients who are presumed to have a particular disease, and then find out what they have in common beyond symptoms. Identifying a biomarker allows the development of interventions that target the disease — gene therapy, antiviral drugs — and enables people with a particular condition to be sorted from those whose symptoms mimic the condition but are caused by something else.

Scientific experts are responsible for searching for long-term biomarkers of the coronavirus. But their research relies on the fundamental question of how someone is classified as having long Covid in the first place, the answer to which has been heavily influenced by patient advocates. Determining who to include in a long Covid study requires a provisional set of exclusion criteria. If the criteria are too stringent, they will exclude people with the condition; If they are very relaxed, they will include people who do not have the condition. Each of these poses a threat to the accuracy of science.

But for patient advocates, strict standards carry additional risks. If implemented, some patients who think they have long Covid will “officially” not have it. This risk was brought to the fore when, shortly after the outbreak, the National Academies of Sciences, Engineering, and Medicine (NASEM) faced the challenge of producing a “uniform core definition” of long Covid. At the time, basic questions remained unanswered: Does long Covid require prior positive testing for SARS-CoV-2? What are the necessary symptoms? How long should they last?

In 2024, with an “emphasis on the patient perspective and interdisciplinary dialogue”, Commission produced Definition of “intentionally inclusive”, “to ensure that patients with long Covid are included in the definition”. They determined that Long Covid is “an infection-associated chronic condition that occurs after infection with SARS-CoV-2 and remains present for at least three months as a persistent, relapsing, relapsing, or progressive disease state affecting one or more organ systems.” Possible symptoms include: shortness of breath, cough, constant fatigue, malaise after exertion, difficulty concentrating, memory changes, frequent headaches, dizziness, rapid heartbeat, disturbed sleep, problems with taste or smell, bloating, constipation, and diarrhea.

According to NASEM’s definition, one display from the list is sufficient. It can be mild or severe. Previous infection “may or may not have been identified” – meaning prior testing for Covid is not necessary. In other words: If you start having trouble sleeping, on and off, for three months, and you attribute it to an unverified case of SARS-CoV-2, you have long-Covid.