A new study of long Covid patients in France, published in November in JAMA Internal Medicine and done by researchers at several universities and medical centers in France and Italy, is complicating that problem.

The researchers surveyed 26,283 patients about their experiences with Covid and any long-lasting symptoms, and also analyzed samples of their blood for antibodies that would confirm their infections.

Their findings: The thing that most predicted whether patients developed long Covid symptoms was whether they believed they had been infected, not whether their infection could be lab-confirmed.

This study hasn’t upended research into long Covid: The field is too new for that.

And it raises the unsettling prospect of having to broach to patients, without being dismissive, that the symptoms they are experiencing may not be caused by Covid at all.

“As an emergency physician, I have seen, firsthand, patients with persistent symptoms after Covid infection that have dramatically shifted their life.

There are so many challenges inherent in carving out a long Covid research agenda, starting with the most basic: No one can say at this point how many people suffer from it.

Here are the results of just a few studies: One conservative estimate in the United Kingdom, based on a survey conducted by Kings College London, landed on 2.3 percent of patients experiencing symptoms 12 weeks beyond their initial illness—while a study by Imperial College London put the proportion, at the same time period, at 37.7 percent.

In China, 26 percent of a cohort of patients who were hospitalized for Covid had difficulty sleeping six months after their symptoms began, and 63 percent had ongoing muscle weakness.

And a systematic review of 57 studies done worldwide, completed in October, found that half of people who had Covid symptoms were still experiencing health problems six months later.

In fact, one study that helped set the agenda for discussing long Covid, published last December by British and American academic researchers and a consortium of patients, lists more than 200 symptoms affecting entire body systems.

SARS-CoV-2 is a respiratory virus, but many of those symptoms reach far beyond the lungs, affecting muscles and joints, the heart and circulatory system, the gut, and the nervous system and brain, including long Covid’s notorious “brain fog.” To complicate the picture further: While some patients continue to experience, for months, the same symptoms they had when they first fell ill, others develop problems in different parts of their bodies—and some don’t develop their long-lasting symptoms until weeks or months after their illness seems to have resolved.

This gets yet more complex once you consider that long duration of symptoms after an infection is not unique to Covid.

Those known effects suggest that researchers will have to ask: Is long Covid simply the expression of such post-infection symptoms, made visible because there has never before been one infection shared in a short period of time by so much of the world.

“Some people are having prolonged respiratory symptoms, shortness of breath, cough; some people are having myocarditis and other cardiac symptoms; some people are having blood clots that are causing strokes,” Horwitz says.

Jeremy Faust, an emergency physician at Boston’s Brigham and Women’s Hospital who analyzed the French long Covid study in his newsletter “Inside Medicine,” worries about what he calls “premature diagnostic closure”—assigning symptoms to an explanation that feels logical, but might not be right.

One challenge of defining long Covid is persuading patients that trauma may be playing a role in their symptoms—without appearing to tell them that it is all in their heads.