Almost from the beginning of the COVID pandemic, reports have accumulated of persistent, weird, disabling symptoms in survivors, a syndrome that’s come to be known as long COVID. The complex of fatigue, confusion, heart arrhythmias, gut disorders, and other problems—which may persist months after an infection begins or arise months after it seems to have concluded—has attracted attention and sympathy, intense patient activism, substantial research interest, and huge government investment. Last December, the US Congress voted in $1.15 billion to fund four years of research into long COVID, and this February, the US National Institutes of Health announced it would use those funds to create a nested set of large studies examining adult and child experiences of the syndrome.
What makes long COVID research urgent is also what makes it, at this point, so challenging. No one has yet been able to determine its cause, beyond the association that it occurs in people who have had COVID—or who think they did but weren’t able to get a test to prove it. This makes it difficult to understand and therefore to predict who is vulnerable: why one patient develops lasting symptoms and another does not.
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 the patients’ experiences with COVID and any long-lasting symptoms, and they also analyzed samples of patients blood for antibodies that would confirm the 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.
“Further research in this area should consider underlying mechanisms that may not be specific to the SARS-CoV-2 virus,” the authors wrote. “A medical evaluation of these patients may be needed to prevent symptoms due to another disease being erroneously attributed to ‘long COVID.'”
This study hasn’t upended research into long COVID: the field is too new for that. But for scientists working on the problem, it emphasizes the difficulty of carving out a research agenda for a syndrome so new, multifarious, and widespread. 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.
There is a long history of new diseases being brought to medical attention by patients—often by women, who between monthly menstruation and routine GYN visits tend to be more in tune with their bodies than men are—and then dismissed by medicine as imagined. Lyme disease is one such example; myalgic encephalomyelitis/chronic fatigue syndrome, another. Researchers are determined that long COVID not go down that road.
“As a physician, but also as a woman, I have seen so many of these poorly defined syndromes get dismissed, and seen patients have no alternative other than quackery, when there really is a pathophysiologic basis for their symptoms,” says Megan Ranney, a physician and associate dean at the Brown School of Public Health and co-director of a new long COVID initiative there. “As an emergency physician, I have seen, firsthand, patients with persistent symptoms after COVID infection that have dramatically shifted their life. They deserve us to bring scientific rigor to the question—and for folks for whom some of these symptoms may exist and may not be due to COVID, they deserve some sort of an explanation and treatment as well.”
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