Melissa Red Hoffman was “feeling really stuck” last summer. A 50-year-old surgeon in Asheville, N.C., Hoffman had been struggling with long COVID since getting infected with the coronavirus two and a half years earlier. “Deafening fatigue” was one of her worst symptoms, she says. “I feel tired behind my eyes from the moment I get up to the moment I go to sleep.” She managed to work part time, but much of her work had shifted to administrative tasks that she did from her couch.

“I was really at a point where I had tried so many different things myself, with so many different providers,” she says, “not really sure what the hell to do next.”

Then she found Remission Biome. It’s a research project started in early 2023 by Tamara Romanuk and Tess Falor, two people with myalgic encephalomyelitis/chronic fatigue syndrome, or ME/CFS, a chronic disease that shares symptoms with long COVID. Project participants have taken medical research into their own hands to determine whether and how changes to their gut bacteria can improve their health. After an initial test with three participants led to some symptom relief, Romanuk and Falor announced last July that they would recruit 50 people with ME/CFS, long COVID or both for a larger test of the project’s protocol.

Hoffman was one of 500 people who applied within 36 hours of the call for volunteers. By the fall, she and 49 other people, dubbed the “Renegade 50,” had joined the project.

Remission Biome’s protocol is a multistep process, which participants undertake in consultation with their physicians. Initial steps involve patients collecting samples of their guts, immune systems and other connected organ systems, either at home or at a health care provider’s office. After those samples are analyzed by a lab to get baseline data, participants take a regimen of over-the-counter supplements, such as probiotics to cultivate certain types of gut bacteria, and then a prescribed antibiotic. Next comes further testing to examine if and how the regimen altered the composition of the gut microbiome. Throughout the process, participants track their symptoms and learn about past research on the microbiome that informed the project, ensuring that they understand the rationale for every step.

Early in the testing process, Hoffman’s fatigue started to lift, she says. “That’s been exciting, just to feel a little bit of a change.”

Alleviating symptoms — which can include debilitating fatigue, trouble sleeping, intense allergic reactions and cognitive problems — motivates many members of the Renegade 50, who come from different countries, age groups and stages of illness. But participants also aim to collect and publish data that will give the broader scientific community more information about ME/CFS and long COVID, two complex, often fluctuating conditions.

Participant María Richardson, a 36-year-old former educator in Mexico City, has dealt with progressively worse ME/CFS symptoms since high school. She received her diagnosis in the United States in 2015, but when she moved back to her native Mexico, where knowledge of the condition is limited, trying to get care “was like starting from zero,” she says. Remission Biome helped her better understand her own symptoms and share scientific information with the ME/CFS community in Mexico, through the ME/CFS advocacy group Millions Missing Mexico.

Remission Biome is one effort in the growing movement of patient-led research, which seeks to investigate chronic conditions that have been under-researched by academic and clinical scientists yet impact many people’s lives.

“People who were ignored by the American health care system … often need to turn to each other in order to gather the data that gets the attention of the mainstream,” says health care researcher Susannah Fox, author of the new book Rebel Health: A Field Guide to the Patient-Led Revolution in Medical Care.

Compared with mainstream medical research that tends to focus on finding biological causes and disease cures, patient-led work is more often rooted in what’s immediately relevant to patients’ daily lives, like identifying symptom triggers or relievers. But the approach faces challenges — particularly a lack of funding and other research resources — as scientific institutions aren’t set up to support these projects.

Patient-researchers and their scientist collaborators say the patient-led approach has big potential to move chronic disease research forward, making it more informed, quicker and more poised to directly improve patients’ lives.

Projects like Remission Biome “are going to change how research into these chronic, multi-organ-system diseases is going to be done,” Hoffman says. The approach may someday become a standard part of more mainstream research.

A history of patient activism and patient-led research