Every year, thousands of Americans develop chronic, persistent symptoms such as fatigue, cognitive impairment (“brain fog”), and other debilitating problems following acute infections with Lyme disease, COVID-19, and other pathogens. Efforts to identify the cause and develop treatments have been unsuccessful. But 16 leading researchers think they know part of the problem: research design.
In the article brainResearchers from institutions such as , Rutgers University, National Institutes of Health, Rockefeller University, New York Medical College, Mount Sinai Icahn School of Medicine, Stony Brook University, and Cold Spring Harbor Laboratory argue that studies of chronic diseases related to infectious diseases are repeatedly hit by problems, including the inability to prove that participants have the relevant pathogens.
Key challenges in Lyme disease research
Of the approximately 476,000 Americans diagnosed with Lyme disease each year, up to 20% develop chronic and persistent cognitive impairment, fatigue, and pain, known as Lyme disease syndrome, after treatment. Researchers have spent decades looking for causes and treatments, but many of their studies focused only on people with Lyme antibodies or bull’s eye rash, rather than documenting it. Borrelia burgdorferithe bacteria that causes Lyme disease.
Unfortunately, Lone Star tick bites, drug reactions, and other conditions can cause similar rashes, and antibody tests only detect past exposure, not active infection. As a result, studies may include people with completely different diseases.
How can a study draw any concrete conclusions about Lyme disease if it doesn’t know whether the patient actually had Lyme disease or symptoms similar to Lyme disease?”
Steven Schutzer, study corresponding author, physician-scientist, and professor at Rutgers New Jersey Medical School, Rutgers University
The authors also identified additional methodological shortcomings in previous studies regarding control groups and sample handling.
Similarities to long-term COVID-19 and wider impact
Research into Long coronavirus, which affects an estimated 9 million Americans, faces similar challenges, particularly the tendency to group patients with potentially different underlying mechanisms into a single population. Research into myalgic encephalomyelitis/chronic fatigue syndrome is made even more difficult because the causative pathogen has not been identified.
But progress can be made even without knowledge of the underlying infection. The authors cite multiple sclerosis (MS) as evidence that rigorous study designs have produced useful FDA-approved treatments.
Looking to the future
“The framework we propose is a major step forward, as it provides rigorous, well-thought-out guidelines for all aspects of conducting clinical trials in this patient population,” said co-author Avindra Nath, a physician-scientist and clinical director of the NIH National Institute of Neurological Disorders and Stroke.
“Patients in a post-infectious state have been waiting too long for answers,” said Jacqueline Becker, a neuropsychologist at the Icahn School of Medicine at Mount Sinai and co-author of the study. “If we want clinical trials that actually lead to treatments, we need to get the basics right: we need to confirm the diagnosis, we need to choose the right comparison group, we need to treat patient populations individually rather than lumping them together. Patients need that rigor.”
