Conference Coverage

Infection-related chronic illness: A new paradigm for research and treatment



Experience with long COVID has shone a spotlight on persistent Lyme disease and other often debilitating chronic illnesses that follow known or suspected infections – and on the urgent need for a common and well-funded research agenda, education of physicians, growth of multidisciplinary clinics, and financially supported clinical care.

“We critically need to understand the epidemiology and pathogenesis of chronic symptoms, and identify more effective ways to manage, treat, and potentially cure these illnesses,” Lyle Petersen, MD, MPH, director of the division of vector-borne diseases at the Centers for Disease Control and Prevention, said at the start of a 2-day National Academies of Science, Engineering, and Medicine (NASEM) workshop, “Toward a Common Research Agenda in Infection-Associated Chronic Illnesses.”

Thinking about infection-associated chronic illnesses as an entity – one predicated on commonalities in chronic symptoms and in leading hypotheses for causes – represents a paradigm shift that researchers and patient advocates said can avoid research redundancies and is essential to address what the NASEM calls an overlooked, growing public health problem.

An estimated 2 million people in the United States are living with what’s called posttreatment Lyme disease (PTLD) – a subset of patients with persistent or chronic Lyme disease – and an estimated 1.7-3.3 million people in the United States have diagnoses of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). More than 700,000 people are living with multiple sclerosis. And as of January 2023, 11% of people in the United States reported having long COVID symptoms; the incidence of long COVID is currently estimated at 10%-30% of nonhospitalized cases of COVID-19.

These illnesses “have come under one umbrella,” said Avindra Nath, MD, clinical director of the National Institute of Neurologic Disorders and Stroke (NINDS), Bethesda, Md.

Dr. Avindra Nath, clinical director of the National Institutes of Neurologic Disorders and Stroke, Bethesda, Md. Dr. Nath

Dr. Avindra Nath

To date, common ground in the literature has grown largely around long COVID and ME/CFS, the latter of which is often associated with a prior, often unidentified infection.

Symptoms of both have been “rigorously” studied and shown to have overlaps, and the illnesses appear to share underlying biologic abnormalities in metabolism and the gut microbiome, as well as viral reactivation and abnormalities in the immune system, central and autonomic nervous systems, and the cardiovascular and pulmonary systems, said Anthony L. Komaroff, MD, professor of medicine at Harvard Medical School and a senior physician at Brigham & Women’s Hospital, both in Boston. (An estimated half of patients with long COVID meet the diagnostic criteria for ME/CFS.)

Although less thoroughly researched, similar symptoms are experienced by a subset of people following a variety of viral, bacterial, and protozoal infections, Dr. Komaroff said. To be determined, he said, is whether the pathophysiology believed to be shared by long COVID and ME/CFS is also shared with other postinfectious syndromes following acute illness with Ebola, West Nile, dengue, mycoplasma pneumonia, enteroviruses, and other pathogens, he said.

Persistent infection, viral reactivation

RNA viral infections can lead to persistent inflammation and dysregulated immunity, with or without viral persistence over time, Timothy J. Henrich, MD, MMSc, associate professor of medicine at the University of California, San Francisco, said in a keynote address.

Dr. Timothy J. Henrich, associate professor of medicine at the University of California, San Francisco

Dr. Timothy J. Henrich


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