SCIENCE: Long Covid | ME/CFS | Neuroinflammation | Clinical Trials

What happens to the brain when a virus takes hold and why do some people never fully recover?

Dr Avindra Nath has spent his career at the intersection of neurology and infectious disease, from the early AIDS pandemic through Zika and Ebola to today's work on Long COVID and ME/CFS. As Clinical Director of the NIH's National Institute of Neurological Disorders and Stroke (NINDS), he is leading some of the most important research into post-viral illness happening anywhere in the world.

In this episode, Dr. Nath explains the neuroscience of viral infection in accessible terms: how viruses enter and adapt inside the brain, how a single infected cell can trigger widespread neurological dysfunction, and why viral remnants (fragments of protein and RNA that linger long after the acute infection) may be enough on their own to cause ongoing damage.

He shares the key findings from the NIH's landmark 2024 deep-phenotyping study of post-infectious ME/CFS patients, including:

• Persistent immune activation and immune exhaustion, even years after infection
• Striking sex differences in immune response: B cell activation dominant in men, T cell activation in women. with major implications for treatment
• Why cohort selection and subtyping matter when designing therapies
• Why a one-size-fits-all treatment approach will not work

Dr. Nath also addresses the controversy around the term "altered effort preference" used in the 2024 paper (a phrase that drew significant criticism from the patient community) and the NIH symposium convened in response.

Looking ahead, he outlines three active NIH trials that could reshape Long Covid treatment:

• Viral Reservoir Study: multi-site biopsies to locate viral remnants throughout the body
• IVIG Study: placebo-controlled crossover trial using immunotherapy
• Checkpoint Inhibitor Study: using pembrolizumab to reverse immune exhaustion; FDA-approved, with enrolment opening the week of 20th April 2026

Emily Kate and Gez break down the science, highlight the findings most relevant to the Long Covid and ME/CFS communities, and discuss some of the criticisms of the NIH team's methodology.

Dr Avindra Nath is Clinical Director of the NIH NINDS, Director of the Translational Neuroscience Center, and Chief of the Section of Infections of the Nervous System.

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