Causes of Symptoms and Symptom Persistence in Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Authors

Anthony L Komaroff
Robert Dantzer

Publication Date

8-19-2025

Journal

Cell Reports Medicine

DOI

10.1016/j.xcrm.2025.102259

PMID

40744021

PMCID

PMC12432373

PubMedCentral® Posted Date

7-30-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Debilitating symptoms for many years can follow acute COVID-19 ("long COVID"), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and various post-acute infection syndromes (PAISs). Together, long COVID and ME/CFS affect 60-400 million individuals, globally. Many similar underlying biological abnormalities have been identified in both conditions including autoantibodies against neural targets, endothelial dysfunction, acquired mitochondrial dysfunction, and a pro-inflammatory gut microbiome. Each of these abnormalities may directly cause some of the symptoms. In addition, the symptoms also may be caused by ancient, evolutionarily conserved symptomatic and metabolic responses to vital threats-sickness behavior and torpor-responses mediated by specific, recently discovered neural circuits. These neural circuits constitute a symptom-generating pathway, activated by neuroinflammation, which may be targeted by therapeutics to quell neuroinflammation. Many factors cause the symptoms to become chronic, including persistent infectious agents (and/or their nucleic acids and antigens) and the fact that many of the underlying biological abnormalities reinforce each other, creating ongoing physiological vicious cycles.

Keywords

Humans, Fatigue Syndrome, Chronic, COVID-19, SARS-CoV-2, Post-Acute COVID-19 Syndrome, Gastrointestinal Microbiome, long COVID, post-COVID condition, myalgic encephalomyelitis/chronic fatigue syndrome, neuroimmunology, neural circuits, sickness behavior

Published Open-Access

yes

Recommended Citation

Anthony L Komaroff and Robert Dantzer, "Causes of Symptoms and Symptom Persistence in Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome" (2025). Faculty, Staff and Student Publications. 5504.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5504