Pre-illness data reveals differences in multiple metabolites and metabolic pathways in those who do and do not recover from infectious mononucleosis

Some patients remain unwell for months after “recovering” from acute COVID-19. They develop persistent fatigue, cognitive problems, headaches, disrupted sleep, myalgias and arthralgias, post-exertional malaise, orthostatic intolerance and other symptoms that greatly interfere with their ability to function and that can leave some people housebound and disabled. The illness (Long COVID) is similar to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) as well as to persisting illnesses that can follow a wide variety of other infectious agents and following major traumatic injury. Together, these illnesses are projected to cost the U.S. trillions of dollars. In this review, we first compare the symptoms of ME/CFS and Long COVID, noting the considerable similarities and the few differences. We then compare in extensive detail the underlying pathophysiology of these two conditions, focusing on abnormalities of the central and autonomic nervous system, lungs, heart, vasculature, immune system, gut microbiome, energy metabolism and redox balance. This comparison highlights how strong the evidence is for each abnormality, in each illness, and helps to set priorities for future investigation. The review provides a current road map to the extensive literature on the underlying biology of both illnesses.

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“…Positive studies: (385,388,407,409) This defect may exist prior to the "infectious-like" event which is followed by ME/CFS (408).…”

Section: Reduced Atp From Glucose Via Tricarboxylic Acid (Tca) Cyclementioning

confidence: 99%

“…Elevated levels of thiobarbituric acid reactive substances, or TBARS (170,425,426), that correlate with severity of symptoms (170,426). This defect may exist prior to the "infectious-like" event which is followed by ME/CFS (408).…”

Section: Decreased Levels Of Antioxidantsmentioning

confidence: 99%

ME/CFS and Long COVID share similar symptoms and biological abnormalities: road map to the literature

Komaroff

Lipkin

2023

Front. Med.

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“…Blood samples were taken from the ME/CFS group, and from those who had recovered from the Epstein-Barr infection without developing a post-viral condition. Pre-illness blood samples of the ME/CFS group had detectable metabolic differences relevant to an immune and inflammatory response 6 . This study implies there may be a molecular signature within the complex immune system that would be a predictive for susceptibility to developing the post viral/stress conditions.…”

Section: Viralmentioning

confidence: 99%

An understanding of the immune dysfunction in susceptible people who develop the post-viral fatigue syndromes Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID

Walker

Peppercorn

Kleffmann

et al. 2023

MRAJ

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Viral infection in most people results in a transient immune/inflammatory response resulting in elimination of the virus and recovery where the immune system returns to that of the pre-infectious state. In susceptible people by contrast there is a transition from an acute immune response to a chronic state that can lead to an ongoing lifelong complex post-viral illness, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. This susceptibility is proposed to be genetic or be primed by prior health history. Complex abnormalities occur in immune cell functions, immune cell metabolism and energy production, and in cytokine immune modulator regulation. The immune system of the brain/central nervous system becomes activated leading to dysfunction in regulation of body physiology and the onset of many neurological symptoms. A dysfunctional immune system is core to the development of the post-viral condition as shown with diverse strategies of immune profiling. Many studies have shown changes in numbers and activity of immune cells of different phenotypes and their metabolism. Immune regulating cytokines show complex altered patterns and vary with the stage of the disease, and there are elements of associated autoimmunity. These complex changes are accompanied by an altered molecular homeostasis with immune cell transcripts and proteins no longer produced in a tightly regulated manner, reflected in the instability of the epigenetic code that controls gene expression. Potential key elements of the altered immune function in this disease needing further exploration are changes to the gut-brain-immune axis as a result of changes in the microbiome of the gut, and viral reactivation from latent elements of the triggering virus or from a prior viral infection. Long COVID, an Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-like illness, is the post-viral condition that has arisen in large numbers solely from the pandemic virus Severe Acute Respiratory Syndrome Coronovirus-2. With over 760 million cases worldwide, an estimated ~100 million cases of Long COVID have occurred within a short period. This now provides an unprecedented opportunity to understand the progression of these post-viral diseases, and to progress from a research phase mainly documenting the immune changes to considering potential immunotherapies that might improve the overall symptom profile of affected patients, and provide them with a better quality of life.

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Altered Lipid, Energy Metabolism and Oxidative Stress Are Common Features in a Range of Chronic Conditions

Morten

Davis

Lodge

et al. 2023

Preprint

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Pre-illness data reveals differences in multiple metabolites and metabolic pathways in those who do and do not recover from infectious mononucleosis

Abstract: Metabolic pathways related to energy production, amino acids, nucleotides, nitrogen, lipids, and neurotransmitters in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) may contribute to the pathophysiology of ME/CFS. 4,501 Northwestern University college...

Cited by 3 publications

References 26 publications

ME/CFS and Long COVID share similar symptoms and biological abnormalities: road map to the literature

ME/CFS and Long COVID share similar symptoms and biological abnormalities: road map to the literature

An understanding of the immune dysfunction in susceptible people who develop the post-viral fatigue syndromes Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID

Altered Lipid, Energy Metabolism and Oxidative Stress Are Common Features in a Range of Chronic Conditions

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