Review An understanding of the immune dysfunction in susceptible people who develop the post-viral fatigue syndromes ME/CFS and Long Covid, 2023 Walker et al

Abstract
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.

Open access, https://esmed.org/MRA/mra/article/view/4083

 

From Prof Tate's team. Have only very quickly skimmed this. It's called a research article but looks more like a review (unless I missed something). It ends on a depressingly realistic note given the lack of progress in finding effective treatments to date. Still, can't help but hope that the first half of the quote below turns out to be wrong (and I'm not sure I understand the very last bit)

 

Yeah, the fact that it is a review is tucked away in the text.
"In this review we have attempted to integrate the many published papers connecting the immune system to the post-viral fatigue syndromes, ME/CFS and LC. The study design was to review the ME/CFS and LC literature and to provide as clear an understanding as is currently possible of the pathophysiology of the two conditions."