A Paradigm for Post-Covid-19 Fatigue Syndrome Analogous to ME/CFS, 2021, Mackay

A significant proportion of COVID-19 patients are suffering from prolonged Post-COVID-19 Fatigue Syndrome, with characteristics typically found in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). However, no clear pathophysiological explanation, as yet, has been provided.

A novel paradigm for a Post-COVID-19 Fatigue Syndrome is developed here from a recent unifying model for ME/CFS. Central to its rationale, SARS-CoV-2, in common with the triggers (viral and non-viral) of ME/CFS, is proposed to be a physiologically severe stressor, which could be targeting a stress-integrator, within the brain: the hypothalamic paraventricular nucleus (PVN). It is proposed that inflammatory mediators, released at the site of COVID-19 infection, would be transmitted as stress-signals, via humoral and neural pathways, which overwhelm this stress-center. In genetically susceptible people, an intrinsic stress-threshold is suggested to be exceeded causing ongoing dysfunction to the hypothalamic PVN's complex neurological circuitry. In this compromised state, the hypothalamic PVN might then be hyper-sensitive to a wide range of life's ongoing physiological stressors. This could result in the reported post-exertional malaise episodes and more severe relapses, in common with ME/CFS, that perpetuate an ongoing disease state. When a certain stress-tolerance-level is exceeded, the hypothalamic PVN can become an epicenter for microglia-induced activation and neuroinflammation, affecting the hypothalamus and its proximal limbic system, which would account for the range of reported ME/CFS-like symptoms.

A model for Post-COVID-19 Fatigue Syndrome is provided to stimulate discussion and critical evaluation. Brain-scanning studies, incorporating increasingly sophisticated imaging technology should enable chronic neuroinflammation to be detected, even at a low level, in the finite detail required, thus helping to test this model, while advancing our understanding of Post-COVID-19 Fatigue Syndrome pathophysiology.

Open access, https://www.frontiersin.org/articles/10.3389/fneur.2021.701419/full

 

A "physiologically severe stressor" in "genetically susceptible people" is as unclear as can be.

The gist of the theory revolves around the hypothalamic paraventricular nucleus (PVN). The authors describe it as follows:

The author has previously written about this, this paper seems to add long covid in the mix.

Mackay A, Tate WP. A compromised paraventricular nucleus within a dysfunctional hypothalamus: a novel neuroinflammatory paradigm for ME/CFS. Int J Immunopathol Pharmacol. (2018) 32:1–8. doi: 10.1177/2058738418812342 17.

Mackay A. A neuro-inflammatory model can explain the onset, symptoms and flare-ups of myalgic encephalomyelitis/chronic fatigue syndrome. J Prim Health Care. (2019) 11:300–7. doi: 10.1071/HC19041​

 

Brain scanning able to detect even low level inflammation, something that seems elusive to pin down in ME.

it would be interesting if some studies included people with Long COVID, another group with ME, plus healthy controls.

 

This looks like a way to try to put BPS theory onto a scientific footing while still ignoring the actual symptoms of the disease. It does not reflect my experience of the disease at all.

It is problematic in that it may be close to the truth but still pushing us towards CBT as a treatment.

The findings from CPET testing that our aerobic cellular respiratory output is compromised carries the implication that a lot of our symptoms could be caused by the response of our bodies to the extreme stress of not having enough battery power to work.

For decades, having ME has been described as being similar to a runner at the end of a marathon so any results showing increased stress responses is most likely to be the correct response to that, not a mistake in the signals. The body is sending out the appropriate distress calls for the situation.

 

LongCOVID is many things (any persistent symptom after SARS-CoV-2 infection), whereas only a minority of people with LongCOVID actually have ME/CFS.

The hypothesis that the illness is caused by hypothalamic paraventricular nucleus dysfunction is weak as there are no consistent neuroendocrine abnormalities (eg related to stress hormones) found - and that has been one of the most investigated avenues since the 1990s (Anthony Cleare and others).