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[CFS-L] PASC: ME and Covid-19

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Dr. Marc-Alexander Fluks

Aug 20, 2021, 2:55:13 AM8/20/21
Source: Frontiers in Neurology
Vol 12, p 701419
Date: August 2, 2021

A paradigm for Post-Covid-19 Fatigue Syndrome analogous to ME/CFS
Angus Mackay
- The Brain Health Research Centre, University of Otago, Dunedin,
New Zealand. Email:

Received: 30 April 2021
Accepted: 09 July 2021
Published: 02 August 2021


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.

Keywords: COVID-19, Post-COVID Fatigue Syndrome, ME/CFS, chronic fatigue
syndrom, stressors, inflammatory mediator, hypothalamic paraventricular
nucleus, neuroinflammation

(c) 2021 Frontiers Media S.A.

Dr. Marc-Alexander Fluks

Aug 27, 2021, 4:02:03 AM8/27/21
Source: Johns Hopkins University
Date: August 26, 2021

For many, long COVID looks a lot like chronic fatigue

A team of researchers, including two from Johns Hopkins Medicine, have
published a review article highlighting similarities between certain
lingering symptoms following COVID-19 illness-a condition called 'long
COVID'-and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS),
a debilitating, complex disorder previously known as chronic fatigue

The researchers say the symptoms shared by the two conditions may
involve a biological response that goes haywire when the body encounters
certain infections or other environmental hazards. 'The body's response
to infection and injury is complex and covers all body systems,' says
lead author Bindu Paul, Ph.D., assistant professor of pharmacology and
molecular sciences at the Johns Hopkins University School of Medicine.
'When that response is in disarray-even just one aspect of it-it can
cause feelings of being tired, brain fog, pain and other symptoms.'

In their review, published Aug. 16, 2021, in the Proceedings of the
National Academy of Sciences, Paul and her co-authors highlight the
evidence seen in both acute COVID and ME/CFS of various underlying
biological disorders. In particular, the researchers suggest a central
role for the way cells behave when too many oxygen molecules pile up in
a cell-a process called oxidative stress or redox imbalance. The team
describes how redox imbalance may be connected to the inflammation and
disorders of metabolism that are found in the two diseases.

Paul has previously studied the role of oxidative stress in conditions
such as Huntington's disease, Alzheimer's disease and Parkinson's

As of August 2021, approximately 36 million Americans have been
diagnosed with COVID-19. 'We do not yet know how many of these patients
will experience long COVID, but it's estimated that at least 7%
experience extended symptoms,' says co-author Anthony Komaroff, M.D.,
the Steven P. Simcox, Patrick A. Clifford and James H. Higby
Distinguished Professor of Medicine at Harvard Medical School.

The expert team urges that some of the recent National Institutes of
Health funding assigned to study the long-term health effects of
COVID-19 be used to investigate both long COVID and ME/CFS. Those
studies, they believe, could shed light on other diseases characterized
by oxidative stress, inflammation and metabolic disorders.

ME/CFS is a complex condition affecting 1 million to 2.5 million people
in the United States. It is characterized by a cluster of symptoms,
including severe and debilitating fatigue, disrupted and unrefreshing
sleep, difficulty thinking (commonly called 'brain fog'), abnormalities
of the autonomic nervous system and post-exertional malaise-a flare-up
of multiple symptoms following physical or cognitive exertion.

The team hopes that this scientific review will spur and help focus
research on the molecular basis of both long COVID and ME/CFS.

(c)2021 Medical Xpress
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