During the Covid-19 pandemic there has been a huge increase in people talking about ME and CFS and it's about bloody time.
It happened because people who had had an acute Covid-19 infection were not recovering after the expected 2 weeks. Most of us had debilitating fatigue, often combined with continuing COVID-19 symptoms involving the lungs or heart or brain in particular. We also had symptoms that were consistent with the sort of post-viral fatigue syndromes that may precede ME/CFS. Many people with Long Covid, myself included, turned to the ME community for help with managing our symptoms of chronic fatigue, insomnia and post exertional malaise. We needed them - a community that has been shunned by the medical profession. Luckily for those of us with Energy Limiting Chronic Illnesses there are researchers who continue to try to find the causes of ME/CFS and with the mass disabling event that is Long Covid hopefully research into one will benefit us all.
The following post cites the recent article by Cort Johnson in Health Rising - "The Big Merge? Are Long COVID and ME/CFS Hypotheses Meshing?" 29 July 2021 and presents research that may do just that.
Rose Cottage Doc Quick Summary
High angiotensin II levels found in ME/CFS/POTS/Long Covid:
Increase sympathetic nervous system activity, produce systemic vasoconstriction (narrowed blood vessels), increase the heart rate, inflammation and oxidative stress.
May damage the mitochondria - the energy producing powerhouses in each of our cells. Especially those in the endothelial cells lining the blood vessels – reducing nitric oxide levels stopping the blood vessels from dilating properly and triggering “vascular aging”.
Can cause a "leaky gut" by damaging the gut lining leading to the production of autoantibodies.
Could cause "brain fog" by causing the guts to leak bacterial molecules into the bloodstream – triggering an immune reaction reaching all the way to the brain.
Increase oxidative stress levels which can damage cells, proteins, and DNA, which can contribute to aging and certain health conditions such as diabetes, cancer, and neurodegenerative diseases such as Alzheimer's.
Increase DAMP levels leading to chronic fatigue and pain.
Last year June 2020 a team published their paper, “Intoxication With Endogenous Angiotensin II: A COVID-19 Hypothesis“, proposed that endothelial dysfunction was a key aspect of COVID – and linked it to high angiotensin II (Ang II) levels. They suggested that the high Ang II levels in COVID-19 had caused “premature vascular senescence” - Senescence is cell ageing.
The renin-angiotensin-aldosterone system (RAAS)
Figure 1. Renin-angiotensin-aldosterone system
The Renin-Angiotensin-Aldosterone System (RAAS) is a hormone system within the body that is essential for the regulation of blood pressure and fluid balance. The system is mainly comprised of the three hormones renin, angiotensin II and aldosterone. Primarily it is regulated by the rate of renal blood flow.
These are the effects of angiotensin II:
Figure 2:Ang II effects
The RAAS paradox
The paradox concerns the renin-angiotensin-aldosterone system that kicks in when low blood volume levels occur. Even in context of the very low blood volumes found in ME/CFS/POTS, the pathway doesn’t kick in, and its critical endpoint, aldosterone, remains at normal or even low levels. This is despite the fact that the levels of Ang II – found in the middle of the pathway – tend to be very high.
The renin-angiotensin-aldosterone system regulates blood volume in the body.
People with ME/CFS and/or postural orthostatic tachycardia syndrome (POTS) tend to have low blood volume.
When low blood volume is present, the activity of the renin-angiotensin-aldosterone system should be increased. In what has been termed the renin-aldosterone paradox – renin and aldosterone levels are decreased in ME/CFS and POTS.
Low levels of some forms of angiotensin suggest that levels of the ACE-2 enzyme – which has been called the protective arm of the RAA system – are decreased. The ACE-2 enzyme breaks down Ang II and other peptides including bradykinin.
High levels of Ang II can increase sympathetic nervous system activity, produce systemic vasoconstriction (narrowed blood vessels), increase the heart rate, inflammation and oxidative stress.
They also believe high Ang II levels in the brain are producing cognitive symptoms.
Low aldosterone levels may be caused by a balky HPA axis in ME/CFS. At the end of the day, though, the cause of the renin-aldosterone paradox and the low blood volume in ME/CFS/POTS is unclear.
The SARS-CoV-2 coronavirus enters the body through receptors for the ACE-2 enzyme. Recent research suggests that many, if not all of the coronavirus’s effects, could derive from its disruption of the renin-aldosterone-angiotensin system and its failure to properly regulate a substance called bradykinin.
The authors brought a whole new perspective to the high Ang II levels found in ME/CFS/POTS. They proposed that high ANG II levels are killing the mitochondria in endothelial cells lining the blood vessels – reducing nitric oxide (N0) levels (inhibiting the blood vessels from dilating properly), and triggering something they called “vascular aging”.
Figure 3: The SARS-CoV-2 virus engages the angiotensin-converting enzyme-2 (ACE-2) protein, displacing its physiological ligand. As a result, angiotensin II (ANG II) accumulates in endothelial cells (ECs), inducing vascular senescence with upregulation of interleukin-6 (IL-6) and reactive oxygen species (ROS), impairing both innate and adaptive immunity. These changes engender dysfunctional coagulation (not shown) and the expression of exhausting markers (EM). In return, these immune defects disrupt viral clearance, engendering a vicious cycle and poor COVID-19 prognosis.
In their new ME/CFS / Long COVID paper, “Endothelial Senescence and Chronic Fatigue Syndrome, a COVID-19 Based Hypothesis” July 2021 highlights the links between Long Covid and ME/CFS/POTS.
The Long COVID researchers were back with a hypothesis they believe explains both long COVID and ME/CFS. It is centered on those high Ang II levels found in ME/CFS.
High Ang II levels can cause more problems than were known. Besides possibly producing blood vessel and mitochondrial problems, it can damage the gut lining, increase oxidative stress levels, interfere with cellular cleanup, and even damage telomeres (parts of our DNA).
The authors proposed that the high Ang II levels were causing the guts of both long-COVID and ME/CFS patients to leak bacterial molecules into the bloodstream – triggering an immune reaction reaching all the way to the brain.
The authors believe that the adrenergic autoantibodies that have received so much attention in ME/CFS may have been produced to deal with the bacterial molecules making their way into the gut.
Ang II also inhibits the phagocytosis or swallowing of damaged and dead cells (efferocytosis) – possibly allowing damaged endothelial cells to accumulate – and the intestinal dysbiosis to worsen.
When phagocytic cells such as macrophages fail to cleanly envelop or swallow damaged cells, the contents of those cells (called damage-associated molecular pattern (DAMP)) can leak into the bloodstream, causing an immune response. High DAMP levels have been associated with unexplained fatigue, chronic pain, exhaustion, and muscle dysfunction in other diseases.
The authors outlined a variety of possible treatments not currently being used in ME/CFS that might help.
Escitalopram, coenzyme Q10 and nicotinamide adenine dinucleotide (NAD) and mildronate used in ME/CFS can restore endothelial functioning
Angiotensin receptor blockers (ARBs) might be helpful.
Factors that improve short-chain fatty acids (SCFAs/fermented dietary fibre) may be able improve intestinal integrity
B-glucan may also be able to damp down microglial activation in the brain.
Metformin may be able to protect the gut barrier.
Aripiprazole (Abilify) a dopamine-enhancing antipsychotic drug that may be protective against the central nervous system effects of COVID-19
A new field of drugs called senotherapeutics (dasatinib, hyperoside, quercetin, fistein, Navitoclax), which target cell death and aging, may present another as yet untested option.
From Health Rising:
"Time will tell whether the current flock of ME/CFS and Long COVID hypotheses will win out, but the fact that most (Systom, Wirth and Scheibenbogen, Fluge/Mella, Patterson, Sfera at. al.) involve problems with the blood vessels, and some are even focusing on the RAA system (which hasn’t gotten much attention in ME/CFS), is nothing if not encouraging".
Rose Cottage Doc takeaways
work on reducing excess sympathetic nervous system activity the so called "fight or fight"
support your mitochondria
work on your gut health
reduced oxidative stress
The Big Merge? Are Long COVID and ME/CFS Hypotheses Meshing?
Endothelial Senescence and Chronic Fatigue Syndrome, a COVID-19 Based Hypothesis https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267916/
Intoxication With Endogenous Angiotensin II: A COVID-19 Hypothesis