Orthostatic Symptoms and Reductions in Cerebral Blood Flow in Long-Haul COVID-19 Patients: Similarities with Myalgic Encephalomyelitis/Chronic Fatigue

[SWAlexander]

Abstract

Background and Objectives: Symptoms and hemodynamic findings during orthostatic stress have been reported in both long-haul COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), but little work has directly compared patients from these two groups. To investigate the overlap in these clinical phenotypes, we compared orthostatic symptoms in daily life and during head-up tilt, heart rate and blood pressure responses to tilt, and reductions in cerebral blood flow in response to orthostatic stress in long-haul COVID-19 patients, ME/CFS controls, and healthy controls. Materials and Methods: We compared 10 consecutive long-haul COVID-19 cases with 20 age- and gender-matched ME/CFS controls with postural tachycardia syndrome (POTS) during head-up tilt, 20 age- and gender-matched ME/CFS controls with a normal heart rate and blood pressure response to head-up tilt, and 10 age- and gender-matched healthy controls. Identical symptom questionnaires and tilt test procedures were used for all groups, including measurement of cerebral blood flow and cardiac index during the orthostatic stress. Results: There were no significant differences in ME/CFS symptom prevalence between the long-haul COVID-19 patients and the ME/CFS patients. All long-haul COVID-19 patients developed POTS during tilt. Cerebral blood flow and cardiac index were more significantly reduced in the three patient groups compared with the healthy controls. Cardiac index reduction was not different between the three patient groups. The cerebral blood flow reduction was larger in the long-haul COVID-19 patients compared with the ME/CFS patients with a normal heart rate and blood pressure response. Conclusions: The symptoms of long-haul COVID-19 are similar to those of ME/CFS patients, as is the response to tilt testing. Cerebral blood flow and cardiac index reductions during tilt were more severely impaired than in many patients with ME/CFS. The finding of early-onset orthostatic intolerance symptoms, and the high pre-illness physical activity level of the long-haul COVID-19 patients, makes it unlikely that POTS in this group is due to deconditioning. These data suggest that similar to SARS-CoV-1, SARS-CoV-2 infection acts as a trigger for the development of ME/CFS.

 

[lenora]

If the tilt table test had been available during my early years with this, I would have registered an exceptionally low b.p. It sounds like most of the test subjects were fairly young.

However as I aged and had an early menopause, my bp became exceptionally high. Have you found this in some people? In other words, it was never just normal. I hope you are doing OK. Yours, Lenora.

 

[Pyrrhus]

Thanks for posting this (van Campen et al., 2021) study from the team of Linda van Campen, Frans Visser, and Peter Rowe:
https://doi.org/10.3390/medicina58010028

There are a number of interesting things to note in this study:

• Only 10 Long Covid patients, 10 controls, and 40 ME patients included (half with POTS), so it's a small study.
• "There were no significant differences in ME/CFS symptom prevalence between the long-haul COVID-19 patients and the ME/CFS patients."
• "All long-haul COVID-19 patients developed POTS during [head-up tilt testing]."
• "The cerebral blood flow reduction was larger in the long-haul COVID-19 patients [with POTS] compared with those ME/CFS patients [who did not have POTS]."
• "Conclusions: The symptoms of long-haul COVID-19 are similar to those of ME/CFS patients, as is the response to tilt testing."

P.S.

(This article belongs to the Special Issue Chronic Fatigue Syndrome: From Clinical Observations to Unifying Hypotheses of Disease Mechanisms)

 

[Pyrrhus]

"The cerebral blood flow reduction was larger in the long-haul COVID-19 patients [with POTS] compared with those ME/CFS patients [who did not have POTS]."

In my opinion, this is the most interesting finding. It suggests that people who develop tachycardia during orthostatic intolerance (POTS) may have worse loss of blood flow to the brain than those who do not get tachycardia with their orthostatic intolerance...

 

[Pyrrhus]

Related studies from these authors:

Cerebral Blood Flow Is Reduced in Severe ME/CFS during a 20 degrees head up tilt test (Van Campen et al 2020)
https://forums.phoenixrising.me/thr...ead-up-tilt-test-van-campen-et-al-2020.80444/

Reductions in Cerebral Blood Flow Can Be Provoked by Sitting in Severe Myalgic Encephalomyelitis... (Van Campen et al. 2020)
https://forums.phoenixrising.me/thr...ncephalomyelitis-van-campen-et-al-2020.81574/

ME/CFS Patients with Joint Hypermobility Show Larger Cerebral Blood Flow Reductions during Orthostatic Stress Testing... (van Campen et al., 2021)
https://forums.phoenixrising.me/thr...c-stress-testing-van-campen-et-al-2021.84635/

Deconditioning does not explain orthostatic intolerance in ME/CFS (van Campen, Rowe, and Visser, 2021)
https://forums.phoenixrising.me/thr...me-cfs-van-campen-rowe-and-visser-2021.83831/

 

[SWAlexander]

Here is another:
The Reduced Brain Blood Flow Diseases? Long COVID, ME/CFS and POTS
Excerpt:
“Orthostatic Symptoms and Reductions in Cerebral Blood Flow in Long‐Haul COVID‐19 Patients: Similarities with Myalgic
Encephalomyelitis/Chronic Fatigue Syndrome” – contained 60 chronic fatigue syndrome (ME/CFS with POTS and without), and long COVID patients, and healthy controls – focused on two critically important factors: orthostatic intolerance and blood flows to the brain.

While only 10 long haulers were assessed there was no picking and choosing, no plucking out the most severe cases, no thumbs being placed on any scales – the group simply put the first 10 long haulers seen in their clinic into their study. All the patients – both the long COVID and the ME/CFS patients – in the study fulfilled the IOM criteria for chronic fatigue syndrome.

They assessed symptoms, then vaulted the participants upon a tilt table, and watched their cardiovascular systems attempt to adjust.

The symptom sets of the two groups were almost identical, with the long COVID group having a slight edge in severity. The group certainly tried to pry the groups apart but even an analysis of 21 different symptom clusters found in the Fukuda, Canadian Criteria, and IOM criteria, found no difference in symptoms between the long COVID and ME/CFS patients (with or without POTS).

Only hypersensitivity to foods and/or chemicals was more common in the ME/CFS group – perhaps suggesting that the hypersensitivity issues tend to show up later.

https://www.healthrising.org/blog/2021/12/26/brain-blood-flows-long-covid-me-cfs-pots/

 

[BrightCandle]

I don't think many ME/CFS patients will be surprised to find out they are identical diseases. I think a lot of long haulers may be dismayed by the news however because they maintain the hope that they will just recover as many have already done so.

I will never forget how the medical community split these two parties apart and reserved drugs and treatments for just one set of patients while the other is still exercised to worse disease.

 

[Violeta]

This may, in some cases, be related to H-P-A axis involvement. COVID is thought to affect the hypothalamus.

The present article reviews the possible routes and mechanisms of neuroinvasion of SARS-CoV-2, with a specific focus on the role of the hypothalamic circuits in mediating the neurological symptoms noted during COVID-19 infection.

https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8002703/

 

[Pyrrhus]

The present article reviews the possible routes and mechanisms of neuroinvasion of SARS-CoV-2, with a specific focus on the role of the hypothalamic circuits in mediating the neurological symptoms noted during COVID-19 infection.

https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8002703/

That's certainly an interesting one. Here's the full abstract:

COVID-19 and Neurological Impairment: Hypothalamic Circuits and Beyond (Mussa et al., 2021)

In December 2019, a novel coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, the capital of Hubei, China. The virus infection, coronavirus disease 2019 (COVID-19), represents a global concern, as almost all countries around the world are affected.

Clinical reports have confirmed several neurological manifestations in COVID-19 patients such as headaches, vomiting, and nausea, indicating the involvement of the central nervous system (CNS) and peripheral nervous system (PNS). Neuroinvasion of coronaviruses is not a new phenomenon, as it has been demonstrated by previous autopsies of severe acute respiratory syndrome coronavirus (SARS-CoV) patients who experienced similar neurologic symptoms.

The hypothalamus is a complex structure that is composed of many nuclei and diverse neuronal cell groups. It is characterized by intricate intrahypothalamic circuits that orchestrate a finely tuned communication within the CNS and with the PNS. Hypothalamic circuits are critical for maintaining homeostatic challenges including immune responses to viral infections. The present article reviews the possible routes and mechanisms of neuroinvasion of SARS-CoV-2, with a specific focus on the role of the hypothalamic circuits in mediating the neurological symptoms noted during COVID-19 infection.

 

[Violeta]

That's certainly an interesting one. Here's the full abstract:

COVID-19 and Neurological Impairment: Hypothalamic Circuits and Beyond (Mussa et al., 2021)

Yes, what to do, though, right?

 

[Violeta]

The adrenergic receptors in the hypothalamus control blood pressure.

"The study was made with the help of a chemitrode placed in various areas of the hypothalamus by the stereotaxic technique, for electrical and chemical stimulation (noradrenaline or isoprenaline) before and after microinjection of respective blockers (phenoxybenzamine or practalol). The results indicated the presence of both alpha and beta-adrenoreceptors in the anterior and dorsomedial hypothalamus producing a depressor response, and, the presence of alpha adrenoreceptors in the posterior and lateral hypothalamus producing a pressor response."

https://pubmed.ncbi.nlm.nih.gov/6122645/

 

[Violeta]

This is interesting. "Subacute sepsis results in an early suppression of maximum contractile force despite an increase in adrenergic receptor sensitivity (pD2). This may be secondary to an elevation in dilator sensitivity combined with a direct effect of sepsis on VSM contractile mechanisms. Later in the septic process, however, alpha-adrenergic hyporesponsiveness ( downward arrow Fmax) is primarily due to changes in VSM contractile machinery."

https://pubmed.ncbi.nlm.nih.gov/10210646/

 

[Violeta]

Post COVID sepsis symptoms:

• Difficulty sleeping, either getting to sleep or staying asleep.
• Fatigue, lethargy.
• Shortness of breath, difficulty breathing.
• Disabling muscle or joint pain.
• Swelling in the limbs.
• Repeat infections, particularly in the first few weeks and months following the initial bout of sepsis.
• Poor appetite.

 

[Violeta]

This is interesting. "Subacute sepsis results in an early suppression of maximum contractile force despite an increase in adrenergic receptor sensitivity (pD2). This may be secondary to an elevation in dilator sensitivity combined with a direct effect of sepsis on VSM contractile mechanisms. Later in the septic process, however, alpha-adrenergic hyporesponsiveness ( downward arrow Fmax) is primarily due to changes in VSM contractile machinery."

https://pubmed.ncbi.nlm.nih.gov/10210646/

So suppose one is constantly in a state of subacute sepsis, septic shock may not occur, but a lesser chronic state.

Endothelial dysfunction in sepsis
https://pubmed.ncbi.nlm.nih.gov/23506494/

Finally, we summarize the potential mechanisms by which H2S may contribute to vascular dysfunction in shock and show an example of how the vascular response to H2S is altered in a rat model of endotoxemia.
https://pubmed.ncbi.nlm.nih.gov/23506499/

 

[SWAlexander]

Repeat infections, particularly in the first few weeks and months following the initial bout of sepsis.

Violeta, that is very interesting - this is what I feel - constant reinfection after sepsis and all "Post COVID sepsis symptoms". Thank you for posting.

 

[Pyrrhus]

So suppose one is constantly in a state of subacute sepsis, septic shock may not occur, but a lesser chronic state.

Endothelial dysfunction in sepsis
https://pubmed.ncbi.nlm.nih.gov/23506494/

That's a really interesting one, thanks for sharing.

Perhaps not directly related to this thread, but it might deserve its own thread, or it can be added to:

Endothelial Dysfunction in ME
https://forums.phoenixrising.me/threads/endothelial-dysfunction-in-me.83521/

 

[Violeta]

That's a really interesting one, thanks for sharing.

Perhaps not directly related to this thread, but it might deserve its own thread, or it can be added to:

Endothelial Dysfunction in ME
https://forums.phoenixrising.me/threads/endothelial-dysfunction-in-me.83521/

Thanks for all you do here.

 

[SWAlexander]

Looks like daily new or overlooked findings rolling in.
Here is another one:
Impaired systemic oxygen extraction long after mild COVID-19: potential perioperative implications
Excerpt:
A central focus of perioperative management has always been maintenance of systemic oxygen delivery (DO2) and tissue perfusion. Toward this end, research has defined how the fundamental relationships between DO2, tissue oxygen consumption (VO2), and oxygen extraction (EO2) shift from the intraoperative setting where VO2 tends to be reduced, to the postoperative period when VO2 increases5. Although a range of postoperative complications has been linked to suboptimal tissue DO26, 7, the incidence of these complications appears relatively low in relation to the documented incidence of perioperative hypoxaemia8, 9, particularly when considered in light of potential coincidence with other common factors such as anaemia, hypovolaemia, and transient hypotension. A contributing factor may be that, as with most physiological systems, evolutionary pressure has yielded compensatory mechanisms for reduced DO2 to many organs. Under most circumstances, when DO2 is low, VO2 is maintained by augmented EO2 to prevent tissue hypoxia10. This compensatory EO2 reserve persists until limits that vary among tissue beds are reached and VO2 becomes DO2-dependent. Ultimately, in the perioperative setting where alterations in regional VO2/DO2 balance occur with regularity it is probable that this EO2 reserve is working continuously ‘behind the scenes’ for organ protection.
https://www.sciencedirect.com/science/article/pii/S0007091221008564
EO2 = oxygen Extraction percentage
DO2 = oxygen Delivery
VO2 = oxygen consumption [transport Volume]

Viruses as Modulators of Mitochondrial Functions
Abstract
Mitochondria are multifunctional organelles with diverse roles including energy production and distribution, apoptosis, eliciting host immune response, and causing diseases and aging. Mitochondria-mediated immune responses might be an evolutionary adaptation by which mitochondria might have prevented the entry of invading microorganisms thus establishing them as an integral part of the cell. This makes them a target for all the invading pathogens including viruses. Viruses either induce or inhibit various mitochondrial processes in a highly specific manner so that they can replicate and produce progeny. Some viruses encode the Bcl2 homologues to counter the proapoptotic functions of the cellular and mitochondrial proteins. Others modulate the permeability transition pore and either prevent or induce the release of the apoptotic proteins from the mitochondria. Viruses like Herpes simplex virus 1 deplete the host mitochondrial DNA and some, like human immunodeficiency virus, hijack the host mitochondrial proteins to function fully inside the host cell. All these processes involve the participation of cellular proteins, mitochondrial proteins, and virus specific proteins. This review will summarize the strategies employed by viruses to utilize cellular mitochondria for successful multiplication and production of progeny virus.
https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC3821892/

 

[SWAlexander]

https://twitter.com/TheWHN
Dec 16

#LongCovid is like other debilitating chronic diseases, including autonomic dysfunction and post exertion flares
@TheWHN
Global Summit Amy Proal, Phd
@microbeminded2
reviews some symptoms of #longcovid.

https://twitter.com/i/web/status/1471561294327291914

 

[SWAlexander]

Long Covid breakthrough from South African scientists

South African researchers from the University of Stellenbosch may have determined the cause behind long Covid.

Physiological sciences professor Etheresia Pretorius and her team found that an excess of inflammatory molecules inside microscopic blood clots could cause some long Covid symptoms.

The team published their research in the journal Bioscience Reports.

According to Pretorius, Covid-19 impacts the circulation system of patients in addition to the adverse effects it has on the respiratory system.

“Acute Covid-19 is not only a lung disease but actually significantly affects the blood flow and blood clotting systems,” she told the Sunday Times.

“A recent study in my lab revealed that there is significant microclot formation in the blood of both acute Covid-19 and long Covid patients,” she said.
More at: https://mybroadband.co.za/news/scie...eakthrough-from-south-african-scientists.html