Redox imbalance links COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome, 2021, Paul, Komaroff et al

Abstract

Although most patients recover from acute COVID-19, some experience postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC). One subgroup of PASC is a syndrome called “long COVID-19,” reminiscent of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS is a debilitating condition, often triggered by viral and bacterial infections, leading to years-long debilitating symptoms including profound fatigue, postexertional malaise, unrefreshing sleep, cognitive deficits, and orthostatic intolerance.

Some are skeptical that either ME/CFS or long COVID-19 involves underlying biological abnormalities. However, in this review, we summarize the evidence that people with acute COVID-19 and with ME/CFS have biological abnormalities including redox imbalance, systemic inflammation and neuroinflammation, an impaired ability to generate adenosine triphosphate, and a general hypometabolic state. These phenomena have not yet been well studied in people with long COVID-19, and each of them has been reported in other diseases as well, particularly neurological diseases.

We also examine the bidirectional relationship between redox imbalance, inflammation, energy metabolic deficits, and a hypometabolic state. We speculate as to what may be causing these abnormalities. Thus, understanding the molecular underpinnings of both PASC and ME/CFS may lead to the development of novel therapeutics.

Open access: https://www.pnas.org/content/118/34/e2024358118

 

Potential Redox-Based Therapeutics
Several therapies targeting redox imbalance already have been utilized or proposed for the treatment of disease. NO inhibits the replication of SARS-CoV-2 in vitro (154) and improves oxygenation in people with COVID-19 when administered by inhalation (155). Small studies of ubiquinol (156) and of a combination of NADH and CoQ10 (157) have reported clinical benefit. Many other potential treatments targeting redox imbalance also deserve consideration: for example, glutathione (and glutathione donors), N-acetyl cysteine, cysteamine, sulforaphane, ubiquinol, nicotinamide, melatonin, selenium, vitamin C, vitamin D, vitamin E, melatonin plus pentoxyfylline, disulfiram, ebselen, and corticosteroids. In two cases of acute COVID-19, glutathione administered therapeutically counteracted dyspnea associated with COVID-19 pneumonia and reduced pulmonary inflammation (158).

In rodents, administering H2S donors reduced inflammation and oxidative stress and attenuated ventilator-induced lung injury as well as injury induced by pneumonia (159, 160). In addition, the H2S donor, GYY4137, suppressed replication of enveloped RNA viruses like SARS-CoV-2 (161⇓–163). Additionally, the H2S donor, sodium hydrosulfide, inhibits platelet activation, NET formation, DNA, and ROS levels while decreasing SOD in the hyperhomocysteinemia (HHcy) group (164). Thus, treatment of acute COVID-19 with H2S donors may be efficacious (165).

A screen for inhibitors of the main protease of SARS-CoV-2 identified ebselen, an organoselenium compound, as a potential inhibitor for the protease, Mpro or NSP5, and a therapeutic agent for COVID-19 (166, 167).

In general, however, oral therapies directed at restoring redox balance have not produced dramatic improvements in conditions associated with redox imbalance (168). No single antioxidant can scavenge or neutralize the wide variety of ROS and RNS singlehandedly. Hence, up-regulating pathways that counteract multiple abnormalities and bolster antioxidant defense and balance may be more beneficial. The timing of intervention may also be critical.

 

It is very interesting looking into NETs (Neutrophil Extracellular Traps) part of this. Seems to play a major role in infections, auto immunity and cancer. A new and promising field worth looking into.

 

Review highlights similarities between long COVID and chronic fatigue syndrome

https://www.news-medical.net/news/2...-long-COVID-and-chronic-fatigue-syndrome.aspx

 

New Atlas Long COVID and chronic fatigue syndrome share striking similarities

The article is also shared on the thread "Possibility of ME or PVFS after Covid-19, Long Covid" here

 

An article on a Danish news site about research explores whether Long Covid and ME is the same thing based on this paper with comments from two experts - one agreeing, one disagreeing.

Videnskab.dk Forskere spekulerer: Er corona-senfølger og kronisk træthedssyndrom (ME) det samme?
google translation: Researchers wonder: Are corona late effects and chronic fatigue syndrome (ME) the same?

quote:
The way you take samples and the way you store and analyze the samples have a huge impact on the result. You really have to be aware of this when comparing results from different studies, Ivan Brandslund explains.

“For example, when you take a blood sample, the cells in the blood stop removing waste products. So it needs to be frozen right away. These samples are so sensitive that abnormalities in the cells, which look the same, may be due to the way the samples were taken and stored, «Ivan Brandslund explains.

So you will have to design a completely new study with the specific purpose of investigating whether the cell disorders are similar in the two conditions.

According to Ivan Brandslund, such a study will have to be international in order to get enough patients to be able to conclude something. Simply because both late sequelae and ME are so relatively rarely a phenomenon.

"It may be true that the symptoms are the same, but basically we still need to find out both what is wrong with the patients and then whether it is the same," he says.

 

Dr Les Simpson from New Zealand found that red blood cells in his ME patients were deformed. He examined fresh blood. Other groups tried to replicate his results but did not find any deformities. They used stored blood where the shape of the cells could have been changed by the preservatives used.

Another piece of research into ME which was neither proved nor disproved just dropped.

 

Review by Tony Komaroff.

"ME/CFS is defined exclusively by symptoms—subjective experiences that are hard to verify by objective testing. For that reason, since interest in ME/CFS began to grow in the 1980s, scientists have been looking for evidence of underlying objective abnormalities that might explain the symptoms.

A recent review, published August 24, 2021, in the Proceedings of the National Academy of Sciences USA, summarizes in detail the evidence demonstrating one of the several objective abnormalities in people with ME/CFS and acute COVID-19: redox imbalance.1 It speculates that redox imbalance may also be present in post-acute COVID-19 syndrome, or “long COVID-19”, although this remains to be studied."

https://cfsformecfs.org/2021/09/15/redox-imbalance-a-core-feature-of-me-cfs-and-acute-covid-19/