Long COVID and the Neuroendocrinology of Microbial Translocation Outside the GI Tract: Some Treatment Strategies 2022 Sfera et al

Abstract
Similar to previous pandemics, COVID-19 has been succeeded by well-documented post-infectious sequelae, including chronic fatigue, cough, shortness of breath, myalgia, and concentration difficulties, which may last 5 to 12 weeks or longer after the acute phase of illness.

Both the psychological stress of SARS-CoV-2 infection and being diagnosed with COVID-19 can upregulate cortisol, a stress hormone that disrupts the efferocytosis effectors, macrophages, and natural killer cells, leading to the excessive accumulation of senescent cells and disruption of biological barriers.

This has been well-established in cancer patients who often experience unrelenting fatigue as well as gut and blood–brain barrier dysfunction upon treatment with senescence-inducing radiation or chemotherapy.

In our previous research from 2020 and 2021, we linked COVID-19 to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) via angiotensin II upregulation, premature endothelial senescence, intestinal barrier dysfunction, and microbial translocation from the gastrointestinal tract into the systemic circulation.

In 2021 and 2022, these hypotheses were validated and SARS-CoV-2-induced cellular senescence as well as microbial translocation were documented in both acute SARS-CoV-2 infection, long COVID, and ME/CFS, connecting intestinal barrier dysfunction to disabling fatigue and specific infectious events.

The purpose of this narrative review is to summarize what is currently known about host immune responses to translocated gut microbes and how these responses relate to fatiguing illnesses, including long COVID.

To accomplish this goal, we examine the role of intestinal and blood–brain barriers in long COVID and other illnesses typified by chronic fatigue, with a special emphasis on commensal microbes functioning as viral reservoirs.

Furthermore, we discuss the role of SARS-CoV-2/Mycoplasma coinfection in dysfunctional efferocytosis, emphasizing some potential novel treatment strategies, including the use of senotherapeutic drugs, HMGB1 inhibitors, Toll-like receptor 4 (TLR4) blockers, and membrane lipid replacement.

https://www.mdpi.com/2673-396X/3/4/58

 

At this point, I can't escape to notice that what people mean by anxiety or stress, especially as a medical concept, explicitly means: things people don't like. Could be pain, working a bad job, having limited options, being pushed around or generally doing things people don't enjoy. I've been looking at it this way for weeks and it's a perfect substitution.

Illness is not enjoyable. It's a terrible experience, in fact. To label it as stressful is equivalent to disliking what it does. The illness experience, losing on normal life, often loss of income or obligations that pile up. All unpleasant experiences. An accumulation of unpleasant experiences is almost perfectly equivalent to how stress is used generally and in medical terms.

Meanwhile the "treatments" are all things people generically enjoy and the common factor in those is not doing unpleasant things: listening to music people enjoy, walking in forests, a good discussion with friends. Those are all good things, presented as the solution to "anxiety" and "stress", which mostly amount to things people dislike.

Stress can be more or less replaced with exertion without losing much meaning, but it has to be unpleasant. That's why recreational exercise is pleasant, and hard physical labor isn't. They're both exertion, but one is pleasant and done by choice, the other is not an option. If exercise were the answer, hard physical labor would do the same, so everyone working in hard physical jobs should be the least "stressed" people out there. And of course they aren't, because they have no choice to do this hard labor. So it's nothing to do with exertion, or exercise, it's about enjoyment, hence recreational.

Our entire culture is built around being forced to do unpleasant things, and explicitly leaving most people with as little enjoyable time as possible. Other than neglected illness, IMO this basically amounts to 95%+ of what people call mental health, stress or anxiety. And sometimes the "treatment" actually involves doing unpleasant things, like getting people to work ASAP, or forcing them to do things they don't like.

But in almost all circumstances, there is a perfect substitution with being forced to do things people dislike or don't want to do. People enjoy free time, having fulfilling lives, experiencing things. Most people can't enjoy that, because of how we built our entire societies to force people into misery so they have no choice to work and do things they dislike or even hate.

And since the definitions are basically one giant blur, this likely also applies for most of what is labeled depression, with the usual whatever is left out of that is simply health issues medicine doesn't understand yet and usually neglects.

Ironically a lot of that was revealed over the whole panic over lockdowns, the way we all live, as something too "stressful", when really it was simply that people weren't enjoying what little they normally can, since most of life consists of obligations and having to do things whether we want to or not.

And of course it's OK to dislike things. But if people stopped doing things they hate, most of the work that makes society function would cease. So instead medicine invented a bunch of myths that pathologized normal behavior. Two wrongs, expecting a right. Foolish stuff.

 

When it comes to Covid 19 and especially Long Covid Anxiety also refers to a racing heart beat, which has an anxious uncertain feeling about it when its inappropriate to the activity level. Our brain interprets that signal of 120 bpm while laying down and 180 bpm when standing as concerning and abnormal. None of the recreational things is going to help with Dysautonomia of this type and neither is any form of talk therapy, its not being driven by the patients thoughts its being driven by something in the body that has gone quite wrong.

There is also the flight/fright system with inappropriate adrenaline which also seems to be kicked off in early ME/Cfs and also in Long Covid, that also gives a fluttery anxious sensation but its a different feeling to the heart rate. Having gone through both I am acutely aware of what these felt like, they feel a little like a concerning social environment with that sort of butterflies feeling but amped up to 11 and they originate completely differently its not something you are forcing yourself into with concern its something happening to you that is concerning.

 

I can't really see a fast heart rate as having anything to do with "anxiety". Exercise/exertion increase heart rate. Too much caffeine. Sepsis. Epinephrine injection. Lots of stuff increases heart rate in ways that have nothing to do with any feelings. It's usually a response to exertion, to an increased demand in energy.

Or if we're equating epinephrine with anxiety, then it basically means nothing. There are just many different things here, it's just a mixed bag of lots of different things labeled incorrectly over a long time. It's just a crude explanation for many complex things that mostly don't have much to do with each other.

 

The previous work mentioned in the abstract may be this:

https://www.s4me.info/threads/endot...d-19-based-hypothesis-2021-sfera-et-al.21465/