Understanding Long COVID; Mitochondrial Health and Adaptation—Old Pathways, New Problems 2022, Nunn et al

Abstract:
Many people infected with the SARS-CoV-2 suffer long-term symptoms, such as “brain fog”, fatigue and clotting problems. Explanations for “long COVID” include immune imbalance, incomplete viral clearance and potentially, mitochondrial dysfunction.

As conditions with sub-optimal mitochondrial function are associated with initial severity of the disease, their prior health could be key in resistance to long COVID and recovery. The SARs virus redirects host metabolism towards replication; in response, the host can metabolically react to control the virus.

Resolution is normally achieved after viral clearance as the initial stress activates a hormetic negative feedback mechanism. It is therefore possible that, in some individuals with prior sub-optimal mitochondrial function, the virus can “tip” the host into a chronic inflammatory cycle. This might explain the main symptoms, including platelet dysfunction.

Long COVID could thus be described as a virally induced chronic and self-perpetuating metabolically imbalanced non-resolving state characterised by mitochondrial dysfunction, where reactive oxygen species continually drive inflammation and a shift towards glycolysis. This would suggest that a sufferer’s metabolism needs to be “tipped” back using a stimulus, such as physical activity, calorie restriction, or chemical compounds that mimic these by enhancing mitochondrial function, perhaps in combination with inhibitors that quell the inflammatory response.

https://www.mdpi.com/2227-9059/10/12/3113

 

I have read anecdotes by many people online who were fit and healthy athletes before they got Covid, and have never recovered. Prior health can't explain the Long Covid symptoms of people like that.

 

I don't think there is a reason to think any of this is "sub-optimal", mitochondria may in fact be doing what they need to be doing, because of an upstream cause, as all illness is. No reason to think the terrible exhaustion from acute illness is fundamentally different than when it is chronic, and that the immune system is actually being very optimal here.

And yeah anyone who's still with the prior health meme or thinks that exertion is a solution here has clearly not done their homework and should simply be ignored. Ignoring reality is a terrible way to solve real problems. It's also terrible at solving fake problems, but it's especially bad at solving real ones.

 

It upsets me when people say they were athletes “before”, almost as if not being an athlete prior to infection means that any resulting ill health is all ‘our own fault’.

Whilst not an athlete, in 2013, I was probably at one of the fittest times of my life (despite a previous brush with PVFS and a healthy attitude to pacing):

I ran a house with 2 teenagers, with all the necessary driving around that involves, all school meetings, was a member of the PTA;
I worked PT a 28 hour Week (technical & quasi legal work), commuting to work 4 days a week with the drive varying from 30 (home)-70 (morning rush hour) mins each way;
I attended a monthly Village History group (and, in addition, volunteered to transcribe legal documents);
Volunteered to assist with a Village Green application
Weekly Pilates class
Weekly dance class
Weekend walks
Oh and we had adopted Happy Hound, who was equally happy to have a meander around the block or sleep on his sofa.

With hindsight, my grasp on pacing that year was pretty poor. I now realise that various symptoms plus about 7 uti’s in one year were warning signs, but it was the non recovery from Sepsis which finally gave me the ME/CFS diagnosis.

 

I've never taken that interpretation from anyone's experiences of Covid or other disease, and any after-effects, short or long-term.

 

When people say this, I take it this way. They're trying to dispel the psychosomatic notion that they're hypochondriacs, deconditioned, or afraid of exerting themselves. If the BPS model was true, we'd basically never see athletes get ME.

 

Indeed. And if they have for example a running time before getting whatever trigger that is known as fast + were completing a training regime then went to struggling to recover from half a day of working it is a pretty easy way of describing the 'cliff'.

In fact athletes will get colds, flus and other issues and be used to taking time out then getting back on the horse and it taking some time to get to where you were - but literally notice a stark difference in how their body operates all of a sudden. If you imagine the 2-day CPET being indicative then those who train (and normally as part of this use some sort of stats and measures) would have noticed this was a 'night and day' issue and not 'fatigue'.

They might have done nothing else other than been athletes and well-rested otherwise, or been busy bees like others, but the reason they note that part is because of what we all now know about PEM and recovery and 'not being able to get fitter' etc being most experimentally observable in these instances for them.

In this instance it was mentioned because of the insinuation in the article being easiest to debunk by noting that a lot of those with long covid who had the type which wasn't 'bad covid' (which shouldn't really be mixed up with the sample without a marker if they were hospitalised necessarily) but became the ME type had been things like fitness trainers. Who might have also thought before covid came along that a bit of pushing through or activity would help ME. Because that's the mindset athletes often have to 'get fitter', so it must have really confounded them when it didn't work (and also happens to be another rebuke for any suggestion of GET if its 'biggest fans' tried it and now have to speak out).

 

Also, we wouldn't even be talking about this if it wasn't for the accusations of laziness and the myth of deconditioning, hardly anyone would feel the need to emphasize it. It's in response to those false accusations that it's said so often. But the accusations and myths are all there is about this model, so countering them is a daily necessity that is simply endless, as those illnesses will never stop as long as they're denied.

So it's the ideologues who force this endless debate. Blame has to be set straight.