Covid, cholesterol and mitochondria

I will start this post with some one-line statements that are not controversial, simply collated recent published work from around the globe..:

In Covid infected patients showing an inflammatory response that led to hospitalisation, here are the following observations regarding mitochondria.:

• Mitochondrial DNA was present in plasma. This is known to trigger inflammation.
• Monocytes are found to have mitochondria that are depolarised and have altered morphology
•  In cells infected with Covid, oxidative respiration is low and anaerobic glycolysis predominates.
• Patients with severe infection may enter hospital with very low oxygen saturation but still be walking … a sign of glycolysis. Compromised lungs could not supply mitochondria with operational levels of oxygen even if the mitochondria were operational.
• Covid viral reproduction takes place within the mitochondria in a manner analogous to phage infection of bacteria

In Covid infected patients like those describe above the lipid profile ( lipidome) is affected as follows:

• Total lipids are reduced by infection. Increasing severity of infection maps to larger reductions.
• For patients that eventually do not survive, the decrease in lipid levels continues until death
• Patients entering treatment with low lipid levels at the start show markedly sharper fall in lipid levels than those with higher starting levels..
• The main lipids lowered by infection are cholesterol, LDL and HDL ... in that order.
• Lipid lowering medication is associated with weight gain and an increase in Type 2 diabetes (obesity and diabetes are associated with poor infection outcomes).
• Vitamin D deficiency is associated with severe symptoms (Vit D is synthesised from cholesterol).

• Use of lipid lowering drugs reached 49% in the over 80s by 2015.

I apologize for not citing the wide range of researchers in labs who have  produced these results within the past year but reading their papers is as interesting for the inter alia text other than the plain findings.

In the first set of results, the conclusion is rightly drawn that mitochondrial damage is very serious but it is hard to fathom a proposed therapy to mitigate it. One finding of low levels of CoQ10 elicited a suggestion that Q10 supplementation may help as it is a well known ‘go-between’ for anaerobic and aerobic respiration.  This is not surprising as few are proposing any mitochondrial ‘well being’ strategies currently

In the second set of results something sad is occurring. Manifestly the lowering of lipid levels is important in the progression of the disease but none of the authors could bring themselves to say that lipid lowering medication should be stopped, quite the opposite they state it should be continued!

This  is astonishing, and as I said above very sad. Clearly  medication used to lower cholesterol and LDL should be considered as something to stop in the light of the evidence above. 

The answer as to why not is I think as follows:

Many, maybe most people, who are capable of reasoning in the logical and rational sense along with those who are frankly not able to do so can fall back onto what is called ‘thematic reasoning’. A term, thirty years ago with which I was not familiar but was explained clearly by a politician ( whose name I don't recall) is the principal mode of thinking of the ‘voting public’. 

Thematic reasoning is simple; bad things cause bad things and vice versa. So for example in a survey on the causes of global warming ( a bad thing ) a random sample of the public were asked which of the following power generation systems caused global warming?  Gas fired power; coal fired power, nuclear power or wind power. Ans? Overwhelmingly the answer was ‘nuclear power’. Wrong of course but obvious in the thematic world, nuclear power is ‘bad’, global warming is bad and  ‘bad ‘causes ‘bad’.

And so it is with cholesterol. The ‘baddest’ of the bad in dietary terms. What lowers cholesterol? Statins, the life saving ‘good guys’ .  Nothing trumps the ‘badness’ of cholesterol in popular mythology and no-one dares challenge the ‘goodness’ of statin therapy.  

I think this must stop. 

Below is some abstracted material from my PhD thesis of forty years ago. We had a very rare colony of 300 rats that spanned the full life of a rat … 0 to 36 months. These colonies are long gone so some of our experiments will never be repeated. We worked on liver mitochondria.

I showed that the composition of the mitochondrion’s outer membrane reflected the levels of dietary cholesterol although as expected this did not occur for the inner membrane. 

In both old and young rat liver mitochondria cholesterol-enriched outer membranes produced less exogenous  Cytochrome C  under osmotic shock treatment than did untreated mitochondria. 

I had already shown that old mitochondria released more Cytochrome C than did young mitochondria and speculated that this was because the outer membrane was providing less of a barrier to the Cytochrome and /or that Cyt C was bound more weakly to the inner membrane.

In 1975 I was unaware that Cytochrome C was the mitochondrial signal to initiate the cascade of events leading to cell death or apoptosis as it is properly known.

 But to me now, and it has been so obvious for so many years, that low cholesterol levels risk compromising mitochondrial function by making the outer-membrane: 

a) leakier (risking apoptosis), 

b) less absorbent of free radicals (Increasing cellular damage).

So, if you have got this far, it will not be a surprise to anyone that I am convinced that cholesterol levels are important to mitochondrial health. Judging by the levels of current de-prescription of lipid lowering drugs in the over 75s, I am also convinced that the science community knows too.

update: December 2021

Below is a link to a mini-review on the relationship of Covid with mitochondria. It is worth reading.

Front. Pharmacol., 28 August 2020 | https://doi.org/10.3389/fphar.2020.578599

Mitochondria Targeted Viral Replication and Survival Strategies—Prospective on SARS-CoV-2

Priya Gatti, Hema Saranya Ilamathi, Kiran Todkar and Marc Germain1Groupe de Recherche en Signalisation Cellulaire and Département de Biologie, Médicale, Université du Québec à Trois-Rivières, Trois-Rivières, QC, Canada

2Centre d’Excellence en Recherche sur les Maladies Orphelines - Fondation Courtois, Université du Québec à Trois-Rivières, Trois-Rivières, QC, Canada

Covid 19 appears to actively target mitochondria and the parts of the smooth endoplasmic reticulum associated with the outer mitochondrial membrane. Like many cancer cells do, the virus down-regulates mitochondrial respiration and the cell-death cascade that mitochondria initiate to destroy malfunctioning cells.  

This tactic allows cancer cells to evade their destruction (which would be signalled by mitochondria) whilst having enough glycolytic energy to divide, and similarly viruses use the same tactic to buy time while they reproduce themselves. The phenomenon of 'living dead' walking into hospitals with incredibly low oxygen levels is clearly part of the story of deactivated mitochondria.

However, mitochondria are not silenced completely. A massive viral infection will set off a great amount of  mitochondrially-mediated cell death which can be seen in the massive sarcopenia in ICU Covid patients.

Once again mitochondria take centre stage and once again their well being is central.