COVID Notes: Mitochondrial Hypoxia

I began writing this post in April of 2020 as a part of a much larger post on COVID and never finished it. I am publishing it now in its unfinished state in the hopes that others might be inspired to pick up where I left off. Although the current hypothesis regarding COVID morbidity and mortality involves micro-coagulopathies believed to emanate from platelet dysfunction, based upon my research, I contend that mitochondrially driven hypoxia cascades are still responsible. I will publish some thoughts on this in a subsequent post. For now, consider the role of molecular hypoxia as a key component of COVID complications.

Mitochondrial Energy Failure

When one has a hammer, everything becomes a nail. My hammer, my framework for understanding every illness, is mitochondrial function. Mitochondria, because they produce cellular energy (ATP), the single most important, non-negotiable requisite for survival, sit at the nexus of health and disease. Absent the ability to produce sufficient ATP, death is imminent. We are seeing this play out on a large scale with the coronavirus (COVID-19). The progression and patterns of illness reported associated with COVID mortalities share striking similarities with what might be deemed an energy failure, where mitochondria initiate every tool in their armament to fight the battle but have not the resources to contain the threat or manage the consequences of such a brutal battle, and so instead, are forced to withdraw, shut down, and slowly die off.

The key pathology of COVID, acute respiratory distress syndrome (ARDS), the one responsible for all of the morbidity and much of the mortality associated with COVID, can be linked directly to mitochondrial failure, as can many of the associated pathologies attributed to the COVID disease process itself. Inasmuch as these same processes also develop with other viral, bacterial, or fungal agents, it suggests that while COVID is undoubtedly unique in its structure, its mechanisms, and its virulence compared to other pathogens, this uniqueness may not be the only variable to address. If entirely different pathogens or stressors can cause similar response patterns, then perhaps it is not the uniqueness of the pathogen that matters as much as the strength and agility of the individual response. That is, perhaps the host response contributes, if not more, at least equally, to pathogenicity. Perhaps distinctions in host response offer more salient clues about surviving this or any other threat than the endless taxonomy of distinctions between threats. And finally, perhaps the use of mechanical ventilation as the treatment option has become medicine’s hammer for too many nails.

Ever since this pandemic began, I have suspected that the respiratory distress syndrome developing with COVID was related more to mitochondrial failure than any mechanical problems with respiration for which the ventilators are designed. Indeed, I suspect that given the high mortality rates associated with mechanical ventilation of any cause, 30-45% according to pooled data, in a good portion of these cases, we have missed a key variable. I think at the root of these deaths and the severity of COVID is molecular hypoxia. Molecular hypoxia emanates not from obstruction, though obstructive fibrosis and fluid build-up may develop later, but from the bottom up; from the inability to utilize O2 in the mitochondria, and thus, efficiently produce ATP. This then initiates a host of self-reinforcing cascades that lead to poor blood oxygenation, sometimes perceived as ‘air hunger’ by patients and often correspondent to an altitude sickness-like effect.

I believe that molecular hypoxia is also responsible for the deregulated immune and inflammatory responses noted in COVID and in a long list of other conditions, many of which impact COVID severity. I believe that molecular hypoxia is both the cause and consequence of disrupted iron homeostasis, as well as the seemingly chaotic autonomic response, the progressive fibrotic and fluid build-up in the lungs, and finally, death by either by a sepsis-like syndrome that leads to multi-organ failure or cardiac arrest. With regard to heart function, it should be noted that disparate or inconsistent ATP availability affects rate and rhythm both in the cardiomyocytes themselves but also via the brainstem with chaotic autonomic nervous system (ANS) signals. In other words, with mitochondrial collapse, death happens by a thousand possible cuts.

What Causes Mitochondrial Collapse?

We like to think of mitochondria as these magical black boxes that provide sufficient ATP no matter what we throw at them. Most of us were taught, absent outright starvation or ‘rare’ mitochondrial disorders, that mitochondria would happily and efficiently do their thing – produce sufficient ATP to meet the demands of living. That is just not the case. Any number of toxicants will damage mitochondria, including pharmaceuticals. That is why what is in one’s diet matters as much or more than the calories in, calories out equation recognizes, and why genetic mitochondrial disorders are not as rare as once believed.

Mitochondria require micronutrients, which many of our diets are starved of, to breathe, to consume O2, and utilize it to convert to ATP. With insufficient micronutrients, even in the face of sufficient or abundant macronutrients, hypoxia develops and with it, each of the cascades noted in COVID, albeit on a lesser scale, are enacted. The metabolic disarray plaguing much of the western world is a direct result of chronic, mitochondrially-driven hypoxia, which is a direct result of micronutrient malnutrition coupled with a continuous onslaught of chemical toxicants. This means that comorbid conditions linked to COVID severity and mortality, share common origins and that COVID, as unique as it is in its delivery of viral pathogenesis, in many ways, enacts exactly the same mitochondrial pathways as everything else but perhaps unlike other viral pandemics, is developing against the backdrop of longstanding, often epigenetic, mitochondrial insufficiency e.g. pre-existing hypoxia cascades.

So while COVID is a particularly virulent pathogen, its virulence is increased exponentially by our own ill-health; by a lifetime (or many lifetimes, if we consider the epigenetic consequences of these chemicals and dietary choices) of accumulated mitochondrial damage. With COVID, it is as if we are asking our bodies to run a marathon while starving and dodging bullets. Many of us simply do not have the energy to make it through because we are already hypoxic, starved for nutrients, and generally, exhausted. And while with age comes mitochondrial decline, age is not the defining variable. The defining variable is mitochondrial health, which if prescription data are any indicator, is progressively declining across all age groups, but most notably, among the young.

If this hypothesis is correct, then how do we survive? By going old school. By supporting the mitochondria so that they have the energy to manage and contain the threat. Oxygen is vital for life. Mitochondria are vital for proper oxygenation. Nutrients are vital for functioning mitochondria. Support the mitochondria and perhaps our capacity to withstand this virus will improve.

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