Understanding Long-Term Effects of COVID-19 on Health: A Deep Dive into Mitochondrial Dysfunction

2023-09-10 23:01:35

Recent studies show that many health problems linked to COVID-19 can persist more than two years following infection. Research suggests that this phenomenon is linked to an attack by the virus on the mechanisms involved in energy production by cells.

The SARS-CoV-2 virus that causes COVID-19 has so far infected more than 677 million people and been responsible for nearly 7 million deaths worldwide.

In addition to this deadly toll, the effects of the virus can persist in certain people and lead to long COVID, that is to say serious following-effects which manifest themselves in pulmonary, cardiovascular, neurological, metabolic (diabetes), renal disorders. or gastrointestinal several months following infection.

Persistent effects

In a recent study, researchers attempted to quantify this long-term damage from COVID by examining the medical records of approximately 140,000 U.S. veterans who survived following contracting COVID-19 in 2020. (1) Their findings health outcomes were subsequently compared to those of 6 million other patients who had not been infected with the virus.

They found a significantly increased risk of dozens of conditions more than two years following illness, particularly among patients who had been hospitalized following the infection. For example, of the 80 health problems that might result from COVID-19, the risk of 52 of them remained higher in infected people compared to uninfected people.

Overall, researchers estimate that the public health impact of COVID-19 may be even greater than that of cancer or heart disease, underscoring how the effects of COVID can be prolonged and not not limited to the lungs.

It should, however, be mentioned that the patients in the study were elderly, mainly male and unvaccinated (vaccines were not yet available), all risk factors for developing severe forms of the disease. These results are therefore probably not fully representative of the risk incurred by the general population.

However, there is no doubt that long COVID represents an important following-effect of the infection that absolutely must be better understood to improve the health and quality of life of those affected.

Mitochondria affected

A major advance in this direction has just been published by a research group specializing in the biology of mitochondria. These intracellular compartments are real energy plants, specialized in the conversion of the energy contained in food (sugar, fat, proteins) into energy usable by the cell (ATP).

Previous work reported that coronavirus infection was associated with major changes in mitochondrial morphology, reduced ATP production and increased free radicals. This suggests that these mitochondria are a prime target of the virus; moreover, nearly 20% of cellular proteins that interact with virus proteins are mitochondrial proteins.

By biochemically examining 700 nasopharyngeal samples and around thirty specimens from autopsies of patients who died from COVID-19, the researchers were able to demonstrate that the virus directly bound to several proteins in the mitochondria, which blocks the expression of several genes essential for cellular energy production. (2)

These dysfunctional mitochondria completely disrupt the balance inside the cell, causing, among other things, inflammation that prevents the cell from functioning while promoting the survival of the virus.

This phenomenon is observed in several organs, notably in the heart, liver, kidneys and lymph nodes, even following immunity has managed to eliminate the virus.

Defective mitochondria might therefore represent a key element that contributes to the following-effects of long COVID affecting several organs.

This is really interesting because there are already drugs like rapamycin and metformin that are known to improve mitochondrial function and therefore might be very useful in treating patients with long COVID.

Prevent infection

In the meantime, it stands to reason that the best way to prevent long-term COVID is to avoid becoming infected with the virus as much as possible.

In Quebec, the vast majority of people are vaccinated and/or have been infected over the last three years and the level of immune defense is incomparable to what it was at the start of the pandemic. On the other hand, the virus has mutated considerably since that time and new variants very different from the original strain are currently in circulation, notably the XBB.1.5 and EG.5 variants (called Eris).

The new vaccine that will be available this fall helps neutralize these variants and it may therefore be useful to receive this booster to reduce the risk of infection, particularly for people who are elderly, have chronic illnesses or are immunosuppressed.

♦ (1) Bowe B et coll. Postacute sequelae of COVID-19 at 2 years. Night. With.published on August 21, 2023.

♦ (2) Guarnieri JW et coll. Core mitochondrial genes are down-regulated during SARS-CoV-2 infection of rodent and human hosts. Sci. Transl Med. 2023; 15:eabq1533.

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