COV-19: What causes long Covid?

‘Long Covid’ occurs when your body’s response to the viral infection continues beyond the initial acute illness (‘viral persistence’). In this post I look at some of the proposed factors which may be causing or contributing to the continued symptoms.

Long Covid may develop in anyone who has been infected by the COV-19 virus, irrespective of its initial severity – including if the initial illness was mild or if they had no symptoms at all during the acute phase.

One study estimated that between September 2020 and February 2021 over 2 million people in the UK may have had long Covid. Official estimates currently suggest over one million people are still suffering from the symptoms of long Covid. It is thought to affect 40% of all those infected by the virus. It impacts all age groups. Women are twice as likely to be affected, but only until around the age of 60; after that the risk level becomes equal between the genders. As with acute COV-19, pre-existing conditions increase the risk. 

What causes long Covid?

We don’t yet know for sure. Proposed explanations include:

·       Immune system dysfunction. Due to persistent abnormalities in the immune cells, there may have been a weak or absent antibody response.

·       Direct effects from the viral infection and associated tissue/organ damage. This would explain some symptoms like brain fog and loss of smell and taste, while damage to blood vessels could lead to heart, lung and brain problems. 

·       Relapse/reinfection of the virus. Fragments of the virus might remain in the body, possibly lying dormant and then becoming reactivated, as happens with the herpes family of viruses (eg cold sores)

 ·      Viral load. Other latent/dormant viruses, such as Epstein Barr, may become reactivated due to immune capacity being overwhelmed by viral load.

·       Damage from the inflammation may trigger a syndrome similar to Mast Cell Activation Syndrome (MCAS)

·       Post-viral autoimmunity. Fragments from the COV-19 genes, while not infectious, may linger and trigger an immune overreaction, which attacks the body’s own tissues. This causes inflammation and tissue damage in the affected areas. 

·       Poor nutritional status

·       Impaired gut function (dysbiosis)

·       Nervous system dysfunction such as stress, anxiety, depression and post-traumatic stress

·       Genetic predisposition, impaired methylation and detoxification

·       Mitochondrial dysfunction

·       Multifactorial: it is likely to be a combination of factors, to produce such a wide range of symptoms. 

Stress

There may also be other stresses in your life, but fighting a viral infection like COV-19 is a huge physical stress on your body. The infection triggers your body’s stress response (“fight or flight”) which releases adrenaline and cortisol. It will also affect the other stress hormones like DHEA and aldosterone. Cortisol is a powerful anti-inflammatory and suppresses the immune response, which will prevent your body from recovering from the infection.

Stress impairs healing

The impact of stress will also exacerbate other accompanying and relevant factors such as Epstein Barr reactivation, which will last longer and/or have greater intensity the bigger the stress.

Especially in those with pre-existing stress-related disorders such as anxiety, depression and PTSD (post-traumatic stress disorder), COV-19 infection may lead to cortisol and adrenaline resistance or desensitisation. Symptoms include a wired-but-tired feeling, agitation, aggression and insomnia, as well as feeling low or depressed (due to upregulation of the kynurenine pathway and its effect on serotonin and melatonin).  

The pandemic has caused worldwide anxiety to reach its highest level since World War II. This global stress will have impaired global immune capacity.

Mitochondrial dysfunction

Mitochondrial function is relevant in most conditions, but especially in ones like long Covid and ME/CFS. Mitochondria are found inside every human cell and they are basically the batteries – they make the energy that powers the cell. Without them the cell cannot function. There are more than one inside cells and their numbers vary, depending on the type of cell eg heart, lung, gastrointestinal, muscle or brain cell. The main symptom of mitochondrial dysfunction is therefore fatigue.

Mitochondria are easily damaged. Viral infection may lead to mitochondrial dysfunction. Oxidative stress is one of the biggest causes of mitochondrial dysfunction. Infection and inflammation result in increased oxidative stress and this is likely to be a significant driver of the fatigue.

Mitochondrial function is also connected to immunity. In ME/CFS, mitochondrial dysfunction has been found in the peripheral blood mononuclear cells which are part of our immune system.

Gender differences and oestrogen

Women appear to be twice as likely to develop long Covid as men, but only until around age 60; thereafter the risk level becomes similar. Whereas men are more likely to develop severe acute COV-19. Carrying more weight increases the risk for both.

Oestrogen is likely to be playing a role in this gender difference. Oestrogen is anti-inflammatory, which may explain how it protects against severe acute COV-19. But it does not protect against long Covid. Oestrogen dominance and the balance of oestrogen with other hormones may be another driving factor. Environmental oestrogens, also known as xenoestrogens, can disrupt normal oestrogen signalling and reduce its protective effect.

Genetic predisposition and impaired methylation

Gene variants and impaired methylation were found to disrupt red blood cell synthesis and cell division resulting in fatigue and lethargy. COV-19 may ‘hijack’ folate and other B vitamins (B2, B3, B6 and B12) to support its own viral replication, as well as deplete blood glucose. Studies also show that through its effects on genes and methylation, COV-19 can result in elevated histamine, oestrogen, adrenaline and homocysteine; and lower serotonin, melatonin, methionine, choline, zinc and magnesium. This is especially relevant for those with anxiety and other mood disorders due to the negative impact on neurotransmitters such as serotonin. Inflammation also disrupts neurotransmitter balance: it reduces GABA and serotonin and increases glutamate. Dopamine and Vitamin C may also be low as a result of adrenaline surges. Disrupted white blood cell synthesis impairs the immune response.  

In my next post in this COV-19 series, I consider whether your symptoms are actually long Covid at all. I look at other conditions which have very similar symptoms, such as Epstein Barr virus reactivation and Mast Cell Activation Syndrome.

Disclaimer: these COV-19 posts were written based on the evidence available at the time of writing. As new information continues to emerge, they may no longer be up to date or correct.