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Graeme Jones

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What’s causing Long COVID?

Imagine you’re in your early 30s, in excellent health. As the pandemic rages you become infected with SARS-Cov2, the virus that causes COVID19. But you bounce back from a mild infection with basic respiratory symptoms and are as good as new in 10 days quietly wondering what the hell was all the fuss.

Then, a few weeks to months later, different symptoms pop up. Headaches, malaise, exercise intolerance, chest pain, inexplicable heart racing, and diarrhea seem to come and go unrelentingly. You feel as though your body is no longer yours, with no end in sight. Welcome to the world of the COVID long hauler, a name which seems to have arisen from one of the first patients who reported these issues.

COVID long haulers

The post viral syndrome associated with COVID long haulers presents differently between individuals. This is not a new topic to us at Nordic Clinic, but we have seen patients having post viral syndrome due to many other types of infections. Sometimes it’s due to residual damage to tissues, but other times there is no explanation. Organs function fine, and blood tests come back as normal. Despite this, there is definitely something going on.

What COVID long haulers experience bears resemblance to chronic fatigue syndrome, also known as ME/CFS. Unfortunately, as is with ME/CFS, there isn’t a clear understanding of the cause, which may be different for everyone. The general consensus is that it’s the immune system, rather than the virus itself, that’s causing long hauler symptoms. Let’s take a look.

Theories behind Long COVID

One theory is that symptoms are caused by persistently elevated inflammation: a prolonged cytokine storm. (1) For one reason or another, the inflammatory process doesn’t resolve in some. As a result, these people chronically experience symptoms consistent with an infection, rather than the normal acute presentation.

A second theory gaining traction is an autoimmune attack. (2) Normally, during a virus infection, we form antibodies that attack the virus. Sometimes, these antibodies also recognise and attack our own tissues, and this is why some infections may cause autoimmune disease. For example, infection with influenza virus A or the Swine flu may cause narcolepsy in individuals with a specific genetic make-up.

Another theory behind the cause of long COVID symptoms involves the gut. A recent paper found that people with a severe initial response to SARS-CoV2 experience changes to their microbiome. (3) These changes correlated with the severity of the disease, and were found to persist in COVID long haulers. Although if the stress of disease changed the microbiota or the other way around is not known. Chronic inflammation can promote changes to the microbiome, and changes to the microbiome may play a role in promoting autoimmune disease, as well as impacting how our immune system functions to control existing dormant viruses.

A final theory is that the herpes virus is involved. That annoying cold sore that you normally get when you are excessively stressed or suffering from a lack of sleep, is due to something called the Herpes Simplex Virus 1 (HSV1). Hold on, is that not very common? Yes, around 66% of the world’s population have a HSV infection, but the immune system normally keeps it under control. COVID-19 may cause changes to the immune system that means suddenly your immune system is not controlling the HSV as it should. The virus changes from a dormant state and becomes reactivated, like waking a bear coming out of hibernation. But HSV1 is not the only herpes virus that may be connected with long COVID. The Epstein Barr Virus (4, 5, 6), Cytomegalo Virus (8), Human Herpes Virus 6 (7), have also been linked with a possible reason why you might be a “long hauler”.  As you age (chronologically or biologically) your immune system also becomes less effective at keeping these viruses in a dormant state (if you have been infected earlier in life). So naturally older people are at greater risk, or those that have chronic disease as they biologically age faster.  Not everyone will have been infected with these viruses at some point in their life, but once you are infected, you do carry them for life. 

It’s important to point out these explanations are not exclusive from one another. Furthermore, the primary driver in one person may not be the same in another.

Unfortunately, since we are early in the discovery of long COVID, any data is preliminary. Some people eventually see a resolution of symptoms, while others are still going almost a year later. Further study is needed to determine what the cause(s) of long COVID are, and how to stratify patients to personalise care.

If you would like to discuss any part of this article further please contact info@nordicclinic.se.

This is a guest post. Any opinions expressed are the writer’s own.

References

  1. https://www.immunology.org/sites/default/files/BSI_Briefing_Note_August_2020_FINAL.pdf
  2. https://www.medrxiv.org/content/10.1101/2020.12.10.20247205v4
  3. https://gut.bmj.com/content/early/2021/01/04/gutjnl-2020-323020
  4. https://assets.researchsquare.com/files/rs-21580/v1/4f2178bd-2481-45b4-966f-9971c46d694d.pdf
  5. https://ccforum.biomedcentral.com/articles/10.1186/s13054-020-03384-6
  6. https://www.ijidonline.com/article/S1201-9712(20)32575-3/fulltext
  7. https://hhv-6foundation.org/lung-disease/does-hhv-6b-reactivation-exacerbate-covid-19
  8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7251217/

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