Two new studies on Long Covid help us understand a little better this complex and mysterious syndrome that afflicts millions of people around the world.
What is Long Covid
According to the World Health Organization it defines itself Long Covid a set of symptoms (more than 200) that emerge within 3 months post acute Sars-CoV2 infection and that persist for at least two months. Long Covid is a multi-organ, multi-system syndrome that does not yet have a unique explanation. Evidence and studies are accumulating that suggest at least four mechanisms behind Long Covid:
- autoimmune response
- viral persistence
- chronic inflammation
- endothelial damage
Obviously these mechanisms are not mutually exclusive and can enhance each other with synergistic effects. The first hypothesis predicts that the Sars-CoV2 infection confuses the host’s immune system, which accidentally attacks ‘self’ and therefore its own structures, triggering an autoimmune disease. A similar mechanism can be observed, for example, in the numerous autoimmune syndromes triggered by the Hepstein-Barr Virus (EBV) infection.
Viral persistence foresees that Sars-CoV2 can nest in the intestine in niches that are difficult to reach by the immune system and from there continue to create inflammation and immune dysfunctions. Chronic inflammation could be partially explained by points 1 and 2. Finally, the hypothesis of endothelial damage predicts that Sars-CoV2 is able to damage the inner lining of blood vessels, the endothelium, and this would cause a series of dysfunctions circulatory systems including micro-clots.
Understanding the pathological mechanisms of Long Covid would help doctors and researchers to develop a specific drug, as currently the treatment of the syndrome is only symptomatic, that is, drugs are used to relieve the symptoms of patients but there is no cure.
Not all Covid sufferers develop Long Covid
The other big question around Long Covid concerns its incidence, in fact fortunately not all subjects recovered from Covid19 develop Long Covid.
Are there any risk factors for Long Covid? Why are some people more prone? Are there any measurable markers that can be linked to Long Covid risk? Two new studies published in recent months partially answer some of these questions.
A blood test reveals who is most at risk
The authors of the first study extracted and analyzed the blood of two groups of people: recovered from Covid19 and never infected. The researchers found that the proteome of subjects infected and then cured of Covid19 changes for at least 6 weeks.
Long Covid: a blood test reveals who risks the most
Il proteoma is the set of all proteins expressed and transported by the blood: we find enzymes, proteins that transport nutrients, simple proteins etc.
This first data should not surprise us too much: we know that Covid19 is not only a respiratory disease so it is normal that some components of the blood are affected by the presence of the virus and the disease. Fortunately, all the protein components of the blood return to within the limit values a few months after infection.
The real discovery made by the researchers is that patients who develop Long Covid have a specific combination of proteins in their blood before infection and Covid19. This means that researchers are able to predict with some precision which patients will develop Long Covid by analyzing the protein profile present in the blood.
These analyzes are not currently available on a large scale and the mechanisms linking the expression of certain proteins to the development of Long Covid have yet to be understood.
The role of hormones and the immune system
The second article that allows us to understand the Long Covid a little better analyzes in detail the hormones and the immune system of subjects affected by the post viral syndrome.
The researchers observed that people with Long Covid have lower levels of the hormone cortisol (the physiological version of the drug cortisone) than the healthy population. Cortisol is a powerful immunomodulator that is a hormone capable of modulating the response of the immune system, the main function is anti-inflammatory and in large quantities it depresses the immune system.
The low concentrations of cortisol in the blood of Long Covid patients may explain symptoms such as chronic inflammation, pain and fatigue. Unexpectedly, however, when cortisone is administered to Long Covid patients it is not enough to cancel the symptoms.
Furthermore, the researchers analyzed the cortisol precursors (i.e. the substances that are transformed into cortisol) and did not notice reductions, this means that in Long Covid patients there is only a lowering of cortisol and not of the whole hormone production chain. .
The second important discovery concerns T lymphocytes, in fact in a percentage of patients with Long Covid these cells of the immune system are “exhausted”. T lymphocytes after fighting a pathogen are defined as exhausted, as they are no longer capable of attacking other pathogens. The depletion of T lymphocytes is a safety mechanism put in place by our immune system to prevent overactive T lymphocytes from attacking their own structures (self) causing autoimmune diseases.
The depletion of T lymphocytes is often a consequence of viral reactivation, that is, when our body fights an infection with a latent virus such as EBV or Herpes. An immune system that actively fights a pathogen creates local and systemic inflammation and low cortisol levels fuel the whole mechanism.
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What we don’t know
Despite these elements we are connected to each other, many questions remain unanswered:
Do Long Covid patients express low cortisol due to the virus? Is cortisol a cause or a consequence? Are T lymphocytes depleted due to Sars-CoV2 or other viruses? Why doesn’t cortisone treatment improve symptoms? Why don’t all patients have depleted T lymphocytes?
Answering these questions is essential to better understand Long Covid disease and to study an effective treatment for the millions of affected patients around the world.
TAKE HOME MESSAGES
- Long Covid afflicts millions of people recovered from Covid, at the moment it has no explanation
- Several hypotheses try to explain the symptoms: autoimmune response, viral persistence, chronic inflammation and endothelial damage
- People who develop Long Covid have a specific composition of proteins in the blood
- People with Long Covid produce little cortisol and have exhausted T lymphocytes
REF:
https://www.the-scientist.com/news-opinion/long-covid-likely-doesn-t-have-just-one-cause-70559
https://www.thelancet.com/action/showPdf?pii=S2352-3964%2822%2900475-3
https://www.science.org/content/article/blood-abnormalities-found-people-long-covid
Aureliano Stingi, doctor in molecular biology works in the field of precision oncology. He collaborates with the World Health Organization in the battle against Covid19-themed fake news
Instagram: Aureliano _Stingi Twitter: @AurelianoStingi