Coronavirus is able to rapidly multiply by hijacking the body and forcing it to produce more receptors it can use to enter and infect organs, a study suggests.
US experts processed 2.5billion genetic combinations of Covid-19 in a super-computer to try and understand how the virus impacts the body.
They believe they have cracked why Covid-19 causes a slew of bizarre symptoms and are now recommending more than 10 potential treatments for the disease.
The team, from the Oak Ridge National Laboratory in Tennessee, found the virus typically infects people through ACE-2 receptors in the nose, where they are most common.
It then races through the body, invading cells in other places where ACE-2 is located, including the intestines, kidneys and heart – explaining the cardiac and kidney damage, and abdominal pains, seen in many patients.
Once inside human cells, though, it tricks the body into producing more ACE-2 receptors where they are normally only present in small numbers, including in the lungs.
This essentially opens the floodgates and allows Covid-19 to rapidly multiply and send armies of viral particles to infect more parts of the body in huge numbers.
A byproduct of this crafty process is that it interferes with the body’s ability to control levels of a chemical called bradykinin, which helps regulate blood pressure, according to the team’s analysis.
This leads to a catastrophic build-up of the chemical, causing a ‘bradykinin storm’ which makes blood vessels leaky and drives up the risk of inflammation, blood clots, strokes and brain damage – deadly symptoms observed in the sickest of patients.
The Oak Ridge scientists are recommending a series of bradykinin-reducing drugs including danazol, stanozolol, and ecallantide, which are already approved in the UK and US for other conditions.
The team, led by Professor Daniel Jacobson, a computational systems biologist at the lab, looked at more than 40,000 genes from 17,000 genetic samples of the coronavirus.
They input the data into Summit, the second fastest super-computer in the world, which analysed 2.5 billion genetic combinations over a week.
This helped the scientists to understand the genetic make-up of the virus, how that could interact with the human body and what symptoms it could cause.
After analysing the results, the team believe the coronavirus interferes with the renin–angiotensin system (RAS), which controls bradykinin levels.
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The full list of symptoms, in order of how predictive they are of the disease, include:
1. Loss of smell/taste
2. Persistent cough
3. Fatigue
4. Loss of appetite
5. Skin rash
6. Hives
7. Fever
8. Severe muscle pain
9. Shortness of breath
10. Diarrhoea
11. Delirium
12. Abdominal pain
13. Chest pain
14. Hoarse voice
15. Eye soreness
16. Sore or painful throat
17. Nausea or vomiting
18. Headache
19. Dizziness or light headedness
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They believe it is the ‘bradykinin storm’ causing the majority of the unusual symptoms, rather than a ‘cytokine storm’, an overreaction by the immune system which sees it attack healthy tissue, which was previously touted as the possible cause.
As bradykinin accumulates in the body, it makes the protective walls around blood vessels less waterproof and more likely to leak.
The researchers say this causes immune cells to leak into vital organs like the lungs, causing deadly inflammation – a useful recovery process when well controlled – that makes it hard to breathe. They have called their theory the ‘bradykinin hypothesis’.
The RAS system is also responsible for keeping the heart beating properly and controlling blood pressure.
The theory would explain why a fifth of Covid-19 hospital patients suffer heart damage, despite many never having previously had cardiac troubles.
And arrhythmias – irregular heart beats – and low blood pressure have also been spotted in a large proportion of patients.
According to Professor Jacobson, it is leaky blood vessels that are triggering Covid-19’s symptoms in the nerves and brain, which have puzzled doctors and scientists alike.
Leaks in a barrier between blood vessels in the skull and brain cells is causing dizziness, seizures, delirium, and stroke – thought to affect half of all hospitalised Covid-19 patients to some degree.
The blood-brain barrier acts as a filter between the organ and the rest of the body, only allowing essential nutrients to pass through and keeping out toxins and pathogens.
When broken down, these cells are able to infiltrate the brain and trigger inflammation and brain damage.
Professor Jacobson told the medical news website Elemental: ‘It is a reasonable hypothesis that many of the neurological symptoms in Covid-19 could be due to an excess of bradykinin.
‘It has been reported that bradykinin would indeed be likely to increase the permeability of the blood-brain barrier. In addition, similar neurological symptoms have been observed in other diseases that result from an excess of bradykinin.’
The scientist said Covid-19’s effect on the body appears to echo nasty side effects of blood pressure-lowering drugs.
Such medications, known as ACE inhibitors, are prescribed to patients with extremely high blood pressure, known as hypertension.
They are known to, in some cases, cause a dry cough, fatigue and loss of taste and smell – three tell-tale signs of the coronavirus.
Professor Jacobson’s theory may also explain why men are disproportionately catching and dying from coronavirus.
Males are dying at twice the rate of the disease in the UK and the findings are consistent worldwide.
Professor Jacobson said there are a higher number of protective proteins that prevent the RAS system from going haywire located on the X chromosome.
This suggests ‘women… have twice the levels of this protein than men’ which ‘could explain the lower incidence of Covid-19 induced mortality in women’, he added.
The peer-reviewed study, published in the journal E Life Sciences, is said to contribute to a better understanding of Covid-19′ and ‘add novelty to the existing literature,’ according to the independent scientists who reviewed it.
Professor Jacobson and his team are now recommending scientists investigate more than 10 bradykinin-blocking drugs on Covid-19 patients.
Many, which have the potential to stop a bradykinin storm, include danazol, which treats endometriosis, a painful disorder affecting the womb, the anabolic steroid stanozolol and ecallantide and icatibant, which treat skin conditions.
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