We know coronavirus attacks the lungs. So why do up to half of hospitalized patients have neurological symptoms such as dizziness, delirium, seizures and strokes?
Why do one in five hospitalized patients have damaged hearts when they never had cardiac issues before?
What explains dry cough and fatigue, two of the most common symptoms, and unusual ones like swollen and bruised toes?
These symptoms and others can all be explained by a new theory called the bradykinin hypothesis. It's a theory in which one of my favorite vitamins, vitamin D, is intimately involved.
Over the summer, medical researchers went to Oak Ridge National Laboratory at the University of Tennessee to put the world's second fastest computer, called Summit, to the test.
These scientists were hoping Summit could help them better understand how COVID-19 effects the human body. They tasked Summit with crunching data on 40,000 genes from 17,000 genetic samples of the virus.
Summit may be fast, but the process involved 2.5 billion genetic combinations and took a week to obtain the results. But it was worth it.
How COVID-19 Tricks the Body
For lead researcher Dr. Daniel Jacobson, Summit provided a "eureka moment," because a new model of the disease emerged that could explain much of the mystery surrounding the virus.
Summit's findings suggest the infection normally begins when the virus enters the nose and latches on to receptors called ACE2 that are abundant there. These act as a doorway for the virus, allowing it to travel to where other ACE2 receptors are located, in the intestines, kidneys and heart. This accounts for symptoms in these areas.
Some of this was already known, but what the supercomputer picked up was that the body is tricked into upregulating ACE2 in places where it’s only expressed at low levels such as the lungs, allowing the virus to multiply rapidly.
Blood Vessels Leak
A byproduct of this process is that the coronavirus interferes with the body's ability to control bradykinin, a small protein (peptide), that’s involved in many processes including dilating blood vessels, lowering blood pressure and contracting smooth muscle in the gut and lungs.
Unable to restrain the peptide, it builds dramatically creating a "bradykinin storm." The researchers believe this to be the main cause of symptoms, rather than the more commonly touted "cytokine storm"-- an inflammatory over-reaction of the immune system.
The effects of a bradykinin storm are alarming, to say the least.
Blood vessels get leaky, including ones in the brain. A bradykinin storm may even cause a breakdown of the blood-brain barrier, allowing toxins and pathogens to enter, leading to inflammation and potential brain damage.
Leaky blood vessels can also explain a condition of much less concern - swollen and bruised "COVID toes."
Heart and Lung Effects
On top of the ACE2 effects on the heart, the bradykinin storm lowers blood pressure and can cause an irregular and unstable heartbeat.
In fact, the heart symptoms of COVID-19 are similar to ones experienced when taking ACE inhibitor drugs for high blood pressure. These drugs also increase bradykinin. Common side effects of ACE inhibitors are dry cough and fatigue, two of the textbook symptoms of COVID-19.
The most disturbing effects are to the lungs. Leaky blood vessels allow the lungs to fill with fluid. Immune cells can also leak out of the lungs to cause inflammation.
Through another mechanism, the body steps up lung production of hyaluronic acid, used in soaps and lotions because it can absorb massive amounts of fluid. When it combines with the lung fluid it forms a hydrogel.
Dr. Jacobson describes the effects as "trying to breathe through Jell-O," and explains why ventilators are mostly ineffective in advanced cases.
The bradykinin hypothesis can even explain why men die at more than double the rate of women. It's because women have twice the number of a protective protein that deters bradykinin from running wild.
Dr. Jacobson and his colleagues suggest nine drugs that can either lower bradykinin production or signaling, reduce hyaluronic acid or increase blood clotting. These include a hormone drug as well as several steroid drugs, plus drugs that affect blood flow and drugs that are designed to selectively interrupt the development of bradykinins directly.
The only non-drug intervention they suggested is vitamin D.
Vitamin D to the Rescue
Vitamin D is important because bradykinin production is controlled by the renin-angiotensin system, a hormonal system that's a central regulator of kidney and cardiovascular functions.
COVID-19 wreaks havoc on this, and it’s this disruption that unleashes bradykinin. The researchers said vitamin D can reduce production of the renin component to prevent a bradykinin storm from developing in the first place.
This information adds to the growing list of studies showing the importance of vitamin D in modulating inflammatory responses to infection.
The researchers wrote, "Patients who are deficient in Vitamin D are at risk for ARDS [acute respiratory distress syndrome] in general and Vitamin D deficiencies have recently been associated with severity of illness in COVID-19 patients."
Now that summer’s behind us and we can’t obtain much vitamin D from the sun, it's more important than ever before to take a supplement. This new research shows that vitamin D can help give you solid protection against a severe infection of COVID-19, as well as the flu during the winter season.
