A supercomputer found a promising theory about why COVID-19 cases go downhill fast. It even explains the bizarre range of symptoms.
Imagine trying to drive a car with a leaky engine. Now imagine there are no brakes, either. Eventually, you're going to run out of fuel or crash. Some passengers might survive — others won't.
The human body may endure a similar experience in response to a coronavirus infection, according to a study from researchers at the Oak Ridge National Laboratory in Tennessee. The lab's supercomputers — one of which is the second-fastest in the world — analyzed lung fluid samples from nine coronavirus patients with severe cases in Wuhan, China.
The computers detected major differences in way these patients expressed certain genes relative to the way healthy people do.
Based on those abnormalities, the researchers came up with a new theory: Patients with severe COVID-19 may experience what's known as a "bradykinin storm."
Bradykinin is a chemical that regulates blood pressure. The researchers found that some people with the coronavirus may produce it in extreme excess. That storm throws major systems — including respiratory, gastrointestinal, and neurological pathways — off balance.
The theory aligns with researchers' growing view of the coronavirus as a vascular disease instead of a respiratory one. Research has shown that COVID-19 can lead to blood clots, leaky capillaries, and inflamed blood vessels — which is why some patients may experience heart damage or stroke.
"We were really scratching our heads for a while, how does this disease have this darn broad set of symptoms across lots of different organ systems?" Dr. Daniel Jacobson, the lead researcher behind the supercomputer study, told Business Insider. "As we looked at the effects of bradykinin, our model was that this virus can affect several different types of tissues, several different organs."
Too much bradykinin can send the body spiraling out of control
Scientists already know that the coronavirus binds to cell receptors called ACE2. That's how the virus sneaks into the body's upper respiratory tract, then infects organs like the lungs, heart, kidneys, or intestines.
But the supercomputers found that coronavirus patients had a 200-fold increase in the expression of ACE2 relative to a healthy person. This suggests the virus is actively influencing our bodies to make them even easier to infiltrate. At the same time, they computers found, coronavirus patients also had an eight-fold decrease in the expression of ACE, a protein that normally works with ACE2 to keep blood pressure in check.
"This system that is normally very carefully balanced — COVID-19 really throws it out of whack," Jacobson said.
This imbalance, the researchers think, is what leads to the over-production of bradykinin, which swoops in to keep blood pressure from getting too high. In severe cases, the cycle seems to go into overdrive: The body can't stop producing bradykinin. This is what researchers call a "bradykinin storm."
An excess of the chemical widens the gaps in blood vessels, which allows fluid to leak out. That fluid, in turn, starts to fill up the alveoli: tiny air sacs in the lungs — hence why patients have trouble breathing.
The supercomputers also found that coronavirus patients may over-produce a highly absorbent substance called hyaluronic acid. When the acid mixes with the fluid in the lungs, patients can feel like they're trying to breathe out of "a balloon full of Jell-O," Jacobson said.
"There may be a tipping point where enough of this hyaluronic acid builds up, then all of a sudden they have respiratory distress," he added. "That explains why some people seem to be doing fine and then they crash and all of a sudden need hospitalization or worse."
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