Darius Settles was sent home from the emergency room twice after contracting COVID-19 in June. The first time, he was told to come back if his condition worsened. On his second visit, his blood-oxygen levels were normal enough to discharge him again. He died in July, the youngest person killed by the coronavirus in Nashville, Tennessee, at that time.

Situations in which patients seem better, get discharged, then see their conditions worsen, have become common over the course of the pandemic. New research suggests it may be related to infections in the brain.

"People seem to have very nice recovery, lung functions are fine, and we send them home just to find out that three days later, the patient becomes so severe that they died," Mukesh Kumar, a virologist at Georgia State University, told Insider. "That usually can only happen when the brain is involved."

Kumar recently published a study in the journal Viruses that examines how COVID-19 affects the brains of mice.

His results showed that three days after the mice were infected with the coronavirus, they displayed high levels of virus in their lungs. By days five and six, their lungs had started to clear up but their brains showed about 1,000 times more virus than the peak levels found in the lungs. That coincided with the arrival of severe symptoms such as labored breathing, disorientation, and weakness.

The virus also triggered an inflammatory response in the brain, marked by the release of chemical signals called cytokines. Under normal circumstances, cytokines tell the immune system to fight off infection but too many cytokines can instruct the body to attack its own cells, triggering dangerous levels of inflammation. The mice brains in the study showed around 10 to 50 times more cytokines than the lungs.

In some mice, the reaction caused immediate death. But in mice with milder cases, the virus seemed to hide out in the brain indefinitely.

Though results of mice studies don't always hold true for humans, Kumar suspects that the brain is a major target for the coronavirus.

"Our brain doesn't have that good immune response like our lungs or our heart, so whenever the virus goes in the brain, it can replicate very well," Kumar said. "It can stay there for a long time."

Viral replication in the brain could also explain why some coronavirus patients have persistent neurological issues, such as dizziness or brain fog, long after they've tested negative for COVID-19. In some cases, Kumar said, there's a risk these neurological problems may give rise to chronic illnesses such as autoimmune disorders, Parkinson's, or multiple sclerosis.

"Depending upon your immune response or antibody levels, it could cause low levels of inflammation, or maybe make you prone to other disease, or maybe reactivate later," he said. "All these are still outstanding questions because we are still only one year into the pandemic."

A woman improperly wears her face mask in Rome, Italy, on April 29, 2020. Andreas Solaro/AFP/Getty Images

COVID-19 is often described as a respiratory disease, since the coronavirus attacks the lungs first. But some researchers suspect it may be a vascular disease, given that some patients develop blood clots, leaky capillaries, and inflamed blood vessels, which can lead to heart damage or stroke.

ADutch study of 184 coronavirus patients in the ICU found that nearly one-third of patients had blood clots. And aJuly study of 100 COVID-19 patients found that 78 of them had some degree of heart damage. Studies have also suggested that nearly 2% of COVID-19 patients have strokes far more than than the rate of strokes among influenza patients.

But Kumar's study didn't detect any virus in the blood of infected mice.

Instead, his research showed that the virus entered the brain through the nasal passages, before attacking the central nervous system. Part of that nervous system controls our sense of smell, which may explain why many coronavirus patients have trouble smelling. Kumar said it's possible that the virus could reach the brain after entering the mouth as well, but the nose is a more direct pathway.

In mice, the coronavirus seemed to have trouble replicating in organs such as the heart, liver, or kidneys. But an infection in the brain can ultimately damage such organs, Kumar said.

"It doesn't even have to go to every organ, because if it can go to the brain, there are several parts of the brain that control all other organs," he said. "So it could also be possible that you don't even need virus in the lungs to cause lung failure."

A patient who has recovered from COVID-19, gestures next to his son as he leaves the Juarez Hospital in Mexico City, Mexico, July 27, 2020. Edgard Garrido/Reuters

Neurological issues are more common among coronavirus patients than scientists originally thought.

An October study found that 82% of coronavirus patients admitted to a hospital network in Chicago in March and April 2020 had neurological symptoms. The issues ranged from relatively minor headaches, dizziness, and loss of smell to serious conditions like brain damage, strokes, and seizures.

In some cases, these symptoms can linger for at least several months.

A recent study from University of Oxford researchers, which is still awaiting peer review, found that 13% of people who got COVID-19 were diagnosed with a psychiatric or neurological illness within six months of testing positive for the virus. Some patients even showed signs of Parkinson's disease or Guillain-Barr syndrome, a rare autoimmune disorder, but those results weren't statistically significant.

Kumar said it's fairly simple to tell whether a patient has a severe neurological condition, since the issue will likely show up on an MRI or CT scan. But mild neurological problems are often difficult to pinpoint.

"Unfortunately, based on other studies, it could be lifelong," Kumar said. "We know patients who are still showing symptoms who were infected a year ago."

The research he did on mouse brains, however, is difficult to replicate in humans.

"The patient has to die to actually find out if the virus is hiding in the brain," he said.

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COVID-19 can hide in the brains of mice, cause neurological issues - Business Insider - Business Insider