In March 2020, New York hospitals filled with desperately ill Covid-19 patients. In many cases, when their fluid-filled lungs could no longer give them oxygen, doctors sedated them and put them on a ventilator.
Patients who recovered were removed from machines and anesthesia. In a day or two, their doctors expected them to wake up.
But that’s when the phone of Dr. Nicholas Schiff, a neurologist at Weill Cornell Medicine, started to turn on.
“We start having all these weird consultations,” recalls Dr. Schiff. “People have been released from anesthesia after surviving Covid, and they’re not waking up.”
Dr Schiff, who had spent 25 years treating disorders of consciousness, was perplexed by the influx of unconscious Covid patients. They took weeks, if not months, to wake up. But then they usually regained consciousness, with no signs of brain damage.
Since then, Dr. Schiff and his colleagues have been trying to make sense of this strange phenomenon. On Monday, he published an article that offers an answer. And the answer is about turtles.
The brains of unconscious Covid patients bear a striking resemblance to those of turtles that spend the winter locked in ice, argued Dr. Schiff and his collaborator, Dr. Emery Brown, a computational neuroscientist at MIT. Turtles survive by placing their neurons in an unusual environment. calm state that lasts for months. Dr Schiff and Dr Brown believe the combination of Covid and sedatives causes a similar response in humans.
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If the theory holds, it could point to new ways to save people from brain damage: by intentionally putting people in this state, rather than doing it by accident.
“If true, this may teach us how to better protect and preserve the brain,” Dr. Schiff said.
Dr. Schiff found that his experience was not unusual. Many other neurologists were seeing Covid patients take a very long time to wake up. In March of this year, Dr Schiff, Dr Brown and their colleagues published a study of 795 severe Covid patients with delayed recovery at three hospitals in New York and Boston. A quarter of patients took 10 or more days after turning off a ventilator to follow simple commands like squeezing a doctor’s finger. After 23 days, 10% were still unconscious.
But the analysis did not offer easy answers as to why they were being so long delayed. Anesthetic drugs alone could not explain the long journey back to consciousness. “Time courses were absurd,” Dr. Schiff said.
Brain damage can lead to months of minimal consciousness, but many Covid patients had healthy brains. “We didn’t expect there to be a problem,” Dr. Schiff said.
For years, Dr. Schiff and Dr. Brown have been developing theories about what happens in the brain during comas, sleep, and anesthesia. Now they have turned their efforts to Covid. Their search for clues unexpectedly led them to turtle studies.
Throughout the Nordic world, cold-blooded turtles that live in fresh water must survive cold winters. They do this by spending months buried in frozen mud, barely breathing. Researchers studying turtles in the lab have found that the animal primes its brain for winter by flooding it with a chemical called GABA. The compound calms the activity of neurons so that they do not waste energy producing electrical impulses.
“It’s like they’re self-anaesthetising,” Dr. Brown said.
During the winter, turtles produce distinctive brain wave patterns, with isolated bursts of electricity separated by long periods of silence. Much like turtles, unconscious Covid patients produce brief bursts of electrical activity between long silences. And these patients were usually given anesthetic drugs that mimic GABA.
Dr. Schiff and Dr. Brown have proposed that in response to GABA-like sedatives and Covid stress, human neurons go into a silent mode in which they don’t need much oxygen to survive. Even after the sedatives wear off, the brain can sustain itself in this state for months.
“I think it’s an intriguing analogy, no doubt,” said Amanda Bundgaard, a postdoctoral researcher at the University of Cologne in Germany who studies the brains of turtles. But she cautioned against taking the analogy too far at this point, because there’s still so much to understand about turtles.
“One thing that’s maybe a bit problematic is that we don’t know how turtles wake up again,” she said.
After months in a state of suspended animation, the turtles return to normal by flooding their brains with oxygen. It’s amazing, because the rush of oxygen should kill their neurons by triggering toxic chemical reactions.
Some studies suggest that turtles absorb extra oxygen with a chemical called neuroglobin. But it is possible that they use a number of other chemicals to create many lines of defense.
“It’s exciting to have a new hypothesis to think about if it helps us create better patient outcomes,” said Martin Monti, a neuroscientist at UCLA who was not involved in the study.
In their paper, Dr Schiff and Dr Brown suggest that neurologists should check cerebrospinal fluid samples taken from Covid patients when they return to consciousness. Like turtles, they could release a surge of neuroglobin to protect their brains.
“That would be a pretty good test of the hypothesis,” Dr. Monti said.
He added that the hypothesis could also lead to new ways to prevent brain tissue from dying after a stroke, heart attack or even traumatic brain injury. A combination of sedatives and other treatments could trigger neurons to protect themselves like a turtle.
“It could ultimately become a new tool in the toolbox to enable patients to not only survive, but also recover as well as possible,” Dr. Monti said.
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