Most patients with severe COVID who are put on ventilators regain consciousness after removal of respiratory support, but recovery may take weeks after the period of mechanical ventilation has ended, according to a new study by investigators at Weill Cornell Medicine, Columbia University Vagelos College of Physicians and Surgeons, Harvard Medical School, New York-Presbyterian and Massachusetts General Hospital. The study also found that patients took longer to recover consciousness the more they experienced episodes of low blood oxygen levels during treatment.

The findings, published online March 7 in the Annals of Neurology, should inform decisions about life-sustaining therapies for unresponsive COVID patients.

“As we started to see the first patients waking up after successful COVID-19 ICU treatments, we also encountered many patients who remained comatose for days and weeks and then regained consciousness to become fully oriented,” said co-senior author Dr. Nicholas D. Schiff, the Jerold B. Katz Professor of Neurology and Neuroscience in the Feil Family Brain and Mind Research Institute and co-director of the Consortium for the Advanced Study of Brain Injury (CASBI) at Weill Cornell Medicine and a neurologist at New York-Presbyterian/Weill Cornell Medical Center. “While before we had rarely encountered such cases in related ICU conditions, we started to have 10 consults a day like this across the two New York centers. We formed a group to try to understand this unprecedented phenomenon.”

“In critical care medicine, one of our main tasks is to advise families about planning in the event a patient does not regain consciousness,” said co-senior author Dr. Jan Claassen, associate professor of neurology at Columbia University Vagelos College of Surgeons and Physicians and associate attending neurologist at New York-Presbyterian/Columbia University Irving Medical Center. “Our findings suggest that for patients with severe COVID, the decision to withdraw life support shouldn’t be based solely on prolonged periods of unconsciousness, as these patients may eventually recover.”

In the study, the researchers conducted a retrospective analysis of 795 patients who were hospitalized with severe COVID at three large medical centers—New York-Presbyterian/Columbia University Irving Medical Center, Massachusetts General Hospital and New York-Presbyterian/Weill Cornell Medical Center—during the first two surges of the pandemic. All of the patients had been on mechanical ventilation for at least six days. Most were also placed in a medically induced coma while on the ventilator, though some patients were already unconscious. After respiratory support was ended, the patients were assessed daily for the ability to follow simple verbal commands to move their arms, a standard measure of consciousness.

Of the 795 patients, 72 percent survived and ultimately regained consciousness prior to discharge. For those who survived, 25 percent recovered consciousness 10 days or longer after they stopped receiving ventilator support, and 10 percent took 23 days or more to recover.

The researchers also looked at a variety of factors that may have explained why some patients took longer to wake up, including severity of symptoms, degree of respiratory distress, exposure to analgesics or sedatives, and brain injury. They found that blood oxygen levels directly correlated with the ability and time to regain consciousness: the more low-oxygen episodes a patient experienced, the longer they took to wake up. Patients who experienced the most episodes of oxygen deprivation took the longest to recover consciousness.  

“These findings provide us with more accurate information to guide families who are deciding whether to continue life-sustaining therapy in unconscious COVID-19 patients,” said co-senior author Dr. Brian Edlow, associate director of the Center for Neurotechnology and Neurorecovery at MGH  and associate professor of neurology at Harvard Medical School.

The findings were consistent across all three medical centers and during the first and second COVID waves.

In most cases, imaging tests revealed little, if any, evidence of brain damage, suggesting that the long recovery times were not due to stroke or bleeding, Dr. Edlow said. The researchers hypothesize that patients with delayed recovery of consciousness may have entered a kind of protective state in which brain function is temporarily reduced before reemerging.

“We’ve seen similar phenomena in rare patients with cardiac arrest who were treated with hypothermia,” Dr. Schiff said. “Hypothermia appears to protect cardiac arrest patients from neurological damage in ways we still don’t understand. We’re now moving forward with studies aimed at uncovering common underlying mechanisms of neuroprotection that might connect these two groups of patients.”

Though time to regain consciousness was related to episodes of low oxygen, increasing ventilator support to raise blood oxygen levels does not usually help. The condition of the patient’s lungs may be preventing oxygen from reaching the bloodstream, and prolonged ventilation can itself cause lung injuries that exacerbate hypoxemia.

The study did not assess the patients’ long-term neuropsychological outcomes. “Encouragingly our study shows that the vast majority of unconscious COVID patients recover consciousness, but it is important to consider that we did not look at the quality of recovery. That’s something that should be the focus of long-term follow-up studies,” Dr. Claassen said.

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