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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 multicenter study. 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 should inform decisions about life-sustaining therapies for unresponsive COVID patients.

“In critical care medicine, one of our main tasks is to advise families about planning in the event a patient does not regain consciousness,” says Jan Claassen, MD, a co-leader of the study, associate professor of neurology at Columbia University Vagelos College of Surgeons and Physicians and associate attending neurologist at NewYork-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.”

The study was published online March 7 in the Annals of Neurology.

“Early in the pandemic, we were perplexed by how long it took some COVID patients to regain consciousness after respiratory support and sedation ended,” Claassen says. “Usually, patients in acute respiratory distress emerge from coma after a week or so. But it was common for COVID patients to go weeks and weeks before they came around.”

In the study, the researchers conducted a retrospective analysis of 795 patients who were hospitalized with severe COVID at three large medical centers—NewYork-Presbyterian/Columbia University Irving Medical Center, Massachusetts General Hospital, and NewYork-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 6 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% survived and ultimately regained consciousness prior to discharge. For those who survived, 25% recovered consciousness 10 days or longer after they stopped receiving ventilator support, and 10% 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,” says Brian L. Edlow, MD, a co-leader of the study and investigator in the Department of Neurology at Massachusetts General Hospital.

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, Edlow says. 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,” said Nicholas D. Schiff, MD, a co-leader of the study, the Jerold B. Katz Professor of Neurology and Neuroscience at Weill Cornell Medicine and attending neurologist with NewYork-Presbyterian/Weill Cornell Medical Center. “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,” Claassen says.

The study is titled, “Prolonged unconsciousness is common in COVID-19 and associated with hypoxemia.” The other contributors and conflicts of interest disclosures are listed in the online version of the paper.

The study was supported by the James S. McDonnell Foundation (JSMF).