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A new University of Florida study finds that patients with COVID-19 who displayed symptoms of disorientation and confusion were three times more likely to go on to develop severe COVID-19 than patients with the virus who did not experience neurological symptoms.

“One of the key things in treating COVID-19 is looking for signs that you might have an aggressive or severe disease course,â€� said the study’s lead author, , a postdoctoral researcher in the at the , part of BOBÌåÓý, the university’s academic health center. “What we found was that certain brain symptoms, specifically a condition known as encephalopathy, may be an early marker of more severe COVID-19. We hope this might equip front-line workers and other health care providers with information to help them be on the lookout for a more severe disease course.â€�

The findings, which appear in , are based on electronic health records from five Florida hospitals of more than 36,600 patients with COVID-19, 12% of whom developed severe COVID-19. The data were made available through the .

The researchers found that, consistent with other national patterns, patients with loss of smell and loss of taste were less likely to develop severe COVID-19. Encephalopathy symptoms were typically seen a few days before or concurrent with the disease progressing to a serious stage requiring intensive treatment, such as admission to the ICU or ventilation.

Spotting signs of encephalopathy in patients with COVID-19 could help physicians initiate therapy much earlier, potentially preventing severe disease, the researchers say.

“I know we’re starting to open up and we’re getting vaccinated, but COVID will be with us for a while, so we need to be smarter than the virus and try to find things that we as physicians and families can identify early on to allow patients to combat the illness much more effectively,� said study co-author , a neurointensivist and assistant professor of neurology at the . “If we become complacent with what we know at this point, we’ll still continue to lose people.�

Early in the pandemic, experts believed that neurological issues in patients with COVID-19 were caused by the virus entering the brain. Scientists now know that when the body mounts a large inflammatory response to the virus � the same process associated with long COVID � brain function can be affected.

Encephalopathy is characterized by general disorientation and confusion, and “the person just doesn’t seem right,� Marra said, adding that it can be likened to the delirious state people may experience as they come out of anesthesia.

“They might not know where they are or be confused about the people around them,� Marra said. “They might not know the date or recent events. If there is a lot of general confusion that’s atypical for that person, that would be suggestive of some type of acute brain dysfunction.�

In addition to health care providers, caregivers and family members can play a role in identifying signs of encephalopathy in patients with COVID-19, Robinson said.

“As a brain doctor, one of the first things I ask a family member is, ‘Is your person thinking normally?� You usually get a majority of insightful information from family members who are around the patient all the time,� said Robinson, a member of . “I think it would be extremely important for family members to be hyper aware of this and to alert health care providers.�

One of the puzzles COVID-19 is prompting scientists to solve: What complications follow the acute course of the disease among long-haulers, or people with long COVID, and why, said co-author , division chief of neurocritical care at BOBÌåÓý, an associate professor in the departments of neurology and neurosurgery and a member of the McKnight Brain Institute.

“Our findings ask us to look into the question of whether or not patients who experience early nervous system symptoms have a higher risk for prolonged symptoms afterward,� she said.

Support for the study was provided by the UF COVID-19 Rapid Response Pilot program, a research fund created by the UF Clinical and Translational Science Institute and the Office of the Senior Vice President for Health Affairs.