COVID-19 News: “COVID-19 Fog” in Mild Cases

When COVID-19 patients started inundating New York City hospitals in March 2020, Anna Nordvig, MD, a neurologist and postdoctoral clinical and research fellow who specializes in cognition and behavior, organized a group of Columbia neurologists to review what was known about the neurological effects of other coronaviruses.

Their review alerted neurologists to watch out for lingering neurological and psychiatric issues in all COVID-19 patients, including those whose symptoms were mild and never required medical attention.

“COVID-19 manifests with many different symptoms,” says Dr. Nordvig, who sees patients in the Department of Neurology’s memory clinic. “Some may escape detection. It may be hard to distinguish what was caused by inflammation from the virus and what was caused by the hospitalization. Patients may not even think to mention certain symptoms to their doctor. To understand the prevalence of persistent neurological symptoms, we need to cast a wide net. Patients and their primary doctors can help this effort.”

During the summer of 2020, Dr. Nordvig said the clinic saw a trickle of patients who had symptoms more serious and persistent compared with the typical brain fog one might experience after a sleepless night. These patients included some in their 20s and 30s. “We’re not seeing a deluge of patients, but I worry that the people we’re seeing are those most attuned to the latest developments about the disease. Some people are just waiting for their symptoms to pass and not getting the help that could alleviate some of their issues.”

At the beginning of the pandemic, doctors in China reported that about a third of patients hospitalized had acute neurological symptoms. The initial epicenters—Asia, Europe, the U.S. coasts—are now following patients for persistent symptoms, such as fatigue, inattention, poor concentration, difficulty working long hours, difficulty getting out of bed, a “brain fog.”

“This is similar to what small studies reported in survivors from the first SARS virus,” says Dr. Nordvig. “Some also have more specific thinking and behavior problems—they forget the names of people they know well, they can’t follow along during business conversations, prioritizing and planning is suddenly difficult, they are inexplicably anxious and sleep poorly.

“Similar to the first SARS virus, patients are experiencing unusual persistent symptoms. Everyone has heard about the loss of smell and taste in COVID-19 and other viruses; we’re also seeing changes in appetite, lightheadedness, body discomfort, and new or worsened headaches that don’t always respond to traditional pain relievers. These are young and middle-aged people who were previously thriving. Now they are having profound changes in the way they think and feel. They’re worried about their careers if this persists. The good news is that most of the patients we’re seeing are getting slowly better, but it takes time and focus.”

The patients coming to the memory clinic are often seeking physicians who have seen this before. “They didn’t go to the hospital when they had COVID-19, and they don’t have other long-term effects, so they are surprised to have these neurological symptoms. The most common thing I hear from patients is, ‘I’m so glad to know that someone has heard of this.’” To help answer these questions, Dr. Nordvig and colleagues published a review this spring in Nature Medicine on post-acute COVID sequelae.

The severe inflammatory response and cytokine storm seen in COVID-19 suggests that COVID-19 symptoms may not all be caused directly by the virus. In hospitalized COVID-19 patients, the effects of systemic inflammation on the brain seem more profound compared with other common infections, such as the flu. The level of inflammatory markers in the blood are often severe, but largely during the initial infection. “I’m not yet convinced that the virus invades the brain’s neurons or its other cells. I think it is more likely that this vast, systemic inflammation affects many organs including the brain and the immune system within the brain, and changes the way the brain extracts nutrients and signals.”

Dr. Nordvig says reports published by Columbia neuropathologists over the past year provide clues that immunological brain changes may be occurring even without infection of the brain cells themselves. 

She presented data from the first 30 patients in her clinic cohort at the BRAIN Conference in London in March and at the American Academy of Neurology conference in April. Dr. Nordvig will be moving to Weill Cornell in September to build an expanded post-COVID “brain fog” clinic and research program