New research highlights an inflammatory driver
By Austin Perlmutter, MD
KEY POINTS
Research suggests that tens of millions of people experience "long COVID," with many dealing with brain-related symptoms
Studies over the last years indicate a number of potential drivers of brain issues in the context of the pandemic, some of which are non-infectious
Inflammation in the brain has emerged as a major potential cause of long COVID brain symptoms (as well as a driver of mental and cognitive issues independent of COVID)
Consideration for lifestyle modification including diet may be an important part of the puzzle moving forward, as it targets multiple pathways implicated in long COVID and more generally in brain health
Throughout the COVID-19 pandemic, theories and opinions on what was actually happening have varied dramatically depending on who was asked, and when the question was posed. Yet as we enter the 3rd year after the virus made its global appearance, there remain some real and significant issues. Among these is the key question of what is “long COVID” and how and why do so many people experience long-term brain effects after infection with the virus. Now, a variety of research is shedding light on this important topic.
After the acute infection with the SARS-CoV-2 virus, many people experience changes to their health that remain long after. In fact, estimates are that over 65 million people around the world suffer from what has been called “long COVID.” Among the problems linked to long COVID are brain-specific issues like mental health conditions, fatigue, issues with sleeping and cognitive impairment. These symptoms correlate with trouble performing basic activities like walking and paying bills.
The wide variety of brain-related issues linked to long COVID and the millions of people suffering from these problems have prompted researchers and the lay public alike to investigate how and why infection with COVID can influence the brain, as well as potential strategies to offset its effects.
Research across a range of studies has highlighted potential avenues by which the COVID pandemic could negatively impact brain health. Some possible contributors include viral spread into the brain, inflammation associated with infection, metabolic challenges, microbiome changes and damage to blood vessels. Yet it’s also important to highlight that many people may experience similar brain issues during the pandemic independent of infection, as a reflection of the stress, unhealthy eating and lifestyle changes that occurred in the context of large-scale lockdown measures. This speaks to the idea that certain brain symptoms thought to be due to COVID infection may in fact be better explained by other factors. To this end, some research finds that a sizable proportion of people attributing their symptoms to COVID may not have evidence of infection with the virus.
Some of the most recent study of the long COVID-brain link specifically doubles down on the idea of brain inflammation as a driver of brain issues. In a March 2023 study published in Brain, Behavior, and Immunity, researchers studied the SARS-CoV-2 virus in animal models and found that the virus activated immune cells in the brain, increasing brain inflammation. Importantly, we now know that immune cells in the brain (called microglia) may have a role to play in mood, cognition and much more. Specifically, activation of inflammatory microglia has been linked to increased risk for brain health conditions.
Despite all the research done to date, concrete answers on exactly what is driving brain symptoms of long COVID remain somewhat elusive. Likely, there are a number of different processes at play. Regardless of the drivers, a continued emphasis on finding solutions for people experiencing related brain issues is critical. To date, protocols for brain symptoms associated with long COVID have been inconsistent in application and efficacy. But with the growing understanding of how alterations in the brain’s immune system (e.g., inflammation) may drive mental and cognitive symptoms, we can’t discount the potential role for lifestyle modifications (e.g., the importance of diet, exercise, sleep, anti-stress, a focus on the gut-brain axis etc.) as an important part of the equation.
Lastly, it’s worth considering that while many millions of people around the world report suffering from long COVID brain symptoms, the overall burden of brain issues globally is in the hundreds of millions, if not billions. Stress, depression and cognitive issues like dementia are on the rise. And regardless of where you stand on COVID, paying attention to brain health and interventions that can help improve it is key.
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