Understanding Long COVID Brain Fog: Insights from Recent Studies

In the wake of the COVID-19 pandemic, medical researchers have been racing to unravel the
mysteries of its long-term effects, commonly referred to as "long COVID." Among the multitude of
symptoms reported by long COVID sufferers, perhaps one of the most debilitating is brain fog, a
cognitive impairment characterised by confusion, memory lapses, and difficulty concentrating.
Recent studies have shed light on the potential causes of this perplexing symptom, offering hope for
future treatments and management strategies.

A study featured in The Guardian suggests that brain fog in long COVID patients may stem from a
phenomenon known as a leaky blood-brain barrier. This is a protective membrane that regulates the
passage of substances between the bloodstream and the brain. When this barrier becomes
compromised, as seen in conditions like Alzheimer's disease and traumatic brain injury, it can lead to
cognitive dysfunction. Researchers found that samples of serum and plasma from patients who self-
reported brain fog contained higher levels of a protein called S100β than those from short – term
COVID patients or people who had not experienced COVID at all. This protein is produced by cells
within the brain, and is not normally found in the blood. They act as inflammatory markers, and the
infiltration of these molecules, and other detrimental substances into the brain parenchyma could
precipitate neuroinflammation and neuronal dysfunction, contributing to the symptoms observed in
long COVID patients, such as brain fog.

Further insights into the mechanisms of brain fog in long COVID come from research highlighted by
CIDRAP. Through a combination of clinical observations and experimental studies, scientists have
identified a specific mechanism behind brain fog, involving the dysregulation of microglia, immune
cells in the brain. Microglia play a crucial role in maintaining brain health and responding to
inflammation (encephalitis). In long COVID, these cells may become hyperactivated, leading to
persistent inflammation and dysfunction. As well as this, the researchers found that in patients with
long COVID-19, the immune system produced elevated levels of a protein called MIF (macrophage
migration inhibitory factor). MIF is known to also be involved in the body's inflammatory response.
Large quantities of MIF were associated with cognitive difficulties, such as memory problems and
difficulty concentrating, commonly reported by individuals with long COVID-19. Understanding this
mechanism opens up possibilities for developing targeted therapies to modulate microglial and MIF
activity and alleviate brain fog in affected individuals.

Moreover, an article from The Conversation delves into the broader neurological impacts of COVID-
19, beyond just brain fog. Mounting evidence suggests that the virus leaves its mark on the brain,
affecting its function, contributing to analytical decline and significant drops in IQ scores among
affected individuals. This highlights the multifaceted nature of COVID-19's neurological
repercussions, ranging from memory lapses and difficulty concentrating to executive dysfunction.
Neuroimaging studies have revealed that the SARS-CoV-2 infection triggers the fusion of brain cells,
short – circuiting brain electrical activity, causing inflammation and abnormalities in brain regions
associated with cognitive processing. The long-term mental sequelae of COVID-19 underscore the
urgent need for comprehensive neurological assessments and tailored interventions to mitigate
cognitive decrease in affected populations.

In conclusion, many recent studies have uncovered compelling evidence linking brain fog in long
COVID patients to disruptions in the blood-brain barrier and vascular integrity. This common
symptom represents a complex interplay of inflammatory, immune, and neurobiological factors. By
elucidating the underlying mechanisms driving brain fog, researchers aim to develop effective
treatments to improve analytical function and quality of life for individuals affected by long COVID.
These insights not only contribute to our understanding of COVID-19 pathology, but also have
broader implications for the management of neurological conditions and brain health.

References:

Davis, N. (2024, February 22). Long Covid Brain Fog May Be Due to Leaky Blood-Brain Barrier, Study
Suggests. https://www.theguardian.com/society/2024/feb/22/long-covid-brain-fog-may-be-due-to-
leaky-blood-brain-barrier-study

Al – Aly, Z. (2024, February 28). Mounting Research Shows that COVID-19 Leaves its Mark on the
Brain, Including with Significant Drops in IQ Scores. https://theconversation.com/mounting-
research-shows-that-covid-19-leaves-its-mark-on-the-brain-including-with-significant-drops-in-iq-
scores-224216

Schnirring, L. (2024, February 22). Researchers Identify Mechanism Behind Brain Fog in Long Covid.
https://www.cidrap.umn.edu/covid-19/researchers-identify-mechanism-behind-brain-fog-long-covid