Lost in the Fog: How Viruses Impact Our Brain Function

Viruses can evade, influence, and attack our immune systems, sometimes leaving us feeling like we are in a fog.

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A high fever, sore throat, and body aches — viral infections usually run their course. But sometimes, something else lingers: a persistent mental haze. Tasks take longer, details evade recall, and concentration falters. 

Viruses like SARS-CoV-2 (the virus causing COVID-19), human immunodeficiency virus (HIV), and herpes simplex virus type 1 (HSV-1) all have the capacity to cause “brain fog,” impairing memory and disrupting brain function, even in people who have not experienced other symptoms.

Viral infections can precipitate lasting negative mental effects by over-activating the immune system, triggering chronic inflammation and structural damage. The result may include short-term memory lapses, trouble focusing, and a general sense of cognitive dulling for those experiencing brain fog.

How a Virus Hijacks the Immune System

Neurologist William T. Hu of Rutgers University thinks that post-COVID cognitive symptoms may be linked to immune system dysfunction in the brain. In a 2024 study, Hu and his colleagues identified an altered immune signature in the cerebrospinal fluid (CSF) of patients with post-COVID brain fog, a hallmark symptom of Long COVID — a condition where symptoms like fatigue, muscle weakness, and cognitive impairment continue long after the initial COVID-19 infection has cleared.

The team analyzed patients nine months after COVID-19 infection and found cognitive dysfunction was common and could not be explained by fatigue, sleep, or mood. “We found a very unifying pattern in people with cognitive Long COVID: a gene signature that recruited more monocytes,” Hu explained. Monocytes, a type of white blood cell, help regulate inflammation, fight infections, and repair dead or damaged cells. 

The team also found abnormal immune cell activation and elevated cytokines — the chemical messengers helping coordinate the body’s immune response — closely followed with cognitive impairment. High cytokine levels in the brain can induce inflammation, disrupting brain function and causing problems with attention, memory, and mental clarity. Their findings suggest the changes in immune cell activation represent a lasting immune response in the brain, not just stress or exhaustion.

“…Something’s off in the crosstalk between immune cells.” — William HuNot everyone exposed to SARS-CoV-2 will develop cognitive impairment. “In people who recover, monocyte recruitment leads to a normal immune response,” Hu explained. “But in those who don’t, the clearance mechanism isn’t what we expect. Something’s off in the crosstalk between immune cells.” As people who fully recovered from COVID did not show the same immune patterns, researchers believe persistent immune dysfunction can drive the cognitive symptoms many Long COVID patients face. 

Other findings suggest SARS-CoV-2 can directly enter the brain and infect neurons, without invoking immune dysfunction, to cause brain fog. These infections may also induce the production of amyloid proteins linked to Alzheimer’s, potentially leading to chronic, excessive protein production and harmful inflammation.
 
Not All Viruses Cause Damage the Same

The mechanisms by which viruses impair memory vary. While some RNA viruses like SARS-CoV-2 can directly affect neuronal cells and induce immune responses that persist for an acute period, other viruses like HIV lie dormant after initial infection.

HIV causes damage to the immune system, triggering inflammation in the brain and spinal cord, attacking T cells — white blood cells helping protect the body from infection — infecting microglia, the brain’s resident immune cells. As viral proteins continue to circulate in the brain, people living with HIV can develop long-term neurocognitive impairments, resulting in a lack of concentration, trouble with memory, and slowed thinking.

Treatments like antiretroviral therapies can keep HIV undetectable and may help prevent or reverse mild cognitive symptoms. But people on these therapies may still experience mild cognitive impairments. “Even though the person doesn't have infectious virus coming out of them, they've still got these proteins that are causing problems, causing immune activation, inflammation, and affecting the brain negatively,” said Ronald Ellis, a board-certified neurologist at University of California San Diego Health who specializes in neurological manifestations of HIV.

Other viruses, like HSV-1 — the common trigger for cold sores — can directly infect neurons, causing inflammation and even neuronal death. Once infected, the virus lies dormant inside nerve cells and evades the immune system for years. 

Researchers are increasingly finding associations between HSV-1 infections and dementia, a more permanent decline in cognitive ability marked by symptoms like those seen in brain fog. One 2023 meta-analysis reviewing 90 studies with nearly 350,000 participants concluded HSV-1 was significantly associated with an increased risk of dementia. Other research using organoids, or tiny lab-grown brain models, found HSV-1 infection can cause inflammation and a buildup of amyloid-beta proteins linked to Alzheimer’s. And head trauma may reactivate dormant HSV-1, jumpstarting inflammation and amyloid buildup. 

What’s Causing the Fog?

Across viral infections leading to brain fog, age, genetic background, and immune health all impact susceptibility to cognitive problems. 

For example, those who carry the APOE4 allele gene, a gene variant linked to a higher risk of Alzheimer’s, are likely to be more vulnerable to memory and cognitive dysfunction. Patients with pre-existing neurological conditions such as Parkinson’s disease, or those who are on immunosuppressive therapy, often struggle to return to their baseline after infection.

The integrity of the blood-brain barrier (BBB), a protective layer separating the brain from the rest of the body’s bloodstream, also plays a critical role. Age, injury, disease and lifestyle choices — like poor diet or drug use — all alter the BBB. A weakened barrier allows immune mediators and pathogens to infiltrate the brain, amplifying damage. “Something that wouldn't tip a healthy person over does tip them over because they're starting from a different place. That's something that's held in common for pretty much every brain disease,” said Ellis.

Still, the brain is a resilient organ. Neuroplasticity, the brain's ability to rewire itself, offers a pathway to recovery. “Neuroplasticity is essential to how the brain recovers from viral insult,” said Tamara Kermani, a family medicine physician at Parkview Health in Fort Wayne, Ind., with expertise in Long COVID.

“With hard work and neuropsychiatric rehab, the brain can remold confused or lost connections to regain memory, attention, and function,” Kermani said. Rehabilitative treatment options, however, remain limited. “Access to cognitive rehab is a major challenge, especially for patients not near large medical centers,” she added. 

Other treatment options for viral-induced cognitive impairments have mixed results to date. One approach, an intravenous immunoglobulin therapy made from donated antibodies used to regulate the immune system responses, hasn’t consistently improved symptoms.

Hu believes there may be hope with antiviral treatments. “Antivirals may have a better shot, especially if we’re dealing with a chronic viral infection, not just a lingering immune response,” he said.

“The big, unanswered question is: Are they all just part and parcel of the same underlying problem? Or is there a level of specificity that you could target one or more of those?” asked Ellis. Determining which biomarkers are relevant for studying each viral infection, whether there is overlap in treating brain fog across viruses, and how to target these shared processes, are all important steps toward identifying potential treatments. “I suspect it's going to be multiple shots on goal — combination therapies. But combination therapies are very hard to study because the clinical trials become incredibly complex, and it is hard to disentangle the effects of things when you have them given at the same time.” 

Determining whether brain fog is caused by lingering inflammation or a virus that has never fully gone away is essential. The answer will tell us whether calming down an overactive immune system or suppressing a virus could help ease patients’ symptoms.  the answer. For those still struggling to think clearly after infection, understanding the difference between the two is the first step toward recovery.

About the Author

Caleb Neal

Caleb Neal is a medical student based in Brooklyn, NY. He played semi-professional hockey in Sweden as a graduate student at Augusta University.