For many people, recovering from COVID-19 does not mean returning immediately to their previous health.
Months or even years after the initial infection, some continue to experience persistent fatigue, difficulty concentrating, memory problems, disturbed sleep, anxiety, or depression.
These symptoms are among the many manifestations of long COVID, a complex condition that scientists are still working to understand.
One leading hypothesis suggests that central nervous system inflammation may contribute to neurological and psychiatric symptoms after SARS-CoV-2 infection.
But does brain inflammation remain elevated long after the infection passes?
A study published in the Journal of Neurology on April 30, 2026, used positron emission tomography (PET) to investigate this question. This imaging technology detects molecular signals associated with immune activity in the brain.
The researchers examined 14 people with long COVID, 11 healthy controls, and 13 people with multiple sclerosis.
Their findings challenged a simple explanation of persistent brain inflammation.
People with long COVID did not show significantly higher overall levels of the measured neuroinflammation-related PET signal than healthy individuals.
However, within the long COVID group, higher PET signals in certain brain regions were associated with more severe depression, anxiety, and poorer quality of life.
The results suggest that neurological symptoms after COVID-19 may involve region-specific biological changes rather than persistently elevated inflammation throughout the brain.
Still, the study was small, and the findings do not establish that inflammation directly causes long COVID symptoms.
Original research: Association Between Post-COVID-19 Neuropsychiatric Symptoms and Persistent Glial Activation in the Limbic System: A TSPO PET Study.
What Is Long COVID?
Long COVID, also known as post-COVID-19 condition, describes health problems that continue or develop after a SARS-CoV-2 infection.
The World Health Organization defines the condition as symptoms that usually begin or persist around three months after infection, last at least two months, and cannot be explained by another diagnosis.
These symptoms can affect multiple organ systems and vary considerably between individuals.
Commonly reported problems include:
- Persistent fatigue or exhaustion.
- Difficulty concentrating or remembering information.
- Headaches and sleep disturbances.
- Shortness of breath.
- Dizziness or palpitations.
- Worsening symptoms after physical or mental activity.
- Anxiety, depression, or other emotional difficulties.
Some people improve gradually, while others experience symptoms that fluctuate or interfere with their ability to work, study, or perform everyday tasks.
According to the WHO’s February 2025 fact sheet, about six in every 100 people who develop COVID-19 may experience post-COVID-19 condition, although estimates vary by population, vaccination history, viral variants, and research methods.
Source: World Health Organization — Post COVID-19 Condition.
Why Are Scientists Investigating Brain Inflammation?
Neuroinflammation refers to immune-related activity within the brain and spinal cord.
It can occur in response to infection, injury, autoimmune processes, or other biological disturbances.
An important part of this response involves glial cells, which support and protect neurons.
Two major types of glial cells are microglia and astrocytes.
Microglia: The Brain’s Immune Surveillance Cells
Microglia are specialized immune cells that help monitor the brain’s environment.
They respond to infection, damaged cells, and changes in surrounding tissue.
Their activity can be protective, clearing cellular debris and supporting normal function.
However, prolonged or dysregulated immune responses may also contribute to tissue stress.
Astrocytes: Supporting Brain Function
Astrocytes help maintain the chemical environment around neurons, support the blood-brain barrier, and regulate communication between brain cells.
They can also change their activity in response to inflammation or injury.
Researchers have proposed that persistent activation of microglia and astrocytes could contribute to symptoms such as brain fog, fatigue, and mood disturbances after COVID-19.
However, immune activation isn’t automatically harmful, and glial activity isn’t synonymous with damaging inflammation.
Scientists therefore need reliable ways to investigate what these cells may be doing in living humans.
How Do PET Scans Detect Neuroinflammation?
Positron emission tomography is an imaging technique that uses small quantities of radioactive tracers to study biological processes inside the body.
Unlike conventional magnetic resonance imaging (MRI), which primarily reveals anatomical structures, PET can provide information about molecular activity.
In the 2026 study, researchers used a tracer called [11C]PK11195.
This tracer binds to a protein known as the 18-kilodalton translocator protein, or TSPO.
TSPO is found in the outer mitochondrial membrane and can show altered expression in activated glial cells.
Because glial activation can accompany neuroinflammation, researchers use TSPO PET imaging to investigate immune-related changes in the brain.
However, there is an important limitation.
TSPO is not an exclusive marker of harmful inflammation.
Its expression is not limited to a single immune cell type, and changes in the PET signal cannot independently identify the exact biological process responsible.
Researchers therefore describe TSPO PET as an indirect marker of glial activation or neuroinflammation-related activity.
The method does not directly show individual inflammatory molecules attacking neurons.
How Was the 2026 Study Conducted?
The research was led by Joel Tuomaala, Maija Saraste, and colleagues affiliated with institutions including the University of Turku and Turku University Hospital in Finland.
The investigators recruited people with persistent neurological symptoms following confirmed SARS-CoV-2 infection.
The study included 38 participants divided into three groups.
Group 1: Long COVID
Fourteen adults experienced persistent neurological or cognitive symptoms that affected their ability to work or study.
Their time since SARS-CoV-2 diagnosis ranged from seven to 33 months, with a median of 15 months.
Group 2: Healthy Controls
Eleven individuals without known neurological symptoms or diseases served as a comparison group.
Their imaging measurements helped researchers determine whether the long COVID group showed unusual TSPO PET signals.
Group 3: Multiple Sclerosis
Thirteen people with multiple sclerosis (MS) served as a positive neuroinflammatory comparison group.
Multiple sclerosis is a chronic, immune-mediated disease that affects the central nervous system.
Researchers included this group because MS can involve inflammatory activity that TSPO PET may detect.
What Tests Did Participants Receive?
All participants underwent:
- TSPO PET imaging using [11C]PK11195.
- High-resolution 3-tesla MRI.
- Blood testing for selected neurological biomarkers.
The long COVID participants also underwent neurological examinations and completed questionnaires assessing psychological symptoms, disability, and quality of life.
The researchers measured serum neurofilament light chain (NfL), a marker associated with nerve-fiber injury, and glial fibrillary acidic protein (GFAP), a marker associated with astrocytic activity or injury.
This combination of imaging, blood tests, and clinical assessments allowed the researchers to examine several possible indicators of nervous system involvement.
Read the full open-access study in the Journal of Neurology.
Key Finding 1: Long COVID Patients Did Not Show Greater Overall TSPO Activity
The most important result was also the most unexpected.
Researchers found no statistically significant differences in TSPO PET binding between the long COVID group and healthy controls in the examined brain regions.
This included both broad brain measurements and selected areas involved in cognition and emotional regulation.
The investigators calculated TSPO tracer binding using a measure called the distribution volume ratio (DVR).
Higher DVR values can indicate greater availability of the tracer-detected molecular target.
However, they must be interpreted in the context of the imaging method and other clinical findings.
The absence of elevated TSPO binding suggests that ongoing, widespread glial activation detectable with this method may not explain persistent neurological and psychiatric symptoms in every person with long COVID.
Importantly, the result does not establish that long COVID symptoms are psychological or imaginary.
It also does not rule out other forms of inflammation, subtle molecular abnormalities, or biological changes that the tracer may not detect.
The study’s small sample size further limits how confidently researchers can exclude modest differences.
Key Finding 2: Longer Disease Duration Was Associated With Lower White Matter TSPO Signals
The researchers divided long COVID participants by how long it had been since their confirmed SARS-CoV-2 infection.
Eight participants had been diagnosed within the preceding 16 months.
Six had a longer disease duration.
The group with a shorter time since infection had a higher TSPO PET signal in normal-appearing white matter.
The reported DVR values were:
- Within 16 months: 1.05.
- More than 16 months: 1.02.
This difference was statistically significant (p = 0.042).
White matter contains nerve fibers that connect different areas of the brain.
The finding suggests that glial activation associated with COVID-19 may become less pronounced over time.
However, the researchers did not repeatedly scan the same participants over multiple years.
Instead, they compared people who had lived with long COVID for different lengths of time.
Consequently, the findings cannot establish that inflammation declined within any particular individual.
The difference may also reflect other participant characteristics.
Larger longitudinal studies will be needed to determine whether TSPO signals genuinely change during recovery.
Key Finding 3: Mental Health Symptoms Were Linked to Signals in the Limbic System
Although long COVID participants did not show elevated overall TSPO binding compared with healthy controls, researchers identified meaningful associations within the long COVID group.
Higher TSPO PET signals in certain brain regions were associated with greater depression and anxiety symptom severity.
These regions included the hippocampus and amygdala, two structures involved in memory and emotional processing.
The researchers also found relationships between PET measurements and self-reported quality of life.
The Hippocampus
The hippocampus supports learning, memory formation, and certain aspects of emotional processing.
Researchers have investigated changes in hippocampal function in numerous neurological and psychiatric conditions.
In the study, higher hippocampal TSPO availability was associated with more severe depression and anxiety questionnaire scores.
The Amygdala
The amygdala plays a major role in processing emotionally significant information, including threat-related signals.
It interacts with wider brain networks involved in stress responses and emotional regulation.
Higher amygdala TSPO availability was also associated with more severe depression and anxiety measures.
The Thalamus
The thalamus helps coordinate the transmission and integration of sensory and other information between brain regions.
The researchers found that higher TSPO signals in the thalamus, hippocampus, and amygdala were associated with lower reported quality of life.
The strength of these quality-of-life correlations ranged from approximately −0.70 to −0.83.
Positive correlations between depression or anxiety symptom scores and relevant limbic TSPO measures ranged from approximately 0.75 to 0.97.
These are substantial correlations within the studied sample.
However, the analyses were exploratory, involved few participants, and examined multiple relationships.
They should not be interpreted as proof that inflammation in these brain regions caused depression or anxiety.
A correlation between brain imaging and symptom severity identifies a potential biological relationship, not a confirmed causal mechanism.
Key Finding 4: Blood Markers Did Not Show Clear Evidence of Persistent Nervous System Injury
The investigators measured two blood biomarkers associated with different aspects of nervous system injury.
Neurofilament Light Chain (NfL)
NfL is a structural protein found in neurons, particularly within their axons.
Elevated blood NfL can occur when nerve fibers are damaged.
The researchers found a statistically significant difference in serum NfL between the long COVID and healthy control groups.
Glial Fibrillary Acidic Protein (GFAP)
GFAP is a protein primarily associated with astrocytes.
Blood GFAP concentrations can increase in certain neurological conditions involving astrocytic injury or activation.
The study found no significant difference in GFAP concentrations between long COVID participants and healthy controls.
These findings suggest that the study did not detect a strong blood biomarker signal of ongoing neuronal or astrocytic injury.
However, normal levels of NfL and GFAP do not rule out all forms of neurological dysfunction.
The sensitivity of blood biomarkers depends on the underlying condition, timing, and nature of the biological changes.
Key Finding 5: MRI Did Not Reveal Significant Brain Volume Differences
Researchers also compared MRI-based measurements of selected brain regions.
They found no statistically significant differences in regional brain volume measures between long COVID participants and healthy controls.
This finding suggests that the study did not detect major structural volume abnormalities in the examined regions.
However, brain volume is only one measure of neurological health.
Functional disturbances, metabolic changes, altered connectivity, autonomic dysfunction, and other abnormalities may occur without obvious volume loss.
The absence of significant MRI differences therefore does not mean that participants experienced no biological consequences from long COVID.
Summary: What Did the Brain Scans Actually Show?
| Measurement | Main finding |
|---|---|
| Overall TSPO PET binding | No significant difference between long COVID and healthy controls |
| Comparison with multiple sclerosis | Lower TSPO signals in long COVID across several regions |
| White matter TSPO binding | Higher in participants scanned within 16 months than in those with longer disease duration |
| Depression and anxiety | Associated with higher hippocampal and amygdala TSPO binding within the long COVID group |
| Quality of life | Lower scores associated with higher TSPO signals in selected limbic regions |
| Blood NfL and GFAP | No significant differences between long COVID and healthy controls |
| MRI brain volume | No significant differences between long COVID and healthy controls |
These findings describe associations observed in a small research study. They do not establish causation or provide a clinical test for diagnosing long COVID.
Source: Tuomaala et al., Journal of Neurology, 2026.
Does This Mean Brain Inflammation Is Not Involved in Long COVID?
No.
The study suggests that persistently elevated, widespread TSPO-detectable glial activation may not be present in all people experiencing long COVID symptoms many months after infection.
That is different from proving that neuroinflammation never contributes to the condition.
Several explanations remain possible.
First, immune-related activity may be more pronounced during earlier phases of long COVID and gradually diminish.
Second, changes could be restricted to particular brain regions or specific cell populations.
Third, different biological pathways may contribute to different symptom patterns.
Finally, TSPO PET has limitations and cannot detect every form of inflammation or cellular dysfunction.
Other investigations have reported different neuroinflammation-related imaging findings in some long COVID populations.
Differences between studies may reflect variations in participant characteristics, time since infection, imaging tracers, statistical methods, and the biological processes being measured.
The 2026 Finnish study adds important evidence but does not settle the broader debate.
Why Might Long COVID Affect Memory, Mood, and Concentration?
Scientists are investigating several possible biological mechanisms.
1. Immune System Dysregulation
SARS-CoV-2 infection can trigger substantial immune responses.
Researchers are investigating whether lingering immune abnormalities or inflammatory signaling contribute to symptoms in some patients.
2. Changes in Blood Vessel Function
The brain depends on a continuous supply of oxygen and nutrients.
Some studies suggest that endothelial dysfunction or abnormalities in small blood vessels may contribute to neurological symptoms following COVID-19.
However, the extent to which these processes explain long COVID remains under investigation.
3. Autonomic Nervous System Dysfunction
The autonomic nervous system helps regulate heart rate, blood pressure, digestion, and other automatic bodily functions.
Some people with long COVID experience orthostatic intolerance, dizziness, or postural orthostatic tachycardia syndrome (POTS).
These problems may contribute to fatigue and make it harder to function.
4. Cellular Energy Metabolism
Researchers have proposed that disruptions in cellular energy production or metabolism could contribute a persistent fatigue and exercise intolerance.
The 2026 PET study’s findings support further investigation of metabolic mechanisms, but they do not directly show that these mechanisms caused participants’ symptoms.
5. Sleep Disturbances and Other Coexisting Conditions
Poor sleep, chronic pain, anxiety, depression, and other medical conditions can interact with cognition and fatigue.
These factors may contribute to symptom severity without fully explaining the underlying illness.
Long COVID is likely heterogeneous, meaning that different patients may have different combinations of biological abnormalities.
A single mechanism may not explain every case.
What Are the Main Limitations of the PET Study?
Although the investigation provides valuable biological insight, several limitations are important.
Small Sample Size
Only 14 people with long COVID participated.
Such a small group limits statistical power and makes results vulnerable to individual differences.
Cross-Sectional Design
Participants were scanned at a single time point rather than repeatedly over the course of their illness.
Therefore, the study cannot establish how brain inflammation changed within individuals over time.
Exploratory Symptom Correlations
Researchers tested relationships between PET measurements and several psychological questionnaires.
Because the sample was small and multiple associations were examined, apparently strong correlations may not remain stable in larger studies.
TSPO Is an Indirect Biomarker
TSPO PET measures tracer binding associated with cellular activity.
It does not directly identify the signal’s cause or prove that damaging inflammation is present.
Differences Between Participant Groups
Although the investigators used comparison groups, other variables—including clinical history, medication use, and previous infections—could influence imaging results.
Limited Generalizability
Long COVID participants had persistent neurological symptoms that affected work or study.
Their findings may not represent people with milder symptoms, predominantly cardiovascular or respiratory long COVID, or different clinical backgrounds.
These limitations mean the study should be considered exploratory rather than definitive.
October 2026 Update: What Does This Mean for Long COVID Diagnosis and Treatment?
As of October 2026, TSPO PET imaging remains a research tool, not an established diagnostic test, for long COVID.
The findings do not provide a validated imaging threshold that clinicians can use to confirm or rule out the condition.
The US Centers for Disease Control and Prevention emphasizes that clinicians diagnose long COVID through clinical evaluation and that no laboratory test can definitively diagnose or exclude it.
This matters because a person can have significant symptoms even when routine clinical tests are normal.
Treatment generally focuses on identifying the most troublesome symptoms, evaluating other medical conditions, and improving daily functioning.
For some patients, this may involve coordinated care addressing sleep problems, cognitive symptoms, autonomic dysfunction, depression, anxiety, and other complications.
People who experience post-exertional malaise—worsening symptoms after physical or mental activity—may need individualized activity management and pacing.
Automatically increasing exercise intensity can be inappropriate when exertion repeatedly triggers symptom deterioration.
The PET study does not establish that anti-inflammatory medications or immunosuppressive treatments will improve neurological long COVID.
Do not start such treatments solely because of research findings involving TSPO imaging.
Source: CDC, Long COVID Clinical Guidance.
What Should People With Long COVID Symptoms Do?
Persistent neurological or mental health symptoms deserve appropriate medical attention.
People experiencing long COVID can benefit from discussing changes in concentration, memory, mood, sleep, activity tolerance, and daily functioning with a healthcare professional.
A clinician may evaluate possible contributing conditions, review medications, and recommend targeted investigations when appropriate.
Clinicians should also assess and treat mental health symptoms when present.
Depression and anxiety after COVID-19 are genuine health concerns, but experiencing them does not mean the underlying physical symptoms are imaginary.
Likewise, finding no clear abnormality on conventional testing does not invalidate the patient’s experience.
Effective care requires attention to both physical symptoms and psychological well-being.
The CDC recommends a patient-centered approach that focuses on symptom management, achievable goals, and appropriate clinical support.
Conclusion: Long COVID Brain Changes Are More Complex Than Persistent Inflammation
The April 2026 Journal of Neurology study provides valuable insight into the relationship between long COVID, glial activity, and neurological symptoms.
Using TSPO PET imaging, researchers found no significant overall increase in the measured neuroinflammation-related signal in people with long COVID compared with healthy controls.
They also observed lower TSPO binding in white matter among participants with longer disease duration, suggesting that immune-related activity may change over time.
At the same time, higher TSPO signals in brain regions associated with emotion and memory were linked to greater depression and anxiety symptoms and poorer quality of life.
These findings suggest that a simple model of widespread, ongoing brain inflammation cannot explain persistent long COVID symptoms.
Instead, different biological mechanisms—including region-specific cellular activity, metabolic dysfunction, and other neurological processes—may interact.
The study provides new clues about the biology of long COVID, but it does not establish a new diagnostic test, prove the cause of psychiatric symptoms, or identify a treatment.
Larger studies that follow patients over time will be essential to determine how brain-related changes evolve and whether they can eventually guide more effective care.
References
1. Original 2026 Research Study
Tuomaala, J., Saraste, M., Smith, E., et al. (2026). Association Between Post-COVID-19 Neuropsychiatric Symptoms and Persistent Glial Activation in the Limbic System: A TSPO PET Study. Journal of Neurology, 273, Article 298.
https://doi.org/10.1007/s00415-026-13842-w
2. Full Open-Access Research Article
Springer Nature, Journal of Neurology.
https://link.springer.com/article/10.1007/s00415-026-13842-w
3. PubMed Research Record
US National Library of Medicine.
https://pubmed.ncbi.nlm.nih.gov/42059960
4. World Health Organization
Post-COVID-19 Condition (Long COVID).
https://www.who.int/news-room/fact-sheets/detail/post-covid-19-condition-%28long-covid%29
5. US Centers for Disease Control and Prevention
Long COVID Clinical Guidance.
https://www.cdc.gov/long-covid/hcp/clinical-guidance/index.html
6. US Centers for Disease Control and Prevention
Long COVID Signs and Symptoms.
https://www.cdc.gov/long-covid/signs-symptoms/index.html
7. University of Helsinki
Research Publication Record: Association Between Post-COVID-19 Neuropsychiatric Symptoms and Persistent Glial Activation in the Limbic System.