Brain clues in the battle against long COVID: study pinpoints neuroinflammation

4 minutes, 16 seconds Read

The coronavirus disease 2019 (COVID-19) pandemic has led to a public health crisis known as post-acute sequelae of COVID-19 or post-acute sequelae of COVID-19 (PASC).

A recent study published bioRxiv* The preprint server analyzed the relationship between circulating markers of vascular dysfunction and neuroinflammation in patients with various symptoms of PASC. used in the study [11C]PBR28 PET neuroimaging to detect neuroinflammation

Study: Neuroinflammation in Post-Acute Sequelae of Covid-19 (PASC). [11C]PBR28 correlates with PET measures of vascular disease.  Image Credit: Meeko Media/Shutterstock.comStudy: Neuroinflammation in the post-acute sequelae of COVID-19 (PASC). [11C]PBR28 correlates with PET measures of vascular disease. Image Credit: Meeko Media/

*Important Notice: bioRxiv Preliminary scientific reports are published that are not peer-reviewed and, therefore, should not be considered conclusive, guidelines for clinical practice/health-related behavior, or established information.


The ongoing COVID-19 pandemic was caused by the rapid outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a highly contagious respiratory virus. According to a recent US Census Bureau Household Pulse Survey report, 11% of adults who contracted SARS-CoV-2 infection developed PASC.

Several non-specific neurological and neuropsychiatric symptoms, such as brain fog, severe fatigue, difficulty concentrating, depression, anxiety, body aches and irregular sleep, have been identified as long-term COVID manifestations.

These symptoms significantly affect the quality of life. Prolonged-Covid is not only associated with severe infection, but also mild SARS-CoV-2 infection can lead to PASC.

Vascular-related problems, inflammation, and coagulation developed during acute SARS-CoV-2 infection may persist and lead to the development of PASC.

Several studies have shown that the brain is exceptionally vulnerable to disruption of vascular health. These studies also indicated that SARS-CoV-2 infection is a risk factor for vascular health disorders. For example, survivors of acute COVID-19 have been shown to be at higher risk of hemorrhagic stroke and cerebral venous thrombosis, particularly in the year following infection.

A longitudinal study compared structural neuroimaging of the same individuals, pre-pandemic and post-Covid. A small but significant decrease in gray matter thickness and whole brain volume was observed. Also, elevated markers of tissue damage were observed in post-Covid samples.

A neuroimaging study based on arterial spin labeling fMRI found decreased neurovascular perfusion in long-covid patients. No PASC studies have found a direct link between neuroinflammation and vascular dysfunction.

About the study

The present cross-sectional, case-control study determined that long-covid patients with various symptoms have a higher risk of neuroinflammation than healthy controls with no history of SARS-CoV-2 infection. This study also investigated whether PASC neuroinflammation was associated with vascular health.

The present study compared PASC with control individuals without a history of Covid-19. Positron emission tomography (PET) neuroimaging was used to determine neuroinflammation in PASC. here, [11C]PBR28 PET neuroimaging standardized uptake value ratio (SUVR) was compared between PASC and controls.

All participants were asked to complete a questionnaire regarding pain and depression. PASC participants answered additional questions related to their PASC symptoms.

Peripheral blood samples were collected from PASC participants immediately after PET scans to understand the relationship between central nervous system (CNS) glial activation in PASC and measures related to inflammation, vascular health, and angiogenesis.

Furthermore, platelet-poor plasma (PPP) was estimated for the PASC group just before [11C]PBR28 exposure.

A modified Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) International Consensus Criteria (ICC) was used as PASC group inclusion criteria. A total of 12 subjects were recruited for the PASC group. These individuals were compared to an existing normative dataset of 43 healthy controls.

Study results

Most of the participants in the PASC did not require hospitalization for their acute SARS-CoV-2 infection. A significant increase [11C]PBR28 signal was observed in a wide range of brain regions, including the thalamus, midcingulate cortex, corpus callosum, anterior cingulate cortex, basal ganglia/striatum, medial frontal gyrus, subfornical organ, and precentral gyrus.

Contrary to the results of previous studies, the current study indicated that the average depression score of the PASC group was milder. In contrast, the control group reported depression in the pre-COVID period. Future studies must include additional COVID-19-recovered individuals for a reference group.

Whole brain PET signal intensity indicates significant positive correlation with blood measurements and vascular health. Variability of PET signal across brain structures reflects differences in vascular anatomy and perivascular immune infiltration.

An elevated level of fibrinogen and SL-selectin, markers of the vascular health multiplex panel, was significantly correlated with neuroinflammation-related PET signal. A previous study indicated that increased fibrinogen levels lead to adverse COVID-19 outcomes.

Activated perivascular glia trigger circulating glia to transport immune components from the brain parenchyma and neurovascular blood to the brain.

This study also revealed that a vascular-related anatomical pattern differs between patients. An increased PET signal, particularly within the left lentiform nucleus of the basal ganglia, was observed.


This study has some limitations, including the small number of participants in the PASC group compared to the control group. There is a need to design a well-defined cohort of PASC phenotypes.

Additionally, the majority of participants in the PASC group were female. Despite limitations, the present study provides evidence that vascular dysfunction and neuroinflammation-related processes are directly linked to PASC.

*Important Notice: bioRxiv Preliminary scientific reports are published that are not peer-reviewed and, therefore, should not be considered conclusive, guidelines for clinical practice/health-related behavior, or established information.

Similar Posts

Leave a Reply

Your email address will not be published. Required fields are marked *

Best Romantic Places To Propose In the World ​Jr Mehmood’s Top Performances: Ghar Ghar Ki Kahani, Aap Ki Kasam And More ​ Most Beautiful Bioluminescent Beaches in The World Health Benefits Of Curry Leaves Benefits Of Amla For Hair Growth