Neuroinflammation was identified across a wide range of brain regions and connected to measures of blood vessel dysfunction

Project lead Dr. Michael VanElzakker

 (Medford MA, May 2, 2024) – Patients with long COVID – the long-term symptoms like brain fog, fatigue, or pain in the months or years following COVID-19 – exhibit widespread brain inflammation, according to new research published today in Brain Behavior and Immunity. 

The study, led by researchers from the Massachusetts General Hospital/Harvard/MIT Martinos Center for Biomedical Imaging, is the first to document neuroinflammation in the long COVID brain along with evidence of vascular problems, shedding new light on how the SARS-CoV-2 virus may cause long-term symptoms. The study was supported by PolyBio Research Foundation’s LongCovid Research Consortium.

According to the CDC, nearly one in five American adults who had COVID-19 experience symptoms of long COVID. The mechanisms that cause long COVID are not fully understood, and treatments that are widely effective in reducing these long-term symptoms have not yet been developed.

This new study shows that long COVID patients have an ongoing neuroinflammatory process that is associated with increased markers of vascular problems in their blood,” said Dr. Michael VanElzakker, PolyBio co-founder and lead investigator of the study. “We’re optimistic that this kind of research on the mechanisms of long COVID can lead to better treatment approaches.”

 Special research methods allow for discovery  

The team found that vascular factors such as fibrinogen correlated with neuroinflammation in long COVID

Long COVID patients have long suspected that brain inflammation could be driving their symptoms. However, the methods required to best document neuroinflammation are only available in research studies and not regular medical clinics. Long COVID participants in the Harvard study spent 90 minutes inside a position emission tomography (PET) scanner with a specialized setup that can measure neuroimmune activation in their brains. 

As a group, the Long COVID patients had more of the PET signal demonstrating neuroinflammation when compared to healthy study participants. Importantly, this neuroinflammation was located in some brain areas that are exposed to circulating blood factors via gaps in the “blood-brain barrier” of the brain’s blood vessels.

This compelled the researchers to measure a selection of blood factors related to vascular health or damage. They found that six such factors showed a correlation with the neuroinflammation signal in the brains of the long COVID study participants. These factors included fibrinogen, a protein involved in forming blood clots in the body, and sL-selectin, a molecule that helps immune cells attach to vasculature during inflammation.

 “This suggests that the neuroinflammation in Long COVID patients may be connected to vascular problems,” said VanElzakker.

 Indeed, other research teams have found small “microclots” or circulating SARS-CoV-2 proteins in the blood of long COVID patients. VanElzakker says these factors could reach the brain and contribute to the neuroinflammation they observed. “But more research is needed to fully understand how blood clotting, viral persistence, and brain inflammation in long COVID may be interconnected.”

Dr. VanElzakker and team have several studies underway to further probe these connections. They are one of several teams working via PolyBio’s LongCovid Research Consortium to document long COVID biology via advanced imaging. Colleagues at the University of San Francisco recently demonstrated T cell activation in the spinal cord and bone marrow of long COVID patients using multimodal PET imaging. “These advanced imaging methods are breaking open the long COVID field” says PolyBio President Dr. Amy Proal. “They can identify abnormalities across the brain and body that the average doctor’s test simply cannot find, clarifying long COVID biomarkers and ultimately treatments.”  

 About PolyBio 

PolyBio Research Foundation is a 501(c)3 transforming how complex chronic conditions like LongCOVID are studied, diagnosed, and treated. PolyBio conceptualizes research projects that identify root cause drivers of chronic conditions and builds collaborative teams to make the projects a reality. PolyBio is supported by numerous donors including Kanro – a philanthropic fund to support open source scientific research established by Vitalik Buterin, creator of Ethereum.