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Neuroinflammation Linked to Long COVID Causes Significant Neurological Symptoms

Though primarily known for its respiratory effects, COVID-19’s impact on the brain is gaining increased attention. Millions of people worldwide, even those with mild infections, are grappling with lingering neurological symptoms, raising serious concerns about the long-term implications of the virus.


These findings concern around 750 million people that are recovered from COVID-19, many of whom may still be at risk of long-term neurological issues. A study was published in the journal Brain, Behavior, & Immunity – Health and conducted at the D’Or Institute for Research and Education (IDOR). It revealed molecular changes that may underlie the neurological symptoms exhibited by some patients affected by the disease, and it highlights the fact that there are still many poorly known consequences of COVID-19.


COVID-19 remains a significant health threat, even a full year after the official pandemic phase. In the first half of 2024 alone, around 22 million new confirmed cases were reported globally, showing the persistent nature of the virus. Although vaccination rates and prior infections have provided some immunity, emerging variants like JN.1 and its descendants have continued to cause infections.


Scientists recently started studying a condition seen after experiencing COVID-19. For some people, the symptoms of COVID-19 last longer than the estimated full recovery time, which is within 12 weeks. This is called long COVID or post COVID-19 syndrome.

Long COVID refers to a range of persistent symptoms that remain or emerge after the acute phase of the disease. In research studies, more than 200 symptoms have been linked to long COVID. Symptoms may stay the same over time, get worse, or go away and come back. Common symptoms of long COVID include extreme tiredness, problems with taste or smell, and many others that mainly concern neurological health. For instance, a significant portion of COVID-19 survivors, even those who had mild cases, may experience cognitive decline and difficulty concentrating for extended periods after the infection.


COVID-19 can cause neural damage indirectly through inflammation. When the immune system responds to the virus, it triggers the release of proteins that lead to inflammation. This inflammation can affect brain cells, disrupt the blood-brain barrier, and contribute to brain alterations. Furthermore, imaging studies of patients show signs of vascular damage, which can include strokes.


Researchers at IDOR observed 35 hospitalized COVID-19 patients aged between 26 and 87 years with neurological symptoms. They then analyzed a fluid that surrounds the brain and the spinal cord, clinical data, brain scans, and viral sequencing. Ten fluid samples from uninfected patients served as a control group.

They found out that patients had varied neurological symptoms that did not always match the severity of their lung issues. No viral traces were found in the brain fluid, but there were signs of widespread inflammation and immune system activity, regardless of the severity of the disease. The analysis revealed that most patients had at least one coexisting condition, with 65.7% having two or more. About 85.7% of patients exhibited neurological symptoms at the time of hospital admission, a clinical picture that was even more pronounced than respiratory symptoms. Furthermore, imaging tests showed that 28.6% of patients had other brain changes including lesions, encephalitis, and stroke.


Dr. Fernanda Aragão, a postdoctoral researcher at IDOR and the study’s first author, commented that the research is one of the first to connect imaging exams and neurological symptoms with neuroinflammatory biomarkers capable of reflecting the severity of an acute disease, a complication that remains difficult to predict.

“This study reveals that neuroinflammation is a common factor in neurological cases of the disease, even in patients with diverse conditions, whether moderate or severe. Identifying these inflammatory markers that connect COVID-19 severity and neuroimaging changes could be very important for developing therapies aimed at both treating acute COVID-19 infections and addressing the persistent effects of what is known as long COVID,” added the author, Dr. Fernanda Aragão.

This research emphasizes the importance of monitoring COVID-19 survivors, as long COVID poses serious neurological risks and these symptoms impact one’s daily life and overall health significantly. Scientists continue to conduct research on long COVID and its outcomes. Ongoing studies could lead to more effective treatments and prevention methods accordingly, which gives hope to millions suffering from these long-lasting effects.

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