Summary: New research uncovers how COVID-19 may cause neuroinflammation, leading to persistent neurological symptoms even after recovery.
The study found elevated levels of pro-inflammatory cytokines and significant changes in cerebrospinal fluid among hospitalized patients, highlighting the brain’s vulnerability to the virus.
These findings suggest that neuroinflammation could play a key role in the cognitive decline seen in “long COVID,” stressing the need for ongoing monitoring and targeted therapies for survivors.
Key Facts:
- COVID-19 patients showed significant neuroinflammation, regardless of disease severity.
- Elevated pro-inflammatory cytokines IL-6 and TNFα were linked to severe cases and brain changes.
- Neuroinflammatory markers may help predict and treat long-term neurological effects.
Source: D’Or Institute
COVID-19 is primarily known for its effects on the respiratory system, but its consequences go far beyond that.
A recent study, published in the journal Brain, Behavior, & Immunity – Health and conducted at the D’Or Institute for Research and Education (IDOR), revealed molecular changes that may underlie the neurological symptoms exhibited by some patients affected by the disease, highlighting the importance of better understanding these still poorly known potential consequences of COVID-19.
COVID-19 Remains a Public Health Challenge
COVID-19 continues to be a concerning disease even after the end of its pandemic phase. In the first half of 2024 alone, it was responsible for over 3,000 deaths in Brazil. Additionally, scientific literature has been extensively documenting the deleterious effects of the infection even after patients have recovered, a condition now known as “long COVID.”
Long COVID refers to a range of persistent symptoms that remain or emerge after the acute phase of the disease. Even after recovering from respiratory symptoms, patients may continue to face significant challenges, especially concerning neurological health. 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. This makes it important to study how the disease affects the brain even in the acute phase, as this may provide clues about these neurological sequelae.
During the infection, the most common neurological symptoms are headaches, fatigue, loss of smell, and even more severe complications such as strokes and encephalitis. Investigating these manifestations is crucial, as we still know little about the mechanisms leading to these complications and how they develop.
How the Study Was Conducted
Seeking biomarkers that could provide clues about neuroinflammatory processes in COVID-19, IDOR researchers analyzed data from patients confirmed to have COVID-19 who were hospitalized in theRede D’Or network between April and November 2020.
The sample included 35 patients aged between 26 and 87 years, divided between moderate and severe cases, all of whom presented significant neurological symptoms during the acute COVID-19 infection. The data were collected from medical records and included imaging exams (MRI and CT scans), blood tests, and cerebrospinal fluid (CSF) analysis—a fluid that surrounds the brain and spinal cord. Ten CSF samples from uninfected patients served as a control group.
Findings Reveal Significant Brain Inflammation
The analysis revealed that most patients had at least one comorbidity, 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.
Imaging exams showed that 28.6% of patients had focal or diffuse brain changes associated with COVID-19, including demyelinating lesions, encephalitis, and stroke.
Blood tests indicated that 66% of patients showed signs of an exacerbated inflammatory response. Proteomic analyses of the CSF revealed an altered protein pattern compared to the controls, with 116 significantly dysregulated proteins related to the immune system and metabolic processes.
Pro-Inflammatory Cytokines Are Associated with Disease Severity
The levels of two pro-inflammatory cytokines, IL-6 and TNFα, were elevated in the CSF of COVID-19 patients, with IL-6 being particularly higher in severe cases. These cytokines are associated with the severity of the disease and the changes observed in imaging exams.
Dr. Fernanda Aragão, a postdoctoral researcher at IDOR and the study’s first author, comments that the research is one of the first to connect imaging exams and neurological symptoms with neuroinflammatory biomarkers capable of reflecting the severity of acute disease, a complication that remains difficult to predict.
Despite the severity distinction found from these biomarkers, the researcher emphasizes that neuroinflammation is independent of disease severity and may be one of the main causes of neurological disorders associated with COVID-19. She points out that even patients with milder cases showed significant changes in the CSF, suggesting that the body’s inflammatory response may affect the brain in ways not yet fully understood.
“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,” adds the author.
Implications for Long-Term Treatment and Monitoring
These findings highlight the need for long-term monitoring of patients who have had COVID-19, especially those at risk of developing persistent neurological complications. Better understanding these mechanisms can help develop more effective treatment and prevention strategies in the future.
IDOR’s research provides valuable insights into the neurological impacts of COVID-19 and paves the way for future studies to explore these findings more deeply and in larger populations.
Thus, continued investigation into the neurological consequences of COVID-19 is presented as a crucial investment, especially with the evolution of new variants and the implementation of vaccination programs, to ensure that the long-term effects of the pandemic are adequately understood and addressed.
About this neurology and long-COVID research news
Author: Maria Eduarda Ledo de Abreu
Source: D’Or Institute
Contact: Maria Eduarda Ledo de Abreu – D’Or Institute
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Changes in neuroinflammatory biomarkers correlate with disease severity and neuroimaging alterations in patients with COVID-19 neurological complications” by Fernanda Aragão et al. Brain, Behavior, and Immunity Health
Abstract
Changes in neuroinflammatory biomarkers correlate with disease severity and neuroimaging alterations in patients with COVID-19 neurological complications
COVID-19 induces acute and persistent neurological symptoms in mild and severe cases. Proposed concomitant mechanisms include direct viral infection and strain, coagulopathy, hypoxia, and neuroinflammation. However, underlying molecular alterations associated with multiple neurological outcomes in both mild and severe cases are majorly unexplored.
To illuminate possible mechanisms leading to COVID-19 neurological disease, we retrospectively investigated in detail a cohort of 35 COVID-19 mild and severe hospitalized patients presenting neurological alterations subject to clinically indicated cerebrospinal fluid (CSF) sampling. Clinical and neurological investigation, brain imaging, viral sequencing, and cerebrospinal CSF analyses were carried out.
We found that COVID-19 patients presented heterogeneous neurological symptoms dissociated from lung burden. Nasal swab viral sequencing revealed a dominant strain at the time of the study, and we could not detect traces of SARS-CoV-2’s spike protein in patients’ CSF by multiple reaction monitoring analysis.
Patients presented ubiquitous systemic hyper-inflammation and broad alterations in CSF proteomics related to inflammation, innate immunity, and hemostasis, irrespective of COVID-19 severity or neuroimaging alterations.
Elevated CSF interleukin-6 (IL6) correlated with disease severity (sex-, age-, and comorbidity-adjusted mean Severe 24.5 pg/ml, 95% confidence interval (CI) 9.62–62.23 vs. Mild 3.91 pg/mL CI 1.5–10.3 patients, p = 0.019).
CSF tumor necrosis factor-alpha (TNFα) and IL6 levels were higher in patients presenting pronounced neuroimaging alterations compared to those who did not (sex-, age-, and comorbidity-adjusted mean TNFα Pronounced 3.4, CI 2.4–4.4 vs.
Non-Pronounced 2.0, CI 1.4–2.5, p = 0.022; IL6 Pronounced 33.11, CI 8.89–123.31 vs Non-Pronounced 6.22, CI 2.9–13.34, p = 0.046). Collectively, our findings put neuroinflammation as a possible driver of COVID-19 acute neurological disease in mild and severe cases.
