Summary: New research reveals how COVID-19 can 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 in hospitalized patients, highlighting the brain’s vulnerability to the virus.
These findings suggest that neuroinflammation may play a key role in the cognitive decline observed in “long COVID,” highlighting the need for continued monitoring and targeted therapies for survivors.
Key facts:
- COVID-19 patients exhibited significant neuroinflammation regardless of disease severity.
- Elevated levels of pro-inflammatory cytokines IL-6 and TNFα have been associated with severe cases and brain changes.
- Neuroinflammatory markers may help predict and treat long-term neurological effects.
Source: Golden 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 and Immunity – Health and conducted at the Institut D’Or pour la Recherche et l’Éducation (IDOR), revealed molecular changes that may be at the origin of the neurological symptoms presented by some patients affected by the disease, highlighting the importance of better understanding these still poorly understood potential consequences of COVID-19.
COVID-19 remains a public health challenge
COVID-19 remains a worrying disease even after its pandemic phase has ended. In the first half of 2024 alone, it was responsible for more than 3,000 deaths in Brazil. In addition, the scientific literature has widely documented the deleterious effects of the infection even after patients recover, a condition now known as “long COVID.”
Long COVID refers to a series of persistent symptoms that persist or emerge after the acute phase of the disease. Even after recovery from respiratory symptoms, patients may continue to face significant challenges, including neurological health. A significant proportion of COVID-19 survivors, even those who had mild cases, may experience cognitive decline and difficulty concentrating for prolonged periods after infection. It is therefore important to study how the disease affects the brain even in the acute phase, as this may provide clues to these neurological sequelae.
During infection, the most common neurological symptoms are headache, fatigue, loss of smell and even more serious complications such as stroke and encephalitis. It is essential to study these manifestations, as we still know little about the mechanisms leading to these complications and how they evolve.
How the study was conducted
In search of biomarkers that could provide clues about the neuroinflammatory processes of COVID-19, IDOR researchers analyzed data from patients confirmed to have COVID-19 and hospitalized in the Rede D’Or network between April and November 2020.
The sample included 35 patients aged 26 to 87 years, divided into moderate and severe cases, all of whom had significant neurological symptoms during acute COVID-19 infection. Data were collected from medical records and included imaging studies (MRI and CT scans), blood tests, and analysis of cerebrospinal fluid (CSF), a fluid that surrounds the brain and spinal cord. Ten CSF samples from uninfected patients served as a control group.
Results 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 had neurological symptoms at the time of hospital admission, a clinical picture even more pronounced than respiratory symptoms.
Imaging scans showed that 28.6% of patients had focal or diffuse brain changes associated with COVID-19, including demyelinating lesions, encephalitis, and stroke.
Blood tests showed that 66% of patients had signs of an exacerbated inflammatory response. CSF proteomic analyses revealed an altered protein profile compared to controls, with 116 significantly deregulated proteins related to the immune system and metabolic processes.
Pro-inflammatory cytokines are associated with disease severity
Levels of two pro-inflammatory cytokines, IL-6 and TNFα, were elevated in the CSF of COVID-19 patients, with IL-6 being particularly elevated in severe cases. These cytokines are associated with disease severity and changes observed on imaging studies.
Dr. Fernanda Aragão, postdoctoral researcher at IDOR and first author of the study, comments that the research is one of the first to link imaging tests and neurological symptoms to neuroinflammatory biomarkers capable of reflecting the severity of the acute disease, a complication that remains difficult to predict.
Despite the difference in severity seen from these biomarkers, the researcher emphasizes that neuroinflammation is independent of disease severity and may be a major cause of neurological disorders associated with COVID-19. She points out that even patients with milder cases showed significant changes in CSF, suggesting that the body’s inflammatory response may affect the brain in ways that are not yet fully understood.
“This study reveals that neuroinflammation is a common factor in neurological cases of the disease, even in patients with diverse pathologies, whether moderate or severe. Identifying these inflammatory markers that link COVID-19 severity and neuroimaging changes could be very important for the development of therapies aimed at both treating acute COVID-19 infections and addressing the persistent effects of so-called long COVID,” the author adds.
Implications for long-term treatment and monitoring
These findings highlight the need for long-term follow-up of patients with COVID-19, especially those at risk of developing persistent neurological complications. A better understanding of these mechanisms may 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 outcomes in more depth and in broader populations.
Thus, continued research into the neurological consequences of COVID-19 is presented as a crucial investment, particularly with the evolution of new variants and the implementation of vaccination programs, to ensure that the long-term effects of the pandemic are properly understood and treated.
About this news on neurology research and long COVID
Author: Maria Eduarda Ledo de Abreu
Source: Golden Institute
Contact: Maria Eduarda Ledo de Abreu – Institut D’Or
Picture: Image credited to Neuroscience News
Original research: Free access.
“Changes in neuroinflammatory biomarkers correlate with disease severity and neuroimaging alterations in patients with COVID-19-related neurological complications” by Fernanda Aragão et al. Brain, behavioral and immune health
Abstract
Changes in neuroinflammatory biomarkers correlate with disease severity and neuroimaging alterations in patients with COVID-19-related neurological complications
COVID-19 causes acute and persistent neurological symptoms in both mild and severe cases. Proposed concomitant mechanisms include direct viral infection and strain, coagulopathy, hypoxia, and neuroinflammation. However, the underlying molecular alterations associated with multiple neurological consequences in both mild and severe cases are largely unexplored.
To shed light on the possible mechanisms leading to COVID-19 neurological disease, we retrospectively studied in detail a cohort of 35 hospitalized patients with mild and severe COVID-19 presenting with neurological alterations and undergoing clinically indicated cerebrospinal fluid (CSF) sampling. Clinical and neurological investigations, brain imaging, viral sequencing, and CSF analyses were performed.
We found that COVID-19 patients had heterogeneous neurological symptoms dissociated from pulmonary burden. Viral sequencing by nasal swab revealed a dominant strain at the time of the study, and we were unable to detect traces of SARS-CoV-2 spike protein in patients’ CSF by multiple reaction monitoring analysis.
Patients exhibited pervasive systemic hyperinflammation and broad CSF proteomic alterations related to inflammation, innate immunity, and hemostasis, independent of COVID-19 severity or neuroimaging alterations.
High CSF interleukin-6 (IL6) level was correlated with disease severity (mean adjusted for sex, age, and comorbidity in severe patients: 24.5 pg/ml, 95% confidence interval (CI): 9.62-62.23 vs. mild patients: 3.91 pg/ml, CI: 1.5-10.3, p = 0.019).
CSF tumor necrosis factor alpha (TNFα) and IL-6 levels were higher in patients with pronounced neuroimaging changes compared with those without (mean TNFα adjusted for sex, age, and comorbidity: 3.4, CI: 2.4-4.4 vs.
Not pronounced 2.0, CI 1.4-2.5, p = 0.022; IL6 pronounced 33.11, CI 8.89-123.31 vs not pronounced 6.22, CI 2.9-13.34, p = 0.046). Collectively, our results place neuroinflammation as a possible driver of acute neurological disease in COVID-19 in both mild and severe cases.
