Overview: 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 among hospitalized patients, highlighting the brain’s vulnerability to the virus.
These findings suggest that neuroinflammation may play a key role in the cognitive decline seen in “long COVID,” underscoring the need for ongoing surveillance 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 associated with 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 and immunity – health and carried out 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, underscoring the importance of better understanding these still poorly understood potential consequences of COVID-19.
COVID-19 remains a public health challenge
COVID-19 continues to be a disease of concern, 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. In addition, scientific literature has widely documented the harmful effects of the infection even after patients have recovered, a condition now known as “long COVID.”
Long COVID refers to a series of persistent symptoms that remain or appear after the acute phase of the disease. Even after recovery from respiratory symptoms, patients may continue to face significant challenges, particularly in terms of neurological health. A significant proportion of COVID-19 survivors, even those who had mild cases, may experience cognitive decline and difficulty concentrating for extended periods after infection. This makes it important to investigate how the disease affects the brain even in the acute phase, as this can provide clues about these neurological sequelae.
During the infection, the most common neurological symptoms are headache, fatigue, loss of smell and even more serious complications such as stroke and encephalitis. Investigating these manifestations is crucial, as we still know little about the mechanisms that lead to these complications and how they develop.
How the survey was conducted
IDOR researchers looked for biomarkers that could provide clues to neuroinflammatory processes in COVID-19 and analyzed data from patients confirmed to have COVID-19 admitted to the Rede D’Or network between April and November 2020.
The sample included 35 patients aged between 26 and 87 years, divided into moderate and severe cases, all of whom showed significant neurological symptoms during the acute COVID-19 infection. The data was collected from medical records and included imaging studies (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.
Results reveal significant brain inflammation
The analysis showed that most patients had at least one comorbidity, with 65.7% having two or more. About 85.7% of patients showed neurological symptoms at the time of hospitalization, a clinical picture that was even more pronounced than respiratory symptoms.
Imaging studies 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 showed signs of an aggravated inflammatory response. Proteomic analyzes of 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 studies.
Dr. Fernanda Aragão, a postdoctoral researcher at IDOR and the study’s first author, comments that the research is one of the first to link imaging studies and neurological symptoms with neuroinflammatory biomarkers capable of reflecting the severity of acute illness , a complication that is still difficult to predict.
Despite the degree of severity found from these biomarkers, the researcher emphasizes that neuroinflammation is independent of the severity of the disease 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 CSF, suggesting that the body’s inflammatory response can 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 various conditions, whether moderate or severe. To identify these inflammatory markers that link the severity of COVID-19 and neuroimaging changes, may 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,” the author adds.
Implications for long-term treatment and monitoring
These findings highlight the need for long-term monitoring of patients who have had COVID-19, particularly those at risk of developing persistent neurological complications. Better understanding of these mechanisms may help develop more effective treatment and prevention strategies in the future.
IDOR’s research provides valuable insight into the neurological effects of COVID-19 and paves the way for future studies to explore these findings more deeply and in larger populations.
Thus, continued study of the neurological consequences of COVID-19 is presented as a crucial investment, especially with the development 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-term COVID research news
Author: Maria Eduarda Ledo de Abreu
Source: D’Or Institute
Contact: Maria Eduarda Ledo de Abreu – D’Or Institute
Picture: Image credited to Neuroscience News
Original Research: Open access.
“Changes in neuroinflammatory biomarkers correlate with disease severity and neuroimaging changes in patients with COVID-19 neurological complications” by Fernanda Aragão et al. Brain, behavior and immune health
Abstract
Changes in neuroinflammatory biomarkers correlate with disease severity and neuroimaging changes in patients with COVID-19 neurological complications
COVID-19 causes acute and persistent neurological symptoms in mild and severe cases. Suggested concomitant mechanisms include direct viral infection and strain, coagulopathy, hypoxia, and neuroinflammation. However, underlying molecular changes associated with multiple neurological outcomes in both mild and severe cases are largely unexplored.
To elucidate possible mechanisms leading to COVID-19 neurological disease, we retrospectively studied in detail a cohort of 35 COVID-19 mild and severe hospitalized patients exhibiting neurological changes subject to clinically indicated cerebrospinal fluid (CSF) sampling. Clinical and neurological examination, brain imaging, viral sequencing and cerebrospinal CSF analyzes were performed.
We found that COVID-19 patients exhibited heterogeneous neurological symptoms separate from pulmonary 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 with ubiquitous systemic hyperinflammation and broad changes in CSF proteomics related to inflammation, innate immunity, and hemostasis, regardless of COVID-19 severity or neuroimaging changes.
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- CI 10.3 patients, p = 0.019).
CSF tumor necrosis factor-alpha (TNFα) and IL6 levels were higher in patients with pronounced neuroimaging changes compared with those who did not (sex-, age-, and comorbidity-adjusted mean TNFα pronounced 3.4, CI 2.4–4 .4 vs.
Not expressed 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). Overall, our findings implicate neuroinflammation as a possible cause of COVID-19 acute neurological disease in mild and severe cases.