New studies on Long-COVID: Insights into the complex brain reactions

From indirect inflammatory reactions to long-term brain injuries: How COVID-19 can affect the brain

Recently, two landmark studies have shed new light on the long-term effects of COVID-19 on the brain, which could significantly expand our understanding of long-COVID and its treatment.

A study just published in Nature Neuroscience, conducted by Charité in Berlin, suggests that neurological symptoms in COVID-19 patients are caused by an inflammatory response throughout the body rather than a direct infection of the brain. These findings suggest that the virus can have indirect but significant effects on the brain, leading to dysfunction.

A second study from the University of Liverpool highlights that long-COVID symptoms, including the often-reported ‘brain fog’, may be the result of virus-related brain injury, which can lead to long-lasting cognitive and mental health problems. Both studies reinforce the physical reality of long-COVID symptoms and call for a re-evaluation of treatment approaches that take into account both the psychological and neurological effects of the disease.

Charité study: Neurological symptoms in COVID-19 not directly caused by virus in the brain

The exact cause of neurological symptoms in COVID-19, such as headaches, memory problems or extreme fatigue, remains a mystery. However, the latest research from Charité in Berlin suggests that these are more likely to be due to inflammation of the body than a direct infection of the brain by SARS-CoV-2, as reported in “Nature Neuroscience”. Previous assumptions of a direct brain infection could not be confirmed, explains Dr. Helena Radbruch from the Institute of Neuropathology. Rather, the study supports the theory that neurological symptoms are caused by a strong immune defense of the body against the virus, supported by detailed results from autopsies.

Study shows: Inflammatory reactions in the body influence brain function

The Charité study analyzed brain samples from 21 people who died of COVID-19 and found no direct signs of viral infection in the brain. In contrast to other parts of the body where SARS-CoV-2 has been detected, immune cells appear to transport the virus into the brain without directly infecting nerve cells. Nevertheless, the brain responded to the inflammation in the body, in particular by activating the interferon signaling pathway in some cells, which could explain neurological symptoms such as fatigue. This response, particularly in the vagus nerve of the brainstem, suggests that inflammatory responses in the body can indirectly affect brain function without a direct infection of brain tissue.

Study finds time-limited brain response and possible link to Long COVID

The Charité study shows that the brain response to COVID-19 inflammation is time-limited, based on comparisons between people who died during the acute phase and those who died weeks after infection. Molecular changes are strongest during the acute phase, but return to normal in most cases. This suggests that persistent inflammation could lead to long-term neurological symptoms in some individuals, which the researchers consider a possible cause of long-COVID symptoms. For further investigation, they plan to analyze the molecular signatures in the cerebrospinal fluid of Long COVID patients in more detail.

Long-COVID possibly identified as brain damage that ages the brain by 20 years

A recently published study by the University of Liverpool takes a different approach: researchers there now believe that these symptoms could be due to a virus-related brain injury that causes long-term cognitive and psychological problems.

In their study of 351 severely ill COVID-19 patients, cognitive tests, brain scans and biomarker analyses revealed signs of long-term brain damage one year later. The patients’ brain deficits resembled 20 years of brain aging and were associated with mental illnesses such as depression and anxiety. The research findings underpin concerns that COVID-19 can cause permanent damage to the brain, with patients showing global cognitive deficits and neuroanatomical changes to the brain, according to study leader Benedict Michael from the University of Liverpool.

Liverpool study confirms: Long-COVID symptoms are not imaginary

The study shows that cognitive deficits in Long COVID patients are real, even if it remains unclear whether the brain damage will persist in the long term. Dr. Karla L. Thompson of the University of North Carolina, who was involved in the work, emphasizes the importance of the research for patients whose complaints have continued to be ignored by many doctors. However, the use of biomarkers provides objective evidence of brain impairment, helping to confirm the physical reality of the condition.

Almost 80 percent of those affected do not find adequate medical help

Many Long COVID patients have difficulty convincing doctors of the seriousness of their physical complaints. Up to 79 percent of those affected reported negative experiences when seeking treatment. The exact cause of the brain damage is uncertain, but oxygen deprivation and inflammatory reactions due to an increased immune response could play a role. The new findings point to neuroprotective effects of steroids to reduce inflammation in the brain.

James C. Jackson of Vanderbilt University therefore emphasizes the need to take long-COVID seriously as a potential brain injury and provide appropriate treatments, such as therapies to improve language, cognitive and motor function, as well as psychological support.

Treatment approaches for long-COVID symptoms as brain injuries

Recognizing Long COVID symptoms as brain injuries could open new avenues to help patients return to normal. According to Dr. Jackson, biomarkers and brain scan differences show clear correlations with people’s daily challenges, such as difficulties with multitasking, memory, meeting deadlines and concentration. Concerns that COVID-19-induced brain aging could have long-term consequences underscore the urgency of taking the impact of the virus seriously, especially regarding the potential early onset of dementia and Alzheimer’s disease in at-risk patients, the study authors said.

This study also highlights the role of neuroinflammation in Alzheimer’s disease and suggests that persistent inflammation may have a similar effect in long-COVID. Despite concrete evidence of virus-related brain damage in severe COVID-19 cases, questions remain about the impact on patients with milder courses and the long-term consequences of brain damage.

Dr. Ziyad Al-Aly points to the need to better understand these mechanisms that allow the virus to access and cause damage in the brain. Research must now clarify whether anti-inflammatory or antiviral drugs and steroids can prevent or mitigate the damage. Given the persistent presence of SARS-CoV-2 in the population, it is crucial to develop strategies to stop long-term or permanent brain damage caused by the virus.

A comprehensive understanding of long-COVID complexity

The latest studies from Charité in Berlin and the University of Liverpool provide important insights into the neurological effects of COVID-19 and shed light on the multi-layered nature of Long COVID. While the Charité study suggests that the neurological symptoms are caused by systemic inflammatory responses rather than direct infection of the brain, the Liverpool research points to long-lasting cognitive and mental health problems that could be interpreted as a result of virus-related brain injury.

Conclusion: Apparent discrepancies not a contradiction, but two aspects of one disease

However, these apparent discrepancies do not underline a contradiction, but rather the complexity of the interactions between COVID-19, the human immune system and the brain. They show that Long-COVID can be characterized by a combination of direct and indirect effects of the virus and the body’s response to it. The Charité study emphasizes the role of the immune response and the potential indirect effects on the brain, while the Liverpool research highlights the long-term consequences of these interactions, possibly exacerbated by oxygen deprivation or inflammatory responses.

These findings call for a holistic view of long-COVID, taking into account both the psychological and neurological dimensions of the disease. They emphasize the need for further research to understand the exact mechanisms that lead to the observed effects and to develop effective treatment strategies to help sufferers regain their quality of life. The work of both research teams provides a valuable contribution to the growing understanding of Long COVID and paints a picture of a disease characterized by the interaction of numerous factors.

Sources for the Charité study:

Sources for the study by the University of Liverpool: