COVID-19's Impact on the Brain: A Comprehensive Review for Clinicians
In his groundbreaking review published in NeuroRegulation, Darius Rountree-Harrison provides a crucial analysis of how COVID-19 affects the nervous system.
Darius Rountree-Harrison offers vital insights for clinicians dealing with both acute cases and long-COVID patients. As our understanding of COVID-19 has evolved from viewing it as primarily a respiratory illness, Rountree-Harrison illuminates the virus's complex neurological implications through both direct viral invasion and secondary systemic effects.
Direct COVID Neural Invasion Mechanisms
Rountree-Harrison explains that SARS-CoV-2 gains access to the nervous system through multiple pathways. The virus's primary point of entry involves binding to angiotensin-converting enzyme 2 (ACE-2) receptors, which are abundantly present in the brain, particularly in the brainstem and hippocampus. This binding mechanism, which Rountree-Harrison aptly describes as a "viral lockpick," allows COVID-19 to breach the nervous system through several routes. COVID-19 graphic © Photomay/Shutterstock.com.
The first and most common pathway is through cranial nerve routes, particularly the olfactory nerve, which explains the frequently reported symptom of smell loss. Additionally, the virus can directly infect blood-brain barrier cells, specifically pericytes, and can also transmit through the circulatory system to brain tissues.
The author emphasizes that this direct viral invasion can lead to serious conditions including encephalitis, strokes, and potential long-term neurodegeneration. Of particular concern is the impact on the brainstem, which controls vital functions like breathing and heart rate.
Indirect Mechanisms and Systemic Effects
Beyond direct viral invasion, Rountree-Harrison details how COVID-19 creates a cascade of indirect effects on the brain. The virus triggers what has become known as a "cytokine storm," an overwhelming inflammatory response that can cause widespread damage throughout the nervous system. This inflammatory cascade is often accompanied by systemic hypoxia from respiratory complications, further compromising brain function. The formation of blood clots and microvascular damage represents another significant threat, as these can lead to strokes and other neurological complications. The author also describes how multi-organ dysfunction can profoundly affect brain function, creating a complex web of systemic effects that can be as damaging as direct viral invasion, particularly in cases of long-COVID.
Electroencephalographic (EEG) Findings
One of the most significant contributions of Rountree-Harrison's review is his analysis of EEG patterns in COVID-19 patients. His research reveals striking statistics: an overwhelming 96.1% of patients show abnormal background activity, while 92.3% demonstrate generalized slowing. Perhaps most concerning is that 22.4% of patients exhibit epileptiform discharges without any prior history of seizure activity. The author also documents distinctive patterns appearing in frontal lobe activity, providing crucial diagnostic markers and potential therapeutic targets for clinicians.
Therapeutic Implications and Future Directions
Rountree-Harrison proposes several promising therapeutic approaches, beginning with neurofeedback as a potential treatment modality. This non-invasive technique shows particular promise for addressing cognitive and neurological symptoms of long-COVID, allowing patients to modulate abnormal brainwave patterns associated with the disease. The author also explores heart rate variability biofeedback as a therapeutic option, noting its potential to address both cardiovascular and neurological symptoms, particularly given the interconnected nature of COVID-19's systemic effects.
The review further examines complementary interventions that may prove beneficial. Low-level laser therapy emerges as a promising option for reducing inflammation, while audiovisual entrainment shows potential for cognitive rehabilitation. The author advocates for an integrated rehabilitation approach that combines multiple modalities to address the complex nature of COVID-19's neurological impacts.
Clinical Recommendations
For clinicians, Rountree-Harrison outlines a comprehensive approach to patient care. He emphasizes the critical importance of early recognition of neurological symptoms, suggesting that clinicians maintain a high index of suspicion for neurological involvement in COVID-19 cases. Regular monitoring of EEG patterns, when possible, can provide valuable insights into disease progression and treatment efficacy. The author advocates for implementing multimodal treatment approaches, recognizing that the complex nature of COVID-19's neurological impacts often requires a multifaceted therapeutic strategy. Long-term follow-up for patients with neurological symptoms is deemed essential, as the full scope of neurological sequelae may only become apparent over time.
Impact and Epidemiology
The author's analysis presents sobering statistics regarding the neurological impact of COVID-19. His research suggests that between 7.7 and 38.8 million people worldwide may experience neurological impacts from the virus, with approximately 24.4% of infected individuals developing long-COVID symptoms. These numbers underscore the critical importance of understanding and effectively treating the neurological aspects of the disease, highlighting the potential scale of the healthcare challenge ahead.
Safety Considerations
In concluding his review, Rountree-Harrison addresses the practical aspects of providing neurological care during the pandemic. He outlines comprehensive safety protocols for clinicians providing face-to-face neuromodulation treatments. These include detailed guidance on proper PPE usage and environmental sanitation protocols. The author provides strategic approaches to risk assessment and emphasizes the importance of vaccination as a primary preventive measure. These safety considerations are presented within the context of maintaining therapeutic efficacy while protecting both healthcare providers and patients.
Critical Analysis
The author acknowledges that while neurofeedback and other neuromodulation treatments show promise for addressing COVID-19's neurological impacts, these applications remain experimental without direct research validation. The recommendations are largely based on analogies to similar conditions and theoretical mechanisms rather than specific clinical trials with COVID-19 patients.
The EEG findings, while extensive, come from a relatively early period in the pandemic, and the patterns observed may not fully represent all variants or presentations of the disease. Additionally, the relationship between specific EEG patterns and causal mechanisms remains speculative, with the author noting that it's still too early to draw definitive associations between reported cases, EEG patterns, and underlying mechanisms.
Rountree-Harrison emphasizes that the statistical projections regarding neurological impacts (ranging from 7.7 to 38.8 million people) are estimates based on limited data and may not accurately reflect the true scope of the problem. The author also notes that the effectiveness of proposed interventions like heart rate variability biofeedback and low-level laser therapy in COVID-19 rehabilitation remains untested, despite showing promise in related conditions.
A significant limitation is the lack of long-term follow-up data, making it difficult to determine the duration and evolution of neurological symptoms over time. The author also cautions that the implementation of neuromodulation therapies during a pandemic poses inherent risks, and clinicians must carefully weigh the benefits against potential transmission risks, even with proper safety protocols in place.
Furthermore, the accessibility and scalability of the proposed interventions pose significant challenges, particularly in resource-limited settings or during periods of high infection rates. The author notes that many of the recommended treatments require face-to-face sessions, which may not be feasible in all circumstances.
These limitations underscore the preliminary nature of our understanding of COVID-19's neurological impacts and the need for continued research to validate proposed therapeutic approaches.
Glossary
ACE-2 (angiotensin-converting enzyme 2) receptors: proteins found on the surface of many cell types, including in the lungs and brain, that SARS-CoV-2 uses to enter cells.
audiovisual entrainment: a therapeutic technique that uses synchronized light and sound patterns to stimulate the brain at specific frequencies, often aimed at improving cognitive function, relaxation, or alertness.
cognitive decline: a reduction in mental capabilities such as memory, attention, and problem-solving, often linked to neurological disorders or damage.
cytokine storm: an excessive immune response characterized by the overproduction of inflammatory molecules, causing widespread tissue damage.
electroencephalogram (EEG): a diagnostic tool that measures electrical activity in the brain, often used to detect abnormalities such as seizures or slowing.
encephalitis: inflammation of the brain, often caused by infection, leading to symptoms such as confusion, fever, and seizures.
encephalopathy: a general term for disease or damage to the brain, often presenting as confusion or altered consciousness.
epileptiform activity: abnormal brain wave patterns resembling those seen in epilepsy, potentially indicating neurological dysfunction.
frontal lobe: the brain region responsible for higher cognitive functions, including decision-making, problem-solving, and voluntary motor activity.
generalized slowing: a pattern observed in electroencephalograms (EEGs) characterized by a reduction in the overall speed of brainwave activity, often indicative of diffuse brain dysfunction or systemic issues like hypoxia.
heart rate variability (HRV) biofeedback: a therapeutic technique that trains individuals to control the variability in their heart rate to improve physiological and psychological health.
hippocampus: a critical brain structure involved in memory formation and spatial navigation.
hypoxia: a condition in which the body or brain is deprived of adequate oxygen supply, potentially leading to cognitive and physical impairments.
inflammation: the immune system's response to infection or injury, which can become harmful when excessive or chronic.
intermittent epileptiform discharges (IEDs): sporadic bursts of abnormal brainwave activity seen on EEGs, often associated with epilepsy or other conditions affecting brain excitability.
long-COVID: a condition characterized by persistent symptoms following recovery from the acute phase of COVID-19, including fatigue, cognitive issues, and neurological symptoms.
low-level laser therapy: a treatment that uses near-infrared light to promote healing and reduce inflammation in tissues, including the brain.
microvascular damage: injury to the small blood vessels in the body, which can impair blood flow and oxygen delivery to tissues, including the brain, and is often linked to inflammation or systemic diseases like COVID-19.
neurofeedback: a technique that provides real-time feedback on brain activity, allowing individuals to train their brainwaves to achieve desired states.
neuromodulation: methods or techniques used to alter nervous system activity, often for therapeutic purposes.
olfactory nerve: the nerve responsible for the sense of smell, which can serve as a pathway for viral entry into the brain.
psychosis: a mental condition marked by disconnection from reality, including symptoms such as hallucinations and delusions.
stroke: a medical emergency caused by the interruption of blood flow to the brain, leading to cell death and potential neurological deficits.
temporal lobes: brain regions located on the sides of the head, responsible for memory, emotion, and language processing.
theta activity: a type of brainwave pattern often associated with drowsiness or low-level cognitive activity, which can be abnormal in certain neurological conditions.
viral invasion: the process by which a virus enters and infects host cells, potentially causing tissue damage and systemic effects.
Open-Access Article
Rountree-Harrison, D. J. H. (2022). COVID-19 and the brain: Infection mechanisms, electroencephalographic findings and clinical implications. NeuroRegulation, 9(1). https://doi.org/10.15540/nr.9.1.48
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