As the COVID-19 pandemic continues, it has become increasingly recognized that neurological symptoms are among the most common persistent effects in confirmed patients. Among these, the most prominent is the persistent cognitive impairment syndrome known as COVID-19 "brain fog." Despite the lack of a unified definition or diagnostic criteria, "brain fog" is generally associated with symptoms such as mental fatigue, impaired information processing speed and executive function, anxiety, difficulty concentrating, and decreased cognitive abilities. [1]
Several hypotheses currently exist regarding its mechanisms: [2]
- Impact of Respiratory System Inflammation: Respiratory system inflammation may cause neurological inflammation through systemic chemokines and other mechanisms. Cytokines, chemokines, and microglial activation in the central nervous system affect various neural cell types, disrupting myelin homeostasis and plasticity, impairing hippocampal neurogenesis, inducing neurotoxic astrocyte reactions, damaging neural circuit function, and thereby affecting cognitive function.
- Autoimmune Response: SARS-CoV-2 may trigger an autoimmune response against the nervous system, leading to autoimmune encephalitis.
- Direct Infection: A small portion of SARS-CoV-2 may directly infect the nervous system.
- Reactivation of Other Viruses: SARS-CoV-2 can trigger the reactivation of latent herpesvirus infections, most notably Epstein-Barr virus (EBV), which can in turn cause further inflammation.
- Neurovascular Dysfunction: This includes blood-brain barrier disruption leading to leakage of fibrinogen and other pro-inflammatory molecules. Additionally, the formation of blood clots may cause neural inflammation and damage.
- Hypoxia and Other Metabolic Disorders: In severe patients, hypoxia and other metabolic disorders caused by lung and multiple organ dysfunction can lead to neurological damage.
Figure 1: Possible mechanisms leading to COVID-19-related cognitive impairment
In fact, the impact of the coronavirus on the central nervous system has been reported since the early stages of the pandemic, and related evidence has continued to accumulate over time. Individuals infected with the SARS-CoV-2 virus face a higher risk of neurological or psychiatric symptoms compared to those who are not infected. Some symptoms, such as mood and anxiety disorders, increase in the short term after infection but gradually return to normal levels. However, some symptoms persist for a longer duration, one of which is "brain fog." Research shows that the majority of COVID-19 patients continue to suffer from cognitive impairments after recovery. 89% of patients report fatigue and memory decline ("brain fog"), 77% report difficulty concentrating, and 46% are diagnosed with mild cognitive impairment through the Montreal Cognitive Assessment (MoCA) test. [3-4]
These data reveal that the coronavirus not only threatens respiratory health but may also accelerate brain aging, leading to cognitive decline. This recognition reminds us that in the post-pandemic era, we must pay attention to the long-term impact of the coronavirus on the brain and take necessary measures to slow the degradation of brain structure and function to better promote human health.
The impact of COVID-19 on the brain represents a significant challenge that demands immediate and sustained attention. By prioritizing research, clinical care, and public health initiatives focused on cognitive health, we can better support individuals affected by COVID-19 and work towards a future where the long-term neurological consequences of the pandemic are effectively managed and mitigated.
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