When the Covid-19 pandemic began in early 2020, doctors had limited knowledge about this new infectious disease and didn’t initially think it affected the brain.
How wrong we were!
Covid-19 may primarily affect the respiratory system, but “brain fog” – characterised by issues with memory and concentration – is a common symptom that can persist for weeks or months as part of long Covid. From the onset of the pandemic, brain fog quickly became recognised as a prevalent health condition experienced by many individuals following Covid-19.
Brain fog is a colloquial term that refers to a state of mental sluggishness, characterised by a lack of clarity and haziness that impairs concentration, memory and clear thinking. A new study in Sweden suggests that mild Covid-19 can cause several years of brain fog.
However, brain fog is not the only neurological effect associated with this infection. Fast forward four years and there is now abundant evidence showing that infection with SARS-CoV-2 – the virus responsible for Covid-19 – can have various adverse effects on brain health.
As many as one in five individuals who have had Covid-19 have experienced short-term memory loss, poor attention span or fatigue. Approximately one in seven individuals who have been infected with the SARS-CoV-2 virus have experienced neurological side effects or symptoms impacting their brain function.
These include anosmia (partial or full loss of smell), headache, cognitive and attention deficits, disturbances in consciousness, anxiety, severe depression, delirium, and in some cases, psychosis, leading to hallucinations, delusions and/or suicidal behaviour.
Additionally, it can cause diseases like acute necrotising encephalopathy, encephalitis, hypoxic brain injury, strokes, myelitis, tonic epilepsy, neurogenic respiratory failure, generalised myoclonic seizures and Kawasaki syndrome.
This diverse array of symptoms and diseases suggests multiple underlying mechanisms of brain injury in Covid-19 patients. Investigating these mechanisms is essential for developing effective treatments for Covid-19-related brain injuries and associated neuropsychiatric symptoms.
Potential pathways
A substantial and increasing body of evidence gathered during the pandemic has highlighted the numerous ways Covid-19 leaves a lasting impact on the brain. However, the exact mechanisms by which the SARS-CoV-2 virus causes these effects are still being uncovered, and there are currently no definitive curative treatments available.
SARS-CoV-2 infection can cause brain damage through several possible pathways, leading to a variety of brain injuries and diseases.
The proposed routes of invasion are:
> Vascular pathway
SARS-CoV-2 compromises the blood-brain barrier, allowing the virus to enter the brain via blood or lymphatic circulation. This pathway facilitates the spread of the virus throughout the brain, leading to widespread damage and inflammation, resulting in confusion, difficulty concentrating and memory issues.
Moreover, the virus can infect and damage blood vessel linings, increasing the risk of blood clots, which can result in strokes and heart attacks, even in young, healthy individuals. Strokes can cause long-term difficulties in speaking or understanding speech, weakness on one side of the body, and other serious symptoms.
> Peripheral nerve pathway
The virus infects the olfactory bulb, trigeminal nerve and vagus nerve, subsequently reaching the brain through trans-neuronal or retrograde axonal transport (i.e. through the nervous system). This route explains the neurological symptoms related to sensory and motor functions.
Additionally, the virus often impacts the brain’s autonomic nervous system, causing irregularities in heart rate and blood pressure.
> Cerebrospinal fluid (CSF) pathway
SARS-CoV-2 enters the brain through circulating CSF, triggering a series of pro-inflammatory and immune responses. These responses can cause various brain injuries and neuropsychiatric symptoms, highlighting the virus’ ability to affect the central nervous system through inflammation and immune activation.
> Immune system overdrive
Another possible reason is that your immune system becomes overwhelmed while fighting off Covid-19, triggering an inflammatory response. This inflammation can damage tissues and organs, potentially causing more harm to your body than the virus itself.
Research findings
Below are some of the most significant research results to date that document the effects of Covid-19 on brain health. Large epidemiological studies have shown that individuals who had Covid-19 are at an increased risk of cognitive deficits, such as memory problems.
Imaging studies conducted before and after Covid-19 infections reveal brain shrinkage and structural changes. Research on people with mild to moderate Covid-19 indicates significant prolonged brain inflammation and changes equivalent to seven years of ageing.
Severe Covid-19 requiring hospitalisation or intensive care can lead to cognitive deficits and brain damage similar to 20 years of ageing. Laboratory experiments using human and mouse brain organoids show that SARS-CoV-2 infection causes brain cells to fuse, disrupting electrical activity and brain function.
Autopsies of severe Covid-19 patients who died months later from other causes found the virus present in brain tissue, suggesting that SARS-CoV-2 can enter the brain, although its role in causing brain problems is still unclear. Even mild Covid-19 confined to the lungs can provoke brain inflammation and impair brain cell regeneration.
The virus can also disrupt the blood-brain barrier, making it “leaky”, as seen in imaging studies of hospitalised Covid-19 patients with brain fog.
A preliminary analysis of data from 11 studies involving nearly one million Covid-19 patients and over six million uninfected individuals shows an increased risk of new-onset dementia in people aged over 60 who had Covid-19.
A recent study published in the New England Journal of Medicine examined the cognitive abilities of nearly 113,000 people who had contracted Covid-19.
The study found significant deficits in memory and executive task performance among those infected, regardless of whether they were infected early in the pandemic or during the dominance of the Delta and Omicron viral variants.
Key findings included drops in IQ as follows:
- Mild and resolved Covid-19 cases showed a cognitive decline equivalent to a three-point IQ loss.
- Those with persistent symptoms experienced a six-point IQ loss.
- Intensive care unit (ICU) admissions resulted in a nine-point IQ loss.
- Reinfections contributed an additional two-point IQ loss, compared to no reinfections.
Given that the average IQ is about 100, with an IQ above 130 indicating high giftedness and below 70 indicating significant intellectual disability, the study’s findings are concerning. A three-point IQ decline could increase the number of American adults with an IQ below 70 from 4.7 million to 7.5 million, adding 2.8 million adults to the number requiring significant societal support.
Another study in the same journal issue, involving over 100,000 Norwegians, documented worsened memory function up to 36 months following a positive SARS-CoV-2 test, further highlighting the long-term cognitive impact of Covid-19.
Future implications
This drastic impact of Covid-19 on the brain severely affects work performance and quality of life, and complicates recovery and rehabilitation. It is crucial to identify those most at risk and understand how these cognitive trends might affect the educational attainment of children and young adults, as well as the economic productivity of working-age adults.
Additionally, the potential influence of these shifts on the epidemiology of dementia and Alzheimer’s disease remains unclear. Research now confirms that Covid-19 significantly impacts the brain, with far-reaching consequences for individuals and the broader economy.
Unravelling the true causes behind cognitive impairments, including brain fog, will require years, or even decades, of global research efforts. Unfortunately, nearly everyone is a participant in this unprecedented study.
Ongoing research seeks to clarify these mechanisms and find effective interventions. Longitudinal studies are especially important for tracking cognitive changes over time and determining the persistence of these deficits.
Understanding the long-term effects of Covid-19 on brain health is vital for creating effective public health strategies, support systems and improving overall outcomes.
By Datuk Dr Nor Ashikin Mokhtar
Published in Star Newspaper, 12 Aug 2024
