The virus has caused a global pandemic, leading to millions of infections and deaths. While the overall fatality rate of COVID-19 is relatively low, ranging from 0.5% to 2%, there are several risk factors associated with the disease’s outcomes.
One such factor is the presence of neuropsychiatric diseases, which have been found to influence the severity and long-term effects of COVID-19.
It has been observed that SARS-CoV-2 can infect cells in both the upper and lower respiratory tracts, as well as other organs and systems in the human body. This includes the immune system, nervous system, and microvessels. As a result, COVID-19 can manifest with various neuropsychiatric symptoms.
Furthermore, recovered COVID-19 patients have been found to have a higher risk of memory decline and other neurological sequelae, which are associated with increased mental stress and the risk of mental disorders.
Additionally, genetic studies have suggested a causal link between decreased intelligence in children and an increased risk of symptomatic COVID-19.
This is a topic that has gained attention in recent years, as the COVID-19 pandemic has affected millions of people worldwide, especially children.
One of the main sources of evidence for this causal link is a Mendelian randomization study by Zhu et al. (2022), which used genetic data from large-scale genome-wide association studies (GWAS) to examine the effect of COVID-19 susceptibility on childhood intelligence. Mendelian randomization is a method that uses genetic variants as natural experiments to infer causal relationships between exposures and outcomes, while avoiding confounding and reverse causation.
Zhu et al. (2022) selected four genetic variants that were strongly associated with COVID-19 (hospitalized vs. population) in a GWAS of 6406 cases and 902 088 controls of European ancestry. They then used these variants as instrumental variables (IVs) to estimate the effect of COVID-19 on childhood intelligence, measured by a standardized test in a GWAS of 12 441 individuals of European ancestry.
The results showed that as the genetic susceptibility to COVID-19 increased, childhood intelligence followed a decreasing trend, according to different MR methods. The inverse variance weighted method, which is the most commonly used MR method, estimated that a one standard deviation increase in COVID-19 susceptibility was associated with a 0.152 standard deviation decrease in childhood intelligence (p = 0.004). The weighted median method, which is more robust to outliers and weak instruments, estimated a similar effect size of -0.134 (p = 0.031).
These findings suggest that there is a causal link between genetically increased COVID-19 and decreased childhood intelligence, implying that COVID-19 may be a risk factor for declines in cognitive development in children. The authors speculated that COVID-19 may impair childhood intelligence through direct or indirect mechanisms, such as inflammation, hypoxia, vascular damage, or psychosocial stress.
However, there are some limitations and caveats to this study that need to be considered. First, the genetic instruments for COVID-19 were based on hospitalized cases, which may not represent the general population or asymptomatic cases. Second, the genetic instruments for childhood intelligence were based on a single test at one time point, which may not capture the full spectrum of cognitive abilities or changes over time. Third, the MR analysis assumed that there were no pleiotropic effects of the genetic variants on other factors that may affect childhood intelligence, such as education, income, or nutrition. Fourth, the MR analysis only estimated the average causal effect across populations, but not the individual-level or subgroup-level effects.
Therefore, more studies are needed to replicate and extend these findings, using different sources of data and methods to address these limitations and explore the mechanisms and moderators of the causal link between decreased intelligence in children and an increased risk of symptomatic COVID-19.
Moreover, there is evidence of an increased risk of Alzheimer’s disease following a COVID-19 diagnosis in elderly individuals. These findings suggest a need for a detailed evaluation of the relationship between COVID-19 and general intelligence.
To explore the potential impact of COVID-19 on intelligence, the researchers conducted a Mendelian randomization (MR) analysis using genome-wide association study (GWAS) summary results. They utilized large-scale datasets of European participants, including those from the UK Biobank.
The analysis revealed causal effects of SARS-CoV-2 infection and critical COVID-19 on intelligence, indicating a potential risk of intelligence decline in COVID-19 patients.
To further understand the biological mechanisms linking COVID-19 and intelligence, the researchers identified shared genomic loci between COVID-19 and intelligence. They found two loci, 2p16.1 and 17q21.31, that influenced both severe COVID-19 and intelligence.
These loci contained genes such as BCL11A, MAPT, KANSL1, and WNT3, which have been implicated in various neurodevelopmental and neurodegenerative disorders. Protein-protein interaction analysis and subnetwork enrichment analysis revealed that these genes formed interconnected networks associated with cognitive decline.
Additionally, the researchers constructed functional pathways connecting COVID-19 and changes in different brain regions using data from structural and functional MRI studies. These pathways highlighted brain abnormalities resulting from COVID-19, such as decreased gray matter thickness, tissue damage in regions connected to the primary olfactory cortex, and reduced overall brain size.
These changes align with patterns of cognitive decline associated with aging and may be attributed to COVID-19-induced dysfunction of microvessels, as well as direct damage to the neuroglial and immune systems.
In conclusion, this study provides evidence supporting the detrimental effect of COVID-19 on intelligence. The MR analysis revealed causal effects of SARS-CoV-2 infection and critical COVID-19 on intelligence, suggesting a potential risk of intelligence decline in COVID-19 patients. The identification of shared genomic loci and functional pathways between COVID-19 and intelligence sheds light on the biological mechanisms underlying this association. Further research is needed.
The study findings were published in the peer reviewed journal: QJM – An International Journal of Medicine (A journal of the Association of Physicians of Great Britain & Ireland – Oxford Academic)
https://academic.oup.com/qjmed/advance-article/doi/10.1093/qjmed/hcad122/7191821
