Severe COVID-19 causes age-like changes in the human brain

In a recent article published in natural agingResearchers have found that severe coronavirus disease 2019 (COVID-19) causes age-like changes in frontal cortex regions of the brain, leading to cognitive impairment. These findings highlight the importance of neurological examination of individuals who have recovered from COVID-19.

study: Severe COVID-19 is associated with molecular features of aging in the human brain. Image credit: Naeblys / Shutterstock.com

Background

Previous studies have reported a decline in overall cognitive performance for an average of 10 years after severe COVID-19. Similarly, some reports show that COVID-19 damages the frontal cortex, a brain region responsible for cognition.

Despite these observations, molecular evidence for the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the brain remains inadequate, and investigators in the current study suggest accelerated aging. I’m assuming the effect is similar.

About research

In this study, researchers analyzed frontal cortex samples obtained from 54 individuals through ribonucleic acid sequencing (RNA-seq) and identified molecular signatures similar to aging associated with severe COVID-19. .

After collection during autopsy, frozen brain samples were prepared using biosafety level 2+ procedures prior to RNA extraction by phase separation. The SARS-CoV-2 genome alignment was then evaluated by aligning the raw sequence reads to the SARS-CoV-2 reference genome. Similarly, researchers determined differential gene expression (DGE) by aligning raw sequencing reads to the reference transcriptome.

The team identified frontal cortex samples in which whole transcriptome analysis produced DEGs with a false discovery rate (FDR) of less than 0.05 in gene set enrichment analysis (GSEA). To reduce the bias of transcriptome profiling methods, an ‘aging index’ was devised using aging and control cohorts as training and test sets.

The geriatric cohort consisted of 21 severely ill patients with COVID-19. One had a history of Alzheimer’s disease (AD), another of hers had a history of epilepsy, but the remaining 19 of her had no known neuropathy.

The elderly group also consisted of 23-year-old individuals with asymptomatic SARS-CoV-2 infection. The control group included 22 age- and sex-matched, SARS-CoV-2-free, non-neuropathic her controls and an age- and sex-matched uninfected person with AD. It was

Another independent control cohort consisting of 9 SARS-CoV-2-uninfected persons aged 22 to 85 years with prior ventilator (VENT) or intensive care unit (ICU) treatment was also included in the final analysis. was included in

Additionally, frontal cortex transcriptomic data from a separate subset of 633 individuals whose brains were donated for the Religious Order Research and Memory and Aging Project (ROSMAP) were studied. These individuals underwent a Mini-Mental State Examination (MMSE) while they were alive.

People in this subset were classified according to their average MMSE score, with a score of 25 indicating high cognitive ability and a score below 25 indicating low cognitive ability. This exercise helped researchers further assess the relationship between her COVID-19-related transcriptomic changes and cognitive function.

Survey results

Except for a 62-year-old individual with epilepsy and a 23-year-old with asymptomatic infection, all COVID-19 cases in the elderly cohort were far from controls, as assessed by clustering analysis. An elderly person in the ICU/VENT cohort also clustered near her SARS-CoV-2-infected person in the elderly cohort.

A total of 6,993 DEGs were identified between COVID-19 cases in the aging cohort and age- and sex-matched controls. Between these two cohorts, 3,330 degrees and he 3,663 degrees were substantially upregulated and downregulated, respectively.

Severe COVID-19 resulted in positive gene enrichment of immune pathways, but negative enrichment of memory and cognitive pathways. The disease also disrupted cellular responses to several biological pathways associated with brain aging, such as deoxyribonucleic acid (DNA) damage and calcium homeostasis. The GSEA also revealed a consistent correlation between his severe COVID-19 and cognitive decline.

Additional analyzes utilizing the aging index confirmed that severe COVID-19 shifts brain molecular age compared to uninfected ICU/VENT and age- and sex-matched controls. rice field.

Interestingly, the gene expression changes observed in severe COVID-19 patient samples were not due to the presence of SARS-CoV-2 RNA in the frontal cortex. Instead, these changes likely occurred due to upregulation of interferon (IFN) and tumor necrosis factor (TNF) response pathways in the frontal cortex, which subsequently caused age-like cognitive deficits.

Conclusion

The current study identifies gene expression changes that mimic aging in severe COVID-19 patients and explain the cognitive deficits observed in recovered cases. Furthermore, the results showed that circulating inflammatory cytokines mediate these senescence-associated gene expression changes.

Based on these findings, researchers recommend that people who have recovered from severe COVID-19 undergo neurological follow-up. Monitoring and early intervention could potentially interfere with age-like neurological pathology and subsequent cognitive decline in these individuals.