The study found severe COVID was linked with many of the same gene expression changes in brain tissue seen in old age.
According to a study using post-mortem brain tissue samples, severe COVID-19 is linked to biochemical indicators of brain ageing. The new study was released in the Nature Aging journal.
The study discovered aging-like gene expression abnormalities in the brains of deceased COVID patients, and the researchers issue a warning that potential long-term neurological issues may manifest in the years after the pandemic.
Scientists continue to work on understanding the long-term effects of this novel coronavirus on the human body as the three-year anniversary of the advent of SARS-CoV-2 approaches. It has become increasingly obvious that COVID-19 can have a wide range of effects on the entire body, from harming heart tissue to raising one’s risk of developing diabetes. For many people, a COVID-19 infection can appear as a mild, flu-like respiratory sickness.
One of the most alarming areas of research over the past few years may have been the effect of SARS-CoV-2 on the brain. From it has been shown since 2020 that COVID affects the brain, neurological symptoms including brain fog and losing one’s sense of smell have long been linked to the disease. But it’s unclear exactly how it impacts the brain.
Earlier this year, hundreds of people were found to have long-term brain alterations, according to a research called “one of the most significant” of the pandemic to far.
One of the first longitudinal imaging investigations of brain alterations linked to SARS-CoV-2 infections was provided by the study. Shortly after that study was published, a new study examining the long-term effects of severe COVID-19 on cognition was released. The University of Cambridge and Imperial College London scientists who conducted the study calculated that a severe COVID case was cognitively equivalent to nearly 20 years of brain ageing.
Six months after being released from the hospital, COVID patients had a barrage of cognitive tests that revealed survivors were less accurate and responded to tasks more slowly than their matched controls. In essence, cognitive test results from a 50-year-old hospitalised with severe COVID were comparable to those of a 70-year-old in good condition.
Since the start of the pandemic, Maria Mavrikaki, a researcher at Harvard Medical School, has been following the increasing data connecting COVID to enduring cognitive issues. She then set out to study what specifically might be causing these cognitive issues. Mavrikaki examined more than 50 brain tissue samples with a number of collaborators, including 21 samples from people who passed away from severe COVID.
The whole-transcriptome analysis method of genetic sequencing was the subject of the study.
Insights about which specific genes were turned on or off in a person at the time of death are possible thanks to this technique, which provides a snapshot of gene activity in a single cell.
“We also observed significant associations of cellular response to DNA damage, mitochondrial function, regulation of response to stress and oxidative stress, vesicular transport, calcium homeostasis, and insulin signaling/secretion pathways previously associated with aging processes and brain aging,” the researchers write in the new study. “Altogether, our analyses suggest that many biological pathways that change with natural aging in the brain also change in severe COVID-19.”
The study also looked at the potential triggers for these particular aging-related gene expression alterations. Two different possibilities have been put forth so far in the discussion of COVID’s effects on the brain. One school of thinking contends that SARS-CoV-2 can directly invade the brain, but the opposing view contends that the neurological symptoms of COVID are caused by the disease’s systemic inflammatory effects.
The latest research looked into both ideas but was unable to find any SARS-CoV-2 virus RNA in the brain tissue samples. Instead, the study did discover the up-regulation of numerous inflammatory pathways (including type I/II interferons and tumour necrosis factor, or TNF), which have been linked to brain ageing in the past.
“We also found that cytokines upregulated the expression of aging-regulated genes that were upregulated in individuals with COVID-19 such as TRIM22, CHI3L1, C1S and IFITM1 and downregulated the expression of aging-regulated genes that were downregulated in individuals with COVID-19 such as CCND2, ACTR3B and EPHA5,” the researchers stated in the study. “Taken together, our data suggest that COVID-19-induced TNF and type I/II interferons may lead to significant deteriorating effects in the brain in the absence of SARS-CoV-2 neuroinvasion.”
The results of the researchers’ further research proved that these particular immune cells can directly affect the expression of various genes linked to ageing.
In conclusion, the researchers advise physicians to be aware that COVID may one day be regarded as a risk factor for dementia, particularly in individuals with pre-existing susceptibilities.
“The generalizability of our results to individuals who had mild COVID-19 or who recovered from COVID-19 remains to be determined,” the researchers conclude. “Given our findings, we advocate for neurological follow-up of individuals who recovered from COVID-19 and suggest potential clinical value in modifying risk factors to reduce the risk or delay the development of aging-related neurological pathologies and cognitive decline.”
Parvathy Sukumaran 
