Severe COVID-19 is associated with molecular signatures of aging in the human brain
by Bob Yirka , Medical Xpress
Severe COVID-19 and cytokine treatment of neurons are associated with increases in predicted age. a, First, a principal-component analysis using DEGs (FDR < 0.05) of young versus old uninfected controls estimated principal component 1 (PC1). The graph presents a two-tailed Pearson correlation of chronological age with aging index (PC1) among young versus old uninfected controls from the aging cohort (training set). n = 20. Gray shadow indicates the 95% confidence interval from a linear regression fit (R2 (18) = 0.58, P = 9.2 × 10−5). b, Two-tailed Pearson correlation of chronological age with predicted aging index (PC1) among uninfected age-matched and sex-matched controls from the COVID-19 cohort (test set). n = 22. Gray shadow indicates the 95% confidence interval from a linear regression fit (R2 (20) = 0.438, P = 7.9 × 10−4). c, Predicted aging index (PC1) of individuals with COVID-19 (n = 22), age-matched/sex-matched uninfected controls (control; n = 22), and an independent group of uninfected cases with ICU/VENT treatment history (n = 9). The line in each group represents the mean ± s.e.m. COVID-19 versus control Welch two-tailed t(42.0) = 5.68, P = 3.4 × 10−6; COVID-19 versus ICU/VENT Welch two-tailed t(21.0) = 3.14, P = 0.015. A Bonferroni correction was used to adjust for multiple comparisons. d, Significant interferon and TNF-related pathways identified using GO biological pathway enrichment analysis of COVID-19 versus age-matched/sex-matched control frontal cortex DEGs. FDR, GSEA FDR (Supplementary Table 3). e, Experimental design of in vitro cytokine treatment in human neurons. Created with BioRender.com. f, Effects of IFN-β, IFN-γ and TNF on predicted aging index, as assessed following in vitro treatment of primary human neurons. The line in each group represents the mean ± s.e.m. n = 3 independent wells (1 × 105 cells per well were plated) for each treatment. IFN-β_LO versus control Welch two-tailed t(2.68) = 4.48, P = 0.16; IFN-β_HI versus control Welch two-tailed t(3.51) = 8.26, P = 0.012; IFN-γ_LO versus control Welch two-tailed t(3.58) = 20.8, P = 4.4 × 10−4; IFN-γ_HI versus control Welch two-tailed t(3.35) = 12.3, P = 4.1 × 10−3; TNF_LO versus control Welch two-tailed t(3.63) = 33.6, P = 6.6 × 10−5; TNF_HI versus control Welch two-tailed t(2.28) = 15.8, P = 0.013. Bonferroni correction was used to adjust for multiple comparisons. Credit: Nature Aging (2022). DOI: 10.1038/s43587-022-00321-w
A group of researchers working at Harvard Medical School has found evidence suggesting that patients who undergo severe COVID-19 infections may experience symptoms of aging in parts of their brains. In their paper published in the journal Nature Aging, Maria Mavrikaki, Jonathan Lee, Isaac Solomon and Frank Slack describe their analyses of brain tissue from deceased patients and what they learned.
As the pandemic continues, albeit in a much less pervasive form, scientists continue to study the impact of the SARS-CoV-2 virus. In this new effort, after reading reports that suggested some people with serious symptoms experienced cognitive decline, the researchers took a closer look at the brains of people who died from serious COVID-19 infections.
The work involved collecting brain tissue samples from the cortexes of 21 people who had died from a COVID-19 infection. They then compared those samples with samples of 22 other people who had died but had never had COVID-19. They also compared them with another control group of people who had never had COVID-19 but had died from other causes after being put on a respirator—an intervention that is known to cause negative side effects.
In their comparison, the researchers found that evidence of activation of genes in the brain associated with inflammation was more common in the people who had died from the COVID-19 infection than in either of the other two groups. They also found that genes associated with cognition and in forming connections between cells in the brain were less active.
The researchers then compared the brain samples from the COVID-19 patients taken for another group of people who had died of other causes, some of whom were relatively young and some of whom were over 71. They found similarities between the change in gene activity in the COVID-19 patients and those who were over age 71.
The researchers acknowledge that their work is just a first step toward making a clear link between COVID-19 infections and premature brain aging and note that they and others are already working on more studies. They also note that the inflammatory changes in the brain may have been due to the inflammation caused by the infection rather than the virus itself.
More information:
Maria Mavrikaki et al, Severe COVID-19 is associated with molecular signatures of aging in the human brain, Nature Aging (2022). DOI: 10.1038/s43587-022-00321-w
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Severe COVID-19 is associated with molecular signatures of aging in the human brain (2022, December 6)
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