Severe COVID-19 is linked to molecular signatures of aging in the human brain

2 (18) = 0.58, P = 9.2 × 10−5). b, Two-tailed Pearson correlation of chronological age with predicted aging index (PC1) among uninfected age- and sex-matched controls from the COVID-19 cohort (test set). n = 22. The gray shadow shows the 95% confidence interval from a linear regression fit (R2 (20) = 0.438, P = 7.9 × 10−4). c, Predicted aging index (PC1) of subjects with COVID-19 (n=22), uninfected age/sex matched 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 ± sem COVID-19 versus the two-tailed Welch control, 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 signaling pathways identified using GO enrichment analysis of COVID-19 biological pathway compared to control age-matched/sex-matched 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 the predicted aging index as assessed after in vitro treatment of primary human neurons. The line in each group represents the mean ± SEM n = 3 independent wells (1 × 10 5 cells per well were plated) for each treatment. IFN-β_LO versus control Welch bilateral t(2.68)=4.48, P=0.16; IFN-β_HI versus control Welch bilateral t(3.51)=8.26, P=0.012; IFN-γ_LO versus control Welch two-sided t(3,58) = 20.8, P = 4.4 × 10−4; IFN-γ_HI versus control Welch two-sided 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-sided t(2.28) = 15.8, P = 0.013. The Bonferroni correction was used to adjust for multiple comparisons. Photo credit: natural change (2022). DOI: 10.1038/s43587-022-00321-w” width=”800″ height=”530″/>

Severe COVID-19 and cytokine treatment of neurons is associated with an increase in predicted age. a, First, a principal component analysis using DEGs (FDR 2(18) = 0.58, P = 9.2 × 10−5). b, Two-tailed Pearson correlation of chronological age with predicted aging index (PC1) among uninfected age- and sex-matched controls from the COVID-19 cohort (test set). n = 22. The gray shadow shows the 95% confidence interval from a linear regression fit (R2 (20) = 0.438, P = 7.9 × 10−4). c, Predicted aging index (PC1) of subjects with COVID-19 (n=22), uninfected age/sex matched 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 ± SEM of COVID-19 versus the two-tailed Welch control 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 signaling pathways identified using GO enrichment analysis of COVID-19 biological pathway compared to control age-matched/sex-matched 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 the predicted aging index as assessed after in vitro treatment of primary human neurons. The line in each group represents the mean ± SEM n = 3 independent wells (1 × 105 cells per well were plated) for each treatment. IFN-β_LO versus control Welch bilateral t(2.68)=4.48, P=0.16; IFN-β_HI versus control Welch bilateral t(3.51)=8.26, P=0.012; IFN-γ_LO versus control Welch two-sided t(3,58) = 20.8, P = 4.4 × 10−4; IFN-γ_HI versus control Welch two-sided 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-sided t(2.28) = 15.8, P = 0.013. The Bonferroni correction was used to adjust for multiple comparisons. Recognition: aging in nature (2022). DOI: 10.1038/s43587-022-00321-w

A group of researchers working at Harvard Medical School have found evidence that patients who undergo severe COVID-19 infection may show signs of aging in parts of their brains. In her article published in the journal natural change, Maria Mavrikaki, Jonathan Lee, Isaac Solomon and Frank Slack describe their analyzes of brain tissue from deceased patients and their findings.

As the pandemic continues, albeit in a much less widespread form, scientists continue to study the effects of the SARS-CoV-2 virus. After reading reports suggesting that some people with severe symptoms had experienced cognitive decline, in this new experiment researchers took a closer look at the brains of people who died from severe COVID-19 infections.

The work involved collecting brain tissue samples from the cortices of 21 people who had died from COVID-19 infection. They then compared those samples to samples from 22 other people who had died but never had COVID-19. They also compared her to another control group of people who never had COVID-19 but had died of other causes after being put on a ventilator — an intervention known to cause negative side effects.

In their comparison, the researchers found that evidence of activation of genes in the brain related to inflammation was more common in the people who died from COVID-19 infection than in the other two groups. They also found that genes linked to perception and the formation of connections between cells in the brain were less active.

The researchers then compared the brain samples of COVID-19 patients taken from a different group of people who had died from other causes, some relatively young and some over 71 years old. They found similarities between the change in gene activity in the COVID-19 patients and those over the age of 71.

The researchers acknowledge that their work is only a first step in establishing a clear link between COVID-19 infections and premature brain aging, and note that they and others are already working on further studies. They also note that the inflammatory changes in the brain may be due to the inflammation caused by the infection rather than the virus itself.

More information:
Maria Mavrikaki et al, Severe COVID-19 Associated with Molecular Signatures of Aging in the Human Brain, aging in nature (2022). DOI: 10.1038/s43587-022-00321-w

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