Brain & Neurons

Harvard Study Links Severe COVID-19 to Accelerated Brain Aging

Researchers discover gene activation patterns associated with accelerated brain aging in patients with severe COVID-19.

By Bennett M. Sherman

Key Points

  • COVID-19 patients exhibit gene activation patterns in the brain associated with accelerated aging.
  • Genes of COVID-19 patients with more activity include immunity and cell stress response-associated genes, while those with less activation relate to cognition.
  • A gene activity-based age calculator suggests that the brains of COVID-19 patients are older, likely due to more brain inflammation.

Most people are aware of COVID-19’s debilitating respiratory symptoms, but many are unaware of the neurological symptoms. For example, many patients report a lack of focus, memory impairment, and depression. What’s more, on average, those who’ve had severe COVID-19 display diminished overall cognitive performance, suggesting severe infections may speed up age-related cognitive decline. While neurological and cognitive impairments suggest COVID-19 may speed up brain aging, no studies have provided firm data confirming this.

As published in Nature Aging, Slack and colleagues from Harvard University link severe COVID-19 infections to gene activity signatures of accelerated aging. Gene activation patterns in COVID-19 infected adults of all ages resembled those of uninfected aged adults. Genes associated with immune and cell stress responses had increased activity, and genes associated with cognitive processes had less activity, conferring a higher predicted age for COVID-19 patients. These findings provide genetic evidence supporting that severe COVID-19 infection accelerates brain aging.

Severe COVID-19 Infection Speeds Up Brain Aging

Slack and colleagues compared gene activity profiles (transcriptomics) between severely-infected COVID-19 patients and uninfected aged adults. Their analyses revealed that severe COVID-19 spurs gene activity signatures seen in older, uninfected individuals. These results suggest that severe COVID-19 infections cause accelerated brain aging.

To get a better idea of how severe COVID-19 patients’ gene activity patterns in the brain relate to aging, Slack and colleagues examined what genes showed changed activity. They found that genes with more activity induced by COVID-19 were associated with immunity and cell stress responses. Genes with less activation in severe, COVID-19-infected patients pertain to learning, memory, and neuronal communication. These findings provide evidence that severe COVID-19 activates genes for immunity, possibly due to higher inflammation levels, and diminishes gene activity related to cognition.

Genes linked to immune and cellular stress responses exhibited increased activity, while those associated with learning, memory, and cognition showed decreased activation.
(Mavrikaki et al., 2022 | Nature Aging) Genes associated with immune and cell stress responses showed elevated activity, while those related to learning, memory, and cognition displayed reduced activation. Gene sets, represented by circles, with a Normalized Enrichment Score (NES) above zero have elevated activation, while NES scores below zero have reduced activity in COVID-19 patient brains.

Slack and colleagues applied an aging calculator based on gene activity levels to the three groups to confirm the association between severe COVID-19 infections and accelerated aging. The predicted aging index based on transcriptomics, an indicator of the predicted age, was highest for the COVID-19-infected group. These results provide further evidence that severe COVID-19 significantly accelerates aging.

The predicted age of the brain is higher in patients severely affected by COVID-19.
(Mavrikaki et al., 2022 | Nature Aging) Predicted age is higher for severe COVID-19-infected patients in the brain. Gene activity analyses were used to calculate the predicted aging index (PC1), an estimate of biological age. Compared to uninfected adults (red circles) and those who’d been in the ICU or on a ventilator (blue circles), COVID-19-infected individuals (green circles) had an elevated predicted aging index.

COVID-19-Induced Inflammation May Accelerate Aging

In search of a mechanism by which severe COVID-19 may initiate accelerated aging, Slack and colleagues examined gene activity data for inflammation-associated proteins. The genes for these proteins, including interferons and tumor necrosis factor (TNF), had higher activation levels in COVID-19 patients. These findings suggest accelerated aging comes from higher inflammation levels.

“Our findings indicate that COVID-19 is associated with molecular signatures of brain aging and emphasize the value of neurological follow-up in recovered individuals,” said Slack and colleagues. The data presented in the study provide some of the first convincing indicators that severe COVID-19 accelerates the pace of aging. Moreover, the data support a link between accelerated aging and inflammation in COVID-19 patients. For this reason, taking steps to mitigate inflammation during and following a bout of COVID-19 may be a way to preserve cognition for these patients. Such steps may include taking anti-inflammatory compounds prescribed by a physician.


Mavrikaki, M., Lee, J.D., Solomon, I.H. et al. Severe COVID-19 is associated with molecular signatures of aging in the human brain. Nat Aging (2022).

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