COVID-19 infection in crucial brain regions may lead to accelerated brain aging

Led by corresponding authors Joy Mitra, Ph.D., Instructor, and Muralidhar L. Hegde, Ph.D., Professor of Neurosurgery, with the Division of DNA Repair within the Center for Neuroregeneration at the Houston Methodist Research Institute, the research team described their findings in an article titled "SARS-CoV-2 and the Central Nervous System: Emerging Insights into Hemorrhage-Associated Neurological Consequences and Therapeutic Considerations" online in press July 16 in the journal Ageing Research Reviews.

Still a major burden on our daily lives, a great deal of research has shown that the impacts of the disease go far beyond the actual time of infection. Since the onset of the pandemic, COVID-19 has surpassed a death toll of over 5.49 million worldwide and over 307 million confirmed positive cases, with the U.S. accounting for almost 90 million of those cases, according to the Our World in Data website.

COVID-19 is known to invade and infect the brain, among other major organs. While a lot of research has been done to help us understand the evolution, infection and pathology of the disease, there is still a great deal that remains unclear about the long-term effects, especially on the brain.

The coronavirus infection can cause long-term and irreversible neurodegenerative diseases, particularly in the elderly and other vulnerable populations. Several brain imaging studies on COVID-19 victims and survivors have confirmed the formation of microbleed lesions in deeper brain regions related to our cognitive and memory functions. In this review study, researchers have critically evaluated the possible chronic neuropathological outcomes in aging and comorbid populations if timely therapeutic intervention is not implemented.

Microbleeds are emerging neuropathological signatures frequently identified in people suffering from chronic stress, depressive disorders, diabetes and age-associated comorbidities. Based on their earlier findings, the investigators discuss how COVID-19-induced microhemorrhagic lesions may exacerbate DNA damage in affected brain cells, resulting in neuronal senescence and activation of cell death mechanisms, which ultimately impact brain microstructure-vasculature. These pathological phenomena resemble hallmarks of neurodegenerative conditions like Alzheimer's and Parkinson's diseases and are likely to aggravate advanced-stage dementia, as well as cognitive and motor deficits.

The effects of COVID-19 infection on various aspects of the central nervous system are currently being studied. For instance, 20-30% of COVID-19 patients report a lingering psychological condition known as "brain fog" where individuals suffer from symptoms such as memory loss, difficulty in concentrating, forgetting daily activities, difficulty in selecting the right words, taking longer than usual time to complete a regular task, disoriented thought processes and emotional numbness.

More severe long-term effects analyzed in the Houston Methodist review article include predispositions for Alzheimer's, Parkinson's and related neurodegenerative diseases, as well as cardiovascular disorders due to internal bleeding and blood clotting-induced lesions in the part of the brain that regulates our respiratory system, following the COVID-19 symptoms. Additionally, cellular aging is thought to be accelerated in COVID-19 patients. A plethora of cellular stresses inhibit the virus-infected cells from undergoing their normal biological functions and let them enter into "hibernation mode" or even die completely.

The study also suggests various strategies to improve some of these long-term neuropsychiatric and neurodegenerative outcomes, as well as outlines the importance of the therapeutic regimen of the "nanozyme" in combination with various FDA-approved drugs that may prove successful to fight against this catastrophic disease.

However, given the ever-evolving nature of this field, associations like the ones described in this review show the fight against COVID-19 is far from over, say the investigators, and reinforce the message that getting vaccinated and maintaining proper hygiene are key in trying to prevent such long-term and detrimental consequences.

Research in the authors' laboratories is supported by grants from the National Institute of Neurological Disorders and Stroke and the National Institute of Aging of the National Institutes of Health (award numbers R01NS088645, RF1NS112719, R03AG064266 and R01NS094535); The Welch Foundation (grant BE-0048); and the Houston Methodist Research Institute.

Other researchers collaborating with Mitra and Hegde on this paper were Houston Methodist investigators Manohar Kodavati, Vincent E. Provasek, K.S. Rao, Sankar Mitra, Dale J. Hamilton, Philip J. Horner, Farhaan S. Vahidy, Gavin W. Britz and Texas A& M professor Thomas A. Kent.