Viruses in the Brain and on the Mind

“If the human brain were so simple that we could understand it, we would be so simple that we couldn’t.”

Emerson Pugh, American research engineer and scientist

“There was more to the pandemic than just the virus, though. There was social isolation, higher levels of stress, and loss of work and other cognitively stimulating activities. In other words, there were lots of reasons for people’s brains to get a little worse during those few years.”

F. Perry Wilson, MD, Yale School of Medicine (“The Pandemic Literally Aged Our Brains,” Medscape, July 22, 2025)

A recent study showed that the COVID-19 pandemic may have accelerated brain aging even in people who were never infected with the etiologic agent, SARS-CoV-2. (Mohammadi-Nejad, A., et al., “Accelerated Brain Aging During the COVID-19 Pandemic, Nature Communications, July 22, 2025).This baffling conundrum triggered my curiosity and seemed like a good starting point for this Germ Gems post reflecting on current concepts about interactions between the nervous system, the immune system, and the gut microbiome. Additionally, as the above-mentioned study was about brain aging, I thought it would be a good time to mention new thinking about viruses implicated in serious brain damage of young people (pediatric influenza-associated acute necrotizing encephalopathy) and the putative involvement of herpes simplex virus-1 in Alzheimer’s Disease (AD)—a devastating pandemic that afflicts more than 2.2 million Americans.

What’s the difference between the “brain” and the “mind”? Let’s start with a simple breakdown of terms. The brain refers to a physical structure composed of cells (neurons and glia) and blood vessels located in the head that carries out specific biological functions like vision, language, and memory. By way of contrast, the mind is not a physical entity but rather it is a concept that encompasses consciousness, thoughts, feelings, and other mental processes. In other words, the brain is the physical hardware, while the mind is the software that allows us to experience and interact with the world.

The mind-body relationship. For time immemorial, ideas about the mind-body relationship captivated the attention of philosophers. It has also been a topic of intense interest to many neuroscientists, psychologists, and psychiatrists for the past two centuries. And, the mind-body relationship could also explain the phenomenon of accelerated brain aging of people during the COVID-19 pandemic who were never infected with SARS-CoV-2.

Ali-Reza Mohammadi-Nejad, PhD, and his colleagues at the University of Nottingham investigated the pandemic’s impact on brain aging using longitudinal brain MRI data from 996 healthy adults participating in the UK Biobank Study. On average, the pandemic group showed a 5.5-month higher deviation of brain age gap at the second timepoint compared with the control group. And the degree of brain aging in the pandemic group was similar in those who were infected with SARS-CoV-2 and those who lived through the pandemic without evidence of a viral infection.

University of Oxford psychiatrist, Dr. Maxime Taquet, commented on the findings saying they raise “important questions about the long-term neurological impact of the pandemic, whether due to infection itself or the broader psychological and social stress it caused.” (Brooks, M., “COVID-19 Pandemic Tied to Accelerated Brain Aging,” Medscape, July 23, 2025). In a statement, Dr.  Mohammadi-Nejad said, “[The study] really shows how much the experience of the pandemic itself, everything from isolation to uncertainty, may have affected our brain health.” (Comment: Perhaps it would be better to say “mind and brain health.”)

No one knows for certain the basis for the accelerated brain aging of non-infected people during the COVID-19 pandemic. If the hypothesis is correct that the minds of many adults were adversely affected by experiencing the COVID-19 pandemic resulting in physical damage (aging) to their brains, then logically one might ask, “how did that happen?” The honest answer: no one knows.

The gut microbiome and COVID-19. Extensive research over the past 50 or more years has demonstrated biological connections between the immune, neuroendocrine, and nervous systems that are activated during mental and emotional stress. (The so-called Brain-Immune Axis). What is newly recognized in this research field is that a Gut Microbiome-Brain axis also exists, and it is involved in stress-related medical conditions.

Bringing the gut microbiome into the picture, results of a large survey of COVID-19 patients in the U.S. and U.K. demonstrated a significant increase in gastrointestinal disorders. (McCreary, J., “COVID’s Gut Punch: Some GI Disorders Rose Post-Pandemic,” MedPage Today, July 31, 2025). Conditions having the largest increases included functional dyspepsia and irritable bowel syndrome.

Viruses that damage the brains of children and older adults. In a number of earlier Germ Gems posts, I dealt with a large variety of viruses that afflict damage in the nervous system, including not only SARS-CoV-2 but also HIV, herpes simplex virus-1, poliovirus, rabies virus, Nipah virus, measles virus, and monkeypox virus. While influenza viruses have also been the focus of many earlier posts, the entity influenza-associated acute necrotizing encephalopathy only emerged as a critical threat to children in the past two flu seasons. ( “Influenza-Associated Acute Necrotizing Encephalopathy in US Children,” Journal American Medical Association, July 30, 2025; Uyeki, T., “Pediatric Influenza-Associated Necrotizing Encephalopathy—Gaps Need to be Addressed,” Journal American Medical Association, July 30, 2025).

Influenza-associated acute necrotizing encephalopathy is a rare but devastating neurological complication affecting previously healthy children. (76% of the cases occurred in kids with no underlying medical conditions.) It has a high mortality rate (27%) and  a high morbidity rate with 63% of survivors being left with moderate to severe disability.

At the other end of age spectrum is Alzheimer’s disease (AD), with a global toll of 55 million people (projected to double by 2050). The etiology of AD is unknown, and its pathogenesis is complex. But a number of infectious agents have been postulated to play a critical role, most notably herpes simplex virus-1. (Brooks, M.,  “Cold Sore Virus Implicated in Alzheimer’s Disease,” Medscape, May 23, 2025; see also, “Is the Alzheimer’s Pandemic Caused by a Microbe,” Germ Gems, January 27, 2021).

Sadly, the first clinical trial of the anti-HSV-1 drug, valacyclovir, demonstrated no benefit in early AD. (George, J.,  “Can a Herpes Drug Slow Alzheimer’s?,” MedPage Today, July 29, 2025). The negative results of the trial of valacyclovir in early AD will weigh heavily on the minds of millions of families of patients with AD, as well as AD investigators.

Brain health is a priority for people of all ages. And, as 43% of the global burden of disease is neurological, it is a highpriority. (“Brain health for all ages: a global call to action,” The Lancet, July 26, 2025).  Thankfully, there’s a vigorous community of researchers who are dedicated to finding an effective treatment not only for AD but also for many other devastating neurological conditions. This sounds like a high-minded goal, but given the quality of the scientists and clinical researchers involved, I believe they have the brain power to achieve extraordinary things.