Virus World

Research into bacteriophages adds to evidence that gut and brain interactions influence our behaviour. Viruses are widely regarded as harmful to our health, but a subset of viruses living in the gut could play a crucial role in regulating stress, research suggests. The discovery adds to mounting evidence that interactions between the gut and brain influence people’s behaviours, and could eventually lead to new treatments for stress-related conditions that target the vast community of viruses living inside us. While previous studies have suggested that the composition of microbes living in the gut changes in response to stress, these have largely focused on bacteria, rather than on this “virome”. “The way the virome interacts with bacteria, and how they affect stress-related health and disease status is largely unexplored,” said Dr Nathaniel Ritz, of the APC Microbiome Ireland research centre at University College Cork. “Our research opens up the potential to target the virome to treat and reduce the effects of stress.”

Ritz and his colleagues focused on a subset of viruses called bacteriophages, which infect bacteria and replicate alongside them. They studied what happened to these viruses when the mice they inhabited were exposed to chronic social stresses, such as being housed alone or in overcrowded conditions, and found that stress exposure led to changes in the composition of the viruses and the bacteria in the animals’ guts. Next, they harvested viruses from the droppings of unstressed healthy animals, and transplanted some of them back in, once the mice had been exposed to chronic social stress. The research, published in Nature Microbiology, suggested these transplants reduced levels of stress hormones and curbed depression- and anxiety-like behaviour in the mice. While further studies are needed to assess whether virus transplants are beneficial to humans suffering from stress-related conditions, the research provides some of the first evidence that gut viruses are involved in the response to stress, and that manipulating them could have therapeutic benefits. “Given that the virome composition varies greatly among individuals, it may open the door for personalised medicine approaches for stress-related disorders in the future,” said Prof John Cryan at APC Microbiome Ireland, who led the research. “One thing for certain, we must acknowledge that not all viruses are bad and they can play a key role in keeping the bad bacteria in our gut at bay especially in times of stress.”

Cited research published in Nature Microbiology (Feb.5, 2024):

https://doi.org/10.1038/s41564-023-01564-y 

Latent herpes virus reactivation has been documented in more than half of astronauts during space shuttle and International Space Station missions, and according to a recent study funded by NASA, the cause is stress.“Herpes virus is a broad category of viruses, beyond the small subset that cause sexually transmitted diseases.Most humans become infected early in life with one or more, and never fully clear these viruses,” Satish Mehta, PhD, senior scientist in the immunology/virology lab at the Johnson Space Center in Houston, told Infectious Disease News.

Results showed that 47 out of 89 (53%) astronauts on short space shuttle flights, and 14 out of 23 (61%) on longer space station missions shed herpes viruses in their saliva or urine samples. According to the study, astronauts shed four of the eight major human herpes viruses: Epstein-Barr, varicella-zoster and herpes simplex-1 in saliva and cytomegalovirus in urine. The researchers said most astronauts were asymptomatic, with only six developing symptoms.

“Larger quantities and increased frequencies for these viruses were found during spaceflight as compared to before or after flight samples and their matched healthy controls,” Mehta and colleagues wrote.  Mehta explained why: “[The] short answer is stress. In people with reduced immunity, such as the elderly or stressed individuals, these viruses can awaken and cause disease,” he said.

“Although NASA believes there is no clinical risk to astronauts during orbital spaceflight, there is concern that during deep space exploration missions, there may be clinical risks related to viral shedding. Although we do not have a serious clinical problem related to herpes viruses, their reactivation is an excellent ‘flag,’ or biomarker, for stress and reduced immunity.”

In the study, Mehta and colleagues noted that continued viral shedding after a flight can pose a potential risk for crew who may encounter infants, seronegative adults or immunocompromised people, so protocols have been put in place. 

The study was published in February 2019  in Frontiers in Microbiology - Virology:

https://doi.org/10.3389/fmicb.2019.00016

Recent stressful experiences, such as the loss of a loved one or economic insecurity are strong predictors as to whether a person hospitalized for COVID-19 will experience symptoms of long COVID a year later.  Led by researchers from NYU Grossman School of Medicine, the study found that adult patients with such “major life stressors”—present in more than 50% of those followed—were at least twice as likely to struggle with depression, brain fog, fatigue, sleep problems, and other long-term COVID-19 symptoms, say the study authors. Published online this week in the Journal of the Neurological Sciences (JNS), the analysis also confirmed the contribution of traditional factors to greater long COVID risk as shown by past studies—older age, disability level to start with, and a more severe initial case of COVID-19. “Our study is unique in that it explores the impact of life stressors—along with demographic trends and neurological events—as predictors of long-term cognitive and functional disabilities that affected quality of life in a large population,” says lead study author Jennifer A. Frontera, MD, professor in the Department of Neurology at NYU Langone Health. “Therapies that lessen the trauma of the most stress-inducing life events need to be a central part of treatment for long COVID, with more research needed to validate the best approaches.”

The research used standard telephone survey tools in the field—the modified Rankin Scale (mRS), the Barthel Index, the Montreal Cognitive Assessment (t-MoCA), and the NIH/PROMIS Neurological Quality Of Life (NeuroQoL) batteries—to measure level of daily function, clear thinking (cognition), anxiety, depression, fatigue and sleep quality. The team attempted follow-up with each of 790 patients six months and a year after COVID-19 hospitalization within NYU Langone Health between March 10, 2020 and May 20, 2020. Of these surviving patients, 451 (57%) completed 6-month and/or 12-month follow-up, and of them, 17% died between discharge and 12-month follow-up and 51% reported significant life stressors at 12-months. In analyses that compared factors against each other for their contribution to worse outcomes, life stressors including financial insecurity, food insecurity, death of a close contact, and new disability were the strongest independent predictors of prolonged COVID-19 symptoms.  These same stressors also best predicted worse functional status, depression, fatigue, sleep scores, and reduced ability to participate in activities of daily living such as feeding, dressing, and bathing. Gender was also a contributor, as past studies have found that women are more susceptible in general to—for instance—autoimmune diseases that could have an impact on outcomes. Additionally, undiagnosed mood disorders may have been unmasked by pandemic-related stressors.

Neurological long COVID may include more than one condition

A second study led by Frontera and colleagues, and published online September 29, 2022, in PLOS ONE, found that patients diagnosed as having long COVID neurological problems can be divided into three symptom groups. Because there is no current biological definition of long COVID, many studies lump disparate symptoms into what is currently a blanket diagnosis, and without an assessment of clinical relevance, says Frontera. The resulting vagueness has made it “difficult to assess treatment strategies.”  For the PLOS ONE study, the research team collected data on symptoms, treatments received, and outcomes for 12 months after hospitalization with COVID-19, with treatment success measured again by standard metrics (modified Rankin Scale, Barthel Index, NIH NeuroQoL). The three newly identified disease groups were:

• Cluster 1: Few symptoms (most commonly headache) in patients who received few therapeutic interventions
• Cluster 2: Many symptoms, including anxiety and depression, in patients who received several treatments, including antidepressants to psychological therapy
• Cluster 3: Primarily pulmonary symptoms such as shortness of breath. Many patients also complained of headache and cognitive symptoms, and mostly received physical therapy.

The most severely affected patients (symptom Cluster 2) had higher rates of disability, worse measures of anxiety, depression, fatigue and sleep disorders. The most severely affected patients had higher rates of disability, worse measures of anxiety, depression, fatigue and sleep disorders. All patients whose treatment included psychiatric therapies reported symptom improvement, compared to 97% who received primarily physical or occupational therapy, and 83% who received few interventions. The Brookings Institution estimated in August 2022 that roughly 16 million working-age Americans (aged 18 to 65) have long COVID, out of whom 2 to 4 million are out of work due to long COVID.

Published in J. Neurological Sciences (Nov.5, 2022):

https://doi.org/10.1016/j.jns.2022.120487