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  • Writer's pictureP.K. Peterson

Psychological Distress: Another Risk Factor for Long Covid

“It is more important to know what sort of person has a disease than to know what sort of disease a person has.”

- Hippocrates, 460 BCE, Greek Physician, father of Western Medicine


“We were surprised by how strongly psychological distress before a COVID-19 infection was associated with an increased risk of long COVID.”

- Siwen Wang, M.D., Research Fellow, Harvard T.H. Chan School of Public Health



In my September 7, 2020 Germ Gems post, “Long Covid: Older Adults at Risk,” I dealt with long Covid, a debilitating illness that older adults (people over 50 years of age) are at increased risk of developing. Recently, researchers at the Harvard T. H. Chan School of Public Health identified psychological distress as another risk factor for long Covid. In today’s Germ Gems post, I summarize their study and discuss psychological distress within the context of how the brain affects the immune system.

Psychological distress as a risk factor for long Covid. In the article “Associations of Depression, Anxiety, Worry, Perceived Stress, and Loneliness Prior to Infection With Risk of Post-COVID-19 Conditions,” published in the September 7, 2022 issue of JAMA Psychiatry, Harvard researchers reported the results of their study on the role psychological distress played in the development of long Covid. This was a prospective cohort study of 54,960 participants that involved predominantly white female health workers.


The results of this study demonstrated that depression, anxiety, worry about COVID-19, perceived stress, and loneliness measured at study baseline before SARS-CoV-2 infection, were each predictive of developing COVID-19-related symptoms lasting four weeks or longer and daily life impairment due to these symptoms following SARS-CoV-2 infection. The researchers concluded that pre-infection psychological distress was associated with an increased risk of developing post-COVID-19 conditions indicative of long Covid. Additionally, they found that psychological distress was more strongly associated with developing long Covid than physical risk factors such as obesity, asthma, or hypertension. Senior Research Scientist, Andrea Roberts, Ph.D. expressed the “take home message” from this study: “We need to consider psychological health in addition to physical health as risk factors of long COVID-19.”


What is distress? It is an ancient idea that the mind and body are connected and influence one another. But it was only in the past century that the anatomical and chemical basis of their connectedness began to be revealed.


In the 1930s, McGill University endocrinologist Dr. Hans Selye introduced the concept of “stress” into the field of medicine. Selye suggested there are two categories of stress: “distress” and “eustress.” Distress is stress that negatively affects a person, whereas eustress is stress that has a positive effect, energizing and motivating people to make a change.


In the 1980s, the interdisciplinary field Psychoneuroimmunology blossomed, and numerous studies showed that psychological distress leads to impaired immune function through pathways involving the nervous and endocrine systems.

Until this century, much of the research on stress focused on how the nervous and endocrine systems alter the immune system. But starting at the turn of this century, when the importance of the microbiome, that is, the large array of microbes that share our body surfaces, first became recognized, many researchers turned their attention to the involvement of the gut microbiome in various emotional states. (For an overview of this research field, see “Gut Microbiota Are Associated With Psychological Stress-Induced Defections in Intestinal and Blood-Brain Barriers,” Frontiers in Microbiology volume 15, 2020).


Implications for prevention and treatment of long Covid. Drs. Siwen Wang, Andrea Roberts, and their Harvard colleagues’ research may spur strategies for the prevention and even treatment of long Covid. But as these researchers pointed out much additional research is needed, including studies to decipher the mechanisms whereby psychological distress fosters development of long Covid.


There already is considerable evidence that psychological distress, operating through the brain-endocrine-immune system axis or via interactions of the microbiome-brain-immune systems, impairs the function of the immune system. Hypothetically, these interactions could help explain the results of the JAMA Psychiatry study.

Waning worry about COVID-19. On September 14, 2022, the head of the World Health Organization announced that the end of the COVID pandemic is in sight. This announcement should help alleviate some of the psychological distress caused by the pandemic and could even lessen the impact of one of the risk factors for developing long Covid. But, while we are close to the end, we are not there yet. Do not throw all caution to the wind. Instead, be sure you are fully vaccinated and get your COVID booster. Also, amplify lifestyle behaviors that promote “eustress,” like eating nutritious food and avoiding alcohol, visiting your family and friends, listening to music, and walking in the woods.

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Main Page images courtesy of Shuxian Hu, MD. Dr. Hu is a scientist in the Neuroimmunology Research Laboratory at the University of Minnesota.

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