Science Update: Pre-existing distress may increase risk for long COVID, NIH-funded study suggests

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Psychological distress before COVID-19 infection—feeling stressed, depressed, anxious, worried, or lonely—may raise the risk for long COVID, suggests a study funded by the National Institutes of Health. Long COVID includes such symptoms as fatigue, brain fog, breathing difficulties, and other symptoms that may persist for months after a COVID-19 infection.

The researchers cautioned that their findings should not be misinterpreted to support the view that long COVID symptoms are psychosomatic. Among study participants who developed long COVID, almost half had no psychological distress before COVID-19 infection. Many symptoms of long COVID, such as breathing difficulties and loss of taste and smell, are not common symptoms of mental illness. The authors called for more research to determine if alleviating psychological distress before COVID-19 infection reduces the chances or severity of long COVID.

The study was conducted by Siwen Wang, M.D., of the Harvard T.H. Chan School of Medicine, and colleagues. It appears in JAMA Psychiatry. The study was funded by NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Heart, Lung, and Blood Institute; National Institute of Environmental Health Sciences; and National Cancer Institute.


Long COVID involves a wide range of symptoms that last more than four weeks and sometimes for many months after a COVID-19 infection. Symptoms, such as fatigue, breathing difficulty, shortness of breath, brain fog (difficulty thinking or concentrating), and loss of taste and smell, may also go away and come back again. Risk factors for long COVID include older age, obesity, severe COVID-19 infection, high blood pressure, depressed immune system, and asthma. 

The researchers analyzed data from three long-term studies, two of which enrolled nurses and a another which enrolled children of nurses. From April 2020 to September 2020, participants, almost 97% female, responded to a baseline questionnaire on whether they were experiencing psychological distress, such as depression, anxiety, worry about COVID-19, stress, and loneliness. After the baseline questionnaire, nearly 55,000 participants responded to monthly questionnaires until November 2021 on their overall health.


During the 19 months after the baseline questionnaire, 6% (3,193 participants) tested positive for COVID-19, with 1,403 long COVID cases.

Long COVID was 32% more likely among those who had symptoms of depression, 42% more likely among those with symptoms of anxiety, 37% more likely among those who were worried about COVID-19, 46% more likely among those who felt stressed, and 32% more likely among those who felt lonely. Participants who reported two or more types of distress were almost 50% more likely to develop long COVID.


The authors concluded that psychological distress before COVID-19 infection may be a risk factor for long COVID. They noted that psychological distress is linked to inflammation and may also suppress the immune system, factors which they theorized could increase the risk for long COVID symptoms.

“We need to consider psychological health in addition to physical health as risk factors of long COVID,” said the study’s senior author, Andrea Roberts, Ph.D., M.P.H., of the Harvard T.H. Chan School of Medicine.


Wang, S, et al. Associations of depression, anxiety, worry, perceived stress, and loneliness prior to infection with risk of post-COVID-19 conditions. JAMA Psychiatry. 2022. doi: 10.1001/jamapsychiatry.2022.2640

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