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High levels of pre-existing psychological distress prior to a COVID-19 infection were associated with an increased risk for developing long COVID symptoms, according to a prospective cohort study.

Participants who self-reported psychological distress -- including probable depression or anxiety, being very worried about COVID-19, and feeling lonely some of the time or often -- had an increased risk of developing post-COVID conditions:

• Depression: risk ratio (RR) 1.32 (95% CI 1.12-1.55)
• Anxiety: RR 1.42 (95% CI 1.23-1.65)
• Worry about COVID: RR 1.37 (95% CI 1.17-1.61)
• Loneliness: RR 1.32 (95% CI 1.08-1.61)

And those in the highest quartile of perceived stress had a 46% higher risk for post-COVID conditions compared to those in the lowest quartile (RR 1.46, 95% CI 1.18-1.81), reported Siwen Wang, MD, of Harvard T.H. Chan School of Public Health in Boston, and colleagues in .

"We found that psychological distress is even more strongly associated with long COVID compared to ... , including obesity, diabetes, and hypertension," Wang told 番茄社区app.

Additionally, the researchers noted that patients who had two or more types of distress prior to infection had a nearly 50% increased risk for long COVID symptoms (RR 1.49, 95% CI 1.23-1.80).

Wang and co-authors emphasized that the results should not be misinterpreted to suggest that long COVID is psychosomatic. For example, 40% of participants who developed long COVID symptoms experienced no distress at baseline, and long COVID symptoms differ substantially from symptoms of mental illness.

Studies have shown that more than half of patients with long COVID report relapses triggered by physical activity, which is considered protective against relapses of mental illnesses, Wang and co-authors said.

At least one previous study on risk factors for long COVID found an association with anxiety disorder, but the new study is one of the first with data from early in the pandemic to focus on the risks of a wider variety of psychological variables, Wang said.

"We understand that mental health conditions [are] so prevalent in the United States, and it has all been linked to those kinds of chronic inflammation, immune dysregulation, which are proposed mechanisms for long COVID," she said. "So we hypothesized that if there is the link, we should probably look at it."

To gather the data, the researchers drew from participants from three ongoing longitudinal studies: the Nurses' Health Study II, the Nurses' Health Study 3, and the Growing Up Today Study.

The analysis included 54,960 participants -- 38% of whom were active healthcare workers -- who completed a questionnaire from April to September 2020 and were followed through November 2021. Mean age was 57.5 years. A positive SARS-CoV-2 test result was reported by 6% during the follow-up period.

In terms of documented risk factors for post-COVID conditions, only asthma (RR 1.18, 95% CI 1.02-1.37), hypertension (RR 1.17, 95% CI 1.02-1.34), and weight (RR 1.07 per 5 BMI increase, 95% CI 1.03-1.11) showed significant associations in the current study. No associations were seen with increasing age, high cholesterol, diabetes, cancer, or in participants with a history of smoking.

While the participants' psychological symptoms and COVID-19 infection were self-reported, Wang said the team is confident in the unique study population for these purposes: "This is predominantly a group of healthcare workers, so self-report should be very accurate, and there are a lot of validation studies in this cohort to validate their self-report on health conditions," she said.

Wang also noted that while the study population aided in some aspects of the analysis, it was also a limitation, in that participants were predominantly white (96.5%) and female (96.6%) and worked in healthcare, so the results might not be generalizable to a wider population.

The findings, however, could help identify new areas of focus for studies into the mechanism of COVID-19 infection and long COVID symptoms, Wang said. "In consideration of how high the prevalence of depression [and] anxiety are in the United States and worldwide, future research might want to look at whether treatment or better management of psychological distress might mitigate symptoms of long COVID or prevent the development of long COVID."

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