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Experiencing psychological distress before becoming infected with SARS-CoV-2 is linked to an increased risk of post-COVID conditions often referred to as “long COVID”, according to new research.
In an analysis of nearly 55,000 adult participants in three ongoing studies, with the Depression, anxiety, worry, perceived stress, or loneliness early in the pandemic, before SARS-CoV-2 infection, were associated with a 50% increased risk of developing long-lasting COVID. These types of psychological distress were also associated with a 15% to 51% increased risk of impaired daily living in people with long-lasting COVID.
Psychological distress was even more strongly associated with the development of long COVID than physical health risk factors – and the increased risk was not explained by health behaviors such as smoking or physical comorbidities, note the researchers.
“Our findings suggest the need to consider psychological health in addition to physical health as risk factors for long COVID-19,” said lead author Siwen Wang, MD, postdoctoral fellow, Department of Nutrition, Harvard TH Chan School of Public Health, Boston, Massachusetts. , Told Medscape Medical News.
“We need to raise awareness of the importance of mental health and focus on getting mental health care to people who need it, by increasing the number of mental health clinicians and improving access to care,” she said.
The conclusions were published online September 7 to JAMA Psychiatry.
“Very little understood”
Post-acute sequelae of SARS-CoV-2 (“long COVID”), which are “signs and symptoms consistent with COVID-19 that extend beyond 4 weeks from the onset of infection “constitute “an emerging health problem”, write the investigators.
Wang noted that eight to 23 million Americans have been estimated to have developed long COVID. However, “despite the high prevalence and daily life impairments associated with long COVID, it is still poorly understood and few risk factors have been established,” she said.
Although psychological distress may be implicated in long COVID, only three previous studies have investigated psychological factors as potential contributors, the researchers note. Additionally, no studies have investigated the potential role of other common manifestations of distress that have increased during the pandemic, such as loneliness and perceived stress, they add.
To investigate these questions, the researchers turned to three large ongoing longitudinal studies: the Nurses’ Health Study II (NSHII), the Nurses’ Health study 3 (NHS3), and the Growing Up Today Study (GUTS).
They analyzed data from a total of 54,960 participants (96.6% female; mean age, 57.5 years). Of the group as a whole, 38% were active healthcare workers.
Participants completed an online COVID-19 questionnaire from April 2020 to September 1, 2020 (baseline) and monthly surveys thereafter. Beginning in August 2020, surveys were administered quarterly. The end of follow-up was in November 2021.
The COVID questionnaires included questions about positive SARS-CoV-2 test results, COVID symptoms and hospitalization since March 1, 2020, and the presence of long-term COVID symptoms, such as fatigue, breathing problems, persistent cough, muscle/joint/chest pain, smell/taste problems, confusion/disorientation/brain fog, depression/anxiety/mood changes, headacheand memory problems.
Participants who reported these post-COVID conditions were asked about the frequency of symptoms and the degree of impairment in daily living.
Inflammation, immune dysregulation involved?
The Patient Health Questionnaire-4 (PHQ-4) was used to assess symptoms of anxiety and depression over the past 2 weeks. It consists of a two-item measure of depression (PHQ-2) and a two-item measure Generalized anxiety disorder Scale (GAD-2).
Non-caregiver providers completed two additional assessments of psychological distress: the four-item Perceived Stress Scale and the three-item UCLA Loneliness Scale.
Researchers included demographic factors, weight, smoking status, marital status, and medical conditions, including diabetes, hypertensionhypercholesterolemia, asthmadiabetes and cancer, and socioeconomic factors as covariates.
For each participant, the investigators calculated the number of types of distress felt high, including likely depression, likely anxiety, worry about COVID-19, being in the top quartile of perceived stress and loneliness.
During 19 months of follow-up (1-47 weeks post baseline), 6% of respondents reported a positive SARS-CoV-2 antibody, antigen, or polymerase chain reaction test result.
Of these, 43.9% reported long COVID conditions, with most reporting that symptoms lasted 2 months or more; 55.8% declared at least an occasional alteration in daily life.
The most common post-COVID conditions were fatigue (reported by 56%), loss of smell or taste problems (44.6%), shortness of breath (25.5%), confusion/disorientation / brain fog (24.5%) and memory problems (21.8%).
Among patients who had been infected, there was a significantly higher rate of psychological distress before infection after adjusting for sociodemographic factors, health behaviors and comorbidities. Each type of distress was associated with post-COVID conditions.
| Psychological distress | Relative risk (95% CI) |
|---|---|
| Probable depression | 1.32 (1.12 – 1.55) |
| Likely anxiety | 1.42 (1.23 – 1.65) |
| Worrying about COVID-19 | 1.37 (1.17 – 1.61) |
| Perceived stress (highest quartile vs lowest quartile) | 1.46 (1.18 – 1.81) |
| Solitude | 1.32 (1.08 – 1.61) |
Additionally, participants who had experienced two or more types of distress prior to infection had an almost 50% increased risk of post-COVID conditions (hazard ratio [RR], 1.49; 95% CI, 1.23 – 1.80).
Among people with post-COVID conditions, all types of distress were associated with an increased risk of impaired daily living (RR range, 1.15 – 1.51).
Lead author Andrea Roberts, PhD, principal investigator at the Harvard TH Chan School of Public Health, noted that the investigators did not examine the biological mechanisms potentially underlying the association they found.
However, “based on previous research, it may be that inflammation and immune dysregulation related to psychological distress play a role in the association of distress with long COVID, but we cannot be sure” , Roberts said.
Contribute to the field
Commenting for Medscape Medical NewsYapeng Su, PhD, a postdoctoral researcher at the Fred Hutchinson Cancer Research Center in Seattle, Washington, called the study “great work contributing to the long COVID research field and revealing important links” with psychological stress before infection. .
Su, who was not involved in the study, was previously at the Institute for Systems Biology writing about the long COVID.
He noted that “the biological mechanism of such an intriguing linkage is certainly the next important step, which will likely require extensive phenotyping of biological samples from these patients longitudinally.”
Wang pointed to previous research suggesting that some patients with mental illness “sometimes develop autoantibodies that have also been associated with an increased risk of long-term COVID.” Additionally, depression “affects the brain in ways that may explain some cognitive symptoms in long COVID,” she added.
More studies are now needed to understand how psychological distress increases the risk of prolonged COVID, Wang said.
The research was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Dean’s Fund for Scientific Advancement Acceleration Award, Harvard TH Chan School of Public Health, Massachusetts Consortium on Pathogen Readiness Evergrande COVID-19 Response Fund Award and Veterans Health Services Research and Development Service funds. Wang and Roberts reported no relevant financial relationship. Revelations from other investigators are listed in the original article. Su does not report any relevant financial relationship.
JAMA Psychiatry. Published online September 7, 2022. Full article
Batya Swift Yasgur, MA, LSW, is a freelance writer with a consulting firm in Teaneck, NJ. She is a regular contributor to numerous medical publications, including Medscape and WebMD, and is the author of several consumer health books as well as Behind the Burqa: Our Lives in Afghanistan and How We Escaped to Freedom (the memoirs of two brave Afghan sisters who told her their story).
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