Preexisting psychological distress may be risk factor for long COVID
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High psychological distress, including anxiety, worry and depression, before SARS-CoV-2 infection may be a risk factor for developing post-COVID-19 symptoms, a recent study published in JAMA Psychiatry found.
According to Siwen Wang, MD, a researcher in the department of nutrition at Harvard University, and colleagues, “sustained psychological distress may cause activation of the hypothalamic-pituitary-adrenal axis and subsequent immune dysregulation.”
“Other common manifestations of distress, such as loneliness and perceived stress, which have increased during the pandemic, have been implicated in chronic disease and early mortality,” they wrote, “but have not been investigated as possible risk factors for post–COVID-19 conditions.”
Post-COVID-19-related symptoms, also referred to as long COVID, can linger following an infection for weeks or months. A CDC survey conducted in June found that about 19% of Americans who had reported having COVID-19 in the past experienced symptoms of long COVID.
For the current study, Wang and colleagues examined data on 54,960 participants from three ongoing longitudinal studies beginning in April 2020, who responded to a baseline and at least one follow-up questionnaire. Among them, 6% reported a positive COVID-19 test result over 19 months. The final analysis included 3,193 participants who had both completed all the necessary questionnaires and tested positive for COVID-19.
Of the participants, the median age was 55.3 years; 96.4% were women; 96.8% were white; and 49% were active health care workers.
Overall, 43.9% of participants (n = 1,403) reported experiencing symptoms consistent with long COVID, with 86.9% (n = 1,219) reporting symptoms lasting up 2 months or longer, according to the Wang and colleagues.
All types of distress that the researchers measured were associated with an increased risk for long COVID symptoms:
- probable depression (RR = 1.39; 95% CI, 1.19-1.63);
- probable anxiety (RR = 1.47; 95% CI, 1.27-1.7);
- being very worried about COVID-19 (RR = 1.43; 95% CI, 1.22-1.68);
- perceived stress (RR = 1.5; 95% CI, 1.21-1.86); and
- being lonely some or most of the time (RR = 1.35; 95% CI, 1.11-1.65).
Participants with more types of distress were at higher risk for developing long COVID symptoms (RR = 1.54; 95% CI, 1.28 to 1.86). The most common long COVID symptoms included fatigue, smell or taste problems, shortness of breath, confusion and memory issues.
The authors reported that psychological distress did not just influence but amplified the presence of post-infection symptoms: all conditions, excluding persistent cough and taste or smell problems, were “more prevalent” in participants with each type of distresses versus those without.
“Symptoms of depression, symptoms of anxiety, worry and perceived stress at baseline were associated with a 25% to 51% increased risk of having symptoms that interfered with activities occasionally to always,” Wang and colleagues wrote.
The researchers noted several study limitations, including participants being predominantly white, female and health care workers; positive COVID-19 tests being self-reported; and potential bias from data not being missing at random.
Wang and colleagues concluded that their findings should be followed up with further research evaluating whether stress reduction may potentially assist in treatment or prevention of long COVID symptoms. They also noted that identifying and treating biological pathways connecting distress with long COVID “may benefit individuals with post-COVID-19 conditions or other chronic post-infection syndromes.”
References:
- Association of psychological distress prior to infection with risk of post-COVID-19 conditions. https://www.eurekalert.org/news-releases/963715. Published Sept. 7, 2022. Accessed Sept 7, 2022.
- Nearly one in five American adults who have had COVID-19 still have ‘long COVID.’ https://www.cdc.gov/nchs/pressroom/nchs_press_releases/2022/20220622.htm. Accessed Sept. 8, 2022.
- Wang S, et al. JAMA Psychiatry. 2022;doi:10.1001/jamapsychiatry.2022.2640.
Perspective
Back to TopLewis S. Nelson, MD
This is an important study because we have been trying to better understand who is at greatest risk of developing long COVID, which itself has been a difficult entity to understand. Because it is a syndrome, defined by a constellation of findings, there is no objective diagnostic test and the findings themselves are typically common or hard to objectively confirm. For example, fatigue, muscle pain and brain fog are common in long COVID but are also found in a number of unrelated syndromes and they are subjective. Because of the syndromic nature of the diagnosis, people can be readily misdiagnosed and there is no practical means to confirm or exclude the diagnosis. Assuming long COVID is eventually understood to have a biological basis, among the issues to address when evaluating a patient for long COVID is whether they have risk factors that predispose them to its development. What this study provides is insight into risk factors that are common among such patients. Not all patients had risk factors, but enough did to suggest there’s a link.
From my perspective, the difficulty in defining the syndrome of long COVID and the variability of the findings among different patients and patient classes suggest that there may not be a simple, unifying, physiological explanation. When people have a disease like sickle cell, we identify the sickle cell gene or sickled red blood cells and make a firm diagnosis. When people have a functional syndrome, like chronic fatigue, there is no satisfactory, identifiable biological explanation that connects all of the patients. Because of this, the specter of having a psychological component is raised, and this is suggested by the findings of the study.
The article does not specify the extent to which a psychological stressor impacts physical health in patients with long COVID, but combined with the variability in the presenting findings among patients, it does show that in patients diagnosed with long COVID, psychological stressors were common.
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