Home News Preexisting psychological distress may be risk factor for long COVID

Preexisting psychological distress may be risk factor for long COVID


October 05, 2022

2 min read


Wang reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

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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.”


Data derived from: Wang S, et al. JAMA Psychiatry. 2022;doi:10.1001/jamapsychiatry.2022.2640.

“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.”


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