Stress and depression are better long Covid indicators than physical comorbidities, new study says

Studies have repeatedly suggested that physical conditions like immunosuppression and hypertension can increase a person’s risk not only for severe Covid but also long Covid. But in a new study, researchers found that psychological stressors such as depression, anxiety, and loneliness were more predictive of Covid patients’ likelihood of experiencing long Covid than classically associated physical factors.

“Unfortunately, there’s a long history of people not taking these conditions as seriously as they might take physical health conditions that might be easier to measure or easier to see,” said Andrea Roberts, a senior research scientist at the Harvard T.H. Chan School of Public Health and the senior author on the study, which was published Wednesday in JAMA Psychiatry. “For long Covid, obviously, then, it becomes very important to look at psychological health, and it raises more broadly the question of the importance of identifying and treating mental health issues.”

The study followed more than 54,000 survey respondents, most of whom were past or present health care workers, for 19 months starting in April 2020. At the beginning of the pandemic, these survey respondents self-assessed the amount of worry they felt about Covid-19, as well as the frequency of depressive or anxiety symptoms as a baseline measure. Non-health care workers were also assessed on their feelings of loneliness or perceived stress.

Researchers used surveys to follow up with the participants to determine whether they had tested positive for Covid; the researchers also identified those who experienced long Covid, defined as four weeks or more of symptoms. Almost 3,200 of the participants eventually contracted Covid. The researchers found that depression, anxiety, perceived stress, loneliness, and worry about the disease were associated with a 1.3- to 1.5-fold increase in risk for reporting long Covid symptoms. Participants reporting two or more types of distress had nearly a 50% increased risk for long Covid.

While the authors suggest biological mechanisms that might link mental health to long Covid symptoms, the study cannot show that stress or anxiety cause the disease. “This is an observational study, not a randomized clinical trial,” said Siwen Wang, a research fellow at Harvard and the study’s lead author. “Under a randomized clinical trial you will say ‘A’ is causal with ‘B.’ But for observational studies, we definitely cannot say for sure ‘this is a causal link that we find’; we only find association but not causal [relationships].”

Nonetheless, Aric Prather, a psychology and behavioral sciences professor at the University of California, San Francisco, who was not involved in the study, called the authors’ endeavors to account for possible confounding factors for long Covid “quite convincing.”

The researchers used three refinement models, first controlling for demographic factors (age, sex, racial identity, health care worker status, and partner’s education), then adjusting for factors like smoking and body mass index, then finally controlling for other common comorbidities including diabetes, hypertension, high cholesterol, asthma, and cancer. In each case, the relationship between prior psychological distress and long Covid remained strong.

Furthermore, of the participants who reported long Covid symptoms, the ones who had reported prior symptoms of psychological distress at the beginning of the pandemic were more likely to have long Covid symptoms severe enough to affect their daily ability to function than those who did not report psychological distress before contracting the disease.

The authors emphasized that these results should not suggest that long Covid symptoms are psychological.

“Often, ‘it’s all in your head’ is another way to say ‘we don’t know what’s going on,’” said Roberts, referring to the way in which clinicians’ dismissal of long Covid symptoms can blame the victim.

In the paper, Roberts and her colleagues pointed to multiple indicators that long Covid is not simply psychosomatic. Besides the fact that more than 40% of respondents did not report psychological distress in the baseline report, long Covid symptoms are also markedly different from mental illness symptoms.

The self-reported nature of both the initial psychological stressors and positive Covid tests injects uncertainty into the study design, but Wang noted that several validation studies show that self-reported health information from health care workers such as the ones surveyed have high validity.

Wang, Roberts, and Prather all pointed out that the survey data were taken from a cohort of predominantly white and predominantly female respondents (96.5% and 96.6%, respectively, of the original 54,960 respondents) and that until the research is replicated in more populations, it’s unknown whether the results can be generalized. However, Roberts noted that they saw the same trends with even stronger associations in the small number of men in the study.

To Wang, the surprising finding that mental stressors were a better indicator of long Covid risk than physical comorbidities is “signal” to health care workers and policymakers that mental health care should be better — and more accessible — for those who need it.

Prather agreed, saying this study shows that “lived experience” and mental health stressors are an important determinant of “who ends up getting sick and who ends up staying sick.”

“It’s a really great first step in this work and taking advantage of this large-scale data,” said Prather. “But obviously, it’s just the beginning of uncovering this story to really get to, more precisely, the factors that are at play.”

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