COVID-19 Linked to Depressive Symptoms

Headache was the most prominent link between COVID-19 and depression.

Roy H. Perlis, MD, MSc (Massachusetts General Hospital)

Roy H. Perlis, MD, MSc (Massachusetts General Hospital)

Following an acute COVID-19 infection, patients can and have felt persistent symptoms involving mood, sleep, anxiety, and fatigue.

These symptoms, while present following a COVID-19 infection, contribute to markedly elevated rates of major depressive disorder found in recent epidemiological studies

A team, led by Roy H. Perlis, MD, MSc, Massachusetts General Hospital, published a new research letter investigating if the symptoms of a COVID-19 infection are linked to the probability of subsequent depressive symptoms.

The Survey

The researchers conducted a survey with data from adults in the US in 8 waves of an internet-based nonprobability survey conducted by Qualtrics with multiple panels of respondents.

The surveys were conducted monthly between June 2020 and January 2021, with 82,319 overall respondents who completed the Patient Health Questionnaire-9 (PHQ-9). There was a total of 3904 nonoverlapping individuals reported prior COVID-19 illness and completed the survey questions used in the final analysis.

Along with standard sociodemographic questions, which included self-identified race and ethnicity in 5 prespecified categories, each respondent was asked whether they had been diagnosed with COVID-19 illness by a clinician or received a positive test results.

The respondents were also asked what months they were ill and to indicate specifics on the presence or absence of symptoms and overall perceived severity of COVID-19 illness.

The participants also completed the PHQ-9, a common screening for symptoms of depression, with each of the 9 items scored from 0-3.

The investigators incorporated indicator variables for each symptom, as well as overall severity using a logistic regression model with PHQ-9 score of 10 or greater as the dependent variable.

The researchers then adjusted for sociodemographic features, such as age, gender, race/ethnicity, geographic region, urban vs suburban or rural, and household income. The mean time since initial COVID-19 symptoms was 4.2 months.


A little more than half of the participants (n = 2046; 52.4%) met the criteria for symptoms of major depressive disorder, while 288 individuals lacked overall COVID-19 severity data.

In the fully adjusted models, the researchers found the presence of headaches was linked to a greater probability of moderate or greater depressive symptoms (aOR, 1.33; 95% CI, 1.10-1.62). This was also linked to greater overall severity (somewhat vs not at all severe: aOR, 2.59; 95% CI, 2.04-3.30; very vs not at all severe: OR, 5.08; 95% CI, 3.93-6.59).

The researchers also found women were less likely to have symptoms than men (aOR, 0.72; 95% CI, 0.61-0.84). The probability of symptoms also decreased with increasing age (aOR, by decade, 0.76; 95% CI, 0.72-0.81).

“In regression models, these symptoms were more likely among younger respondents compared with older respondents and among men compared with women as well as among those with greater self-reported overall COVID-19 severity compared with those with lower severity,” the authors wrote.


However, the study differed from previous studies looking at the relationship between the loss of smell and taste and depressive symptoms among 114 participants, but rather headache was the crucial symptom to watch for.

However, 1 limitation of the study was that the researchers cannot exclude the possibility that individuals with baseline depression would be more likely to report symptoms of a headache. The researchers also couldn’t attribute the symptoms to new onset depression.

“Nevertheless, our results add to a growing body of evidence suggesting the importance of considering potential neuropsychiatric sequelae of COVID-19 infection,” the authors wrote. “Our results also suggest the importance of considering strategies that might mitigate the elevated risk of depressive symptoms following acute infection.”

The study, “Association of Acute Symptoms of COVID-19 and Symptoms of Depression in Adults,” was published online in JAMA Network Open.

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