Study shows high prevalence of depression, anxiety and post-traumatic stress disorder after COVID-19

In a study involving 425 patients who recovered from moderate and severe COVID-19, researchers at the University of São Paulo (USP) in Brazil observed a high prevalence of cognitive deficits and psychiatric impairments. The assessments were conducted between six and nine months after discharge from Hospital das Clínicas (HC), the hospital complex run by the university’s Medical School (FM-USP).

Half the participants (51.1%) reported memory decline after the infection. About one in eight (13.6%) were diagnosed with post-traumatic stress disorder. A similar proportion (15.5%) were diagnosed with generalized anxiety disorder, which began in 8.14% after they had recovered from the disease. A smaller group (8%) were diagnosed with depression, which began only after hospital discharge in 2.5%.

The study was supported by FAPESP. An article with the complete findings is published in the journal General Hospital Psychiatry.

“A key finding is that none of the cognitive or psychiatric alterations observed in these patients correlated with the severity of their condition. Similarly, we found no associations with the clinical conduct adopted during hospitalization or with socio-economic factors such as deaths of family members or financial losses during the COVID-19 pandemic,” said Rodolfo Damiano, a resident physician at FM-USP’s Institute of Psychiatry and first author of the article.

The study was part of a broader project led by Geraldo Busatto Filho, a professor at FM-USP and head of its Psychiatry Neuroimaging Laboratory (LIM21). In this project, a large group of patients treated at HC between 2020 and 2021 are being tracked by professionals in several areas, including ear, nose and throat (ENT) specialists, physiatrists and neurologists, to check for complications left by SARS-CoV-2. 

“While I was studying for my PhD, I conducted the neuropsychiatric part of the study, whose preliminary results are described in the article,” Damiano told. The principal investigator for this part was Eurípedes Constantino Miguel Filho, Head of the Department of Psychiatry at FM-USP. 

“One of our goals was to understand whether this coronavirus and the disease it causes have a long-term impact on and produce manifestations in the central nervous system,” Miguel Filho said. The fact that no clear correlation was found between psychiatric alterations and the severity of the disease or the patient’s socio-economic status bears out the hypothesis that delayed inflammatory processes associated with infection by SARS-CoV-2 can give rise to psychiatric impairments. “Many of these patients have cognitive alterations and neurological symptoms such as anosmia [loss of smell], suggesting that the disease can cause late alterations linked to immune responses that lead to neuroinflammation,” he added.

Methodology

All participants were submitted to a battery of tests to evaluate mental state and cognitive functions, such as memory, attention, verbal fluency, and spatial and temporal orientation.

“We observed substantial cognitive impairment,” Damiano said. “For example, in the test that measures processing speed, patients took twice as long as expected for their age [based on average values reported in the scientific literature for the Brazilian population]. This was the case for all age groups. In addition, more than half said they had suffered memory decline.”

The volunteers also had a structured interview with a psychiatrist and answered standard questionnaires used to diagnose depression, anxiety, and post-traumatic stress.

As noted by the authors of the article, the prevalence of “common mental disorder” (depressive symptoms, anxiety, irritability, fatigue, insomnia, impaired memory, or difficulty concentrating) in the study samples (32.2%) was higher than previously reported in epidemiological studies for the Brazilian population (26.8%).

In these patients, the prevalence of generalized anxiety disorder (14.1%) was considerably higher than the average for the overall population (9.9%). The prevalence of depression (8%) also exceeded the estimated average (4%-5%).

“Patients who progress to severe COVID-19 tend to be clinically compromised [by heart or kidney problems, diabetes, and other comorbidities] and therefore already have more psychiatric symptoms,” Damiano said. “This was taken into consideration in the analysis. Even after correcting for this factor, the prevalence observed in the study was very high.”

Psychiatric symptoms typically worsen after acute infections, he continued, “but such a sharp difference hasn’t been observed in other viral diseases, and COVID-19 does appear to cause significant cognitive impairment in many patients. The effect of the virus on the central nervous system is a possible explanation. We don’t yet know if patients can recover from these losses.”

Next steps

The researchers are currently studying blood samples collected from the volunteers during their hospital stay. The aim is to analyze the cytokine profile (cytokines are immune system proteins that regulate the inflammatory response) in order to find out whether the degree of inflammation in the acute phase of COVID-19 correlates with the development of neuropsychiatric symptoms.

“If we do find a correlation, the next step will be to see if drugs that inhibit interleukins [one of the types of cytokine] can be used to prevent the appearance or worsening of psychiatric symptoms,” Damiano said.

Patients already affected should seek vaccination and psychiatric treatment. “Evidence has been amassed that physical exercise helps reverse cognitive alterations associated with severe disease, and cognitive rehabilitation can be applied under the supervision of a qualified neuropsychologist. Personally, I also believe meditation can be beneficial,” he said.

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About São Paulo Research Foundation (FAPESP)

The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the State of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration. You can learn more about FAPESP at www.fapesp.br/en and visit FAPESP news agency at www.agencia.fapesp.br/en to keep updated with the latest scientific breakthroughs FAPESP helps achieve through its many programs, awards and research centers. You may also subscribe to FAPESP news agency at http://agencia.fapesp.br/subscribe.