A major registry study in Denmark shows that the risk of developing a mental disorder after an infection was not further increased by COVID-19 compared with other infections of similar severity. A researcher says that these findings may influence how to manage the long-term sequelae of COVID-19 and other infections.
There has been much discussion about whether COVID-19 entails a particularly increased risk of developing a subsequent mental disorder based on many examples of people developing COVID-19 and then a mental disorder.
But overall, a major cohort study now concludes that COVID-19 is not associated with a higher increased risk of developing a subsequent mental disorder compared with other infections of similar severity that are also associated with an increased risk.
The study included all adults in Denmark and investigated the link between COVID-19 and the risk of developing a subsequent mental disorder.
The study concludes that the risk of developing a mental disorder was not higher among people with a positive polymerase chain reaction (PCR) test result for SARS-CoV-2 than among those with a negative test result. Being hospitalised with COVID-19 does not appear to be associated with a higher risk of developing a mental disorder than being hospitalised with other infections.
“Our results very clearly indicate that infections increase the risk of developing new-onset mental disorders but also that COVID-19 is not associated with a greater risk than other infectious diseases of similar severity. This knowledge should perhaps influence how we manage long-term sequelae among people with COVID-19. Perhaps this kind of follow-up support should be extended to people who have long-term sequelae from other infectious diseases,” explains Michael Benros, Professor and Head of Research, Mental Health Centre Copenhagen and the Department of Immunology and Microbiology, University of Copenhagen.
The research has been published in JAMA Psychiatry.
The study was carried out in collaboration with Vardan Nersesjan, doctor and PhD Fellow, Mental Health Centre Copenhagen and Department of Immunology and Microbiology, University of Copenhagen; Daniel Kondziella, Clinical Research Associate Professor and Consultant Neurologist, Department of Neurology, Neuroscience Centre, Rigshospitalet and Department of Clinical Medicine, University of Copenhagen; and Rune Christensen, senior statistician at the Mental Health Centre Copenhagen.
All residents of Denmark without a previous mental disorder were included in the study
The researchers reviewed the results of about 36 million PCR test results for more than 4 million people. They linked the results from the PCR tests to data from the Danish Civil Registration System, the Danish Microbiology Database, the Danish National Hospital Registry and the Danish National Prescription Registry. The researchers thus found differences in the incidence of new-onset mental disorders between people with a negative or a positive PCR test result versus the other people who had not been tested.
The researchers followed the participants from 1 March 2020 to 31 December 2021. People younger than 18 years and those with a history of mental disorder were excluded.
In addition, the researchers investigated whether individuals who had been hospitalised with COVID-19 had a higher incidence of a subsequent mental disorder than individuals hospitalised with infections other than COVID-19.
“This is the first nationwide study including all PCR test results and investigating the risk of developing a subsequent mental disorder and being treated with psychotropic drugs. There has been some concern about whether COVID-19 can affect multiple organ systems, including the brain, and this has also been observed at the individual level but has not previously been demonstrated in large population studies based on a whole country and including all PCR test results and hospital contacts,” says Michael Benros.
Being hospitalised with infections is associated with increased risk of a mental disorder
The results should allay the concerns of many people, since the researchers found that COVID-19 is not associated with a specific increased risk of a subsequent mental disorder.
The study shows that the risk of a subsequent mental disorder increased by 24% among people with a positive PCR test result compared with those who did not have any result.
This initially suggests an increased risk, but there was no further increased risk compared with people with a negative PCR test result.
The risk of developing a subsequent mental disorder was 2.54 times higher among individuals hospitalised for COVID-19 compared with individuals not hospitalised with COVID-19. However, among individuals hospitalised with non-COVID-19 infections, the risk of new-onset mental disorders was comparable, increased by 2.52 times compared with individuals not hospitalised. Specifically, the risk was 2.42 times greater among individuals hospitalised with non-COVID-19 respiratory-tract infections and 2.62 times greater among individuals hospitalised with pneumonia.
Further, hospitalisation both with and without COVID-19 was associated with an increased risk of organic mental disorders, including dementia, schizophrenia spectrum disorders, affective disorders and neurotic, stress-related and somatoform disorders.
“The results show quite clearly that infection in general increases the risk of new-onset mental disorders but also that COVID-19 does not increase that risk further,” explains Michael Benros.
Inflammation is probably the link between infection and a mental disorder
Michael Benros says that a 2.5 times greater risk of a mental disorder is a considerable increase in risk, but many people hospitalised with COVID-19 or other infectious diseases are already older, which is why an infectious disease can cause greater problems in the brain than among younger people.
This is also how both COVID-19 and other infectious diseases can lead to the development of a mental disorder.
Michael Benros explains that, for most people, an infectious disease will be linked with a mental disorder through the inflammatory reaction in the body, creating a hyperinflammatory response to the infection, which can cross the blood–brain barrier and thus acutely affect the brain.
This is also why one third of the people hospitalised with COVID-19 develop delirium.
“This can cause long-lasting mental health symptoms, and in rare cases, infections in the brain or autoimmune reactions that cross-react with brain tissue can occur, which also increases the risk of being diagnosed with a mental disorder. The severity of the infection was particularly associated with subsequent new-onset mental disorders, and here older individuals were more prone to being very seriously ill and hospitalised with COVID-19 or other infectious diseases. Besides inflammatory reactions, in some, the lack of oxygen, a stroke or other complications after intensive care may be the reason why they later develop a mental disorder,” concludes Michael Benros.