Microbiome & Microbiology Review

By Pooja Toshniwal PahariaMay 30 2023Reviewed by Lily Ramsey, LLM

In a recent study published in JAMA Psychiatry, researchers estimated psychiatric disorders and psychotropic medication usage risks among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected versus uninfected individuals, those who did not undergo coronavirus disease 2019 (COVID-19) testing, and individuals hospitalized due to non-COVID-19 respiratory tract infections.

Study: COVID-19 and Risk for Mental Disorders Among Adults in Denmark. Image Credit: mapush/Shutterstock.com

Background

COVID-19 has caused unprecedented morbidity and mortality across the globe. Besides the respiratory tract, SARS-CoV-2 may infect various organs, including the brain, as indicated by studies reporting an increased prevalence of persistent neuropsychiatric sequelae of acute COVID-19.

The neuropsychiatric effects may result from indirect immunological mechanisms, and therefore, the impact of SARS-CoV-2 infection on the brain may be comparable to that observed after other conditions of similar severity.

However, national-level studies assessing the neuropsychiatric outcomes of SARS-CoV-2 infections are scarce. Moreover, previous studies included specific cohorts such as United States (US) veterans or individuals from healthcare organizations, limiting the generalizability of the study findings.

The results may also be biased due to potential confounding factors such as socioeconomic status and family history of psychiatric disorders.

About the study

In the present national-level study, researchers investigated psychiatric disorders risks among SARS-CoV-2-positive individuals and whether the associations were specific to SARS-CoV-2 infections.

The study included 4,152,792 adult residents of Denmark registered with the Danish Civil Registration System and alive between 1 January and 1 March 2020, excluding 616,546 individuals with prior history of mental disorders.

Follow-up assessments were performed until 31 December 2021 until the censoring, outcome, or termination of follow-up. The study exposure was polymerase chain reaction (PCR) results for SARS-CoV-2 infection and associated hospitalization.

The outcomes were the risk of incident mental disorders [according to the International Classification of Diseases, Tenth Revision (ICD-10) codes] and psychotropic medication use [based on the Anatomical Therapeutic Chemical (ATC) codes].

Individuals hospitalized with an infection between 2010 and 1 March 2020 were excluded from the analysis. Survival analysis was performed using Cox proportional hazards regression modeling to calculate the hazard rate ratio (HRR) values.

Data adjustments were made for gender, age, psychiatric disorders among parents, level of education, household income, employment status, and comorbidities assessed using the Charlson Comorbidity Index (CCI).

Data were obtained from Danish national registries linked to the participants using unique personal identification numbers and anonymized for analysis.

The registries included the Danish Psychiatric Central Research Register, the Danish Microbiology Database, the Danish National Hospital Registry, the Danish National Prescription Registry, and the Database for Integrated Labour Market Research.

Results

The sample population included 501,110 individuals who had not undergone PCR testing (mean age of 61 years; 55% males), 526,749 PCR-positive (mean age of 41 years; 50% males), and 3,124,933 PCR-negative (mean age of 49 years; 51% females).

Most (93%) of individuals were followed for two years. In total, the team analyzed 39,528,002 PCR reports.

Psychiatric disorders risks increased among PCR-positive individuals (HRR 1.2) and PCR-negative individuals (HRR 1.4) in comparison to those who did not undergo PCR testing.

Compared to PCR-negative individuals, incident psychiatric disorders risks were lower among PCR-positive individuals aged between 18 and 29 years (hazard rate ratio 0.8), whereas those aged ≥70.0 years had an elevated risk (hazard rate ratio 1.3).

Similar trends were observed for the use of psychotropic medications, with a lower risk among individuals aged between 18 and 29 years (hazard rate ratio 0.8) and a higher risk for individuals aged ≥70.0 years (HRR 1.6).

Incident psychiatric disorders risks were considerably higher for hospitalized COVID-19 patients than the public (HRR 2.5); however, there were non-significant differences in risk compared to individuals hospitalized for infections not associated with COVID-19 (HRR 1.0).

Conclusions

Overall, the study findings showed that the risk of mental disorders among SARS-CoV-2-infected individuals was comparable to that among uninfected individuals, except for individuals aged ≥70.0 years.

However, individuals with SARS-CoV-2 infection-associated hospitalizations had a considerably higher risk than the public but a similar risk as those with hospitalizations due to other infections. The findings indicated that mental health deterioration after COVID-19-associated hospitalization occurs commonly but is not more frequent than after other equivalently severe infections.

Further research must be conducted with longer follow-ups and immune system-associated biomarkers to improve our understanding of the effects of COVID-19 severity on post-infectious mental health.